Court filing

Complaint — CHD v. FDA

Filed January 24, 2022 in Children's Health Defense v. Food & Drug Administration; one of 7 filings from this case.

Record facts

Court	U.S. District Court for the Western District of Texas, Waco Division
Filed	2022-01-24

U.S. District Court for the Western District of Texas, Waco Division · No. 6:22-cv-00093-ADA-JCM · Doc. 1 · 2022-01-24 · Docket on CourtListener

Full text

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 1 of 237

UNITED STATES DISTRICT COURT
FOR THE WESTERN DISTRICT OF TEXAS

CHILDREN’S HEALTH DEFENSE, Case No. 6:22-cv-93
DEBORAH L. ELSE, an individual, and
SACHA DIETRICH, an individual,

Plaintiffs,

v. COMPLAINT

FOOD & DRUG ADMINISTRATION, and
JANET WOODCOCK, acting commissioner
of Food & Drugs,

Defendants.

INTRODUCTION

The greatest threat to a government is often itself. The most dangerous tool of

government is emergency power. This case concerns the misuse of that power by

Defendant Food & Drug Administration (“FDA”). By claiming emergency powers, the

FDA eliminated the notice-and-comment process, ignored citizen petitions, abandoned

traditional safety mechanisms for assessing drugs injected into interstate commerce,

ignored express legislative limits on their actions, and now claim to be beyond judicial

review. Defendants used this precarious emergency power to push dangerous drugs on

minors, mislabel and misbrand those drugs to the public, knowing their mislabeling

would lead these mislabeled drugs to be mandated on children as young as 5 years old.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 2 of 237

SUMMARY

Under the pretext of Emergency Use Authorization powers (two years into this
“emergency”’), Defendant FDA authorized a dangerous drug for minor children as young as
5 years old to address COVID-19, which poses less risk to a 5-year-old than the ordinary
flu. The FDA, using its emergency powers, redefined this drug as a “vaccine” even though it
did not meet the century-long definition of the term, leading to the broadening of the
definition of “vaccine” to include this new experimental biologic. The FDA failed to
provide for any notice-and-comment period, failed to provide for any citizen petition
recognition nor redress of petitioner concerns and grievances, claimed these emergency
powers provided for no legislative limit beyond their expansive claims, and even claimed
these emergency powers prevent and preclude judicial review by citizens. The FDA has
become an agency that declares its own law, enforces its own law, and adjudicates its own

law, with children now the sacrificial lamb to this precarious power grab.

As an agency founded on regulating interstate labeling of products (not as a supervisory
medical or scientific agency), the core of the Defendants’ work is making sure the marketing
of drugs conform to their known qualities, especially highlighting the drug’s risks, the limits
on the drug’s proven efficacy, and conforming the marketing of any drug to the
requirements of informed consent, the universal governing medical norm and jus cogens
principle governing all civilized societies, as codified in the Nuremberg Code of 1947.
Instead, the FDA shirked their purpose and rushed an untested product to market,
mislabeled this experimental gene therapy a “vaccine”, and allowed it to be mandated upon

minors without their informed consent.
3.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 3 of 237

The FDA ignored, violated, and discarded their own laws and rules limiting the
marketing of drugs, and pushed this drug onto minor children with false and manipulative
advertising, even stooping so law as to use the popular children’s program Sesame Street,

and the children’s favorite character, Big Bird to promote this mislabeled product.

The FDA’s unchecked and unbridled reign over COVID-19 pharmaceuticals is the
foundation of all vaccination policies and mandates in the United States today. The FDA
determines which drugs can be mandated because it’s authorization, approval and labeling is
the first foundational centerpiece of any drug being mandated in the first place. Children
now face loss of access to needed transplants, medical care, educational programs, travel,

and even basic participation in public life based on the FDA’s actions.

PARTIES

Plaintiff CHD is a not-for-profit membership organization incorporated under the laws of
Georgia. Plaintiff sues in its own capacity and on behalf of its constituent members who
have been affected by Defendants’ actions. FDA’s conduct toward children, including
misuse of emergency powers to authorize the drug, then the public marketing and
mislabeling of the drug to minor children as young as 5 years old, caused a serious diversion
of the organization’s resources from its original mission in public education and protection
of children to correct this critical error and try to protect the members and mission of CHD
from Defendants’ illicit actions and ill effects thereof. Additionally, CHD was denied its
right to petition, the chance at notice-and-comment, and its procedural remedies under the
Administrative Procedures Act because of the FDA’s misuse of its emergency powers rather

than following the proper protocol for biologic licenses for children.

3
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 4 of 237

6. Plaintiff Deborah L. Else is a member of CHD and a resident of Bell County, Texas. She
is a long-time pharmacist and the parent of R.E., a 10-year-old student at Thomas Amold
Elementary School in Salado, Texas. Her child is at imminent risk of immediate harm from
FDA’s action to authorize Pfizer’s COVID-19 biologic for children aged 5-11, and her child
is in the class the Defendant agencies targeted with their unlawful authorization and illicit
marketing of this drug.

7. Plaintiff Sacha Dietrich is a resident of Bell County, Texas. She is the parent of H.D. and
K.D., who are 11 and 7 years old, respectively. Her children are at imminent risk of
immediate harm from this Emergency Use Authorization (EUA) biologic, including but not
limited to coercion and pressure to receive the biologic, local and school mandates, and
severe adverse reactions should they receive the drug, and her child is in the class the
Defendant agencies targeted with their unlawful authorization and illicit marketing of this
drug.

8. Defendant FDA is an agency within the U.S. Department of Health and Human Services.
The FDA is primarily a labeling and marketing agency, “responsible for protecting the
public health by assuring the safety, effectiveness, quality, and security of human and

ool

veterinary drugs, vaccines, and other biological products.

9. Defendant Janet Woodcock is sued in her official capacity as Acting FDA Commissioner.
JURISDICTION AND VENUE
10. This action arises out of Defendants’ misuse of emergency powers under 21 U.S.C. §

360bbb-3, and their non-compliance with the Administrative Procedures Act, 5 U.S.C. §

'! FDA Fundamentals, U.S. Food & Drug Administration, available at
https://www.fda.gov/about-fda/fda-basics/fda-fundamentals.
4
11.

12.

13.

14.

15.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 5 of 237

500 et seq.
This lawsuit raises federal questions over which this Court has jurisdiction pursuant to 28
U.S.C. §§ 1331, 1361.

Pursuant to 28 U.S.C. § 1391(e), venue is proper in the Western District of Texas, where
Plaintiffs Deborah L. Else and Sacha Dietrich reside. Under 5 U.S.C. § 703, venue is proper
in any court of competent jurisdiction.

An actual and justiciable controversy exists between Plaintiffs and Defendants. Plaintiffs
are in the class directly injured by this illicit marketing of this drug to minor children, and

Plaintiff organization must, and has, diverted substantial resources due to it.

STATEMENT OF FACTS

We face an unparalleled moment in the history of the FDA and public health: the race to
rush a vaccine authorization for very young minor children without adequate clinical trials,
without consideration of relevant information, without robust debate, and without even
meaningful public participation in the citizen petition process. The FDA’s extraordinary
emergency authorization for young, minor children aged 5-11, who face less risk from
COVID-19 than from the seasonal flu, endangers their safety, as these biologics lack good
manufacturing policies, lack strict safety safeguards, lack liability accountability, and indeed
do not even fit the traditional definition of “vaccine.”

This biologic uses experimental technology to combat a novel virus from a viral family
with no history of vaccine success and attempts to attack a virus that continues to mutate in
ways prior vaccine studies did not even address. This unwarranted authorization endangers

vaccine confidence, as it follows a historic path littered with disastrous debacles of unsafe
16.

17.

18.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 6 of 237

yet sanctioned drugs and biologics that have devastated confidence in public health
generally.

On October 29, 2021, the FDA granted an Emergency Use Authorization (EUA) for
Pfizer-BioNTech’s COVID-19 biologic for children ages 5-11, even though this product
poses imminent risk to that portion of the population without proportionate benefit.

To justify the authorization, the FDA ignored, and even hid, data showing severe short-
term risks of COVID-19 vaccination for children and never admitted that the agency’s
abbreviated studies couldn't have been long enough in duration to assess long-term severe
and irreversible injury. The FDA could not, and did not, arrive at a reasoned explanation of
whether benefits outweigh the risk of injury for children aged 5-11. The small-cohort
clinical trials, too short to render meaningful data, are still in the process of being
conducted. If this dangerous rollout is allowed to continue, there are certain to be untold
casualties and injuries. Children, expected to have the greatest number of years of life ahead
of them, run the greatest risk of vaccine injury, yet have the lowest risk from COVID-19
itself than any other age group.

In this, the latest in a series of premature approvals and authorizations, Defendants have
abused their emergency powers, denied CHD its procedural right to seek redress via citizen
petition, redefined the term “vaccine” in violation of procedural due process, failed to
satisfactorily articulate standards for assessing the safety, efficacy, and necessity for the
vaccine, and promoted the fraudulent marketing of a drug targeted at children, in violation
of the Administrative Procedures Act (“APA”). Furthermore, the FDA failed to perform the
function for which the agency was intended: address the health and safety concerns

regarding drugs administered to the American public.

6
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FDA’s Grant of Emergency Use Authorization for Children Ages 5-11

19.

20.

21.

22.

23.

On January 31, 2020, Alex M. Azar, I, the Secretary of Health and Human Services,
declared the existence of a public health emergency pursuant to § 319 of the Public Health
Service Act, 42 U.S.C. § 247d et seq. Shortly after, on March 13, 2020, President Trump
declared a national emergency.

Section 564 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. § 360bbb-
3, authorizes the FDA to issue an EUA for a biologic under certain emergency
circumstances, allowing a product to be introduced and administered to the public even
when it has not gone through the review process necessary for approval and licensure.

In such an emergency, the Secretary of Health and Human Services may issue EUAs if he
concludes that the following facts exist: (1) a serious or life-threatening disease is present;
(2) a product “may be effective” in treating or preventing it; (3) there is“‘no adequate,
approved, and available alternative to the product for diagnosing, preventing, or treating
such disease or condition;” (4) a risk-benefit analysis that measures both the known and
potential benefits of the product against the known and potential risks of the product is
positive; and (5) that the patient’s option to accept or decline the product is protected
through informed consent. 21 U.S.C. § 360bbb-3(c)(1)-(5).

On October 29, 2021, the FDA abused its discretion under the emergency use statute and
recklessly granted Emergency Use Authorization for a pediatric Pfizer-BioNTech COVID-
19 vaccine for 5- through 1 1-year-olds.

On October 26, 2021, the FDA held a Vaccines and Related Biological Products

Advisory Committee (“VRBPAC”’) meeting to discuss Pfizer’s request to amend its EUA to
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 8 of 237

allow for the use of the Pfizer-BioNTech COVID-19 vaccine in children ages 5-11 (Exh.

4).?

Inadequacy of Clinical Trials

24.

25.

26.

27.

FDA’s press release (Exh. 1) announcing authorization of Pfizer-BioNTech for 5-
through 1 1-year-olds noted that the authorization was based on a trial that included,
"approximately 3,100 children aged 5 through 11 who received the vaccine,” and concluded
that “no serious side effects have been detected in the ongoing study.”? The press release
went on to state, "The Pfizer-BioNTech COVID-19 Vaccine for children 5 through 11 years
of age is administered as a two-dose primary series, 3 weeks apart, but is a lower dose (10
micrograms) than that used for individuals 12 years of age and older (30 micrograms).”

Although Defendant Janet Woodcock, the acting commissioner of FDA, did not sign the
press release, she still bears responsibility for the FDA's actions as pleaded herein.

The clinical trials performed to test safety and efficacy of the COVID-19 biologics were
woefully inadequate and rife with fraudulent error that nullifies the reliability of the results.

Since the Defendant agency’s first issuance of an EUA for Pfizer-BioNTech COVID-19
vaccine for individuals 16 years of age and older on December 11, 2020, the FDA has
continued to issue EUAs to Pfizer even though its Phase III clinical trials remain, at the time

of this filing, incomplete. Pfizer's clinical trial Estimated Primary Completion Date is

? Vaccines and Related Biological Products Advisory Committee October 26, 2021 Meeting
Announcement, FDA (October 26, 2021), available at https://www.fda.gov/advisory-
committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-
committee-october-26-202 | -meeting-announcement.

3 FDA Authorizes Pfizer-BioNTech COVID-19 Vaccine for Emergency Use in Children 5
through I1 Years of Age, available at https://www.fda.gov/news-events/press-
announcements/fda-authorizes-pfizer-biontech-covid- 1 9-vaccine-emergency-use-children-5-
through-1 1-years-age.

8
28.

29.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 9 of 237

November 2, 2022, and the Estimated Study Completion Date is May 2, 2023.4

The few clinical trials that have been conducted are untrustworthy and riddled with error.
On November 2, 2021, the British Medical Journal published alarming information brought
forward by whistleblower Brook Jackson, a regional director at the Ventavia Research
Group, regarding Pfizer’s Phase III clinical trial for the COVID-19 vaccine. Ventavia
Research Group is a privately owned clinical research company in Texas responsible for
completing a portion of the clinical research upon which Pfizer, the FDA, and the public,
based their faith on the safety and efficacy of COVID-19 vaccines. Jackson conveyed that
“the company falsified data, unblinded patients, employed inadequately trained vaccinators,
and was slow to follow up on adverse events reported in Pfizer’s pivotal phase II trial.”
Jackson expressed her concerns regarding “poor laboratory management, patient safety
concerns, and data integrity issues” to her supervisors at Ventavia, to no avail.
Documentation gathered by Jackson demonstrates that these problems have been
continuously occurring since shortly after the clinical trial began. When Jackson was
unsuccessful in submitting her concerns to Ventavia, she called and emailed a written
complaint to Defendant FDA on September 25, 2020 regarding the unsound practices she
had witnessed. That same day, Jackson was fired from Ventavia.°

The email sent to the FDA documents a number of concerning practices Jackson had
witnessed: “participants placed in a hallway after injection and not being monitored by

clinical staff;” “lack of timely follow-up of patients who experienced adverse events;”

4 See Study to Describe the Safety, Tolerability, Immunogenicity, and Efficacy of RNA Vaccine
Candidates Against COVID-19 in Healthy Individuals, CLINICALTRIALS.GOV,
https://clinicaltrials.gov/ct2/show/NCT04368728.

> Paul Thacker, Covid-19: Researcher Blows the Whistle on Data Integrity Issues in Pfizer’s
Vaccine Trial, available at https://www.bmj.com/content/375/bmj.n2635.full.print.

9
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 10 of 237

“protocol deviations not being reported;” “vaccines not being stored at proper

99 66

temperatures;” “mislabeled laboratory specimens;” and “targeting of Ventavia staff for
reporting these types of problems.”° Although the FDA responded to her email, the agency
failed to follow up or inspect Ventavia after the complaint was made.’

30. A former Ventavia employee expressed that the FDA “rarely does anything other than
inspect paperwork, usually months after a trial has ended.”* Indeed, a 2007 Department of
Health and Human Services report found that “the FDA inspected only 1% of clinical trial
sites” and “inspections carried out by the FDA’s vaccines and biologics branch have been
decreasing in recent years, with just 50 conducted in the 2020 fiscal year.”?

31. Inthe FDA advisory committee meeting held on December 10, 2020, to discuss Pfizer’s
first application for EUA for its COVID-19 vaccine, Pfizer failed to mention any problems
at the Ventavia site. Indeed, the FDA admits in its published summary of inspections of
Pfizer’s clinical trials that only nine of the trial’s 153 sites were inspected; Ventavia was not
one of them. “Since Jackson reported problems with Ventavia to the FDA in September
2020, Pfizer has hired Ventavia as a research subcontractor on four other vaccine clinical
trials.”!°

32. Furthermore, the FDA did not conduct any clinical trials that properly tested the altered
formula administered to children. As was stated during the VRBPAC October 26, 2021

meeting, the stabilizer used in the biologic during the trials is different from what was

authorized. While manufacturers have claimed that safety studies continue and that they are

6 Thid.
1 Ibid.
8 Thid.
° Thid.
10 Tbid.
10
33.

34,

35.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 11 of 237

still following subjects for long-term safety, the absence of any control group makes that
claim risible.

The FDA stopped short of citing adequate data—only promising future follow-up: “Our
comprehensive and rigorous evaluation of the data pertaining to the vaccine’s safety and
effectiveness should help assure parents and guardians that this vaccine meets our high
standards,” stated Acting FDA Commissioner Janet Woodcock, M.D.!!

This hauntingly echoes the FDA's confirmation in its August 23, 2021 EUA reissuance
that vaccine safety and efficacy for the 12-year-old through 15-year-old age group had not
been established.'? The FDA's memorandum for extension to 12- through 15-year-olds

99 66

acknowledges “unknown benefits and data gaps” in “duration of protection,” “effectiveness
in certain populations at high risk of severe COVID-19,” “effectiveness in individuals
previously infected with SARS-CoV-2,” “vaccine effectiveness against asymptomatic

99 66.

infection,” “vaccine effectiveness against mortality,” and “vaccine effects against
transmission,” proving that almost nothing is actually known about the benefits of the Pfizer
biologic in the 12- through 15-year-old age group.!°

The World Health Organization expressed a similar sentiment in July 2021: “More

evidence is needed on the use of the different COVID-19 vaccines in children to be able to

'! FDA Authorizes Pfizer-BioNTech COVID-19 Vaccine for Emergency Use in Children 5
through I1 Years of Age, available at https://www.fda.gov/news-events/press-
announcements/fda-authorizes-pfizer-biontech-covid-19-vaccine-emergency-use-children-5-
through-1 1-years-age.

'2 Letter of Authorization (Reissued), U.S. Food & Drug Administration, August 23, 2021.

'3 Emergency Use Authorization (EUA) Amendment for an Unapproved Product Review
Memorandum, U.S. Food & Drug Administration, available at
https://www.fda.gov/media/148542/download.

11
36.

37.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 12 of 237

make general recommendations on vaccinating children against COVID-19."'*

Furthermore, Pfizer willfully ignored health concerns raised by clinical trials not directly
testing the cohort at issue and failed to investigate further prior to authorization. A Pfizer
clinical trial found that the mRNA dosage of the Pfizer vaccine has caused severe fevers in
younger children.!> The clinical trial found that children ages2-5 who received 10
micrograms of mRNA experiences fevers that were both more common and more severe
than those other age cohorts.'° As a result, Pfizer opted to lower the dosage in future tests
from 10 micrograms to 3 micrograms for children aged 2-5, for which the vaccine is not yet
authorized.'!’ However, the same 10-microgram dosage is administered to and authorized for
children ages 5-12, with no adjustment for weight. 5-year-olds receive the same dosage that
causes severe fevers in children ages 3-4, although the size and robustness of many 5-year-
olds is not significantly different than children a year or two younger.

Despite this, Defendants have continued to recklessly and heedlessly push this drug on
innocent Children. On January 3, 2022, the FDA authorized a third Pfizer booster shot for
children ages 12-15 without going through the proper authorization process. On January 18,
2022, GOP lawmakers drafted a letter to the FDA and Acting Commissioner Janet

Woodcock in response, questioning why the agency did not rely on its typical committee

'4 COVID-19 Advice for the Public: Getting Vaccinated, World Health Organization (Nov. 15,
2021), available at https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-
vaccines/advice.

'S Analyst and Investor Call to Discuss the First COVID-19 Comprehensive Approach: Pfizer-
BioNTech Vaccine and Pfizer’s Novel Oral Antiviral Treatment Candidate, Pfizer, December 17,
2021, available at Presentation Title (q4cdn.com).

'6 Td,

'” Pfizer and BioNTech Provide Update on Ongoing Studies of COVID-19 Vaccine, Pfizer
(December 17, 2021), available at https://www.pfizer.com/news/press-release/press-release-
detail/pfizer-and-biontech-provide-update-ongoing-studies-covid-19.

12
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 13 of 237

approval process prior to authorizing a third Pfizer shot for children ages 12-15.'8 More
than two dozen members of the House and Senate signed the letter demanding an
explanation for why the FDA decided to forego consultation with the Vaccines and Related
Biological Product Advisory Committee (VRBPAC) prior to issuing authorization. As of
the time of this filing, Defendants have failed to respond or provide an explanation for the
omission.

38. Plaintiffs are therefore justifiably concerned of the untold risks that this experimental
injection may pose for children in the 5-11 age group due to the inadequacy of the clinical

trials and Defendants’ insufficient guarantee of safety.
Approving Drugs and Biologics: Citizen Participation

39. CHD filed a Citizen Petition with the FDA (Exh. 2) on May 16, 2021, asking the FDA to
refrain from licensing COVID-19 vaccines and to revoke EUAs for the three existing
COVID-19 vaccines. Individuals have submitted over 30,000 comments on this petition.

40. Despite a dismissive and unsatisfactory response on August 23, 2021 (Exh. 3), the same
day the agency approved the Pfizer “Comirnaty” biologic, the FDA has done nothing to
assuage the public concerns outlined in the Citizen Petition. Rather, the FDA has forged
ahead on its path to inject this experimental drug into every American’s arm.

41. Nothing destroys public confidence in vaccines more than rushing their authorization and
approval without addressing public concerns and without the regulatory agencies explaining

the standards, if any, used for authorization, approval, and licensure.

'8 GOP Lawmakers Ask FDA for Answers in Pfizer COVID-19 Booster Approval Process for
Children: ‘Quite Troubling,’ Fox News, January 19, 2022, available at

https://www.foxnews.com/politics/gop-lawmakers-fda-answers-pfizer-booster-children.
13
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 14 of 237

42. The FDA Citizen Petition process is meant to prevent this from happening. Citizen
participation, through a Citizen Petition, confers some democratic participation in the drug
or biologic approval process, provides for the kind of free discussion and public engagement
that imposes the scientific method on the process, and engenders public confidence in the
vaccine itself. If you cannot trust the process, you cannot trust the result of that process. A
study in May 2021 showed that roughly half the U.S. population does not trust the FDA,
CDC, or other major public health organization; this percentage is guaranteed to be higher
now. If more than half of the population is unprepared to trust the FDA’s results and
recommendations, the relevance of the Citizen Petition process cannot be understated.

43. Defendant has denied Plaintiffs their procedural right to participate in the notice and

comment process or answers to their concerns in the Citizen Petition.
Pfizer’s Experimental mRNA Biologic is not a “Vaccine,” but is a Gene Therapy

44. These COVID-19 pharmaceutical drugs do not fall under the traditional definition of
“vaccine” because they are excluded by their composition.

45. The CDC’s definition of vaccine is “‘a preparation that is used to stimulate the body’s
immune response against diseases.”’!? More specifically, a vaccine is “a suspension of
attenuated or killed microorganisms (viruses, bacteria, or rickettsiae), administered for
prevention, amelioration, or treatment of infectious diseases.””°

46. Pfizer-BioNTech’s experimental mRNA biologic is among the first of its kind, utilizing a

brand-new delivery system and gene therapy technology. Unlike vaccines that have come

'° Immunization: The Basics, Centers for Disease Control and Prevention, available at
https://www.cdc.gov/vaccines/vac-gen/imz-basics.htm.

20 Vaccine, The Free Dictionary — Medical Dictionary, available at https://medical-
dictionary.thefreedictionary.com/vaccine.

14
47.

48.

49.

50.

51.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 15 of 237

before it, the Pfizer-BioNTech biologic does not contain SARS-CoV-2, the virus that causes
COVID-19, but rather consists of mRNA that infiltrates the body’s cells and yields the
production of a spike protein that mimics the SARS-CoV-2 coronavirus.

The FDA has misled government leaders, health care providers, and the public by
branding Pfizer-BioNTech’s COVID-19 mRNA biologic as a “vaccine.” This is an
inaccurate statement that has led to false confidence in the safety of the experimental
technology.

The CDC even went so far as to alter the definitions of “vaccine” and “vaccination” to

broaden the scope of what falls under those terms.

Prior to the change, a “vaccine” was defined as "a product that stimulates a person's
immune system to produce immunity to a specific disease, thereby protecting against that
disease." Under the new definition, a vaccine is "a preparation used to stimulate the body's

immune response against a specific disease".

The original definition of “vaccination” was “the act of introducing a vaccine into the
body to produce immunity to a specific disease.” Compare that to the new definition, which
states that vaccination is “the act of introducing a vaccine into the body to produce

protection from a specific disease.”

The CDC and FDA have orchestrated a guise under which a product that confers neither

*1 Why has the CDC changed the definition of a vaccine?, Verificat, September 29, 2021,
available at https://www.verificat.cat/vaccines/entry/why-has-the-cdc-changed-the-definition-of-
a-vaccine.

2 The CDC Suddenly Changes the Definition of “Vaccine” and “Vaccination,” Citizens Journal,
September 13, 2021, https://www.citizensjournal.us/the-cdc-suddenly-changes-the-definition-of-
vaccine-and-vaccination/.

15
52.

53.

54.

55.

56.

57.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 16 of 237

immunity nor protection is considered a “vaccine.”

However, while not a “vaccine,” this biologic does fall under the FDA Office of Cellular,
Tissue, and Gene Therapies’ definition of “gene therapy products.”

EUAs are particularly risky in the COVID-19 vaccine context as all three available
vaccines are gene therapies.

Moderna, in its 2020 filing to the Securities and Exchange Commission, stated:
“Currently, mRNA is considered a gene therapy product by the FDA."”? Pfizer
acknowledged the same in its SEC filing.**

Gene therapies are defined as “[p]products that mediate their effects by transcription
and/or translation of transferred genetic material and/or by integrating into the host genome
and that are administered as nucleic acids, viruses, or genetically engineered
microorganisms. The products may be used to modify cells in vivo or transferred to cells ex
vivo prior to administration to the recipient.”

To date, gene therapy vaccines have been used in cancer patients and those with inherited
metabolic disorders, whose risk profile is radically different from that of healthy children

and adults. They have never been used widely in a general population.

FDA's guidance to industry on gene therapy, issued in January 2020 as COVID vaccine

3 Moderna, Inc., United States Securities and Exchange Commission, Form 10-Q, Quarterly
Report Pursuant to Section 13 or 15(D) of the Securities Exchange Act of 1934 (for the quarterly
period ended June 30, 2020),
ttps://www.sec.gov/Archives/edgar/data/1682852/00016828522000001 7/mrna-20200630.htm.

4 BioNTech SE, United States Securities and Exchange Commission, Form F-1 Registration
Statement, filed Sept. 9,

2019, https://www.sec.gov/Archives/edgar/data/1776985/0001 19312519241 112/d635330df1 .ht

5 Manufacturing of Gene Therapies: Ensuring Product Safety and Quality, FDA (2006),
available at https://www.fda.gov/media/81682/download.

16
58.

59.

60.

61.

62.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 17 of 237

development was commencing, states:

“FDA generally considers human gene therapy products to include all products
that mediate their effects by transcription or translation of transferred genetic
material or by specifically altering host (human) genetic sequences. Some
examples of gene therapy products include nucleic acids (e.g., plasmids, in vitro
transcribed ribonucleic acid (RNA)), genetically modified microorganisms (e.g.,
viruses, bacteria, fungi), engineered site-specific nucleases used for human
genome editing (Ref. 2), and ex vivo genetically modified human cells. Gene
therapy products meet the definition of “biological product” in section 351(i)
of the Public Health Service (PHS) Act (42 U.S.C. § 262(i)) when such
products are applicable to the prevention, treatment, or cure of a disease or
condition of human beings.””°

Because this is a novel technology being used on new populations, it is exceptionally
important that the FDA apply both its specific gene therapy scientific criteria and general
biologic standards in evaluating safety and efficacy.

The mechanism of gene therapy vaccines differs substantially from all other vaccines that
have ever been used as they work on the premise of gene delivery.

Gene therapy COVID vaccines involve a modified virus or an encapsulated segment of
RNA entering human cells and utilizing the host cell machinery to produce spike protein.
This is an entirely different mechanism than that of traditional vaccines such as inactivated,
attenuated, subunit or protein-based vaccines that do not penetrate human cells.

The gene therapy standards are more stringent than the criteria FDA applies to vaccines
generally. Upon information and belief, the FDA did not apply these standards, including
long-term safety follow-up, in the EUA approval process.

The failure to examine and regulate COVID-19 vaccines as gene therapy products,

6 Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy
Investigational New Drug Applications (INDs), U.S. FOOD & DRUG ADMINISTRATION, Guidance
Document (Jan. 2020), https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/chemistry-manufacturing-and-control-cmc-information-human-gene-therapy-

investigational-new-drug.

17
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particularly for young children, constitutes arbitrary and capricious action and should have
prevented the FDA from issuing EUAs initially.

63. Furthermore, the FDA is required to perform an environmental assessment for gene
therapy products.”’ Because gene therapy vaccines may shed or spread genetic material into
the environment, manufacturers are required to supply data to FDA for review. There is no
evidence that such data were provided, nor that the FDA conducted the required

environmental assessment as it must according to its own guidelines.
Constitutional Origins, Informed Consent, and Citizen Participation

64. In addition to the Informed Consent principle, the First Amendment guarantees the right
to petition one’s government and the necessity of robust debate following strict scientific
standards. Further, the APA limits what drugs and biologics can be authorized, the purposes
they can be authorized for, the individuals they can be prescribed for, and the notices and
consent required before they can be administered. The Emergency Use Authorization
statute, 21 U.S.C § 360bbb-3, further codifies these standards, including the obligation of
Informed Consent derived from the Nuremberg Code.

65. Born of this informed consent, democratically-driven process, the FDA biologic
authorization and approval process outlines protocols with public input and robust debate,
citizen petition and judicial oversight, substantive limits on its methodology and procedural
requirements. Only a rigorous scientific review with meaningful public participation,

through citizen petitions answered by the FDA, could even authorize the introduction of a

27 Determining the Need for and Content of Environmental Assessments for Gene Therapies,
Vectored Vaccines, and Related Recombinant Viral or Microbial Products: Guidance for
Industry, FDA (March 2015), available at https://www.fda.gov/media/91425/download.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 19 of 237

novel biologic. As President Biden advised, no citizen should take a drug without

“transparency, transparency, transparency” from the government.”®

66. The FDA has spectacularly failed to fulfill that promise, and in doing so has also blocked
out the public from meaningful participation to ensure that the processes through which the
FDA conducts its investigations, which form the foundation for all public health policies
regarding COVID-19, are dependable, accurate, and truthful.

67. | Exceptional situations should not give an unelected federal agency the authority to

abrogate the Constitutional rights of the people.
Vaccine Adverse Events Reporting System: Unprecedented Alarm Signals

68. More than a year after the COVID-19 biologics have been introduced to the American
public en masse, the reports of adverse events and death from the injections are staggering,
and far exceeds that which has been seen from any vaccine in human history.

69. Data released January 14, 2022 by the Centers for Disease Control and Prevention (CDC)
showed that since Dec. 14, 2020, a total of 1,214,267 adverse events following injection
were reported to the Vaccine Adverse Event Reporting System (VAERS), with 23,978
deaths reported.”” These numbers far exceeds those of any other vaccine in human history.

70. The Vaccine Adverse Event Reporting System (VAERS) is a 30-year-old voluntary
adverse event reporting system for vaccines, jointly managed by FDA and CDC. Injured

parties, their healthcare providers and others may file reports. Doctors and vaccine

°8 Biden White House Pledges Data, Transparency, Respect for Free Press, Reuters (January 20,
2021), available at
https://www.reuters.com/article/us-usa-biden-briefing-idUSKBN29Q08S.
° Vaccine Adverse Event Reporting System (VAERS), CDC Wonder, available at
https://wonder.cdc.gov/controller/datarequest/D8;jsessionid=67A4CC 1 D3 E7D207433E5332EA
BDF.

19
71.

72.

73.

74,

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 20 of 237

manufacturers are mandated to report severe injuries and deaths that may be linked to
vaccination. This is the nation’s foremost adverse event reporting system, despite its
inadequacies.

According to senior CDC and FDA scientists, “During 2011-2014, VAERS averaged
around 30,000 U.S. reports annually, with 7% classified as serious. Healthcare professionals
submitted 38% of reports, vaccine manufacturers 30% and patients and parents 14%.”°°

CDC and FDA have both said that VAERS is suitable for providing early warnings of
vaccine side effects but cannot be used to establish causality. Warning signals must
therefore be investigated using other methods, which are believed to be more accurate and
complete. According to the article cited above, “VAERS is primarily a safety signal
detection and hypothesis generating system. Generally, VAERS data cannot be used to
determine if a vaccine caused an adverse event.”?!

How the reporting rate of adverse events to VAERS compares with the actual rate of
vaccine-associated adverse events is unknown. The same CDC and FDA authors confirmed
this, stating, “VAERS lacks information on total number of individuals vaccinated and total
number who experience an adverse event, as well as incidence of adverse events in
unvaccinated individuals.” The authors further emphasized this critical point: “Reporting
efficiency, which is the proportion of adverse events that actually get reported to VAERS, is

unknown....”

Past attempts to investigate the VAERS reporting rate have suggested that between 1%

3° Citizen Petition from Scientific Advisory Board on behalf of Children’s Health Defense, Food
and Drug Administration (May 16, 2021), available at
https://www.regulations.gov/document/FDA-2021-P-0460-0001.

31 Td.

20
75.

76.

77.

78.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 21 of 237

and 13% of actual adverse effects get reported; however, because CDC changed VAERS
reporting recently to include additional data, it is not possible to estimate the degree of
underreporting based on past attempts to do so. *”

The CDC has failed to account for this underreporting in its representation of VAERS
data, underestimating the number of adverse events to the public and thus ignoring the
actual prevalence of COVID-19 biologic harm.

Even when strong scientific evidence has been presented of their misconduct, CDC and
FDA have refused to issue any corrections, and continue to misrepresent the VAERS data as
if VAERS reporting rates reflected accurate adverse event rates.

The VAERS data on myocarditis and pericarditis are especially concerning, with 11,132
and 7,233 cases reported respectively as of January 14, 2022.°° The absence of data from
other FDA- and CDC-accessible databases ought to be alarming. With over 60% of the
United States vaccinated, it is inexplicable that we still do not know the actual rates of
myocarditis in the population. This information may be being concealed to garner licenses
for the vaccines in the pediatric population.

Furthermore, the input of event reports to VAERS since the COVID vaccines were rolled
out is greater than all cumulative adverse event reports to VAERS for the prior thirty
years: an alarming statistic. Death reports for 2021 are also greater than cumulative deaths

reported to VAERS over the preceding 30 years. To the FDA, this is a taboo subject since

3? Varricchio F, Iskander J, Destefano F, Ball R, Pless R, Braun MM, Chen RT. Understanding
vaccine safety information from the Vaccine Adverse Event Reporting System. Pediatr Infect
Dis J. 2004 Apr;23(4):287-94. doi: 10.1097/00006454-200404000-00002. PMID: 15071280.

33 Vaccine Adverse Event Reporting System (VAERS), CDC Wonder, available at
https://wonder.cdc.gov/controller/datarequest/D8;jsessionid=67A4CC 1 D3 E7D207433E5332EA
BDF.

21
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no public health official has explained this. The CDC, which is charged with investigating
every reported death in VAERS, simply waves its hands and claims none are due to

vaccination, without providing any data.

All Deaths Reported to VAERS by Year
20000
18000
16000 l
14000
12000
10000

8000
6000

8
Oo oO

2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015
2016
2017
2018
2019
2020
2021

79. Although VAERS cannot be used to accurately calculate the rates of any adverse reaction
due to the underreporting inadequacy, CDC did exactly that for anaphylaxis, claiming the
rate of VAERS reporting was the rate of occurrence, even though it was almost guaranteed
to be an underestimate.*4

80. When a high-quality study of Massachusetts General Hospital and Brigham hospital
employees showed that anaphylaxis occurred in 250 per million employees,** CDC failed to

update its website and still claims, as of October 18, 2021, that anaphylaxis occurs only 2-5

34 Meryl Nass, Did CDC Deliberately Mislead Public on Allergic Reactions to Moderna
Vaccine?, The Defender (January 28, 2021) available at
https://childrenshealthdefense.org/defender/did-cdc-mislead-public-allergic-reactions-moderna-
vaccine/.
35 Blumenthal KG, Robinson LB, Camargo CA, et al. Acute Allergic Reactions to mRNA
COVID-19 Vaccines. JAMA. 2021;325(15):1562—1565. doi:10.1001/jama.2021.3976.

22
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 23 of 237

times per million COVID vaccines.*° Which begs the question: how accurate are CDC's
other adverse event rates?

81. CDC has made a number of changes to its standard practices since the beginning of the
pandemic. Here is just one example: beginning on May 1, 2021, for CDC to accept a report
of a “breakthrough” case, or a case of COVID in a vaccinated individual, the infected person
must have required hospitalization or died and had their infection confirmed with a PCR test
using 28 or fewer cycles.>’ Other problems with data acquisition of breakthrough cases**
have further contributed to keeping the official number of such cases much lower than they
really are. In the UK, in all age cohorts of 30 years and up, there is a higher rate of COVID

cases in the vaccinated compared to the unvaccinated.*?

36 Selected Adverse Events Reported after COVID-19 Vaccination, Centers for Disease Control
and Prevention (Nov. 30, 2021) available at https://www.cdc.gov/coronavirus/2019-
ncov/vaccines/safety/adverse-events.html.
37 Ensuring COVID-19 Vaccines Work, Centers for Disease Control and Prevention
(Novhttps://www.cdc.gov/vaccines/covid-19/health-departments/breakthrough-cases.html
38 Erin Banco, Holes in reporting of breakthrough Covid cases hamper CDC response, Politico
(August 25, 2021) available at https://www.politico.com/news/2021/08/25/cdc-pandemic-
limited-data-breakthroughs-506823.
3? COVID-19 Vaccine Surveillance Report — Week 42, UK Health Security Agency, availabe at
https://assets. publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file
/1027511/Vaccine-surveillance-report-week-42.pdf.

82.

83.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 24 of 237

COVID-19 vaccine surveillance report — week 42

Table 2. COVID-19 cases by vaccination status between week 38 and week 41 2021

Received Received

Cases reported one dose one dose, snag 4 itn in Rates among
by specimen date " Not (1-20 days 221 days - persons not
between week 38 Total Deane vaccinated before before ges canst Bees _ vaccinated
and week 41 2021 we ~ ate (per 100,000) (per 100,000)
Under 18 397,882 24,292 351,148 10,698 11,001 743 314.1 3,013.6
18-29 62,885 7,512 20,902 758 8,404 25,309 462.1 615.4
30-39 92,257 7,346 21,726 636 6,545 56,004 956.7 751.1
40-49 130,904 7,297 13,022 293 3,800 106,492 1,731.3 772.9
50-59 88,020 4,790 5,399 80 1,632 76,119 1,075.3 528.6
60-69 45,155 2,614 1,872 24 617 40,028 704.1 347.1
70-79 27,360 1,559 658 12 215 24,916 537.9 267.6
280 11,907 854 382 7 215 10,449 406.8 304.1

* Individuals whose NHS numbers were unavailable to link to the NIMS

*“* Interpretation of the case rates in vaccinated and unvaccinated population is particularly susceptible to changes in denominators and should be interpreted

with extra caution

One 12-year-old, Maddie de Garay, was healthy when she volunteered to enter Pfizer's

pediatric COVID vaccine trial at the University of Cincinnati with her two siblings,

believing that she was helping her country solve the COVID crisis. She became ill

immediately after the second dose with high fever and then a wide range of symptoms.

Over the subsequent six months, she had about a dozen ER visits and six hospitalizations.

She has required a feeding tube to be nourished and uses a wheelchair. Dr. Frenck, the

Principal Investigator for the Pfizer pediatric clinical trial at his hospital, was her physician

and is aware of these problems. Yet Maddie de Garay was not reported as a serious adverse

event in the trial documents, and when her trial data were published in the New England

Journal of Medicine, there were no serious vaccine-related adverse events listed for any

subject. Dr. Frenck, Maddie’s physician, was the first author of the NEJM study. How

many other subjects in Pfizer's trials were similarly injured, but went unreported? How

many Principal Investigators issued positive reports despite knowing of severe injuries?

According to VAERS, FDA actions have buried people in addition to data. The FDA has

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 25 of 237

not shared actual data on efficacy, side effects and all injuries to educate the public on the
risks of these vaccines. Nor have they seemingly utilized this information effectively via

risk assessments and safety analyses when granting EUAs.

Far-Reaching and Long-Lasting Potential Side Effects

84.

85.

86.

87.

There is a myriad of short-term vaccine side effects that have been witnessed and
reported since the rollout of the vaccine. However, scientists and health care professionals
have long been raising the alarm over the long-term implications that this mRNA gene
therapy technology can have on a recipient’s health.

In truth, we know nothing about the long-term risk of the COVID-19 biologic in children.
This biologic tested on human subjects for less than five months of data collection in Phase
II and III clinical trials before being administered to the public under an EUA.*°

COVID-19 vaccines have not gone through testing for genotoxicity, mutagenicity,
teratogenicity, and oncogenicity by the FDA’s own admission.*! In plain English, no one
can be assured that these products don’t cause birth defects, infertility, or cancer; the so-
called experts just don’t know. This alone should deprive these products of licensure and
EUA status given these severe potential risks, especially for children who should have the
greatest number of years ahead of them.

We now know that vaccine-induced spike proteins, the putative antigen induced by
Pfizer-BioNTech COVID vaccine, are a toxin. They are produced and enter the circulatory

system, have predictable negative consequences to vascular endothelium, they activate

40 About Our Landmark Trial, Pfizer, available at
https://www.pfizer.com/science/coronavirus/vaccine/about-our-landmark-trial.
“1 Package Insert — Comirnaty, FDA (8/2021), available at
https://www.fda.gov/media/151707/download.

25
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platelets, and cross the blood-brain barrier. Spike proteins circulate throughout the body and
accumulate in large concentrations in organs and tissues, including the spleen, bone marrow,
liver, adrenal glands, and especially the ovaries.** Since there exists no way to turn off spike
production, the actual dose of spike protein may vary by orders of magnitude from person to
person, which raises concern regarding the FDA’s methods of determining dosage.

88. The potency of the product cannot be established nor the duration of time during which it
is effective. This is a regulatory conundrum that the FDA has not solved. Since measuring
potency is required for all drugs and biologics, it must solve this problem before any
licensure, thus requiring vacatur of the EUA for the Pfizer-BioNTech COVID-19 vaccine
for this age group.

89. In addition, spike proteins would be expected to trigger the destruction of cells that
produce it and present it on their surfaces. Products that induce the production of spike
protein should only be used after careful consideration of the individual recipient’s risks and
benefits. They should not be employed in mass vaccination programs where there is no
learned practitioner to weigh appropriate use, nor in individuals with a very low risk of
serious COVID disease.

90. Furthermore, strong but not yet conclusive evidence links spike protein in vivo to blood
clots, thrombocytopenia, hemorrhages, heart attacks and strokes, the very severe effects of
COVID-19 disease itself. The damage the spike protein may be causing must be fully
elucidated. The toxicity of the spike protein means that no vaccine using this design can be

assumed to be safe until proven otherwise, and none should continue under an EUA or be

#2 SARS-CoV-2 mRNA Vaccine Biodistribution Study, https://www.docdroid.net/xq0Z8BO0/pfizer-
report-japanese-government-pdf.

26
91.

92.

93.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 27 of 237

licensed.

Studies have also shown that antibody-dependent enhancement (“ADE”) poses a severe
threat to vaccinated individuals.*? “ADE occurs when the antibodies generated during an
immune response recognize and bind to a pathogen, but they are unable to provide infection.
Instead, these antibodies act as a “Trojan horse,’ allowing the pathogen to get into cells and
exacerbate the immune response.’”’** Thus, when dealing with different strains of COVID-
19, ADE caused by the COVID-19 biologic may accelerate the virus infecting the cells and
resulting in more severe illness. Therefore, children who receive the COVID-19 biologic
are at risk of increased severity if they are exposed to similar viruses.

In addition, the myocarditis risk immediately after vaccination in older children is
considerable, potentially life-threatening, and increases exponentially with decreasing age,
suggesting that young children are at particularly high risk.

The pediatric clinical trials are too small to quantify the risk from myocarditis and most
other adverse events. Indeed, in the approval for Pfizer’s Comirnaty vaccine, the FDA
ordered further studies into myocarditis and pericarditis (Exh. 6).*° As FDA
acknowledged when discussing its post-marketing requirements for its Comirnaty
vaccine, “[w]e have determined that an analysis of spontaneous post-marketing adverse
events reported under section 505(k)(1) of the FDCA will not be sufficient to assess

known serious risks of myocarditis and pericarditis and identify an unexpected serious

‘3 Infection-enhancing anti-SARS-CoV-2 antibodies recognize both the original Wuhan/D614G
strain and Delta variants. A potential risk for mass vaccination? Yahi, Nouara et al.Journal of
Infection, Volume 83, Issue 5, 607 - 635, doi: https://doi.org/10.1016/j.jinf.2021.08.010.

“4 Antibody-dependent Enhancement and Vaccines, Children’s Hospital of Philadelphia,
available at https://www.chop.edu/centers-programs/vaccine-education-center/vaccine-
safety/antibody-dependent-enhancement-and-vaccines.

4S BLA Approval, U.S. Food and Drug Administration (August 23, 2021), available at
https://www.fda.gov/media/151710/download.

27
94.

95.

96.

97.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 28 of 237

risk of subclinical myocarditis. Furthermore, the pharmacovigilance system that FDA is
required to maintain under section 505(k)(3) of the FDCA is not sufficient to assess these
serious risks.’”*°

FDA told BioNTech-Pfizer that since FDA was unable to assess the myocarditis risk, it
expected BioNTech-Pfizer to do so. FDA wants Pfizer’s final reports on myocarditis to be
submitted in 2024 and 2025. It is unacceptable to ponder the inevitability that tens or
hundreds of millions of the world’s children will be vaccinated before BioNTech-Pfizer tells
us to what extent their vaccines damage children's hearts, if this EUA is allowed to continue.

According to the Jerusalem Post on October 7, 2021, the health ministry was considering
whether “individuals vaccinated with the Pfizer coronavirus vaccine may be asked to avoid
strenuous exercise [including swimming] and other physical activity for one week after
receiving each dose due to cases of myocarditis....”47

Four Nordic countries recently halted the use of Moderna's vaccine in some age groups

due to the risk of myocarditis. It was reported by the Wall Street Journal that FDA paused
its review of the Moderna vaccine for teenagers in response to the Nordic countries’ action.
The article was subtitled, “Agency holds off decision on expanding use of shot to 12-to-17-
2948

year-olds while it looks into risk of rare heart condition.

FDA should have held off its expansion of the Pfizer shot to 5-to-11-year-olds until it

“©BLA Approval, U.S. Food and Drug Administration (August 23, 2021), available at
https://www.fda.gov/media/151710/download.

47 Maayan Jaffe-Hoffman, Health Ministry to consider asking newly vaccinated to avoid working
out, The Jerusalem Post (October 7, 2021), available at https://www.jpost.com/health-and-
wellness/health-ministry-to-consider-asking-newly-vaccinated-to-avoid-working-out-68 1317/.

48 FDA Delays Moderna Covid-19 VAccine for Adolescents to Review Rare Myocarditis Side
Effect, The Wall Street Journal (October 15, 2021), https://www.wsj.com/articles/fda-delays-
moderna-covid-19-vaccine-for-adolescents-to-review-rare-my ocarditis-side-effect- 11634315159.

28
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has completed this review since Pfizer's shot also causes myocarditis.

98. The bottom line is that we have no idea of either the short or long-term risk of the Pfizer
vaccine in 5-to-11-year-old children, but it is reasonable to assume the risk of myocarditis
could be considerable. Other risks have not been quantified but could also be substantial.
We do not even know their magnitude in adults, after 6.8 billion COVID vaccinations have
been administered throughout the world.*? It cannot be justified to vaccinate children with a
biologic for which the world's public health professionals have failed to collect and analyze
the most rudimentary data on safety during the largest rollout of (mostly experimental)
pharmaceutical products in the history of the world.

99. While there is no justification for pediatric vaccinations, as herd immunity is impossible
to achieve with current vaccines, there is a substantially high and concerning risk of several
adverse effects, including death. The FDA is therefore encouraging superfluous vaccination

that will put children at more risk of vaccine harm than they face from COVID-19.
Vaccination of Children is not Medically Necessary

100. The real-world experience of gene therapy vaccines continues to undermine claims of
efficacy. The efficacy of the Pfizer vaccines is now estimated to be under 50%, even though
public health officials set 50% as the minimum efficacy level required.°°

101. The Biden Administration has already called for “booster” shots because of this waning
effectiveness. These children are being set up for a lifetime of booster shots for subverted

immune systems.

More than 8.22 Billion Shots Given:Covid-19 Tracker, Bloomberg (December 6, 2021),
available at https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/.
°° Development and Licensure of Vaccines to Prevent COVID-19: Guidance for Industry,
available at Attps://www.fda.gov/media/1 39638/download.

29
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102. The Court must take action to protect children from what may be crimes against
humanity. Waiting around for the law enforcement arm of FDA, the Office of Criminal
Investigations, to conduct a criminal investigation against itself is futile.

103. The risks demonstrably outweigh the benefits of COVID vaccination for young children.
The actual risk of hospitalization, death, and multisystem inflammatory syndrome (MIS-C)
from COVID-19 in children aged 5-11 years is the lowest for severe disease and death than
all other age cohorts. The risk of death and severe illness in children or young adults is
exceptionally rare.°' Children are usually asymptomatic or mildly symptomatic from
COVID infections. As such, Pfizer cannot make accurate conclusions about the impact on
hospitalizations or severe illness in children 5 to 11 years old.

104. John Hopkins faculty member Marty Makary published an Op-Ed in the Wall Street
Journal detailing the finds when he and a research team reviewed about 48,000 cases of
children under 18 reported to have COVID-19 between April and August of 2020.*°* Their
findings were shocking: a mortality rate of zero among children without a pre-existing
medical condition.~*

105. According to the Associated Press, the FDA required what is called an immune
“bridging” study — evidence that the younger children developed antibody levels already

proven to be protective in teens and adults — and that’s what Pfizer reported in a press

>! Clare Smith, David Odd, Deaths in Children and Young People in England following SARS-
CoV-2 infection during the first pandemic year: a national study using linked mandatory child
death reporting data, (July 7, 2021), doi: https://doi.org/10.21203/rs.3.1rs-689684/v1.

°° The Flimsy Evidence Behind the CDC’s Push to Vaccinate Children, The Wall Street Journal
(July 19, 2021), available at https://(www.wsj.com/articles/cdc-covid-19-coronavirus-vaccine-
side-effects-hospitalization-kids- 11626706868.

3 Td.

30
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release, not a scientific publication.~

106. By comparison, scientific authors found the bulk of normalized post-vaccination deaths
occurred mostly in the elderly with high comorbidities, while the normalized post-
vaccination deaths were small, but not negligible, in children. Dr. Peter Marks, FDA chief,
said the pediatric studies should be large enough to rule out any higher risk to young
children.*° Yet, Pfizer’s study isn’t large enough to detect any extremely rare side effects,
such as the heart inflammation that sometimes occurs after the second dose, mostly in young
men, Marks said.>°

107. CDC tries to counter that there is a real danger to children from COVID-19. Exaggerated
reports such as CDC reports 94 COVID-19 deaths with COVID since January 1, 2020 in the
5 through 11 age group are inaccurate since CDC designates these as deaths “involving
COVID” or “with COVID” rather than due to COVID.°’

108. The October 2021 Pediatrics issue included a report by David McCormick et al.
showing that of 112 pediatric deaths associated with SARS-CoV-2, 86% had comorbidities,
especially obesity, neurologic and developmental conditions. The mean age of decedents
was 17.%°

109. Itis impossible to separate deaths with COVID from those due to COVID in the U.S.

4 Pfizer says COVID-19 vaccine works in kids ages 5 to 11, AP News, available at
https://apnews.com/article/business-science-health-coronavirus-pandemic-coronavirus-vaccine-
202cb6e44b90270ec4d1 f19690ed94c5.
°° Ibid.
°° Ibid.
°7 Weekly Updates by Select Demographic and Geographic Characteristics, CDC National
Center for Health Statistics, https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm.
°8 David W. McCormick, LaTonia Clay Richardson, Paul R. Young, et al., Deaths in Children
and Adolescents Associated With COVID-19 and MIS-C in the United
States. Pediatrics November 2021; 148 (5): 2021052273. 10.1542/peds.2021-052273

31
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because the CDC does not distinguish them. But what we do know is that child deaths due
to COVID in Germany, according to the BILD newspaper, were a total of 20 by May 2021,
in a country with 85 million people. Pediatric deaths were “under 30” through March 2021
according to the UK government, with 60 million people.*?

110. Regarding MIS-C, the data are sparse. The U.K.'s Joint Committee on Vaccination and
Immunisation (JCVI) stated on September 3, 2021, based on data from the UK, Canada and

the US:

“There are no clinical trial data of vaccine efficacy against PIMS-TS [MIS-
C], nor any real-world estimates of vaccine effectiveness. Post-COVID-19
syndrome (often called ‘long COVID’) has been reported in children and
young people. Existing studies suggest that longer term (=8 weeks)
symptoms following SARS-CoV2 infection occur in about <1% to 10% of
persons after COVID-19, with controlled studies generally reporting rates at
the lower end of this range.”

111. Inone report in Hospital Pediatrics,°' of 146 hospitalized pediatric COVID cases during
5 months in 2020, only 20 (14%) were deemed “significantly symptomatic.” Only 24
actually admitted because of COVID. Of those significantly symptomatic, 60% were obese
and 35% had asthma. COVID-19 was either incidental or minimally related to the reason for
hospitalization in 86% of the admissions. Of the 4 pediatric deaths in this series, only one
was attributed to COVID by the authors, in a "medically complex patient admitted for

respiratory failure.”

°° JCVI Statement on COVID-19 Vaccination of Children and young People Aged 12 to 17 years,
UK Department of Health and Social Care (August 4, 2021), available at
https://www.gov.uk/government/publications/jcvi-statement-august-202 1-covid-19-vaccination-
of-children-and-young-people-aged-12-to-17-years/jcvi-statement-on-covid-19-vaccination-of-
children-and-young-people-aged-12-to-17-years-4-august-2021.
°° Tid.
6! Webb NE, Osburn TS. Characteristics of Hospitalized Children Positive for SARS-CoV-2:
Experience of a Large Center. Hosp Pediatr. 2021 Aug;11(8):e133-e141. doi:
10.1542/hpeds.2021-005919. Epub 2021 May 19. PMID: 34011567.

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112. Pediatric vaccinations cannot be justified as necessary for herd immunity when herd
immunity itself is impossible to achieve with current vaccines. Given the rapid waning of
protection and the inability of current vaccines to prevent transmission of SARS-CoV-2,
admitted by CDC Director Walensky,” it is not possible to achieve herd immunity with
vaccination. In fact, the U.K.'s head of the Oxford Vaccine Group, Professor Sir Andrew
Pollard, told Parliament that herd immunity due to vaccination was a myth, and "not a
possibility."©

113. While protecting the elderly has sometimes been used as the justification for vaccinating
children (for example, against influenza) it is unethical to have one group take on risk to
protect another group. It is even more problematic when the group being asked to assume
the risk, children, cannot give informed consent on their own behalf. When the magnitude of
the risk is significant (of myocarditis, for example) but has not been quantified, and the
long-term risks of vaccination are unknown, demanding that children shoulder this risk for
others is ethically untenable.

114. Furthermore, natural immunity is broader and longer lasting than immunity derived from

current COVID vaccines.“ From exposure to COVID-19 over the past 2 years, natural

immunity occurs in 40% of children, a higher proportion than in any other age group. They

6? Kyle Becker, CDC Director Changes Her Story, Now Admits COVID Vaccines Don’t Prevent
Virus Transmission, Becker News (August 6, 2021), available at
https://beckernews.com/walensky-180-40752/.
63 Mychael Schnell, Herd Immunity ‘Not a Possibility’ with Delta Variant, Oxford Vaccine
Group Head Says, The Hill (August 11, 2021), available at
https://thehill.com/policy/healthcare/5674 14-herd-immunity-not-a-possibility-with-delta-variant-
oxford-vaccine-group.
°4 Kristen Cohen, Susanne Linderman, Zoe Moodie, et al., Longitudinal analysis shows durable
and broad immunity memory after SARS -CoV-2 infection with persisting antibody responses and
memory B and T cells, Cell Reports Medicine, July 14, 2021, DOI:
https://doi.org/10.1016/j.xcrm.2021.100354.

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were tested using anti-nucleocapsid antibodies. Since then, they have had a summer in
which to play together and two months of in-person schooling, and their immunity could be
approaching 50%. Vaccinating these children will expose them to excess risk without the
prospect of benefit, as vaccination when one has natural immunity is contraindicated. This is
sheer nonsense.

115. FDA allows Pfizer to use anti-nucleocapsid antibody tests to identify and exclude
prospective subjects for clinical trials who have preexisting immunity; they cannot be
included in the efficacy analysis. Yet Americans are forbidden from demonstrating they are
immune, since the FDA and CDC do not allow ordinary American children or adults to use
the identical test to demonstrate that they are already immune and don't need vaccination for
COVID-19. An infinitesimally small percentage of children require COVID vaccination.

116. Given that nearly half of all children have natural immunity to COVID, according to the
CDC, there is no ethical justification for superfluous vaccination that will put children at

elevated risk of vaccine harm.®
The FDA is Facilitating the Big Pharma Monopoly

117. Pfizer is projected to earn $36 billion dollars this year in vaccine sales, and more than
that next year; indeed, Pfizer expects to make almost as much from COVID-19 vaccines

alone as it did for all products in 2020. To say that there is a conflict of interest here is an

°° Vaccines and Related Biological Products Advisory Committee October 26, 2021 Meeting
Announcement, FDA (October 26, 2021), available at https://www.fda.gov/advisory-
committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-
committee-october-26-202 1-meeting-announcement.
6 Jake Epstein, Pfizer Expects to Make Nearly as Much Revenue Just From COVID-19 Vaccines
in 2021 as it Earned in All of 2020, Business Insider (Nov. 2, 2021), available at

34
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understatement. It is naive to think Pfizer-BioNTech will try to identify the actual rate of
myocarditis in children when so much money is at stake. Pfizer is the world's largest drug
company. It is also noteworthy that Pfizer has paid more in fines to federal and state
governments than any other pharmaceutical company. In 2009, Pfizer was ordered to pay a
criminal fine of $1.195 billion as part of one of the biggest fraud settlements in the US for
misbranding a pharmaceutical product with the intent to defraud or mislead; this is the
largest criminal fine ordered in the United States ever.°” This evidence suggests that Pfizer
is neither reliable nor trustworthy.

118. Pfizer contracted with the US government, which has possession of all COVID vaccines
across the country. An October 19, 2021, Public Citizen report titled Pfizer's Power,

discussing Pfizer and its COVID vaccine contracts notes:

"... neither Pfizer nor the U.S. government can make ‘any public announcement
concerning the existence, subject matter or terms of this Agreement, the
transactions contemplated by it, or the relationship between the Pfizer and the
Government hereunder, without the prior written consent of the other.’ The
contract contains some exceptions for disclosures required by law."

119. Furthermore, one of the FDA’s briefers who failed to find adverse event signals in the
Vaccine Safety Datalink (VSD) was Nicola Klein, who is the Principal Investigator (PI) in
multiple COVID vaccine studies for Pfizer conducted in both adults and children. Those

Pfizer clinical trials have brought in many millions of dollars to her institution. This conflict

https://www.businessinsider.com/pfizer-202 1-vaccine-revenue-close-to-2020-total-earnings-
2021-11.
°7 Justice Department Announces Largest Health Care Fraud Settlement in its History, US
Department of Justice (September 2, 2009), available at https://www.justice.gov/opa/pr/justice-
department-announces-largest-health-care-fraud-settlement-its-history.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 36 of 237

of interest was undisclosed.°®

120. What we don't know yet, or haven't been told, is critically important. In furtherance of a
clandestine deal, FDA rushes the shots into young children.

121. Unethical coercive pressure will be applied to children and their parents, as has occurred
with older children and adults, to receive these EUA vaccines. To grant authorization is to
abet unethical coercion that violates the Nuremberg Code’s first principle that informed
consent of the individual is “absolutely essential,” without duress or coercion.

122. There is no available care for children injured by COVID shots. The science and
medicine have not yet developed, and most families will be unable to cover the costs of
potential catastrophic injuries.

123. Obviously, the deck is stacked. Policies were put in place such that we will never know
the risks of COVID vaccinations nor be apprised of the magnitude of those risks.

124. Some children likely will die or be permanently injured from these vaccines based on the
authorization for children 5-to-11-year-olds.

125. Inan act of true salesmanship, the FDA exaggerated the harms to children from COVID-
19 and magnified the benefits of vaccination to claim that benefit exceeds risk. This was
accomplished via datasets that inexplicably failed to yield adverse event signals, conflating
deaths and hospitalizations “with” COVID as if all were “due to” COVID, ignoring the
existence of naturally acquired immunity and making overly optimistic assumptions about
the efficacy and duration of vaccine-induced protection. However, if you use more realistic

data, such as presented here, the risk exceeds benefit in the 12-15 age group and will exceed

68 Klein NP, Lewis N, Goddard K, et al. Surveillance for Adverse Events After COVID-19
mRNA Vaccination. JAMA. 2021;326(14):1390—1399. doi:10.1001/jama.2021.15072.
36
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benefit in the 5-to-1 1-year age group also.

Attack on the Unvaccinated

126. FDA’s authorization of the Pfizer COVID-19 vaccine for children is leading to egregious
discrimination against unvaccinated children that has the potential to pose far more of a
health risk to children than COVID-19.

127. Children in Texas are being denied medical services, including transplants, without
vaccination. This is purely due to FDA’s authorization and its misleading and false claim
that the product available to children is fully licensed and FDA approved for adults.

128. This erroneous narrative has led hospitals, medical clinics, and schools to implement
COVID-19 vaccination policies for young children.

129. Defendants once again granted this authorization for an experimental injection knowing
full well that their actions are destined to result in nationwide-school vaccine mandates and
inclusion on childhood vaccine schedules. States have already set the precedent for
compulsory immunizations to attend public and private schools from kindergarten up
through secondary education; a COVID-19 vaccine mandate for children following
authorization is inevitable in some locations. For example, California’s Governor Gavin
Newsom has already made it clear that students in kindergarten through sixth grade would
be phased into the state’s vaccine mandate requirement, with all students K-12 being
required to receive the COVID-19 biologic for the 2022-2023 school year. Other districts in
California have begun implementing independent mandates that are stricter than the

anticipated state-wide mandate. The harm that may befall a significant number of children

6° 4s LA Schools Backtrack on COVID Vaccine, Dozens More Districts Push to Mandate It,
ABC10 (January 19, 2022), available at https://www.abc10.com/article/news/local/california/as-
37
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in the state of California will occur as a direct result of Defendant FDA’s action.

130. Unless and until all children inject these experimental biologics into their developing
bodies — often against the children’s wishes and without informed consent — they will slowly
be pushed out of society, denied an education, and worse. The precedent has already been
set for adults, many of whom already have been denied their livelihoods due to their refusal
to take a COVID-19 vaccine. All of this is unprecedented, unwise, unnecessary, and
unlawful.

131. In what sane society must a child take an experimental drug that fails to protect them
from a virus that has an infinitesimal chance of hospitalizing or killing them, to have access
to the same services and opportunities as the rest of the population?

132. The risk posed to a child from COVID-19 is not even comparable to the risk posed from
not receiving a life-saving transplant or medical service, or even the denial of education or
the cultural experience of living life without being asked to show one’s papers. The question
remains how many children will need to suffer such abuse and discrimination before the

FDA will be held accountable for the consequences of their actions.

The Inglorious History of Medical Experiments Continues

133. Born amidst malaria and smallpox pandemics, the Constitution authorized no emergency
exception to the liberties secured under it. The Founding Fathers understood the virus of
concentrated power posed more of a threat than any biological virus could. The Ninth
Amendment to the Constitution safeguarded all ancient rights and liberties, including the

ancient tort of battery. United States Constitution, Amendment IX. The right against battery

la-schools-backtrack-on-covid-vaccine-dozens-more-districts-push-to-mandate-it/103-729bbb6b-
1a49-4dbd-8909-9f5573aaa73d.
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assured “the right of every individual to the possession and control of his own person, free
from all restraint or interference of others,” which would be “sacred” and protected under
the law. Union Pacific R. Co. Botsford, 141 U.S. 250, 251 (1891). The famed Justice
Benjamin N. Cardozo defined the doctrine as the universal right of every person “to
determine what shall be done with his own body.” Schloendorff v. Society of New York
Hospital, 105 N.E. 92, 93 (1914). This right to informed consent incorporates necessarily
the right to refuse treatment: “The forcible injection of medication into a nonconsenting
person’s body represents a substantial interference with that person’s liberty.” Washington
v. Harper, 494 U.S. 210, 229 (1990). The Nuremberg Code enshrines the right of informed
consent as a matter of universal law, so widely recognized, courts consider it a jus cogens
legal principle enforceable everywhere. Abdullah v. Pfizer, Inc., 562 F.3d 163 (2d Cir.
2009). Based on these precepts, courts require clear and convincing evidence that a person
poses an imminent, severe risk to others before those individuals may be subject to forced
medical care. O’Conner v. Donaldson, 422 U.S. 563 (1975); Addington v. Texas, 441 U.S.

418 (1978).

Eugenics Era

134. We only deviated from this Informed Consent standard of medical care during the
Eugenics Era, a diseased doctrine birthed in the medical academies of the United States at
the turn of the last century, as a deformed outgrowth of the then in-vogue school of Social
Darwinism. A trio of decisions carved out emergency exceptions to Constitutional liberties,
including authorizing a fine for not taking a vaccine (Jacobson v. Massachusetts, 197 U.S.

11 (1905)), forced sterilizations of poor and politically unprotected populations (Buck v.

39
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Bell, 274 U.S. 200 (1927), which relied exclusively on expanding Jacobson), and the
decisions culminated in the kind of “emergency exception” logic that led a court to
authorize forced detention camps based on race alone. Korematsu v. United States, 323 U.S.
214 (1944). This trilogy of infamy sees its corpses rise again as “precedents” seemingly

permitting governments to reinstate Eugenics-Era logic across the legal landscape.

Nuremberg Code Era

135. Reeling from the moral horror of the Nazi regime, and its enthusiastic embrace of
eugenics, American jurists led the way in reestablishing the Constitutional order by
invalidating the eugenics-era precedents and by instituting the Nuremberg Code of 1947,
whose governing principles of Informed Consent for all matters of medicine form a jus
cogens principle of universal, internationally recognized law, enforceable amongst all
civilized nations. The right to bodily autonomy formed the foundation for Supreme Court
recognition of the right to privacy and guided the standards governing all matters of medical
care concerning the state. Only clear and convincing evidence of an imminent danger to
others justifies forced medical care. Washington v. Harper, 494 U.S. 210, 229 (1990);
Addington v. Texas, 441 U.S. 418 (1978). Only business necessity warrants a place of public
accommodation or employer to discriminate against someone based on her perceived
medical status. 42 U.S.C. § 12101. The Nuremberg Code-derived governance of medical
authority reversed the eugenics-era precedents, empowered individuals with a meaningful
participatory role, and empowered democratic oversight, judicial supervision, and
procedural safeguards on the medical regulatory process, enshrining informed consent as the

ethical foundation of modern medicine and a fundamental human liberty so universal that

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courts acknowledge it as a peremptory norm.
Rushed Drugs & Medical Experiments

136. The concern over uninformed, nonconsensual, and pharmacological failures haunts the
history of rushed drugs, biologics and negligent courts. From Tuskegee to the military, from
the foster homes of young women to Indian health care services on reservations, from
facilities for the mentally ill to jails for women, the least powerful and most trusting have
been victimized by government medical experimentation, without recourse or remedy.
Deceptive denial of syphilis treatment, forced sterilizations, testing of radioactive
ingredients on unwitting patients, psychological experimentation on unsuspecting students
(such as the MK-Ultra type testing on Ted Kaczynski at Harvard), the LSD testing on
government employees, the chemical testing over San Francisco or in New York City
subways, the mustard gas secret tests on drafted soldiers — history has taught us that
government must be reined in lest it treat its citizenry as rats in a cage or guinea pigs for
experimentation.

137. In 1955, regulators rushed approval of a polio vaccine that caused an outbreak of polio in
hundreds of children, known as the Cutter Incident. Later scholars attributed the blame to
the federal government’s failures in rushing the product to market. In 1959, the Belgian
Congo rushed another polio vaccine. Twenty-five years later, a new virus emerged in the
population: AIDS. Detailed journalistic investigations have attributed it to the use of
contaminated monkey kidneys in the development of polio vaccines. ’° In 1963, Americans

discovered that the polio vaccine from monkey kidneys contained the Simian Virus 40 that

7° Edward Hooper, The River: A Journey to the Source of HIV and AIDS (1999).
4]

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 42 of 237

could cause cancer in humans.’! In 1976, the Ford administration rushed a vaccine for
swine flu. The virus proved less deadly than anticipated, but the vaccine proved far more
dangerous, causing thousands of Americans to develop a serious neurological disorder
known as Guillain-Barre Syndrome, causing paralysis. As the “60 Minutes” report from the
time identified, the FDA was again the source of failure because of the rushed, pressured
political environment of the time.’” Most recently, in 2018, the World Health Organization
rushed approval of a vaccine against Dengue Fever, despite warnings from dissident

doctors, which left hundreds of children dead and thousands more injured.”
Effectiveness of Alternative Treatments

138. Early treatment against COVID is highly effective, but for the FDA to acknowledge this
would prevent EUAs from being issued for COVID vaccines and on-patent drugs such as
Regeneron's monoclonal antibodies, Gilead’s Remdesivir and Merck’s Molnupiravir.

139. There are well-studied, safe, approved and readily available medical products to prevent
and treat COVID-19. Given all the known and unknown risks of existing COVID vaccines,
these alternatives are preferable to vaccination, yet the FDA has failed to rigorously evaluate
them let alone encourage their use.

140. These alternatives include Ivermectin, Methylprednisolone, Fluvoxamine,

Hydroxychloroquine, Vitamin C, Vitamin D3, Zinc, Aspirin, corticosteroids and other

7! Debbie Bookchin and Jim Schumacher, The Virus and the Vaccine (July 1, 2005).

? 60 Minutes: Swine Flu (1976), available at
https://www.youtube.com/watch?v=4bOHYZhLOWQ.

3 Michaeleen Doucleff, Rush to Produce, Sell Vaccine Put Kids In Philippines At Risk, NPR
(May 3, 2019), available at
https://www.npr.org/sections/goatsandsoda/2019/05/03/719037789/botched-vaccine-launch-has-
deadly-repercussions

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accessible therapies. Randomized-controlled trials and observations by front line medical
experts have confirmed that COVID-19 is preventable and treatable, especially at early
onset stages, with medicines and practices that have a decades long utilization proving their
safety.”

141. Various treatment methods using combinations of such medications have proven
effective. There has been substantial and significant progress on early, ambulatory multi-
drug therapy for high-risk COVID-19 patients, resulting in as much as 85% reductions in
both hospitalizations and death.’°

142. For example, both Ivermectin and Hydroxychloroquine can be taken in a weekly dose to
prevent infection from SARS-CoV-2, with great effectiveness. ’°

143. Ivermectin, whose safety has been established with at least a billion doses administered
and which is listed on the WHO’s list of essential drugs, along with the chloroquine drugs,

has been shown to have substantial prophylactic and treatment capabilities. ’”

™ McCullough PA, Kelly RJ, Ruocco G, et al. Pathophysiological Basis and Rationale for Early
Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection. Am J Med. 2021;134(1):16-22.
doi:10.1016/j.amjmed.2020.07.003; McCullough PA, Alexander PE, Armstrong R, et al.,
Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-
CoV-2 infection (COVID-19). Rev Cardiovasc Med. 2020 Dec 30;21(4):517-530. doi:
10.31083/j.rcm.2020.04.264. PMID: 33387997.
™ McCullough PA, Alexander PE, Armstrong R, et al., Multifaceted highly targeted sequential
multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19). Rev
Cardiovasc Med (2020) 21:517—530. doil0.31083/j.rcm.2020.04.264.
7 McCullough PA, Kelly RJ, Ruocco G, et al., Pathophysiological Basis and Rationale for Early
Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection. Am J Med. 2021 Jan;134(1):16-22.
doi: 10.1016/j.amjmed.2020.07.003. Epub 2020 Aug 7. PMID: 32771461; PMCID:
PMC7410805; McCullough PA, Alexander PE, Armstrong R, et al., Multifaceted highly targeted
sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-
19). Rev Cardiovasc Med. 2020 Dec 30;21(4):517-530. doi: 10.31083/j.rcm.2020.04.264. PMID:
33387997.
™ Kory, Pierre MD, Meduri, Gianfranco Umberto MD; Varon, Joseph MD; Iglesias, Jose DO;
Marik, Paul E. MD, Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin
43
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144. In Africa, Ivermectin is given once or twice yearly to prevent river blindness, and
chloroquine or Hydroxychloroquine is taken once weekly to prevent malaria. Thus, they
function like vaccines when used in advance of exposure. Rates of COVID-19 cases and
deaths in Africa have turned out to be only a small fraction of what they are in the US.”

145. Many countries and regions have been administering over the counter Ivermectin for
COVID with excellent reported treatment success.

146. The probable efficacy of chloroquine drugs for coronaviruses was demonstrated in
experiments published by the CDC in 2005 and by Dr. Fauci's National Institute of Allergy
and Infectious Diseases (NIAID) in 2014.” This prior knowledge, obtained by CDC and
NIH regarding these drugs' efficacy at standard doses and their safety at standard doses,
while agency officials suppressed their use during the pandemic, is clear evidence of willful

misconduct and should nullify liability protection for these federal officials.

147. In addition, these two inexpensive, readily available drugs are effective regardless of viral
variant or strain, and their effects, used weekly, do not wear off after a few months,
requiring additional booster shots with possible side effects.

148. Yet, the FDA has exhibited bias regarding the effective and safe use of such alternatives,

in the Prophylaxis and Treatment of COVID-19, AMERICAN JOURNAL OF THERAPEUTICS,
May/June 2021 - Volume 28 - Issue 3 - p e299-e3 18,
https://journals.lww.com/americantherapeutics/Fulltext/2021/06000/Review_of_ the Emerging _
Evidence Demonstrating the.4.aspx.

78 Guerrero R, Bravo LE, Mufioz E, Ardila EKG, Guerrero E. COVID-19: The Ivermectin
African Enigma. Colomb Med (Cali). 2020 Dec 30;51(4):e2014613. doi:

10.25100/cm.v5 114.4613; Hisaya Tanioka, Sayaka Tanioka, Kimitaka Kaga, Why COVID-19 is
not so spread in Africa: How does Ivermectin affect it?, Europe PMC 2021 Mar 26. doi:
https://doi.org/10.1101/2021.03.26.21254377.

™ Martin J Vincent, Eric Bergeron, et al., Chloroquine is a potent inhibitor of SARS coronavirus
infection and spread, BMC Virology Journal (August 22, 2005), available at
https://doi.org/10.1186/1743-422X-2-69.

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denying their effectiveness and failing to consider them as a viable, and potentially
preferential, method to alleviate severe disease and death, nullifying the need for any
vaccination scheme. Not only that, but they have also encouraged the vilification of such
resources.

149. Many medical professionals suspect FDA’s feigned ignorance about Ivermectin was a
prerequisite to issuing EUAs for COVID vaccines, given the EUA requirement that no
approved drug be available for the same indication.

150. If children and adults were treated early with proven drug combinations, very few would
progress to the inflammatory and thrombotic stages of COVID-19. While this statement
may appear controversial, forest plots of the compiled literature on Hydroxychloroquine and
Ivermectin for COVID are very compelling, with average efficacy against the different
endpoints of 64% to over 80%.

151. There is no COVID-19 emergency for children aged 5-11. There are safer drugs that
could be used prophylactically and therapeutically for COVID in children. There is
extensive and compelling medical evidence for this assertion; and FDA’s decision to eschew
use of these drugs in favor of a demonstrably dangerous vaccine is arbitrary and capricious.

152. The law on “authorization for medical products for use in emergencies” requires that the
EUA designation be used only when “there is no adequate, approved, and available
alternative to the product for diagnosing, preventing, or treating such disease or condition.”
21 U.S.C. § 360bbb-3(3) (emphasis added).

153. Recognizing and approving Hydroxychloroquine, Ivermectin, and other successful
alternative treatments would have prevented COVID-19 biologics from receiving any

emergency use authorization. As such, the FDA’s revocation of the EUA for chloroquine

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phosphate and Hydroxychloroquine for use on COVID-19 patients was a de facto attempt to
stop doctors prescribing and treating patients with it, to ensure that the path was clear to

grant EUAs for these so-called vaccines. °°

CAUSE OF ACTION I:
VIOLATION OF THE ADMINISTRATIVE PROCEDURES ACT

154. Plaintiffs incorporate the foregoing paragraphs as if fully set forth herein.

155. The Administrative Procedures Act (APA) requires “[e]ach agency [to] give an interested
person the right to petition for the issuance, amendment, or repeal of a rule.” 5 U.S.C.

§ 553(e).

156. The APA does not set fixed timelines for agency action and, instead, requires agency
action within a “reasonable” time by providing judicial review to “compel agency action
unlawfully withheld or unreasonably delayed.” 5 U.S.C. § 706(2). A “reasonable time for
agency action is typically counted in weeks or months, not years,” Jn re Am. Rivers & Idaho
Rivers United, 372 F.3d 413, 419 (D.C. Cir. 2004), and an agency action’s exigent context
may demand expedited review. Fund for Animals v. Norton, 294 F.Supp.2d 92, 114 (D.D.C.
2003) (“pressing human health concerns...demand prompt review”).

157. Congress requires that courts “shall hold unlawful and set aside” any agency “action,”
“finding,” or “conclusion” whenever the agency failed to follow the necessary process for
reasoned decision-making. 5 U.S.C. § 706(2)(A). The traditional judicial protocol is to
vacate the agency action and remand the matter to the agency for compliance with the

requisite process before taking any further action.

8° Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for
Chloroquine and Hydroxychloroquine, U.S. Food & Drug Administration, available at
https://www.fda.gov/news-events/press-announcements/coronavirus-covid- 19-update-fda-
revokes-emergency-use-authorization-chloroquine-and.

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158. The Administrative Procedures Act protects the public from arbitrary and capricious
executive branch action by imposing the rule of reason and the rule of law through judicial
oversight. An agency is “required to engage in reasoned decision making.” Michigan v.
EPA, 576 U.S. 743, 750 (2015). This requires that the agency “examine the relevant data.”
Motor Vehicle Mfrs. Ass’n of U.S., Inc. v. State Farm Mut. Auto Ins. Co., 463 U.S. 29, 43
(1983). This also requires that the agency “articulate a satisfactory explanation for its
action.” Motor Vehicle Mfrs. Ass’n of U.S., Inc. v. State Farm Mut. Auto Ins. Co., 463 U.S.
29, 43 (1983). An agency action is considered “arbitrary and capricious” if it fails to comply
with the rules of reason articulated in Motor Vehicle Mfrs. Ass’n of U.S., Inc. v. State Farm

Mut. Auto Ins. Co., 463 U.S. 29, 43 (1983).
The FDA abused its power under the emergency use statute

159. The emergency use authorization statute, which allows the FDA to authorize emergency
drugs without going through the formal, comprehensive approval process, and under which
the FDA has authorized the use of the COVID-19 vaccine for children ages 5-16, requires
that an actual emergency exist. This is an essential prerequisite to a loophole that removes
barriers to approval that are in place to ensure safety and effectiveness.

160. This is a high burden to meet, as evidenced by the fact that an EUA has never been
previously granted for a brand-new vaccine. The only vaccine to have been authorized for
emergency use was AVA, an anthrax vaccine, which had already been formally approved by

the FDA for other purposes.*!

8! Jonathan Iwry, From 9/11 to COVID-19: A Brief History of FDA Emergency Use

Authorization, Harvard Law Petrie-Flom Center (January 28, 2021), available at

https://blog.petrieflom.law.harvard.edu/202 1/01/28/fda-emergency-use-authorization-history/.
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161. To support an EUA declaration, certain circumstances must exist to justify the
authorization. § 564(b)(1). As the FDA admits, “a determination under section 319 of the
Public Health Service Act that a public health emergency exists, such as the one issued on
January 31, 2020, does not enable FDA to issue EUAs.”*?

162. The FDA here has failed to justify its conclusion that children ages 5-11 face an
emergency that warrants subjecting them to life-threatening short-term adverse effects, and
untold long-term adverse effects.

163. Young children are the /east at risk from SARS-CoV-2. Children that do contract
COVID-19 typically do not become as sick as adults, with most children having mild or no
symptoms.** Those few that have experienced severe symptoms or death from COVID-19
have almost exclusively had comorbidities or other underlying health conditions.** The
survival rate of children who have tested positive for COVID-19 is exceptionally high.

164. Even assuming that children are at risk from SARS-CoV-2, given that the Pfizer-
BioNTech COVID-19 biologic has only been marginally effective at reducing severe
symptoms hospitalization, or death, which children ages 5-11 are not highly susceptible to,
and ineffective at reducing transmission, which children are affected by, it is medically

unnecessary for children to receive this biologic.

82 Emergency Use Authorization, U.S. Food & Drug Administration (December 3, 2021),
available at https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-
and-policy-framework/emergency-use-authorization.
83 COVID-19 (coronavirus) in babies and children, Mayo Clinic, available at
https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-in-babies-and-
children/art-20484405.
84 Clare Smith, David Odd, Rachel Harwood, et al., Deaths in Children and Young People in
England following SARS-CoV-2 infection during the first pandemic year: a national study using
linked child death reporting data, Research Square (July 7, 2021), DOI: 10.21203/rs.3.rs-
689684/Vv1, available at https://www.researchsquare.com/article/rs-689684/v1.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 49 of 237

165. Meanwhile, the adverse effects from the COVID-19 biologic that have been witnessed in
children can be serious and deadly. The FDA has failed to properly address these risks and
are still analyzing them through clinical trials that are not scheduled to be completed until
this drug has been marketed to young children for several years.

166. As the risk of COVID-19 to children 5-11 cannot be categorized as an emergency, the
FDA is not at liberty to utilize the emergency use authorization statute to carry out their

agenda of putting this Pfizer biologic in the arms of every American, no matter the cost.

The FDA was not entitled to use its emergency powers on the grounds that Congress failed
to conduct its six-month review of national emergencies

167. The National Emergencies Act (NEA) is intended to provide the executive with
flexibility and unique powers in dire and urgent times. Congress, however, is ordered to
provide a check and balance on the executive’s emergency powers to prevent a potential
abuse of authority.

168. The FDA has based its emergency authorization authority, in part, upon the declaration of
a national emergency.

169. S50U.S.C. § 1622, which addresses the termination of national emergencies, requires that
“(not later than six months after a national emergency is declared, and not later than the end
of each six-month period thereafter that such emergency continues, each House of Congress
shall meet to consider a vote on a joint resolution to determine whether that emergency shall
be terminated.” 50 U.S.C. § 1622(b).

170. More than a year after the COVID-19 national emergency was declared on March 13,
2020 by President Trump, Congress had still not met to consider whether the COVID-19

emergency should continue. In May 2021, several representatives introduced a joint

49
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 50 of 237

resolution to terminate the COVID-19 emergency declared under the National Emergencies
Act (NEA).*® This joint resolution was never voted on, nor was another joint resolution ever
introduced.

171. Congress has failed to perform its function as a safeguard against this abuse of power.
The national emergency declaration is not set to expire until March 1, 2022, nearly two
years after the initial designation with no checks and balances.

172. It is within this culture of an unmitigated “national emergency” that the Defendant
agency has taken extreme and unauthorized liberties to deliver COVID-19 vaccines to the
public, no matter the consequences or the number of victims of such activity.

173. Defendants capitalized upon this national emergency declaration to provide an excuse for

their grift against the American people.

The FDA denied CHD its procedural right to seek redress via citizen petition, a right
conforming to the right to petition under the First Amendment.

174. The First Amendment guarantees the right to petition one’s government and the
necessity of robust debate following strict scientific standards.

175. “A private citizen exercises a constitutionally protected First Amendment right anytime
he or she petitions the government for redress.” Fregia v. Bright, No. 1:16-CV-187, 2017
U.S. Dist. LEXIS 179667, *11 (E.D. Tex. Aug. 15, 2017). Citizens are guaranteed by the
First Amendment “the right of access to all branches of the government for the redress of
wrongs.” Noles v. Dial, No. 3:20-CV-3677-N-BK, 2021 U.S. Dist. LEXIS 178694, *17

(N.D. Tex. Aug. 25, 2021).

85 Gosar Introduces Joint Resolution to Terminate the COVID-19 Emergency Declaration, May
20, 2021, available at
https://gosar.house.gov/news/email/show.aspx?ID=N5POWQSNCMBCEN7YPCI4Z4PJIU.

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176. Plaintiff CHD exercised that right by filing a citizen petition on May 16, 2021, which
garnered more than 30,000 comments from individuals, requesting that the FDA halt the
licensing of COVID-19 until such time as the concerns outlined in the petition be alleviated
and the proper scientific and administrative processes be followed.

177. Defendants failed to adequately address the concerns in their response, which was
delivered on the same day that the Pfizer “Comirnaty” vaccine received its official approval.
Defendants’ response did nothing to ameliorate the legitimate and grave grievances
presented in the petition.

178. This latest in the series of EUAs that Defendants have granted, this time aimed at young
children who are least at risk from COVID-19, is a continuation of the violative and harmful
actions Defendants have taken in their promotion of the COVID-19 Pfizer biologic.

179. Unless and until Defendants properly allow for citizen engagement, follow the laws
governing their role as an administrative agency, and address the underlying concerns
presented by Plaintiff CHD in the original citizen petition, Defendants unbridled contempt
for the rights of citizens guaranteed by the Constitution and their resulting illegal wielding

of power over the public’s health must be stopped.

The FDA redefined the term “vaccine” in violation of procedural due process,

180. The FDA and CDC have altered the traditional definitions of “Vaccine” and
“Vaccination” to encompass the COVID-19 biologics and have the ability to market and
administer them as vaccines, although they do not fit the century-long definition of the
word.

181. Defendants failed to provide a citizen participation or notice-and-comment process when

it labeled the COVID-19 biologics as vaccines. This erroneous labelling has misled the
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public and created an unfounded trust in the biologic. By promoting it as a “vaccine,” which
comes with a connotation of a medical miracle, rather than its true label of an experimental
pharmaceutical gene therapy, Defendants have been able to propagate a national vaccination
campaign based on the public's erroneous beliefs.

182. Plaintiffs Deborah L. Else and Sacha Dietrich, on behalf of their children, and CHD, on
behalf of their members, have themselves felt the harm that has come from this false
designation through the mass vaccination scheme, as well as the pressure, coercion and

discrimination that has resulted.

Mislabeling the Drug & Marketing it to Children

183. Defendants marketed this emergency use only drug to children as if it were a biologic
licensed drug, failing to follow restrictions on marketing biologics to children, or in general,
without disclosing it does not fit the traditional and historic medical definition of a vaccine,
without disclosing any fair balance between risks and efficacy, and without disclosing the
very low risks of the disease the drug “treats” for children.

184. Plaintiffs are directly affected by the advertisements and societal pressures encouraging
their children to receive the COVID-19 Pfizer-BioNTech biologic.

185. The FDA's illegal actions have encouraged people in positions of authority to push this
experimental biologic on our nation’s youth. Plaintiff Deborah Else attests to
recommendations by her children’s school to receive the Pfizer BioNTech biologic, which is
available at vaccine clinics provided on school grounds. Pediatricians have also sent notices
to parents encouraging vaccination, despite the almost zero risk of serious symptoms or

death in children who contract COVID-19. This societal push toward vaccination has

52
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culminated in an inundation of pro-vaccine messaging; advertisements on television, radio
shows, announcements and signage in stores, and even the manipulation of popular
children’s characters such as Sesame Street’s Big Bird have been employed to propagandize
the public and the youth.

186. Plaintiff Sacha Dietrich attests that because of FDA’s unlawful EUA, her children are
constantly harassed by directives to receive the COVID-19 biologic and are continuously

pressured by the media and other children.

Defendants Failed to Articulate Any Standard for Assessing Risk

187. This agency process requires Defendants to articulate a clear standard for assessing the
safety, efficacy, and necessity of any drug or biologic, whether for an EVA or license. This
is especially so when the product is likely to be mandated to millions of people around the
world. Burlington Truck Lines v. United States, 371 U.S. 156, 158 (1962). This also
requires that the agency “articulate a satisfactory explanation for its action.” Motor Vehicle
Mfrs. Ass’n of U.S., Inc. v. State Farm Mut. Auto Ins. Co., 463 U.S. 29, 43 (1983).

188. The FDA failed to articulate any standard for assessing an individualized, stratified risk
for children between the ages of 5 and 11 from the various vaccines, including any risk
assessment specific to the variants of the virus, the efficacy of the vaccines to variants of the
virus, or the risks of the vaccines themselves by any statistical measurement to children in
that age group. The FDA’s failure violated their obligation to make such a standard, provide
the individualized, stratified analysis, and give some measurable assessment for children,
and their parents, to assess the risks of each option for themselves.

189. This is further demonstrated by the documented fraud in Pfizer’s clinical trials, of which

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Defendants were fully aware and refused to investigate. Defendants turned a blind eye to
falsified data, ignoring adverse reported adverse events, failing to follow protocols,
revealing confidential participant information, and adverse actions taken against staff who
spoke out against these issues. As such, without a widespread investigation into Pfizer’s
clinical trial practices, Defendants have failed to explain how and why their findings from
these studies should be relied upon in order to justify the issuance of EUAs for children
aged 5-11 and how their risk assessment is accurate.

190. Since the launch of the first COVID-19 biologic in 2020, the FDA’s method for assessing
risk for all individuals, but especially children aged 5-11, has been wholeheartedly
inadequate and is still shrouded in mystery.

191. The FDA also failed to examine and regulate mRNA COVID-19 vaccines as gene
therapies. The failure to apply these required criteria, which are more stringent than the
criteria the FDA applies to vaccines generally and the complete lack of an assessment

standard for these gene therapies in FDA’s EUA assessment, is arbitrary and capricious.
Defendants failed to Examine Relevant Data

192. As part of “reasoned decision making,” an agency is required to “examine the relevant
data.” Motor Vehicle Mfrs. Ass’n of U.S., Inc. v. State Farm Mut. Auto Ins. Co., 463 U.S. 29,
43 (1983)

193. Defendant failed to address the inadequacies regarding its clinical trials. Scientists from
other countries readily acknowledge that "[c]linical trials for these inoculations were very
short-term (a few months), had samples not representative of the total population, and for

adolescents/children, had poor predictive power because of their small size. Most

54
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importantly, the clinical trials did not address long-term effects that, if serious, would be

borne by children/adolescents for potentially decades.”*°

194. In addition, the FDA ignores the fact that "[t]he bulk of the official COVID-19 attributed
deaths per capita occur in the elderly with high comorbidities, and the COVID-19 attributed
deaths per capita are negligible in children."*’ Children don’t need these vaccines. The
argument that children must risk their health to protect adults is completely unethical if not
evil. Children and adolescents tend to have milder symptoms compared to adults, so unless
they are part of a group at higher risk of severe COVID-19, it is less urgent to vaccinate
them. The FDA cannot grant an emergency use authorization when there is no emergency
for this age group.

195. The FDA’s proclivity to curry favor to pharmaceutical companies under a thinly veiled
guise of protecting children is painfully obvious. The statistics are clear, healthy children
have a miniscule risk of contracting COVID-19. What’s more, the mortality rate in children
is negligible, and many are thought to have had COVID-19, providing them with natural
immunity anyway. In fact, nearly half of all children have natural immunity to COVID,
according to the CDC.

196. Defendants have furthermore ignored adverse events that have been documented through

the VAERS database, despite the fact that the input of event reports to VAERS since the

COVID vaccines were rolled out is greater than all cumulative adverse event reports to

86 Why are we vaccinating children against COVID-19?, Science Direct, available at
https://www.sciencedirect.com/science/article/pii/S22 1475002100161 X?via%3Dihub.
87 Kostoff RN, Calina D, Kanduc D, Briggs MB, Vlachoyiannopoulos P, Svistunov AA,
Tsatsakis A. Why are we vaccinating children against COVID-19? Toxicol Rep. 2021;8:1665-
1684. doi: 10.1016/j.toxrep.2021.08.010. Epub 2021 Sep 14. Erratum in: Toxicol Rep. 2021 Oct
7;: PMID: 34540594; PMCID: https://pubmed.ncbi.nlm.nih.gov/34540594/.

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VAERS for the prior thirty years. The failure to investigate this fact before administering
this experimental injection to our nation’s children goes beyond arbitrary and capricious
action; it is amoral.

197. Meanwhile, Defendants have dismissed the effectiveness of alternative treatments, which
have the potential to significantly reduce hospitalizations and death to the extent that any
vaccination program may have been wholly unnecessary. Such treatments, had they been
recognized by the FDA, would have threatened the agency’s ability to issue EUAs.

198. Defendants’ hype is outweighed by tidbits of truth that the public is forced to ferret out
from an ever-increasingly censored media. These experimental and prematurely licensed
vaccines are not only dangerous and defective, but their efficacy has also been grossly
exaggerated. There is substantial evidence that vaccine effectiveness wanes substantially
after only six months, hence the narrative that booster shots are necessary for remaining
protected, which Defendants have ignored. Defendants have willfully ignored data critical of
the Pfizer biologic, opening up children to be victims of a consistent schedule of COVID-19
injections that are inadequately tested and, based on empirical evidence, potentially
dangerous. In so doing, Defendants have demonstrated that they are willing to arbitrarily
and capriciously gamble with the lives of tens or hundreds of millions of children.

199. Dr. Eric Ruben, an advisory committee member to the FDA, said this about the COVID
vaccine in children 5-11 during an official FDA hearing: “We’re never going to learn about

how safe the vaccine is until we start giving it. That’s just the way it goes.”*®

88 FDA Panelist on Vaccinating 5-year-olds: “We're never going to learn about how safe the
vaccine is until we start giving it,” 93.1FMWIBC (October 27, 2021) available at
https://www.wibc.com/blogs/mock-n-rob/fda-panelist-on-vaccinating-5-year-olds-were-never-
going-to-learn-about-how-safe-the-vaccine-is-until-we-start-giving-it/.

56
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200. CDC's Acting Director Dr. Rochelle Walensky stated, on the one hand “Our vaccines are
working exceptionally well. . .” She clarifies with “They continue to work well for Delta,
with regard to severe illness and death — they prevent it. But what they can't do anymore is
prevent transmission."*

201. This lawsuit simply asks the FDA to follow its own rules and hit the pause button on this
pedicide, this rush to pharmapocalypse. It seeks vacatur of the authorization for children
aged 5-11, as well as remand for the Defendants to abide by their legal obligations, statutory
duties, and scientific processes.

202. The FDA has failed to engage in a pluralistic, critical, open, transparent, and scientific
dialogue with the public based on careful, deliberative evaluation of all relevant research
and experience since it authorized COVID-19 vaccines. On the contrary, it recklessly rushed
the Pfizer- BioNTech COVID-19 biologic authorization without proper evaluation in
violation of the APA.

203. Plaintiffs bring this action because the FDA is failing to carry out its mission and is once
again shamelessly displaying its true colors as a captured agency that ignores health and
safety while granting favors to pharma. Plaintiffs seek this Court’s intervention to put the

FDA back on the path to lawful protection of the public in these precarious times.

204. Defendants' arbitrary and capricious actions warrant a stay, a vacatur and remand.

CAUSE OF ACTION Il: DECLARATORY RELIEF

205. Plaintiffs incorporate the foregoing paragraphs as if fully set forth herein.

206. Plaintiffs seek a declaratory judgment that the defendants cannot use the emergency

8° Vaccines fail to prevent transmission, The Situation Room Twitter, available at
https://twitter.com/CNNSitRoom/status/1423422301882748929.
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authorization statute to mislabel drugs as vaccines, mislabel drugs that have not been
thoroughly tested as safe and effective, mislabel drugs as permitted to be compelled without
informed consent, and to mislabel drugs to children that result in mandates being issued
concerning those children’s access to basic services, including medical and educational
services, rather than the regular biologic licensure process which incorporates citizen

participation provisions, including the right of a citizen petition and response thereto.

207. Congress expressly created this remedy of declaratory relief for federal courts as a critical
check on the abuse of power by an executive branch agency, and thereby authorize by law
that this Court “may declare the rights and other legal relations of ay interested party

seeking such declaration.” 28 U.S.C. § 2201.

PRAYER FOR RELIEF

WHEREFORE, Plaintiff s Children’s Health Defense, Deborah L. Else, and Sacha Dietrich

respectfully ask this Court:

i. To enjoin any further marketing or promotion of the drug to children, to stay the
FDA’s decision to grant Emergency Use Authorization for Pfizer-BioNTech’s
COVID-19 vaccine for children aged 5-11, and to vacate and remand the decision
to the agency;

il. To award attorneys’ fees and costs, as authorized under 28 U.S.C. § 2412; and
ill. To grant all other appropriate relief as necessary.
Dated: January 24, 2022 Respectfully submitted,

/s/ Robert E. Barnes
Robert E. Barnes, Esq.
Member of the Western District of Texas

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 59 of 237

Email: robertbarnes@barneslawllp.com
BARNES LAW

700 South Flower Street, Suite 1000
Los Angeles, California 90017
Telephone: (310) 510-6211

Robert F. Kennedy, Jr., Esq.

Mary S. Holland, Esq.

Subject to admission Pro Hac Vice

Email: mary.holland@childrenshealthdefense.org
Children’s Health Defense

1227 N. Peachtree Pkwy, Suite 202

Peachtree City, GA 30269

Counsel for Plaintiffs CHILDREN’S HEALTH
DEFENSE, Deborah L. Else, and Sacha Dietrich.

59
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 60 of 237

Exhibit 1
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 61 of 237

FDA NEWS RELEASE

FDA Authorizes Pfizer-BioNTech COVID-19 Vaccine for Emergency Use
in Children 5 through 11 Years of Age

For Immediate Release:
October 29, 2021

Espafiol (/news-events/press-announcements/la-fda-autoriza-vacuna-contra-el-covid-19-de-pfizer-biontech-para-uso-de-emergencia-en-ninos-de-5-11)

Today, the U.S. Food and Drug Administration authorized the emergency use of the Pfizer-BioNTech COVID-19
Vaccine for the prevention of COVID-19 to include children 5 through 11 years of age. The authorization was based
on the FDA’s thorough and transparent evaluation of the data that included input from independent advisory
committee experts who overwhelmingly voted in favor of making the vaccine available to children in this age group.

Key points for parents and caregivers:

e Effectiveness: Immune responses of children 5 through 11 years of age were comparable to those of
individuals 16 through 25 years of age. In addition, the vaccine was found to be 90.7% effective in preventing
COVID-19 in children 5 through 11.

e Safety: The vaccine’s safety was studied in approximately 3,100 children age 5 through 11 who received the
vaccine and no serious side effects have been detected in the ongoing study.

¢ The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices
(https://www.cdc.gov/vaccines/acip/index.htm]) will meet next week to discuss further clinical

recommendations.

“As a mother and a physician, I know that parents, caregivers, school staff, and children have been
waiting for today’s authorization. Vaccinating younger children against COVID-19 will bring us
closer to returning to a sense of normalcy,” said Acting FDA Commissioner Janet Woodcock, M.D.
“Our comprehensive and rigorous evaluation of the data pertaining to the vaccine’s safety and
effectiveness should help assure parents and guardians that this vaccine meets our high
standards.”

The Pfizer-BioNTech COVID-19 Vaccine for children 5 through 11 years of age is administered as a two-dose
primary series, 3 weeks apart, but is a lower dose (10 micrograms) than that used for individuals 12 years of age and
older (30 micrograms).

In the U.S., COVID-19 cases in children 5 through 11 years of age make up 39% of cases in individuals younger than
18 years of age. According to the CDC, approximately 8,300 COVID-19 cases in children 5 through 11 years of age
resulted in hospitalization. As of Oct. 17, 691 deaths from COVID-19 have been reported in the U.S. in individuals
less than 18 years of age, with 146 deaths in the 5 through 11 years age group.

“The FDA is committed to making decisions that are guided by science that the public and
healthcare community can trust. We are confident in the safety, effectiveness and manufacturing
data behind this authorization. As part of our commitment to transparency around our decision-
making, which included our public advisory committee meeting earlier this week, we have posted
documents today supporting our decision and additional information detailing our evaluation of
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 62 of 237

the data will be posted soon. We hope this information helps build confidence of parents who are
deciding whether to have their children vaccinated,” said Peter Marks, M.D., Ph.D., director of the
FDA’s Center for Biologics Evaluation and Research.

The FDA has determined this Pfizer vaccine has met the criteria for emergency use authorization. Based on the
totality of scientific evidence available, the known and potential benefits of the Pfizer-BioNTech COVID-19 vaccine
in individuals down to 5 years of age outweigh the known and potential risks.

FDA Evaluation of Available Effectiveness Data

The effectiveness data to support the EUA in children down to 5 years of age is based on an ongoing randomized,
placebo-controlled study that has enrolled approximately 4,700 children 5 through 11 years of age. The study is
being conducted in the U.S., Finland, Poland and Spain. Children in the vaccine group received two doses of the
Pfizer-BioNTech COVID-19 Vaccine containing 10 micrograms of messenger RNA per dose. The FDA analyzed data
that compared the immune response of 264 participants from this study to 253 participants 16 through 25 years of
age who had two higher doses of the vaccine in a previous study which determined the vaccine to be effective in
preventing COVID-19. The immune responses of the younger age participants were comparable to the older
participants.

The FDA also conducted a preliminary analysis of cases of COVID-19 occurring seven days after the second dose.
In this analysis, among participants without evidence of prior infection with SARS-CoV-2, 3 cases of COVID-19
occurred among 1,305 vaccine recipients and 16 cases of COVID-19 occurred among 663 placebo recipients; the
vaccine was 90.7% effective in preventing COVID-19.

FDA Evaluation of Available Safety Data

The available safety data to support the EUA include more than 4,600 participants (3,100 vaccine, 1,538 placebo)
ages 5 through 11 years enrolled in the ongoing study. In this trial, a total of 1,444 vaccine recipients were followed
for safety for at least 2 months after the second dose.

Commonly reported side effects in the clinical trial included injection site pain (sore arm), redness and swelling,
fatigue, headache, muscle and/or joint pain, chills, fever, swollen lymph nodes, nausea and decreased appetite.
More children reported side effects after the second dose than after the first dose. Side effects were generally mild
to moderate in severity and occurred within two days after vaccination, and most went away within one to two days.

The FDA and CDC safety surveillance systems have previously identified increased risks of myocarditis
(inflammation of the heart muscle) and pericarditis (inflammation of tissue surrounding the heart) following
vaccination with Pfizer-BioNTech COVID-19 Vaccine, particularly following the second dose, and with the observed
risk highest in males 12 through 17 years of age. Therefore, the FDA conducted its own benefit-risk assessment
using modelling to predict how many symptomatic COVID-19 cases, hospitalizations, intensive care unit (ICU)
admissions and deaths from COVID-19 the vaccine in children 5 through 11 years of age would prevent versus the
number of potential myocarditis cases, hospitalizations, ICU admissions and deaths that the vaccine might cause.
The FDA’s model predicts that overall, the benefits of the vaccine would outweigh its risks in children 5 through 11
years of age.

Ongoing Safety Monitoring

Pfizer Inc. has updated its safety monitoring plan to include evaluation of myocarditis, pericarditis and other events
of interest in children 5 through 11 years of age. In addition, the FDA and the CDC have several systems in place to
continually monitor COVID-19 vaccine safety and allow for the rapid detection and investigation of potential safety
problems.
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 63 of 237

It is mandatory for Pfizer Inc. and vaccination providers to report to any serious adverse events, cases of
Multisystem Inflammatory Syndrome and cases of COVID-19 that result in hospitalization or death in vaccinated
individuals. It is also mandatory for vaccination providers to report all vaccine administration errors to VAERS for
which they become aware and for Pfizer Inc. to include a summary and analysis of all identified vaccine
administration errors in monthly safety reports to the FDA.

Data Supports New Vaccine Formulation to Improve Stability and Storage Conditions

The FDA today also authorized a manufacturing change for the vaccine to include a formulation that uses a
different buffer; buffers help maintain a vaccine’s pH (a measure of how acidic or alkaline a solution is) and
stability. This new formulation is more stable at refrigerated temperatures for longer periods of time, permitting
greater flexibility for vaccination providers.

The new formulation of the vaccine developed by Pfizer Inc. contains Tris buffer, a commonly used buffer in a
variety of other FDA-approved vaccines and other biologics, including products for use in children. The FDA
evaluated manufacturing data to support the use of Pfizer-BioNTech COVID-19 Vaccine containing Tris buffer and
concluded it does not present safety or effectiveness concerns.

Related Information

e Pfizer-BioNTech COVID-19 Vaccine (/emergency-preparedness-and-response/coronavirus-disease-2019-
covid-19/comirnaty-and-pfizer-biontech-covid-19-vaccine)

¢ COVID-19 Vaccines (/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-
vaccines)

e Emergency Use Authorization for Vaccines Explained (/vaccines-blood-biologics/vaccines/emergency-use-

authorization-vaccines-explained)

HEE

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by
assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological
products for human use, and medical devices. The agency also is responsible for the safety and security of our
nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating
tobacco products.

Inquiries
Media:

EDA Office of Media Affairs (mailto:fdaoma@fda.hhs.gov)
& 301-796-4540

Consumer:
& 888-INFO-FDA

© More Press Announcements (/news-events/newsroom/press-announcements)
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 64 of 237

Exhibit 2
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 65 of 237

Children’s
Health Defense

May 16, 2021

Division of Dockets Management
Department of Health and Human Services
Food and Drug Administration

Acting Commissioner Janet Woodcock, M.D.
5630 Fishers Lane, Room 1061

Rockville, MD 20852

Dear Acting Commissioner Woodcock:

Enclosed is a Citizen Petition filed on behalf of Children’s Health Defense by Meryl
Nass, M.D., Scientific Advisory Board member, and Robert F. Kennedy, Jr., Board Chair and
Chief Litigation Counsel, requesting that the FDA revoke Emergency Use Authorizations for
existing COVID vaccines and refrain from approving and licensing them.

Dr. Nass and Mr. Kennedy look forward to your timely review of this petition. They are
available to answer questions and to provide any additional relevant information.

Sincerely yours,

Mf S bef

Mary Holland

President and General Counsel

(845) 445-7807

mary. holland@childrenshealthdefense.org

1227 North Peachtree Parkway, Suite 202. Peachtree City, GA 30269
www.childrenshealthdefense.org
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 66 of 237

VIA ELECTRONIC FILING
May 16, 2021

Division of Dockets Management
Department of Health and Human Services
Food and Drug Administration

5630 Fishers Lane, Room 1061

Rockville, MD 20852

UNITED STATES DEPARTMENT OF HEALTH AND HUMAN SERVICES
AND THE FOOD AND DRUG ADMINISTRATION

PETITION FOR ADMINISTRATIVE
ACTION REGARDING COVID-19 Docket No.
VACCINES

CITIZEN PETITION

On behalf of Children’s Health Defense, the undersigned submit this petition under 21
C.F.R. § 10.20, § 10.30, § 50.23, § 600 — 680, § 601.2; 10 U.S.C. § 1107(f), § 1107a; 21 U.S.C.
§ 355()(4), § 360bbb-3; 42 U.S. Code § 247d; § 564 of the Federal Food, Drug, and Cosmetic Act
(FDCA); the Public Readiness and Emergency Preparedness Act; the Public Health Service Act,
and § 553(e) of the Administrative Procedures Act.

We request the Acting Commissioner of the Food and Drugs Administration (FDA) to
issue, amend, revoke, or refrain from taking the administrative actions listed below regarding
emergency use authorizations (EUAs), current and future new drug applications (NDAs), and
biologics license applications (BLAs) for all COVID vaccines.

I. ACTIONS REQUESTED

1. FDA should revoke all EUAs and refrain from approving any future EUA, NDA or
BLA for any COVID vaccine for all demographic groups because the current risks of serious
adverse events or deaths outweigh the benefits, and because existing, approved drugs provide
highly effective prophylaxis and treatment against COVID, mooting the EUAs.

2. Given the extremely low risk of severe COVID illness in children, FDA should
immediately refrain from allowing minors to participate in COVID vaccine trials, refrain from
amending EUAs to include children, and immediately revoke all EUAs that permit vaccination of
children under 16 for the Pfizer vaccine and under 18 for other COVID vaccines.

3. FDA should immediately revoke tacit approval that pregnant women may receive
any EVA or licensed COVID vaccines and immediately issue public guidance to that effect.
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 67 of 237

4. FDA should immediately amend its existing guidance for the use of the chloroquine
drugs, ivermectin, and any other drugs demonstrated to be safe and effective against COVID, to
comport with current scientific evidence of safety and efficacy at currently used doses and
immediately issue notifications to all stakeholders of this change.

5. The FDA should issue guidance to the Secretary of the Defense and the President
not to grant an unprecedented Presidential waiver of prior consent regarding COVID vaccines for
Servicemembers under 10 U.S.C. § 1107(f) or 10 U.S.C. § 1107a.

6. The FDA should issue guidance to all stakeholders in digital and written formats to
affirm that all citizens have the option to accept or refuse administration of investigational COVID
vaccines without adverse work, educational or other non-health related consequences, under 21
U.S.C. § 360bbb-3(e)(1)(a)(ii)(IID) | and the informed consent requirements of the Nuremberg
Code.”

7. Pending revocation of COVID vaccine EUAs, FDA should issue guidance that all
marketing and promotion of COVID vaccines must refrain from labeling them “safe and
effective,” as such statements violate 21 U.S.C. § 360bbb-3.

II. STATEMENT OF GROUNDS
A. Safety

8. Vaccine Adverse Event Reporting System (VAERS) data reveal unprecedented
levels of deaths and other adverse events since the FDA issued Emergency Use Authorizations
(EUAs) for three COVID vaccines. As of May 10, 2021, VAERS reported 4,434 deaths of people
who received at least one COVID vaccination.’

9. FDA and CDC have not responded to these data by issuing any warnings or
restricting the use of these vaccines. Furthermore, the VAERS database is the only safety database
to which the public has access. The government withholds extensive safety information from the
public despite having at least ten additional data sources and expert consultants to analyze these
data, according to Nancy Messonier, MD, the Director of the National Center for Immunization
and Respiratory Diseases.* Examples include databases from the Centers for Medicare and

'21 U.S.C. § 360bbb-3, Authorization for medical products for use in emergencies,
https://www.govinfo.gov/content/pkg/USCODE-201 1-title2 1/pdf/USCODE-201 1-title2 1-chap9-
subchap V-partE-sec3 60bbb-3 .pdf.

? Nuremburg Code, BRITISH MEDICAL JOURNAL, No. 7070, Volume 313, p. 1448 (Dec. 7, 1996),
https://media.tghn.org/medialibrary/2011/04/BMJ_No_7070_Volume_313_The Nuremberg Co
de.pdf.

3 VAERS Vaccine Adverse Event Reporting System data, available at https://vaers.hhs.gov/.

+ FDA meeting on COVID 19 and Emergency Use Authorization, Part 1 (Video), Dec. 10, 2020,

available at https://www.c-span.org/video/?507053-1/fda-meeting-covid-19-vaccine-emergency-
authorization-part-1.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 68 of 237

Medicaid, the Veterans Administration, the Defense Department (DMSS), the Vaccine Safety
Datalink and the “Genesis” database, which is operated in cooperation with the National Institutes
of Health and Brown University and includes 250 long-term care facilities and 35,000 residents.

10. Dr. Messonier told the FDA and its Vaccines and Related Biological Products
Advisory Committee (VRBPAC) on December 10, 2020 that it had 11 systems that would evaluate
COVID vaccine safety. Five systems would be active at the start of the vaccine program, and an
additional six systems would become active over ensuing weeks. She said that the VAERS system
was being enhanced for long-term care facilities, and added, “Hopefully you'll understand how
robust these systems are.” Below is the graphic she presented to the VRBPAC and the public on
December 10, 2020.

YMINISTRATION (FDA)
(CBER)
ica

11. The CDC website, updated on May 11, 2021 states, "These vaccines have
undergone and will continue to undergo the most intensive safety monitoring in U.S. history. This

monitoring includes using both established and new safety monitoring systems to make sure that
COVID-19 vaccines are safe."°

12. The CDC website states that “CDC and FDA physicians review each case report of
death as soon as notified and CDC requests medical records to further assess reports.”° By contrast,
a CDC official told a reporter for The Daily Beast that it lacks a "good way to track deaths that
occur after vaccination in real time.” Furthermore, CDC told the reporter, "there are no current
plans to include vaccination data in the current CDC Covid-19 mortality analysis."”

> CDC, Safety of COVID-19 Vaccines (updated May 11, 2021),
https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/safety-of-vaccines.html.

® CDC, Selected Adverse Events Reported after COVID-19 Vaccination (updated May 11, 2021),
https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events. html.

7 Erin Banco, White House asks CDC to study how many have died after COVID vaccine shots,
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 69 of 237

13. Children's Health Defense asked CDC for information on post-vaccination deaths
and injuries in early March 2021 and has yet to receive a response.®

14. Normally, licensed biologics manufacturers review adverse event reports pursuant
to 21 C.F.R. § 600.80, while to date the CDC and the manufacturers appear to dispute most causal
links to COVID vaccines. Any COVID vaccine license applicant “assumes responsibility for
compliance with the applicable product and establishment standards” according to 21 C.F.R. §
600.3.’ CDC asserts that a “review of available clinical information, including death certificates,
autopsy, and medical records has not established a causal link to COVID-19 vaccines,” yet recent
assessments acknowledge “a plausible causal relationship between the J&J/Janssen COVID-19
vaccine and a rare and serious adverse event—blood clots with low platelets—which has caused
deaths.”'° Denmark, among other nations, has banned the EUA J&J/Janssen COVID vaccine,
stating, “the benefits of using the COVID-19 vaccine from J&J do not outweigh the risk of causing
possible adverse effect in those who receive the vaccine.”"!

15. CDC calculated rates of adverse effects for anaphylaxis post-vaccination
improperly, using VAERS reports as the numerator, even though CDC officials have
acknowledged "it is not possible to use VAERS data to calculate how often an adverse event occurs
in a population.”!? When Massachusetts General-Brigham hospitals evaluated the rate of
anaphylaxis in employees post COVID vaccination, they found anaphylaxis rates approximately
50-100 times greater than the rates CDC calculated using VAERS data. (Pfizer rate 2.7/10,000
vaccinees and Moderna rate 2.3/10,000 vaccinees).'* Anaphylaxis after vaccination has led to
deaths. If this degree of underestimation holds true for other adverse events using the VAERS
database, then the safety of COVID vaccines is considerably worse than it currently appears. This
rate could be verified by querying the ten databases whose results have been hidden from the

DAILY BEAST (Jan. 28, 2021), https://www.thedailybeast.com/white-house-asks-cdc-to-study-
how-many-have-died-after-covid-vaccine-shots.

8 Megan Redshaw, 64 Days and Counting — Why Won’t the CDC Answer Our Questions? THE
DEFENDER (May 11, 2021), https://childrenshealthdefense.org/defender/64-days-why-wont-cdc-
answer-questions/.

? Code of Federal Regulations Title 21 § 600.3,
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcft/cfrsearch.cfm? fr=600.3.

0 CDC, Selected Adverse Events Reported after COVID-19 Vaccination (updated May 11,
2021), https:/www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html.

"| Vincent West, Denmark ditches J&J COVID-19 shots from vaccination programme, REUTERS
(May 3, 2021), https://www.reuters.com/world/europe/denmark-excludes-jj-shot-vaccine-
programme-local-media-reports-2021-05-03/.

” CDC, Vaccine Adverse Event Reporting System (VAERS),
https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/vaers/index.html.

'3 Blumenthal K. G., Robinson L. B., Camargo C. A., et al., Acute Allergic Reactions to mRNA
COVID-19 Vaccines. JAMA, Vol. 325, No. 15, pp. 1562-1565 (Mar. 8, 2021),
https://jamanetwork.com/journals/jama/fullarticle/2777417.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 70 of 237

public.

16. Other problems with vaccine safety assessment may exist because of inadequate
animal toxicology and pharmacokinetic studies of COVID vaccines. Animal experiments failed to
measure the quantity, duration and organ distribution of spike protein production. The animal
experiments, incomprehensibly, failed to inject the actual vaccine to be tested during certain
pharmacokinetic and toxicology tests. For example, in study 2.6.5.5B, only 2 of the 4 lipid
nanoparticle (LNP) components were labeled and injected into rats, and their distribution and
persistence in many organs were assessed at animal necropsy, from 15 minutes to 48 hours post-
injection. For most organs, at 48 hours the amount of the two LNP components in each organ was
still increasing. Thus, the ultimate distribution and persistence of the LNPs are unknown. And we
have no information regarding duration and persistence of the mRNA or spike protein production
in organs based on this study.'*

17. A surrogate for mRNA (coding for spike protein) was an entirely different mRNA
(coding for luciferase) in LNP injected into mice. In study 2.6.5.5A, bioluminescence was
measured in liver through 9 days as a surrogate measure, while no attempt was made to evaluate
the presence of spike protein in animal tissues, including in the brains of the experimental
animals.'> These surprising omissions have significant potential safety implications.

18. Given that only 1 to 13% of adverse reactions have been reported to the FDA and
CDC via the VAERS passive reporting system, according to Lazarus et al., the high number of
adverse events and deaths following COVID vaccines is alarming.!® While the Pfizer vaccine has
now been used for five months and administered to more than 60 million Americans, FDA has
issued no new guidance about the vaccine based on these troubling data, apart from expanding its
use in children.

19. The FDA must be aware that the only avenue for an injured party to claim benefits
as a result of a COVID vaccine injury is the Countermeasures Injury Compensation Program
(CICP).'’ The CICP requires petitioners to prove that the COVID vaccine caused their injuries;
the program has an extremely short statute of limitations of one year. If the FDA, working with

'4 Study 2.6.5.5.B Pharmacokinetics: Organ Distribution. SARS-CoV-2 mRNA Vaccine (English
Portion) (BNT162, PF-07302048), pp. 15-18, https://www.pmda.go.jp/drugs/202 1/P20210212001/.

Td.

'6 See Lazarus et al., Electronic Support for Public Health-Vaccine Adverse Event Reporting
System, AGENCY FOR HEALTHCARE RESEARCH AND QUALITY, DEPT. OF HEALTH AND HUMAN
SERVICES (Sept. 30, 2010), https://digital.ahrg.gov/ahrq-funded-projects/electronic-support-
public-health-vaccine-adverse-event-reporting-system; Shimabukuro et al., Safety monitoring in
the Vaccine Adverse Event Reporting System (VAERS), VACCINE (Nov. 4, 2015),
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632204/; S. Rosenthal and R. Chen, The
reporting sensitivities of two passive surveillance systems for vaccine adverse events, AM J PUBLIC
HEALTH (Dec. 1995), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615747/.

'7 Health and Human Services Administration, Countermeasures Injury Compensation Program
(CICP), https://www.hrsa.gov/cicp.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 71 of 237

the vaccine manufacturers, does not compile and publish an accurate list of adverse reactions,
which is required for licensing, then these petitioners will have virtually no opportunity to prove
injury or receive compensation.

B. Effectiveness

20. As with safety data on COVID vaccines, effectiveness data continue to evolve.
Recently CDC acknowledged “vaccine breakthrough cases” where vaccinated subjects fall ill and
potentially transmit the virus. CDC acknowledges that a “small percentage of people who are fully
vaccinated against COVID-19 will still get sick and some may be hospitalized or die from COVID-
19. It’s also possible that some fully vaccinated people might have infections, but not have
symptoms (asymptomatic infections).””!®

21. As of April 26, 2021, CDC reported over 9,000 “breakthrough cases” and 132
COVID-caused deaths among vaccinated people.!? CDC tracks reports of breakthrough cases via
the National Notifiable Diseases Surveillance System (NNDSS)*’ and has recently stopped
reporting breakthrough cases absent death or hospitalization.”! The British government has also
identified efficacy problems stating, “The resurgence in both hospitalisations and deaths is
dominated by those that have received two doses of the vaccine, comprising around 60% and 70%
of the wave respectively.”

22. The U.K. data modelers attribute these rates to the high level of vaccine uptake in
the most at-risk elderly age group.”* Overall, the U.K. believes “evidence shows vaccines are
sufficiently effective in reducing hospitalisations and deaths in those vaccinated.””4 The U.K.
caveat “sufficiently” is significant compared to the unqualified “effective” label that the FDA
currently permits to be communicated to the public.

'8 CDC, What You Should Know About the Possibility of COVID-19 Illness After Vaccination;
(updated April 21, 2021), https://www.cdc.gov/coronavirus/2019-
ncov/vaccines/effectiveness/why-measure-effectiveness/breakthrough-cases.html.

'° CDC, COVID-19 Breakthrough Case Investigations and Reporting (updated April 30, 2021),
https://www.cdc.gov/vaccines/covid-19/health-departments/breakthrough-cases.html.

2° CDC, National Notifiable Diseases Surveillance System (NNDSS), https://wwwn.cdc.gov/nndss/.

21 CDC, COVID-19 Breakthrough Case Investigations and Reporting (April 30, 2021),
https://www.cdc.gov/vaccines/covid-19/health-departments/breakthrough-cases.html.

22 SPI-M-O: Summary of further modelling of easing restrictions — Roadmap Step 2, p. 10 (Mar.
31, 2021),
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file
/975909/S1182_ SPI-M-O Summary of modelling of easing roadmap step 2 _restrictions.pdf.

23 Td.

4 Gov.UK; COVID-19 Response-Spring 2021 (Summary) (Feb. 22, 2021),
https://www.gov.uk/government/publications/covid-19-response-spring-202 1/covid-19-response-
spring-202 1-summary.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 72 of 237

C. Misbranding as “Safe, Effective and FDA Approved”

23. Recently the FDA sent a warning letter “RE: Unapproved and Misbranded Products
Related to Coronavirus Disease 2019 (COVID-19).””° FDA warned that labeling COVID therapies
as Safe, Effective or FDA Approved when they are not proven to be so by FDA standards violates
§ 505(a) of the FDCA, 21 U.S.C. § 355(a). The same standard should apply to COVID vaccines,
as any such products are misbranded drugs and violate § 502 of the FDCA and 21 U.S.C. § 352.

24. The introduction or delivery for introduction of any such product into interstate
commerce is prohibited under § 301(a) and (d) of the FDCA and 21 U.S.C. § 331(a) and (d). The
FDA specifically warned a vendor: “We advise you to review your websites, product labels, and
other labeling and promotional materials to ensure that you are not misleadingly representing your
products as safe and effective for a COVID-19-related use for which they have not been approved
by FDA and that you do not make claims that misbrand the products in violation of the FD&C
Act.”

25. FDA must ensure against misrepresenting COVID vaccine products as “safe and
effective” when FDA has not so designated them. FDA’s description of COVID vaccines pursuant
to § 564(d)(3) of the Act states: “based on the totality of scientific evidence available to FDA...it
is reasonable to believe that Pfizer-BioNTech COVID-19 Vaccine may be effective in preventing
COVID-19 when used in accordance with this Scope of Authorization (Section II), pursuant to
Section 564(c)(2)(A) of the Act.” The FDA language on effectiveness provides a qualification
similar to the above-mentioned U.K. regulatory language. FDA’s precise technical language to
manufacturers does not match its unequivocal “effective” claims on official government websites,
including that of the CDC, as illustrated below.”°

2° EDA, Warning Letter to Mercola.com, LLC (Feb. 18, 2021), https://www.fda.gov/inspections-
compliance-enforcement-and-criminal-investigations/warning-letters/mercolacom-llc-607133-
02182021.

© CDC, Key things to know about COVID-19 vaccines (May 10, 2021),
https://www.cdc.gov/coronavirus/2019-ncov/vaccines/keythingstoknow.html;

CDC, Safety of COVID-19 vaccines (udated May 11, 2021),
https://www.cdc.gov/coronavirus/2019- ncov/vaccines/safety/safety-of-vaccines.html;

FDA, Letter to Pfizer (May 10, 2021), https://www.fda.gov/media/144412/download.

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 73 of 237

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D. EUA revocation, additional EUAs, and off-label use clarification for COVID
therapies

26. On February 4, 2020 the Secretary of the Department of Health and Human
Services (HHS) determined that there is a public health emergency that has a significant potential
to affect national security or the health and security of United States citizens living abroad and that
involves the virus that causes Coronavirus Disease (COVID-19). Based on this determination, the
Secretary on March 27, 2020 declared that circumstances justify emergency use of drugs and
biological products during the COVID-19 pandemic pursuant to § 564 of the FDCA (21 U.S.C. §
360bbb-3).

27. Since December 2020, several manufacturers have received EUAs for COVID
vaccines. One of the criteria for these authorizations, beyond the existence of an emergency, is that
there are “no adequate, approved, and available alternatives.”?’ Many medical professionals and
elected officials have objected to the inconsistent handling of EUAs for alternative treatments. Dr.
Peter McCullough testified to the Texas Senate on March 10, 2021 that an 85% lower mortality
rate from COVID would have been possible if government agencies had publicly recommended

27 EDA, Emergency Use Authorization (updated May 11, 2021),
https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-
framework/emergency-use-authorization;

FDA, FAQs on Emergency Use Authorizations (EUAs) for Medical Devices During the
COVID-19 Pandemic (updated April 23, 2021), https://www.fda.gov/medical-
devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/faqs-
emergency-use-authorizations-euas-medical-devices-during-covid-19-pandemic.

10
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 74 of 237

early treatments.?? Now that COVID cases and deaths are decreasing because many if not most
Americans are immune, the relative benefit of COVID vaccines has diminished.”?

28. Three U.S. Senators asked the FDA to clarify why it revoked the previously granted
EUAs for hydroxychloroquine (HCQ) and chloroquine (CQ) and under what authority it regulates
the practice of medicine. The Senators also asked what authority states have to regulate the
prescribing and dispensing of drugs.*° FDA issued and revoked EUAs for HCQ and CQ donated
to the Strategic National Stockpile in a way that confused medical professionals, resulting in their
reluctance to prescribe the drugs, including those not under EUA. FDA improperly recommended
against the use of chloroquine drugs in outpatients, and against early treatment, which is when
these antiviral drugs are likely to be effective. FDA appears to have collaborated with officials in
dozens of states and even with certain pharmaceutical and pharmacy companies to restrict the
prescribing and dispensing of chloroquine drugs against COVID. These unprecedented actions
require explanation. The FDA must immediately revoke its recommendations for the limited use
and withholding of these drugs during a life-threatening pandemic and must publicize its
revocation widely.

29. Medical professionals also question FDA's approval of Investigational New Drug
(IND) human trials performed by the University of Pittsburg (REMAP-COVID)*! and the
University of Philadelphia (PATCH)*® using knowingly borderline lethal doses of HCQ in humans.
There were more deaths in the HCQ arm than in the control arm of the REMAP-COVID study and
in the other two large multicenter studies, the Solidarity and Recovery studies, that used excessive
doses. The PATCH study ended after enrolling only 5 subjects.

30. In other FDA guidance regarding the chloroquine drugs, FDA made the misleading
claim that “Hospitalized patients were likely to have greater prospect of benefit (compared to

8 Dr. Peter McCullough’s testimony to the Texas Senate HHS Committee (Mar. 10, 2021),
https://www.youtube.com/watch?v=QAHi31X30GM.

° Dr. Peter McCullough et al., SARS-CoV-2 mass vaccination: Urgent questions on vaccine
safety 2 that demand answers from international health agencies, regulatory 3 authorities,
governments and vaccine developers (May 8, 2021), https://www.andrewbostom.org/wp-
content/uploads/2021/05/Bruno-et-al.-Vaccine-Safety-Urgent-Manuscript-Preprint-May-8-

2021.pdf.
3° Senators Ted Cruz, Mike Lee, Ron Johnson, Letter to FDA Commissioner Stephen Hahn (Aug.

18, 2020), https://(www.hsgac.senate.gov/imo/media/doc/2020-08-
18%20RHJ%20Letter™%20to%20FDA%200n%20HCQO%20+%20CQ. pdf.

31 UNIVERSITY OF PITTSBURG, Department of Critical Care, UPMC Leads Global Efforts to Fast-
track COVID-19 Therapies, https://www.ccm.pitt.edu/node/1110.

32 Penn Launches Trial to Evaluate Hydroxychloroquine to Treat, Prevent COVID-19, PENN
MEDICINE NEWS (April 3, 2020), https://www.pennmedicine.org/news/news-releases/2020/
april/penn-launches-trial-to-evaluate-hydroxychloroquine-to-treat-prevent-covid19;

The PATCH Trial (Prevention And Treatment of COVID-19 With Hydroxychloroquine) (PATCH),
CLINICALTRIALS.GOV (updated Dec. 10, 2020), https://clinicaltrials.gov/ct2/show/NCT04329923.

11
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 75 of 237

ambulatory patients with mild illness),” and that chloroquine drugs have a “slow onset of action.”
In its justification for restricting the use of chloroquine drugs, FDA also opined that “it is no longer
reasonable to believe that oral formulations of HCQ and CQ may be effective in treating COVID-
19, nor is it reasonable to believe that the known and potential benefits of these products outweigh
their known and potential risks.”**

31. These claims fly in the face of substantial evidence of positive effects of the drugs
when used early in the disease at usual, approved, therapeutic doses. FDA has chosen to ignore
the many trials that were properly conducted. The FDA buttresses its contention of the dangers of
these drugs based in part on the FDA-approved trial and other trials that administered excessive,
non-therapeutic doses of HCQ and resulted in more deaths in the treated group than the placebo

group.

32. Similarly, FDA exhibited bias regarding the effective and safe use of ivermectin
for prophylactic use of COVID. In March 2021, the agency stated: “The FDA has not reviewed
data to support use of ivermectin in COVID-19 patients to treat or to prevent COVID-19; however,
some initial research is underway.”** Yet already on April 10, 2020, FDA had issued a public
warning against the use of ivermectin because, it claimed, Americans were purchasing over the
counter (OTC) veterinary ivermectin as a COVID treatment.*> Research from Australia had been
published online a week earlier, on April 3, 2020, supporting use of ivermectin for COVID based
on in vitro studies.*°

33. Thus, FDA was aware at least 13 months ago that Americans were using ivermectin
to treat and prevent COVID. How could FDA not have reviewed data on ivermectin during an
entire year after it was informed about this use? That was a year during which dozens of studies
about the drug’s use were available as publications or preprints for both prophylaxis and treatment;
during which there was a Senate hearing on the drug; and during which half a million Americans
died from the disease, who had not been treated with effective medications because of FDA
guidance.

34. Furthermore, ivermectin has been used OTC for COVID in many countries and
regions with excellent reported treatment success. The drug's safety has been established with at

33 FDA Letter revoking EUA for Hydroxychloroquine (Jun. 15, 2020),
https://www.fda.gov/media/138945/download.

34 EDA, Why You Should Not Use Ivermectin to Treat or Prevent COVID-19 (updated May 10,
2021), https://www.fda.gov/consumers/consumer-updates/why-you-should-not-use-ivermectin-
treat-or-prevent-covid-19.

33 FDA Letter to Stakeholders, Do Not Use Ivermectin Intended for Animals as Treatment for
COVID-19 in Humans (April 10 2020), https://www.fda.gov/animal-veterinary/product-safety-
information/fda-letter-stakeholders-do-not-use-ivermectin-intended-animals-treatment-covid-19-
humans.

3° Leon Caly, Julian D. Druce, The FDA-approved drug ivermectin inhibits the replication of
SARS-CoV-2 in vitro, ANTIVIRAL RESEARCH, vol. 178, 104787 (Jun. 2020),
https://reader.elsevier.com/reader/sd/pii/S0166354220302011.

10
12
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 76 of 237

least a billion doses used, and the drug is on the World Health Organization's list of essential drugs.

35. Many medical professionals suspect FDA's feigned ignorance about the drug was
a prerequisite to issuing EUAs for COVID vaccines, given the EUA requirement that no approved
drug may be available for the same indication. Ivermectin and hydroxychloroquine, both of which
have extremely long biological half lives, can be given infrequently as prophylaxis for COVID.
Hydroxychloroquine or chloroquine are used weekly to prevent malaria, and they have been used
in the same way to prevent COVID. Ivermectin can be used once or twice yearly to prevent river
blindness (onchocerciasis), and it has been used weekly or bi-weekly to prevent COVID. Many
clinical trials have documented the benefits of both drugs for COVID prevention. Yet FDA has
remained silent about these benefits, even though the efficacy of these preventive treatments
probably supercedes that of COVID vaccines.

36. This petition encourages FDA to expeditiously evaluate existing ivermectin
research and issue accurate guidance for its use against COVID, e.g., where “18 randomized
controlled treatment trials of ivermectin in COVID-19 have found large, statistically significant
reductions in mortality, time to clinical recovery, and time to viral clearance.”*” Additional studies
have found it highly effective for both pre- and post-exposure prophylaxis of COVID.*®

37. Finally, reflecting on the FDA’s regulatory history is helpful: A proven association
between the 1976-1977 swine influenza vaccine and approximately 400 cases of Guillain—Barré
syndrome halted that particular national vaccination campaign.*? The reported deaths following

37 P. Kory, G. Meduri et al., Review of the Emerging Evidence Demonstrating the Efficacy of
Ivermectin in the Prophylaxis and Treatment of COVID-19, AMERICAN JOURNAL OF
THERAPEUTICS (May-Jun 2021), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088823/.

Ahmed, Sabeena et al., 4 five-day course of ivermectin for the treatment of COVID-19 may
reduce the duration of illness, INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, vol. 103, pp.
214-216 (Feb. 2021), https://pubmed.ncbi.nlm.nih.gov/33278625/;

Jans D. A. and Wagstaff K. M., The broad spectrum host-directed agent ivermectin as an
antiviral for SARS-CoV-2? BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol.
538, pp. 163-172 (2021), https://pubmed.ncbi.nlm.nih.gov/33341233/.

Formiga, Fabio Rocha et al., Ivermectin: an award-winning drug with expected antiviral activity
against COVID-19, JOURNAL OF CONTROLLED RELEASE, vol. 329, pp. 758-761 (Jan. 2021),
https://pubmed.ncbi.nlm.nih.gov/33038449/.

Bhowmick, Subhrojyoti et al., Safety and Efficacy of Ivermectin and Doxycycline Monotherapy
and in Combination in the Treatment of COVID-19: A Scoping Review, DRUG SAFETY, pp. 1-10
(Apr. 16, 2021), https://pubmed.ncbi.nlm.nih.gov/33864232/.

38 Tyermectin for COVID-19: real-time meta analysis of 55 studies, COVID ANALYSIS (version 81,
May 15, 2021), https:/ivmmeta.com/.

3° See CDC, H1N1 Flu, FACT SHEET: GUILLAIN- BARRE SYNDROME (GBS) (Dec. 15, 2009),
https://www.cdc.gov/h1n1 flu/vaccination/factsheet_gbs.htm#:~:text=Getting%20GBS%20from
%20a%20vaccination, got%20the%20swine%20flu%20vaccine.

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that swine flu vaccination campaign, 30 out of 40-45 million vaccinees,*® were insignificant
compared to the current reported death toll of 4,434 due to COVID vaccines, Today’s death rate
is more than 50 times higher than that which ended the swine flu vaccine campaign.

38. Regarding the halted swine flu vaccine program, the CDC’s Emerging Infectious
Diseases Journal concluded, “In 1976, the federal government wisely opted to put protection of
the public first.”*' FDA should learn from this past experience and again put protection of the
public first. It is imperative that the FDA swiftly take action to authorize alternative treatments.

E. Children

39. According to the National Center for Health Statistics data as of May 5, 2021, 282
children have died “involving COVID,” whereas over 560,000 Americans have died “involving
COVID.’”” Three thousand children have been diagnosed with a multi-system inflammatory
disorder, of whom about 1%, or approximately 30, have died. Thus the relative risk for children
due to COVID is very low.

40. By contrast, recent VAERS reports include the deaths of several children following
COVID vaccination.” Five of the child death reports footnoted below involve apparent cardiac
related deaths, and two were infants. There is one reported death in a 15 year old after receiving
the Pfizer BioNTech vaccine, and another reported death of a 15 year old after receiving a Moderna

40 Rick Perlstein, Gerald Ford Rushed Out a Vaccine. It Was a Fiasco, THE NEW YORK TIMES
(Sept. 2, 2020), https://www.nytimes.com/2020/09/02/opinion/coronavirus-vaccine-trump.html];
Donald G. McNeil, Jr., Don’t Blame Flu Shots for All Ills, Officials Say, THE NEW YORK TIMES
(Sept 27, 2009), https://www.nytimes.com/2009/09/28/health/policy/28vaccine.html.

“1 Sencer D. J., Millar J., Reflections on the 1976 Swine Flu Vaccination Program, EMERGING
INFECTIOUS DISEASES, Vol. 12, No. 1, pp. 29-33 (Jan. 2006),
https://wwwnc.cdc.gov/eid/article/12/1/05-1007 article.

* CDC, Weekly Updates by Select Demographic and Geographic Characteristics, Provisional
Death Counts for Coronavirus Disease 2019 (COVID-19) (updated May 12, 2021),
https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm#SexAndAge.

“8 VAERS reports include:

A 1-year-old,
https://medalerts.org/vaersdb/findfield.php? IDNUMBER=1261766&WAYBACKHISTOR Y=ON;

a 2-year-old,
https://medalerts.org/vaersdb/findfield. php? IDNUMBER=1255745&WA YBACKHISTOR Y=ON;

two 15-year-olds, https://www.medalerts.org/vaersdb/findfield.php?IDNUMBER=1187918 and
https://www.medalerts.org/vaersdb/findfield.php? IDNUMBER=1242573;

two 16-year-olds, https://www.medalerts.org/vaersdb/findfield.php?IDNUMBER=1225942;

a 17-year old, https://www.openvaers.com/openvaers/1199455;

and an infant, https://www.medalerts.org/vaersdb/findfield. php? IDNUMBER=1 166062.

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vaccine. Each child must have been enrolled in a clinical trial, since their ages would have
precluded them getting the vaccine legally under the EUA. There were only about 1,000 children
in the 12-15 year age group in the vaccine arm of Pfizer’s trial and probably about the same number
in the vaccine arm of Moderna’s trial. Thus, the death rate following either vaccination in this age
group, assuming these children were trial enrollees, is approximately 2 in 2,000 or 0.1%.

41. There are 74 million children in the United States. So far, 282 have died "Involving
Covid." Two hundred eighty-two in 74 million is a rate of 0.00038%. While many children may
not have been exposed to COVID, CDC estimated that 22.2 million children aged 5-17 had had
COVID and 127 had died, at the May 12, 2021 meeting of the Advisory Committee on
Immunization Practices, or 0.00057%.“ Available evidence strongly suggests that the vaccine is
much more dangerous to children than the disease.

42. A recent opinion piece in the British Medical Journal noted that “the likelihood of
severe outcomes or death associated with COVID-19 infection is very low for children,
undermining the appropriateness of an emergency use authorization for child covid-19 vaccines.”
The authors also suggested child vaccinations could strategically harm vaccination efforts and
increase vaccine hesitancy.*°

F. Servicemembers' Prior Consent

43. Certain citizens and elected officials have recently encouraged the President of the
United States to waive U.S. Servicemembers’ right to prior consent for COVID vaccines.*”
According to 10 U.S.C. §1107(f), only the President of the United States may order such a waiver
if he determines, in writing, that obtaining consent is not in the national security interest. The intent
of any waiver of consent must be related to a member's participation in a “particular military
operation,” as opposed to the broad sweep some are encouraging.

44. Such a waiver is only permissible when obtaining prior consent is infeasible or
contrary to the best interests of the military member. Clearly, prior consent for current
servicemembers is feasible for COVID vaccines.** Because the President’s authority is contingent
on the standards set forth in § 505(1)(4) of the FDCA and 21 U.S.C. § 355(i)(4), and since the chain
of command requires consultation with HHS, the FDA may issue guidance to the President on this

“4 Helen Branswell, CDC advisory group gives green light to Pfizer’s Covid vaccine for
adolscents,’ STAT (May 12, 2021), https://www.statnews.com/2021/05/12/cdc-advisory-group-
gives-green-light-to-pfizers-covid-vaccine-for-adolescents/.

4 W. Pegden, V. Prasad, S. Baral, Covid vaccines for children should not get emergency use
authorization, BMJ (May 7, 2021), https://blogs.bmj.com/bmj/202 1/05/07/covid-vaccines-for-
children-should-not-get-emergency-use-authorization/.

“6 Td.

47 Jimmy Panetta, Letter to President Biden (Mar. 24, 2021),
https://www.documentcloud.org/documents/20521870-panetta dod-covid-vaccine-waiver.

4891 U.S.C. § 50.23: Exception from general requirements, https://www.ecfr.gov/cgi-bin/text-
idx?node=se21.1.50 123&rgn=div8.

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matter.*”

45. The specific law on EUA vaccines was codified in 10 U.S.C. § 1107a.°° The
§ 1107a language is similar to § 1107(f) to ensure that troops are granted prior consent and have
the “option to accept or refuse administration of a product.” National leaders should continue to
honor and respect servicemembers’ rights. No President has ever waived servicemembers’ prior
consent under 10 U.S.C. § 1107(f) or 10 U.S.C. § 1107a, and FDA should advise that current
circumstances do not warrant such drastic action.

G. Coercion and Compulsion

46. COVID vaccines are optional in accordance with 21 C.F.R. § 360bbb-3(e)(1)(a) as
EUA products.*! Yet throughout the United States, schools, businesses, government and industry
are using coercive tactics to encourage, incentivize and compel COVID vaccination as a condition
of employment, education and daily living. It is unlikely that most Americans would support such
coercion if they were fully informed that COVID vaccines are for emergency use only,
investigational, unapproved, and that individuals have the explicit right to refuse by law. Some
states are considering or have approved legislation or executive action to bar vaccine mandates.”
Some professional medical associations also have expressed opposition to these coercive tactics.*?

47. Coercion and compulsory vaccination are inconsistent with the legal requirements
to inform both healthcare workers administering EUA vaccines and vaccine recipients of the
significant known and unknown benefits and risks of such use. Most importantly, the FDA must
ensure all parties are aware of the “option to accept or refuse” administration of all EUA products
and that alternatives are available. These disclosure requirements are entirely inconsistent with
coercion, and government agencies should not publish information that violates the law.
Information on the government websites of the Equal Employment Opportunity Commission

” Td.

°° 10 U.S.C. § 1107a - Emergency use products, https://www.govinfo.gov/app/details/USCODE-
2010-title 10/USCODE-2010-title 1 0-subtitleA-partII-chap55-sec1107a/summary.

>! § 360bbb-3. Authorization for medical products for use in emergencies,
https://www.govinfo.gov/content/pkg/USCODE-201 1-title2 1/pdf/USCODE-2011-title2 1-chap9-
subchapV-partE-sec360bbb-3 .pdf.

>? Pearson L., Brofsky J., et al., 50-state Update on Pending Legislation Pertaining to Employer-
mandated Vaccination, HUSCH BLACKWELL (updated April 20, 2021),
https://www.huschblackwell.com/newsandinsights/50-state-update-on-pending-legislation-
pertaining-to-employer-mandated-vaccinations.

°3 Dr. Paul M. Kempen, Open Letter from Physicians to Universities: Allow Students Back
Without COVID Vaccine Mandate, ASSOCIATION OF AMERICAN PHYSICIANS AND SURGEONS
(Apr. 24, 2021), https://aapsonline.org/open-letter-from-physicians-to-universities-reverse-covid-
vaccine-mandates/.

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(EEOC)™ and the Occupational Safety and Health Administration (OSHA)> in fact ignore these
federal disclosure requirements.

48. The armed forces' experience with the very first EUA vaccine mandate against
anthrax is instructive.°° The military now administers the anthrax vaccine on a voluntary basis with
informed consent, but only after a federal court halted the mandatory anthrax vaccine program
because the FDA had improperly issued a license.>’

49. The only language in the EUA law, 21 U.S.C. § 360bbb-3(e)(1)(A)Gi)CI-IID, that
could possibly be construed to imply mandates is the term “consequences” in clause II. Both
statutory analysis and legislative history suggest that it is far more likely that this term applies to
health-related consequences only, 1.e., medical risks and benefits, since that is the topic of that
statute section and because it does not refer to punitive measures or consequences, such as
termination of employment or education.°*

50. Another hazard of coercive policies and broad liability for industry is reliance on
subpar manufacturers. One of the COVID vaccine manufacturing subcontractors today, Emergent
BioSolutions, is the same company, with the same President and Board Chairman, which the FDA
cited under its previous name, BioPort, for numerous violations of Good Manufacturing
Practices.°’ The image below, taken from an FDA form in 2000, shows the citation to BioPort for

>4 EEOC, What You Should Know About COVID-19 and the ADA, the Rehabilitation Act, and
Other EEOC Laws, §§ K1 & K7 (updated Dec. 16, 2020), https://www.eeoc.gov/wysk/what-
you-should-know-about-covid-19-and-ada-rehabilitation-act-and-other-eeo-laws.

°> Jeff Yoders, OSHA Imposes New Guidance For Employer-Required COVID-19 Vaccines,
ENR (May 3, 2021), https://www.enr.com/articles/5 169 1-osha-imposes-new-guidance-for-
employer-required-covid-19-vaccines.

°° FDA, Anthrax Vaccine Adsorbed (AVA) EUA —ARCHIVED INFORMATION,
https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-
framework/emergency-use-authorization-archived-information#anthrax.

>? Determination and Declaration Regarding Emergency Use of Anthrax Vaccine Adsorbed for
Prevention of Inhalation Anthrax, FEDERAL REGISTER (Feb. 2, 2005),
https://www.federalregister.gov/documents/2005/02/02/05-2027/determination-and-declaration-
regarding-emergency-use-of-anthrax- vaccine-adsorbed-for-prevention-

of ?fbclid=IwAR22J58y3SOQ2tVoEUINgZVU-PmRxoou0P0519 WqS4S UiOc]9HyaiUJ8Dvreg.

°8 Parasidis E., Kesselheim A. S., Assessing The Legality Of Mandates For Vaccines Authorized
Via An Emergency Use Authorization, HEALTH AFFAIRS (Feb. 16, 2021),
https://www.healthaffairs.org/do/10.1377/hblog20210212.410237/full/.

°° Richard Luscombe, Emergent chief sold $10m in stock before company ruined 15m Covid
vaccines, THE GUARDIAN (Apr. 26, 2021),

https://www.theguardian.com/business/202 1/apr/26/emergent-biosolutions-robert-kramer-stock-
covid-vaccines-error.

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deviations from acceptable manufacturing standards for vaccines.

DEPARTMENT OF HEALTH AND HUMAN SERVICES CBER/OCBQ
PUBLIC HEALTH SERVICE 1401 Rockville Pike, HFM-604. Suite 200N
FOOD AND DRUG ADMINISTRATION Rockville. MD 20852 1301) 827-419!
NAME OF PADIVIDUAL TO WHWZM REPO ISSUED PERIOD OF INSPECTION CF. NUMBER
TO: KpAeer a Vener 10/t0-26/00 1873886
TITLE-GE Sey IDU AL : TYPE OF ESTABLISHMENT INSPECTED
hs) CH EE _OPERATI Nb OFEICER Vaccine/Blood Products Manufacturer
r NAME Of FIRM, BRANCH OR UNTT INSPECTED
BioPort Corporation same
STREET ADDRESS STREET ADDRESS OF PREMISES INSPECTED
3500 N. Martin Luther King, Jr. Blvd. same
CITY AND STATE (Zip Code) CITY AND STATE (Zip Code)
Lansing, MI_ 48909 same

DURING THE INSPECTION OF YOUR FIRM WE OBSERVED:

AY? The design and construction of the filling suite (Rms 307, 308, 309), environmental monitoring, cleaning,
and employee practices do not assure sterility of products filled in the suite, in that,

51. Today, Emergent BioSolutions, despite apparent FDA oversight, shipped out
unauthorized bulk COVID vaccine ingredients for finishing and filling. Emergent BioSolutions
shipped those ingredients to another entity, and the shipments eventually reached buyers in at least
four other countries, according to the New York Times.©° The FDA halted distribution in the U.S.
and cited quality deviations®' that mirrored those that American servicemembers witnessed 20
years ago with the anthrax vaccine. People need to be informed about these manufacturing
deviation patterns given the importance and wide use of these products.

52. States may lawfully mandate certain vaccines. But that is not the case for
investigational, unapproved EUA medical products. The preemption doctrine,“ based on the
Supremacy Clause of the U.S. Constitution, Article VI., § 2,°4 requires that the federal
requirements for informed consent supersede state laws and regulations that may violate EUA
provisions. The FDA should support, defend and enforce federal laws that govern biologics,

6° Chris Hamby, Baltimore Vaccine Plant’s Troubles Ripple Across 3 Continents, THE NEW
YORK TIMES (May 6, 2021), https://www.nytimes.com/2021/05/06/world/baltimore-vaccine-
countries.html.

6! FDA, HHS, Form FDA 483, Inspectional Observations (Apr. 20, 2021),
https://www.fda.gov/media/147762/download.

® Historic FDA Form 483 Deviation Report Documenting that “The manufacturing process for
Anthrax Vaccine is not validated.”

https://nebula.wsimg.com/30662205620a26a4b2 1274dc49888891?AccessKeyId=0BA19F97E21
CB8613CD7&disposition=0&alloworigin=1.

63 Preemption, CORNELL LAW SCHOOL, Legal Information Institute,
https://www.law.cornell.edu/wex/preemption.

64 U.S. Const. art. VI., § 2 , “This Constitution, and the Laws of the United States which shall be
made in Pursuance thereof; and all Treaties made, or which shall be made, under the Authority of
the United States, shall be the supreme Law of the Land; and the Judges in every State shall be
bound thereby, any Thing in the Constitution or Laws of any State to the Contrary
notwithstanding.” https://www.archives.gov/founding-docs/constitution-transcript.

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including EUA products. The option to refuse COVID vaccines is codified in federal law, and
President Biden has affirmed this, saying, “I don't think it [vaccination against COVID] should be
mandatory. I wouldn't demand it to be mandatory.”®

H. Conclusion to Statement of Grounds

53. The FDA’s mission is “protecting the public health by ensuring the safety, efficacy,
and security of human and veterinary drugs, biological products.” President Roosevelt’s signing
of the Federal Food, Drug, and Cosmetic Act (FDCA) closed many safety and efficacy loopholes
and improved the landscape of consumer protection forever.°’ The 1962 Harris-Kefauver
amendment® set in motion regulatory standards for biologics licensure that require proven
efficacy, and the 1972 review sought to ensure proof of efficacy and no misbranding for biologics.
These historic advances require reflection. The preamble to the 1972 review stated, ‘“The
importance to the American public of safe and effective vaccines...and other biological products
cannot be overstated.””©?

54. Biologics, as with all drugs and devices, must have adequate directions for use and
be proven safe and effective before FDA approval and licensure. The FDA erred with the anthrax
vaccine, and it took a Citizen Petition’? and federal court decision to make the FDA comply with
the FDCA.’' At other times, the FDA has upheld its mission without prompting to make tough
regulatory rulings, as the Supreme Court has acknowledged.” With this Petition, we look forward

6 Julia Manchester, Biden: Coronavirus vaccine should not be mandatory, THE HILL (Apr. 12,
2021), https://thehill.com/homenews/campaign/528834-biden-coronavirus-vaccine-should-not-

be-mandatory.
6° FDA, What We Do; https://www.fda.gov/about-fda/what-we-do#mission.

67 FDA, 80 Years of the Federal Food, Drug, and Cosmetic Act (Nov. 7, 2018),
https://www.fda.gov/about-fda/fda-history-exhibits/80-years-federal-food-drug-and-cosmetic-act.

68 FDA, Kefauver-Harris Amendments Revolutionized Drug Development (Oct. 9, 2012),
https://www.fda.gov/consumers/consumer-updates/kefauver-harris-amendments-revolutionized-
drug-development.

6° HHS, FDA, Biological Products March 1936-March 1978, Preamble, p. 56, 37 Fed. Reg.
16679.

7 Citizen Petition, FDA Docket 01P-0471/CP1, https://img1.wsimg.com/blobby/go/4fa7f468-
a250-4088-926e-3c56a998dfl f/downloads/citizen%20petition’e20ava%20rempfer%20
dingle.pdf?ver=1620969217312, and Response thereto, https://downloads.regulations.gov/FDA-
2001-P-0119-0003/attachment_1.pdf.

"| Doe #1 v. Rumsfeld, 297 F. Supp. 2d 119, 135; see par. F, reference to Citizen Petition, FDA
docket 01p-0471,
https://nebula.wsimg.com/2617051f041708e6b5335b6c885478d7?AccessKeyld=0BA19F97E21
CB8613CD7&disposition=0&alloworigin=1.

U.S. Reports: Weinberger v. Hynson, Westcott & Dunning, 412 U.S. 609 (1972),
https://tile.loc.gov/storage- services/service/Il/usrep/usrep4 12/usrep4 12609/usrep412609.pdf.

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to the FDA’s appropriate, tough regulatory action to bring its COVID vaccine regulations and
guidance into line with federal law.

55. Although EUA law is relatively recent, we ask the FDA to be ever cognizant of its
longstanding, statutory mission and duty to protect the public health and to ensure that the
American public receives only safe and effective vaccines. Most Americans are not aware of the
strict compliance requirements for EUA COVID vaccines nor do they know that these biologics
are “investigational” and “unapproved medical products.””? They do not know that the FDA has
not fully approved these vaccines as safe and effective under the FDCA. The reason Americans
are unaware is because the FDA has failed to provide and enforce accurate public messaging.
Reversing this trend is imperative; the FDA must comply with law.

56. Acting on this Citizen Petition will enhance the FDA’s credibility with the public.
Given the obvious safety, effectiveness, labeling and branding concerns over COVID vaccines
detailed above, along with anticipated comments on this docket, we respectfully appeal to the FDA
to implement the actions requested in this Petition.

Tt. ENVIRONMENTAL IMPACT

57. The undersigned hereby state that the relief requested in this Petition will have no
environmental impact, and therefore an environmental assessment is not required under 21 C.F.R.
§§ 25.30 and 25.31.

IV. ECONOMIC IMPACT

58. Economic impact information will be submitted upon request of the Acting
Commissioner.

Vv. CERTIFICATION

59. The undersigned certify that, to their best knowledge and belief, this Petition
includes all information and views on which the Petition relies, and that it includes representative
data and information known to the Petitioners that are unfavorable to the Petition.

Respectfully submitted,

/s/ Meryl Nass
Meryl Nass, MD, Scientific Advisory Board
Member

/s/ Robert F. Kennedy, Jr.
Robert F. Kennedy, Jr., Board Chair and
Chief Litigation Counsel

3 FDA, Emergency Use Authorization for Vaccines explained (updated Nov. 20, 2020),
https://www.fda.gov/vaccines-blood-biologics/vaccines/emergency-use-authorization-vaccines-

explained.

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Exhibit 3
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 85 of 237

ADMINISTRATION

* g (Bus. Foop & DRUG

August 23, 2021

Meryl Nass, M.D.

Robert F. Kennedy, Jr.
Children’s Health Defense
1227 North Peachtree Parkway
Suite 202

Peachtree City, GA 30269

Re: Citizen Petition (Docket Number FDA-2021-P-0460)

Dear Dr. Nass and Mr. Kennedy,

This letter responds to the citizen petition dated May 16, 2021 that you submitted to the Food
and Drug Administration (FDA, the Agency, we) on behalf of Children’s Health Defense
(Petitioner) relating to: clinical trials, Emergency Use Authorization, licensure, and advertising
and promotion of vaccines to prevent Coronavirus Disease 2019 (COVID-19) caused by severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (the Petition).

In the Petition, Petitioner requests that FDA:

1. “revoke all EUAs and refrain from approving any future EUA, NDA, or BLA for any
COVID vaccine for all demographic groups”;

2. “immediately refrain from allowing minors to participate in COVID vaccine trials, refrain
from amending EUAs to include children, and immediately revoke all EUAs that permit
vaccination of children under 16 for the Pfizer vaccine and under 18 for other COVID
vaccines”;

3. “immediately revoke tacit approval that pregnant women may receive any EUA or licensed
COVID vaccines and immediately issue public guidance to that effect’;

4. “immediately amend [FDA’s] existing guidance for the use of the chloroquine drugs,
ivermectin, and any other drugs demonstrated to be safe and effective against COVID...and
immediately issue notifications to all stakeholders”;

5. “issue guidance to the Secretary of the Defense [sic] and the President not to grant an
unprecedented Presidential waiver of prior consent regarding COVID vaccines for
Servicemembers [sic]”;

6. “issue guidance...to affirm that all citizens have the option to accept or refuse
administration of investigational COVID vaccines without adverse work, educational or other
non-health related consequences”; and

U.S. Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
www.fda.gov

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Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 86 of 237

7. “[p]ending revocation of COVID vaccine EUAs, FDA should issue guidance that all
marketing and promotion of COVID vaccines must refrain from labeling them ‘safe and
effective.’”

Petition at 1-2.

In this letter, we discuss the safety of licensed and authorized vaccines. We then turn to the
requests contained in the Petition. We consider each of your requests in light of the legal
standards for FDA action, and provide our conclusions based on the facts, the science, and the
law.

This letter responds to the Petition in full. FDA has carefully reviewed the Petition and other
relevant information available to the Agency. Based on our review of these materials and for the
reasons described below, we conclude that the Petition does not contain facts demonstrating any
reasonable grounds for the requested action. In accordance with 21 CFR § 10.30(e)(3), and for
the reasons stated below, FDA is denying the Petition.

Here is an outline of our response:

I. Background
II. | Vaccines That Are FDA-Licensed or Receive an Emergency Use Authorization
Meet Relevant Statutory Requirements
a. Vaccines that are FDA-Licensed are Safe
i. Vaccines that are FDA-Licensed are Shown to Be Safe at the Time
of Licensure
ii. Vaccine Safety Continues to Be Monitored Post-Licensure
b. An Emergency Use Authorization for a COVID-19 Preventative Vaccine
Is Issued Only If the Relevant Statutory Standards Are Met
IH. Discussion
a. Investigational New Drugs
b. The Citizen Petition
i. Petitioner’s Request to Revoke all Emergency Use Authorizations
for COVID-19 Vaccines and Refrain from Issuing any Future EUA
or Approving any Future NDA, or BLA for any COVID-19
Vaccine for all Demographic Groups because the Current Risks of
Serious Adverse Events or Deaths Outweigh the Benefits, and
Because Existing, Approved Drugs Provide Highly Effective
Prophylaxis and Treatment against COVID-19, Mooting the EUAs
1. Petitioner’s Request to Revoke all Emergency Use
Authorizations for COVID-19 Vaccines
2. Petitioner’s Request to Refrain from Granting any Future
EUA for a COVID-19 Vaccine for any Population
3. Petitioner’s Request to Refrain from Approving any Future
NDA for any COVID-19 Vaccine for any Population

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4. Petitioner’s Request to Refrain from Licensing any Future
BLA for any COVID-19 Vaccine for any Population
il. Petitioner’s Request Regarding COVID-19 Vaccines in Children
1. Request to Immediately Refrain from Allowing COVID-19
Vaccine Trials to Include Pediatric Subjects
2. Request that FDA Refrain from Issuing EUA Amendments
for Authorized COVID-19 Vaccines to Include Indications
for Pediatric Populations
3. Request that FDA Immediately Revoke all EUAs for
COVID-19 Vaccines with Pediatric Indications
ili. Petitioner’s Request that FDA Immediately Revoke Tacit
Approval that Pregnant Women may Receive any EUA or
Licensed COVID-19 Vaccines and Immediately Issue Public
Guidance
1. Covid-19 in Pregnancy
2. Certain Content and Format Requirements for Prescription
Drug Labeling for Products Approved Under NDAs or
BLAs
3. Inclusion of Contraindications and Pregnancy Information
in the Labeling for the Authorized COVID-19 Vaccines
4. Inclusion of Contraindications and Pregnancy Information
in the Labeling for Licensed COVID-19 Vaccines
iv. Petitioner’s Request that FDA Immediately Amend its Guidance
regarding Certain Approved Drugs [chloroquine drugs, ivermectin,
“and any other drugs demonstrated to be safe and effective against
COVID”]
v. Petitioner’s Request that FDA Issue Guidance to the Secretary of
Defense and the President
vi. Petitioner’s Request that FDA Issue Guidance to Stakeholders
Regarding the Option to Refuse or Accept Administration of
Investigational COVID-19 Vaccines
vii. Petitioner’s Request that FDA Issue Guidance Regarding
Marketing and Promotion of COVID-19 Vaccines
c. Conclusion
Appendix I: Aspects of Vaccine Development and Process for Licensure

I. Background

There is currently a pandemic of respiratory disease, COVID-19, caused by a novel coronavirus,
SARS-CoV-2. The COVID-19 pandemic presents an extraordinary challenge to global health.
On January 31, 2020, the Department of Health and Human Services (HHS) issued a declaration

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of a public health emergency related to COVID-19.'On February 4, 2020, pursuant to section
564 of the FD&C Act (21 U.S.C. § 360bbb-3), the Secretary of HHS determined that there is a
public health emergency that has a significant potential to affect national security or the health
and security of U.S. citizens living abroad, and that involves the virus that causes COVID-19.”
On the basis of such determination, on March 27, 2020, the Secretary then declared that
circumstances exist justifying the authorization of emergency use of drugs and biological
products during the COVID-19 pandemic (“COVID-19 EUA Declaration”), pursuant to section
564(b)(1) of the FD&C Act.? In addition, on March 13, 2020, the President declared a national
emergency in response to COVID-19.4

Commercial vaccine manufacturers and other entities are developing COVID-19 vaccine
candidates, and clinical studies of these vaccines are underway and/or have been

completed. Between December 11, 2020 and February 27, 2021, FDA issued emergency use
authorizations for three vaccines to prevent COVID-19, including vaccines sponsored by Pfizer
Inc. (Pfizer); ModernaTX, Inc. (Moderna); and Janssen Biotech, Inc. (Janssen), a pharmaceutical
company of Johnson & Johnson. FDA received a Biologics License Application (BLA) for the
COVID-19 vaccine, BNT162b2, intended to prevent COVID-19 in individuals 16 years of age
and older. As announced by FDA on August 23, 2021, the Agency is issuing a biologics license
for this COVID-19 vaccine (COVID-19 Vaccine, mRNA; Comirnaty) to BioNTech
Manufacturing GmbH.°

II. Vaccines That Are FDA-Licensed or Receive an Emergency Use Authorization Meet
Relevant Statutory Requirements
a. Vaccines that are FDA-Licensed are Safe

i. Vaccines that are FDA-Licensed Are Shown to Be Safe at the Time of
Licensure

FDA has a stringent regulatory process for licensing vaccines.°’ The Public Health Service
Act (PHS Act) authorizes FDA to license biological products, including vaccines, if they have

' Secretary of Health and Human Services Alex M. Azar, Determination that a Public Health Emergency Exists.
(Originally issued on Jan. 31, 2020, and subsequently renewed),
https://www.phe.gov/emergency/news/healthactions/phe/Pages/default.aspx

2 HHS, Determination of Public Health Emergency, 85 FR 7316, February 7, 2020,
https://www.federalregister.gov/documents/2020/02/07/2020-02496/determination-of-public-health-emergency.
3 HHS, Emergency Use Authorization Declaration, 85 FR 18250, April 1, 2020,
https://www.federalregister.gov/documents/2020/04/01/2020-06905/emergency-use-authorization-declaration.

4 Proclamation on Declaring a National Emergency Concerning the Novel Coronavirus Disease (COVID-19)
Outbreak, issued March 13, 2020, https://trumpwhitehouse.archives. gov/presidential-actions/proclamation-
declaring-national-emergency-concerning-novel-coronavirus-disease-covid-19-outbreak/ .

> BioNTech Manufacturing GmbH is the biologics license holder for this vaccine, which is manufactured by Pfizer
Inc. for BioNTech Manufacturing GmbH (hereinafter “BioNTech”). The basis for FDA's licensure decision is set
forth in FDA's Summary Basis for Regulatory Action (SBRA) for the BioNTech application. This memorandum
will be posted on fda.gov. We incorporate by reference the SBRA for the BLA.

6 CDC, Ensuring the Safety of Vaccines in the United States, February 2013,
https://www.cdc.gov/vaccines/hcp/patient-ed/conversations/downloads/vacsafe-ensuring-bw-office.pdf.

7 FDA, Vaccine Safety Questions and Answers, last updated March 2018, https://www.fda.gov/vaccines-blood-
biologics/safety-availability-biologics/vaccine-safety-questions-and-answers.

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been demonstrated to be “safe, pure, and potent.”® Prior to approval by FDA, vaccines are
extensively tested in non-clinical studies and in humans. FDA’s regulations describe some of the
extensive data and information that each sponsor of a vaccine must submit to FDA in order to
demonstrate the product’s safety before FDA will consider licensing the vaccine. FDA requires
that the sponsor’s biologics license application (BLA) include, among other things, data derived
from nonclinical and clinical studies showing the product’s safety, purity, and potency; a full
description of manufacturing methods for the product; data establishing the product’s stability
through the dating period; and a representative sample of the product and summaries of results of
tests performed on the lot(s) represented by the sample.”

As is evident from the language of the PHS Act and FDA’s regulations, the licensure process for
a vaccine requires the sponsor to establish, through carefully controlled laboratory and clinical
studies, as well as through other data, that the product is safe and effective for its approved
indication(s) and use. FDA’s multidisciplinary review teams then rigorously evaluate the
sponsor’s laboratory and clinical data, as well as other information, to help assess whether the
safety, purity, and potency of a vaccine has been demonstrated.!? Only when FDA’s standards
are met is a vaccine licensed.

FDA regulations explicitly state that “[a]pproval of a biologics license application or issuance of
a biologics license shall constitute a determination that the establishment(s) and the product meet
applicable requirements to ensure the continued safety, purity, and potency of such products.”!!
Therefore, the manufacturers of vaccines that have been licensed in the U.S. have necessarily
demonstrated the safety of the vaccines within the meaning of the applicable statutory and
regulatory provisions before the vaccines were licensed and allowed to be marketed.

For more information on FDA’s thorough process for evaluating the safety of vaccines, see
Appendix I of this letter, Aspects of Vaccine Development and Process for Licensure.

ii. Vaccine Safety Continues to Be Monitored Post-Licensure

FDA’s oversight of vaccine safety continues after licensure of the product. Once the licensed
vaccine is on the market, post-marketing surveillance of vaccine safety is conducted in order to
detect any rare, serious, or unexpected adverse events, as well as to monitor vaccine lots. FDA
employs multiple surveillance systems and databases to continue to evaluate the safety of these
vaccines. In certain cases, FDA may require the manufacturer to conduct post-marketing studies
to further assess known or potential serious risks.

b. An Emergency Use Authorization for a COVID-19 Preventative Vaccine Is Issued
Only If the Relevant Statutory Standards Are Met

Congress established the Emergency Use Authorization (EUA) pathway to ensure that, during
public health emergencies, potentially lifesaving medical products could be made available
before being approved. The EUA process allows the Secretary of HHS, in appropriate
circumstances, to declare that EUAs are justified for products to respond to certain types of

842 US.C. § 262(a)(2)(C)(4)(1).

° 21 CFR § 601.2(a).

10 FDA, Vaccines, last updated January 2021, https://www.fda.gov/vaccines-blood-biologics/vaccines.
1! 21 CFR § 601.2(d) (emphasis added).

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threats. When such a declaration is made, FDA may issue an EVA, which is different from the
regulatory process for vaccine licensure.

Section 564 of the Food Drug & Cosmetic Act (FD&C Act) (21 U.S.C. § 360bbb-3) authorizes
FDA to, under certain circumstances, issue an EUA to allow unapproved medical products or
unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or
prevent serious or life-threatening diseases or conditions caused by chemical, biological,
radiological, or nuclear threat agents when there are no adequate, approved, and available
alternatives.

On February 4, 2020, pursuant to section 564(b)(1)(C) of the FD&C Act (21 U.S.C. § 360bbb-
3(b)(1)(C)), the Secretary of HHS determined that there is a public health emergency that has a
significant potential to affect national security or the health and security of United States (U.S.)
citizens living abroad, and that involves the virus that causes COVID-19.'? On the basis of such
determination, on March 27, 2020, the Secretary then declared that circumstances exist justifying
the authorization of emergency use of drugs and biological products during the COVID-19
pandemic, pursuant to section 564(b)(1) of the FD&C Act (21 U.S.C. § 360bbb-3(b)(1)).'°

e The agent referred to in the March 27, 2020 EUA declaration by the Secretary (SARS-
CoV-2) can cause a serious or life-threatening disease or condition.

e The known and potential benefits of the product, when used to diagnose, prevent, or treat
the identified serious or life-threatening disease or condition, outweigh the known and
potential risks of the product.

e There is no adequate, approved, and available alternative to the product for diagnosing,
preventing, or treating the disease or condition.

Although EUAs are governed under a different statutory framework than BLAs, FDA has made
clear that issuance of an EUA for a COVID-19 vaccine would require that the vaccine
demonstrated clear and compelling safety and efficacy in a large, well-designed Phase 3 clinical
trial. In the guidance document Emergency Use Authorization for Vaccines to Prevent COVID-
19 (October 2020 Guidance), FDA has provided recommendations that describe key information

2. HHS, Determination of Public Health Emergency, 85 FR 7316, February 7, 2020,
https://www.federalregister.gov/documents/2020/02/07/2020-02496/determination-of-public-health-emergency.
'3 HHS, Emergency Use Authorization Declaration, 85 FR 18250, April 1, 2020,
https://www.federalregister.gov/documents/2020/04/01/2020-06905/emergency-use-authorization-declaration.

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that would support issuance of an EUA for a vaccine to prevent COVID-19.'* In the October
2020 Guidance, FDA explained that, in the case of such investigational vaccines, any assessment
regarding an EUA will be made on a case-by-case basis considering the target population, the
characteristics of the product, the preclinical and human clinical study data on the product, and
the totality of the available scientific evidence relevant to the product.'? FDA has also stated, in
this guidance, that for a COVID-19 vaccine for which there is adequate manufacturing
information to ensure its quality and consistency, issuance of an EUA would require a
determination by FDA that the vaccine’s benefits outweigh its risks based on data from at least
one well-designed Phase 3 clinical trial that demonstrates the vaccine’s safety and efficacy in a
clear and compelling manner. '©

A Phase 3 trial of a vaccine is generally a large clinical trial in which a large number of people
are assigned to receive the investigational vaccine or a control. In general, in Phase 3 trials that
are designed to show whether a vaccine is effective, neither people receiving the vaccine nor
those assessing the outcome know who received the vaccine or the comparator.

In a Phase 3 study of a COVID-19 vaccine, the efficacy of the investigational vaccine to prevent
disease will be assessed by comparing the number of cases of disease in each study group. For
Phase 3 trials, FDA has recommended to manufacturers in guidance that the vaccine should be at
least 50% more effective than the comparator, and that the outcome be reliable enough so that it
is not likely to have happened by chance.!’ During the entire study, subjects will be monitored
for safety events. If the evidence from the clinical trial meets the pre-specified criteria for
success for efficacy and the safety profile is acceptable, the results from the trial can potentially
be submitted to FDA in support of an EUA request.

Investigational COVID-19 vaccines continue to be studied in Phase 2 or Phase 3 trials.
Following clinical trials, manufacturers analyze data prior to submitting to FDA a BLA to
request approval from FDA to market the vaccine. A BLA for a new vaccine includes
information and data regarding the safety, effectiveness, chemistry, manufacturing and controls,
and other details regarding the product. During the current public health emergency,
manufacturers may, with the requisite data and taking into consideration input from FDA, choose
to submit a request for an EUA.

Importantly, FDA has made clear that any vaccine that meets FDA’s standards for effectiveness
is also expected to meet the Agency’s safety standards. FDA has stated that the duration of
safety follow-up for a vaccine authorized under an EUA may be shorter than with a BLA (which
the Agency expects will ultimately be submitted by manufacturers of vaccines that are
authorized under an EUA). Specifically, FDA’s guidance to manufacturers recommends that
data from Phase 3 studies to support an EUA include a median follow-up duration of at least 2
months after completion of the full vaccination regimen.'? Furthermore, robust safety
monitoring is conducted after a vaccine is made available. The monitoring systems include the

4 Emergency Use Authorization for Vaccines to Prevent COVID-19; Guidance for Industry, October 2020 (October
2020 Guidance), https://www.fda.gov/media/142749/download.

IS Td. at 3.

16 Td. at 4.

'7 Development and Licensure of Vaccines to Prevent COVID-19; Guidance for Industry, June 2020,
https://www.fda.gov/media/139638/download.

'8 October 2020 Guidance at 10-11.

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Vaccine Adverse Event Reporting System (VAERS), FDA’s Biologics Effectiveness and Safety
(BEST) System, and the Centers for Disease Control and Prevention’s (CDC) Vaccine Safety
Datalink. In addition, FDA has a partnership with the Centers for Medicare & Medicaid
Services (CMS) to study vaccine safety. Other tools to monitor vaccine safety are under
development. Collectively, these programs will help detect any new, unusual and rare side
effects after vaccination that might not have been observed during clinical trials, as well as
monitor for increases in any known side effects.

It is FDA’s expectation that, following submission of an EUA request and issuance of an EUA, a
sponsor would continue to evaluate the vaccine and would also work towards submission of a
BLA as soon as possible.

III. Discussion

The Petition makes a request regarding clinical trials of COVID-19 vaccines that include or
propose to include children. FDA’s investigational new drug process applies to the development
of new drugs and biological products, including vaccines. !”

a. Investigational New Drugs

Before a vaccine is licensed (approved) by FDA for use by the public, FDA requires that it
undergo a rigorous and extensive development program to determine the vaccine’s safety and
effectiveness. This development program encompasses preclinical research (laboratory research,
animal studies”) and clinical studies. At the preclinical stage, the sponsor focuses on collecting
the data and information necessary to establish that the product will not expose humans to
unreasonable risks when used in limited, early-stage clinical studies. Clinical studies, in humans,
are conducted under well-defined conditions and with careful safety monitoring through all the
phases of the investigational new drug process. FDA’s regulations governing the conduct of
clinical investigations are set out at 21 CFR Part 312.

Before conducting a clinical investigation in the U.S. in which a new drug or biological product
is administered to humans, a sponsor must submit an investigational new drug application (IND)
to FDA.”! The IND describes the proposed clinical study in detail and, among other things,
helps protect the safety and rights of human subjects.” In addition to other information, an IND
must contain information on clinical protocols and clinical investigators. Detailed protocols for
proposed clinical studies permit FDA to assess whether the initial-phase trials will expose
subjects to unnecessary risks. Information on the qualifications of clinical investigators
(professionals, generally physicians, who oversee the administration of the experimental drug)
permits FDA to assess whether they are qualified to fulfill their clinical trial duties. The IND

'9 See 21 CFR § 312.2 (explaining that the IND regulations apply to clinical investigations of both drugs and
biologics).

2° We support the principles of the “3Rs,” to reduce, refine, and replace animal use in testing when feasible. We
encourage sponsors to consult with us if they wish to use a non-animal testing method they believe is suitable,
adequate, validated, and feasible. We will consider if such an alternative method could be assessed for equivalency
to an animal test method.

71 See 21 CFR § 312.20(a).

22 For additional information regarding the IND review process and general responsibilities of sponsor-investigators
related to clinical investigations see Investigational New Drug Applications Prepared and Submitted by Sponsor-
Investigators; Draft Guidance for Industry, May 2015, https://www.fda.gov/media/92604/download.

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includes commitments to obtain informed consent from the research subjects, to obtain review of
the study by an institutional review board (IRB),”° and to adhere to the investigational new drug
regulations.

Once the IND is submitted, the sponsor must wait 30 calendar days before initiating any clinical
trials, unless FDA informs the sponsor that the trial may begin earlier. During this time,

FDA reviews the IND. FDA’s primary objectives in reviewing an IND are, in all phases of the
investigation, to assure the safety and rights of subjects, and, in Phase 2 and Phase 3, to help
assure that the quality of the scientific evaluation of drugs is adequate to permit an evaluation of
the drug’s effectiveness and safety.74

FDA’s regulations provide that, once an IND is in effect, the sponsor may conduct a clinical
investigation of the product, with the investigation generally being divided into three phases.
With respect to vaccines, the initial human studies, referred to as Phase | studies, are generally
safety and immunogenicity studies performed in a small number of closely monitored subjects.
Phase 2 studies may include up to several hundred individuals and are designed to provide
information regarding the incidence of common short-term side effects such as redness and
swelling at the injection site or fever and to further describe the immune response to the
investigational vaccine. If an investigational new vaccine progresses past Phase 1 and Phase 2
studies, it may progress to Phase 3 studies. For Phase 3 studies, the sample size is often
determined by the number of subjects required to establish the effectiveness of the new vaccine,
which may be in the thousands or tens of thousands of subjects. Phase 3 studies provide the
critical documentation of effectiveness and important additional safety data required for
licensing.

Additionally, FDA regulations require that an IRB must review clinical investigations involving
children as subjects covered by 21 CFR 50, subpart D and only approve those clinical
investigations involving children as subjects that satisfy the criteria in 21 CFR 50, subpart D,
Additional Safeguards for Children in Clinical Investigations. As explained in the preamble to
the final rule, “[t]hese safeguards are intended to ensure that the rights and welfare of children
who participate in clinical investigations are adequately protected.”*°

At any stage of development, if data raise significant concerns about either safety or
effectiveness, FDA may request additional information or studies; FDA may also halt ongoing
clinical studies. The FD&C Act provides a specific mechanism, called a “clinical hold,” for
prohibiting sponsors of clinical investigations from conducting the investigation (section

3 The IRB is a panel of scientists and non-scientists in hospitals and research institutions that oversees clinical
research. IRBs approve clinical study protocols, which describe the type of people who may participate in the
clinical study; the schedule of tests and procedures; the medications and dosages to be studied; the length of the
study; the study's objectives; and other details. IRBs make sure that the study is acceptable, that participants have
given consent and are fully informed of the risks, and that researchers take appropriate steps to protect patients from
harm. See The FDA's Drug Review Process: Ensuring Drugs Are Safe and Effective web page, last updated
November 2017, https://www.fda.gov/drugs/drug-information-consumers/fdas-drug-review-process-ensuring-drugs-
are-safe-and-effective.

24.91 CFR § 312.22(a).

5 Preamble to final rule, “Additional Safeguards for Children in Clinical Investigations of Food and Drug
Administration-Regulated Products” (78 FR 12937 at 12938, February 26, 2013),
https://www.federalregister.gov/documents/2013/02/26/2013-04387/additional-safeguards-for-children-in-clinical-
investigations-of-food-and-drug.

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505(1)(3) of the FD&C Act; 21 U.S.C. § 355(1)(3)), and FDA’s IND regulations in 21 CFR §
312.42 identify the circumstances that may justify a clinical hold. Generally, a clinical hold is an
order issued by FDA to the sponsor of an IND to delay a proposed clinical investigation or to
suspend an ongoing investigation.”°

b. The Citizen Petition

i. Petitioner’s Request to Revoke all Emergency Use Authorizations for
COVID-19 Vaccines and Refrain from Issuing any Future EUA or
Approving any Future NDA, or BLA for any COVID-19 Vaccine for all
Demographic Groups because the Current Risks of Serious Adverse
Events or Deaths Outweigh the Benefits, and Because Existing,
Approved Drugs Provide Highly Effective Prophylaxis and Treatment
against COVID-19, Mooting the EUAs

Petitioner makes several requests regarding COVID-19 vaccines in the Petition and, in support of
these requests, argues that (1) the rates of serious adverse events or deaths outweigh the benefits
of these vaccines and (2) approved drugs provide highly effective prophylaxis/treatment against
COVID, thereby “mooting” the EUAs. We interpret this as an argument that the authorizations
of COVID-19 vaccines to date did not meet the relevant legal standard. Below, we address each
of Petitioner’s requests and the information provided by Petitioner in support of these requests.

1. Petitioner’s Request to Revoke all Emergency Use
Authorizations for COVID-19 Vaccines

In this section, we address Petitioner’s request that FDA “revoke all EUAs . . . for any COVID
vaccine for all demographic groups because the current risks of serious adverse events or deaths
outweigh the benefits, and because existing, approved drugs provide highly effective prophylaxis
and treatment against COVID, mooting the EUAs.” Petition at 1.

a. EUAs for COVID-19 Vaccines

As noted above in Section II above, FDA may issue an EUA during the COVID-19 public health
emergency after FDA concludes that the statutory requirements provided in section 564 of the
FD&C Act are met. In an attempt to prevent the spread of disease and to control the pandemic,
numerous COVID-19 vaccine candidates have been developed. COVID-19 vaccines that have
been developed or are currently in development are based on various platforms and include
mRNA, DNA, viral vectored, subunit, inactivated, and live-attenuated vaccines. Most COVID-
19 candidate vaccines express the spike protein or parts of the spike protein, 1.e., the receptor
binding domain, as the immunogenic determinant.

To date, FDA has issued EUAs for three COVID-19 vaccines (“the Authorized COVID-19
Vaccines’), as described in the Scope of Authorization for these COVID-19 vaccines, pursuant

2621 CFR § 312.42(a).

10
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to section 564 of the FD&C Act. Additionally, FDA has expanded the authorized age range for
one COVID-19 vaccine.

e On December 11, 2020, FDA issued an EUA for emergency use of Pfizer-BioNTech
COVID-19 Vaccine for the prevention of COVID-19 in individuals 16 years of age and
older.

o On May 10, 2021, FDA authorized the emergency use of Pfizer-BioNTech
COVID-19 Vaccine to include individuals 12 through 15 years of age.

e On December 18, 2020, FDA issued an EUA for emergency use of Moderna COVID-19
Vaccine for the prevention of COVID-19 in individuals 18 years of age and older.

e On February 27, 2021, FDA issued an EUA for emergency use of Janssen COVID-19
Vaccine for the prevention of COVID-19 in individuals 18 years of age and older.

The Agency issued these EUAs after a thorough evaluation of scientific data regarding the
safety, effectiveness, and manufacturing information (which helps ensure product quality and
consistency) of these COVID-19 vaccines and after reaching a determination that these vaccines
meet the statutory requirements under section 564 of the FD&C Act. This letter incorporates by
reference the EUA Review Memoranda for the Authorized COVID-19 Vaccines,*’ which discuss
this determination, and the data upon which it was based, in detail as well as the Summary Basis
of Regulatory Action for the BioNTech COVID-19 vaccine (COVID-19 Vaccine, mRNA;
Comirnaty).78

Petitioner argues that the authorizations for these vaccines should be revoked, and that future
COVID vaccines should not be authorized or licensed, because (1) “the current risks of serious
adverse events or deaths outweigh the benefits,” and (2) “existing, approved drugs provide
highly effective prophylaxis and treatment against COVID, mooting the EUAs.” We address
each of Petitioner’s arguments, and data submitted in the Petition in support of these arguments,
below.

FDA disagrees with Petitioner’s position that the Authorized COVID-19 Vaccines did not meet
the statutory standard at the time of authorization, and finds no basis in the information
submitted in the Petition, or in any postmarket data regarding these vaccines, to support a
revocation of any of these authorizations. FDA is not aware of any information indicating that
the known and potential benefits of the Authorized COVID-19 Vaccines are outweighed by their
known and potential risks, nor has Petitioner provided any such information in the Petition. The

27 EDA, Pfizer-BioNTech COVID-19 Vaccine EUA Decision Memorandum (Dec. 11, 2020),
https://www.fda.gov/media/144416/download; FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Amendment
Decision Memorandum for Authorization in Individuals 12-15 Years of Age (May 10, 2021),
https://www.fda.gov/media/148542/download; FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Amendment
Decision Memorandum for Authorization of an Additional Dose in Certain Immunocompromised Individuals
(August 12, 2021) https://www.fda.gov/media/151613/download; FDA, Moderna COVID-19 Vaccine EUA
Decision Memorandum (Dec. 18, 2020), https://www.fda.gov/media/144673/download; FDA, Moderna COVID-19
Vaccine EUA Amendment Decision Memorandum for Authorization of an Additional Dose in Certain
Immunocompromised Individuals (August 12, 2021) https://www.fda.gov/media/151611/download; FDA, Janssen
COVID-19 Vaccine EUA Decision Memorandum (Feb. 27, 2021), https://www.fda.gov/media/146338/download.
28 This letter incorporates by reference FDA's Summary Basis for Regulatory Action (SBRA) for the BioNTech
BLA. This memorandum will be posted on www.fda.gov.

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known and potential benefits of the Authorized COVID-19 Vaccines continue to outweigh their
known and potential risks, given the risk of COVID-19 and related, potentially severe,
complications. Furthermore, as explained below, there is no adequate, approved, and available
alternative to the Authorized COVID-19 Vaccines for preventing COVID-19. Accordingly, this
request is denied.

b. Standard for Revocation of EUAs is not Met for the
Authorized COVID-19 Vaccines

Section 564(g)(2) of the FD&C Act provides the standard for revocation of an EUA. Under this
statutory authority, FDA may revise or revoke an EUA if:

(A) the circumstances described under [section 564(b)(1) of the FD&C Act] no longer
exist;

(B) the criteria under [section 564(c) of the FD&C Act] for issuance of such authorization
are no longer met; or

FDA’s guidance entitled Emergency Use Authorization of Medical Products and Related
Authorities (“EUA Guidance”),”’ notes that once an EUA is issued for a product, in general, that
EUA will remain in effect for the duration of the EUA declaration under which it was issued,
“unless the EUA is revoked because the criteria for issuance . . . are no longer met or revocation
is appropriate to protect public health or safety (section 564(f),(g) [of the FD&C Act]).”*°
Regarding the circumstances that would make a revision or revocation appropriate to protect the
public health or safety, FDA explains in the EUA guidance that

Such circumstances may include significant adverse inspectional
findings (e.g., when an inspection of the manufacturing site and
processes has raised significant questions regarding the purity,
potency, or safety of the EUA product that materially affect the
risk/benefit assessment upon which the EUA was based); reports
of adverse events (number or severity) linked to, or suspected of
being caused by, the EUA product; product failure; product
ineffectiveness (such as newly emerging data that may contribute
to revision of the FDA's initial conclusion that the product "may be
effective" against a particular CBRN agent); a request from the
sponsor to revoke the EUA; a material change in the risk/benefit
assessment based on evolving understanding of the disease or
condition and/or availability of authorized MCMs; or as provided
in section 564(b)(2), a change in the approval status of the product
may make an EUA unnecessary.

2° Emergency Use Authorization of Medical Products and Related Authorities; Guidance for Industry and Other
Stakeholders, January 2017 (EUA Guidance), https://www.fda.gov/media/9732 1/download.
3° Td. at 28.

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EUA guidance at 29.

Thus, in addressing Petitioner’s request for FDA to revoke the Authorized COVID-19 Vaccines,
we assess whether any of the statutory conditions under which FDA may revoke an EUA are
met, namely: (1) whether the circumstances justifying their issuance under section 564(b)(1) of
the FD&C Act no longer exist, (2) whether the criteria for their issuance under section 564(c) of
the FD&C Act are no longer met, and (3) whether other circumstances make a revision or
revocation appropriate to protect the public health or safety.

i. Circumstances Continue to Justify the Issuance of
the EUAs for the Authorized COVID-19 Vaccines

As explained above in section II.b., on February 4, 2020, pursuant to section 564(b)(1)(C) of the
FD&C Act (21 U.S.C. § 360bbb-3(b)(1)(C)), the Secretary of HHS determined that there is a
public health emergency that has a significant potential to affect national security or the health
and security of U.S. citizens living abroad, and that involves the virus that causes COVID-19.°!
On the basis of such determination, on March 27, 2020, the Secretary then declared that
circumstances exist justifying the authorization of emergency use of drugs and biological
products during the COVID-19 pandemic (“COVID-19 EUA Declaration”), pursuant to section
564(b)(1) of the FD&C Act (21 U.S.C. § 360bbb-3(b)(1)).*7

Based on this declaration and determination, under section 564(c) of the FD&C Act (21 U.S.C. §
360bbb-3(c)), FDA may issue an EUA during the COVID-19 pandemic after FDA concludes
that the statutory requirements provided in section 564(c) are met. Section 564(b)(2) sets forth
the statutory standard for termination of an EUA declaration. An EUA declaration remains in
place until the earlier of: (1) a determination by the HHS Secretary that the circumstances that
precipitated the declaration have ceased (after consultation as appropriate with the Secretary of
Defense) or (2) a change in the approval status of the product such that the authorized use(s) of
the product are no longer unapproved. Neither of those statutory criteria is satisfied with respect
to the Authorized COVID-19 Vaccines.

Thus, the circumstances described under section 564(b)(1) of the FD&C Act continue to exist.
FDA therefore is not revoking the EUAs for the Authorized COVID-19 Vaccines under the
authority in section 564(g)(2)(A) of the FD&C Act.

ii. The Criteria for The Issuance of the Authorized
COVID-19 Vaccines Continue to Be Met

This section describes in detail why the criteria under section 564(c) of the FD&C Act continue
to be met with respect to the Authorized COVID-19 Vaccines and why, therefore, FDA is not
revoking the EUAs for the Authorized COVID-19 Vaccines under the authority in section
564(g)(2)(B) of the FD&C Act.

31 HHS, Determination of Public Health Emergency, 85 FR 7316, February 7, 2020,
https://www.federalregister.gov/documents/2020/02/07/2020-02496/determination-of-public-health-emergency.
>? HHS, Emergency Use Authorization Declaration, 85 FR 18250, April 1, 2020,
https://www.federalregister.gov/documents/2020/04/01/2020-06905/emergency-use-authorization-declaration.

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1. Serious or life-threatening disease or
condition.

Section 564(c)(1) of the FD&C Act requires that, for an EUA to be issued for a medical product,
FDA must conclude “the agent(s) referred to in [the HHS Secretary’s EUA declaration] can
cause a serious or life-threatening disease or condition.” FDA has concluded that SARS-CoV-2,
which is the subject of the EUA declaration, meets this standard.

The SARS-CoV-2 pandemic continues to present an extraordinary challenge to global health
and, as of August 3, 2021, has caused more than 199 million cases of COVID-19 and claimed the
lives of more than 4.2 million people worldwide.* In the United States, more than 34 million
cases and over 611,000 deaths have been reported to the CDC.** On January 31, 2020, the U.S.
Secretary of Health and Human Services (HHS) declared a public health emergency related to
COVID-19 and mobilized the Operating Divisions of HHS, and the U.S. President declared a
national emergency in response to COVID-19 on March 13, 2020.

FDA is not aware of science indicating that there is any change in the ability of the SARS-CoV-2
virus to cause a Serious or life-threatening disease or condition, namely COVID-19, nor has
Petitioner provided any information about such a change. Therefore, the criterion under section
564(c)(1) continues to be met with respect to the Authorized COVID-19 Vaccines.

2. Evidence of Effectiveness

Section 564(c)(2)(A) of the FD&C Act requires that, for an EUA to be issued for a medical
product, FDA must conclude “based on the totality of scientific evidence available to the
Secretary, including data from adequate and well-controlled trials, if available, it is reasonable to
believe that the product may be effective to prevent, diagnose, or treat such serious or life-
threatening disease or condition that can be caused by SARS-CoV-2.”

FDA issued EUAs for the Authorized COVID-19 Vaccines after determining that, among other
things, these products were demonstrated in clinical trials to prevent symptomatic and severe
COVID-19 in vaccinated clinical trial subjects.*°> FDA is not aware of any data that changes this
conclusion, nor has Petitioner provided any such data in the Petition. This section addresses
Petitioner’s arguments regarding the effectiveness of the Authorized COVID-19 vaccines and
explains why the information submitted by Petitioner does not change FDA’s analysis regarding
the effectiveness of these vaccines.

After FDA approves a vaccine or authorizes a vaccine for emergency use, the vaccine continues
to be studied to determine how well it works under real-world conditions. FDA, CDC, and other
federal partners have been assessing, and will continue to assess, COVID-19 vaccine

33 Johns Hopkins University School of Medicine, Coronavirus Resource Center,
https://coronavirus.jhu.edu/map.html.

34 CDC, COVID Data Tracker, https://covid.cdc.gov/covid-data-tracker/#trends_dailytrendscases.

35 FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Decision Memorandum (Dec. 11, 2020), at 23,
https://www.fda.gov/media/144416/download; FDA, Moderna COVID-19 Vaccine EUA Decision Memorandum
(Dec. 18, 2020), at 24, https://www.fda.gov/media/144673/download; FDA, Janssen COVID-19 Vaccine EUA
Decision Memorandum (Feb. 27, 2021), at 25, https://www.fda.gov/media/146338/download.

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effectiveness under real-world conditions. Such evaluations will help us understand if vaccines
are performing as expected outside the more controlled setting of a clinical trial.

Petitioner raises concerns regarding the post-market effectiveness of the Authorized COVID-19
Vaccines (Petition at 6). Petitioner points to CDC-reported “breakthrough cases” to suggest that
the Authorized COVID-19 Vaccines are not effective and argues that the EUAs for the
Authorized COVID-19 Vaccines should therefore be revoked because the current risks of these
vaccines outweigh their benefits. This perspective fails to recognize several important points
regarding the concept of breakthrough cases and regarding the CDC publication cited in the
Petition.

First, we note that the Letters of Authorization for the Authorized COVID-19 Vaccines require
EUA-holders to report to VAERS “cases of COVID-19 that result in hospitalization or death,
that are reported to [the EUA holder].”°° Thus, the possibility that individuals who received one
of the Authorized COVID-19 Vaccines could develop breakthrough COVID-19 cases was
recognized by FDA when the Agency evaluated the EUA requests for these vaccines and
determined that their known and potential benefits outweigh their known and potential and risks.

Second, the Authorized COVID-19 Vaccines are indicated to prevent symptomatic COVID-19,>”
not to prevent SARS-CoV-2 infection. Over 353 million doses of COVID-19 vaccines have
been administered in the United States*® and FDA’s ongoing post authorization monitoring
informs us that the known and potential benefits continue to outweigh the known and potential
risks. Additionally, CDC’s post-authorization data regarding the Authorized COVID-19
Vaccines continues to support FDA’s conclusion that these vaccines prevent symptomatic
COVID-19.°?

Third, a vaccine does not need to be 100% effective in preventing the target disease in order to
meet the licensure or EUA standard. It is expected that some vaccinated individuals will contract
the target disease despite having been vaccinated against it. No FDA licensed or authorized
vaccine is 100% effective, but scientific data has nevertheless demonstrated that vaccinations
have been a very effective approach to protecting the public's health in the United States.*°

36 Section 8, Requirements and Instructions for Reporting Adverse Events and Vaccine Administration Errors,
Pfizer-BioNTech COVID-19 Fact Sheet for Healthcare Providers Administering Vaccine,
https://www.fda.gov/media/144413/download; Section 8, Requirements and Instructions for Reporting Adverse
Events and Vaccine Administration Errors, Moderna COVID-19 Fact Sheet for Healthcare Providers Administering
Vaccine, https://www.fda.gov/media/144637/download; Section 8, Requirements and Instructions for Reporting
Adverse Events and Vaccine Administration Errors, Janssen COVID-19 Fact Sheet for Healthcare Providers
Administering Vaccine, https://www.fda.gov/media/146304/download.

37 FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Decision Memorandum (Dec. 11, 2020), at 23,
https://www.fda.gov/media/144416/download; FDA, Moderna COVID-19 Vaccine EUA Decision Memorandum
(Dec. 18, 2020), at 24, https://www.fda.gov/media/144673/download; FDA, Janssen COVID-19 Vaccine EUA
Decision Memorandum (Feb. 27, 2021), at 25, https://www.fda.gov/media/146338/download.

38 CDC, COVID Data Tracker Weekly Review, Interpretive Summary for August 13, 2021,
https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html

39 CDC, COVID-19 Vaccine Effectiveness Research, https://www.cdc.gov/vaccines/covid-19/effectiveness-
research/protocols.html.

© Vaccine Safety Questions and Answers, last updated March 2018, https://www.fda.gov/vaccines-blood-
biologics/safety-availability-biologics/vaccine-safety-questions-and-answers.

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Similarly, a COVID-19 vaccine need not be 100% effective in preventing symptomatic COVID-
19, or even close to 100% effective in doing so, in order to have a significant effect in altering
the course of the COVID-19 pandemic. As FDA noted in its June 2020 Guidance for Industry,
Development and Licensure of Vaccines to Prevent COVID-19, (“The Vaccine Development
and Licensure Guidance’’) “[t]o ensure that a widely deployed COVID-19 vaccine is effective,
the primary efficacy endpoint point estimate for a placebo-controlled efficacy trial should be at
least 50%, and the statistical success criterion should be that the lower bound of the appropriately
alpha-adjusted confidence interval around the primary efficacy endpoint point estimate is
>30%.’’*! This statistical consideration provided in the Vaccine Development and Licensure
Guidance reflects FDA’s assessment that a vaccine with at least 50 percent efficacy would have
a significant impact on disease, both at the individual and societal level.

Finally, we note that Petitioner refers to “CDC-reported” breakthrough cases in support of its
argument that there are effectiveness concerns with the Authorized COVID-19 Vaccines but fails
to acknowledge that CDC reported a set of breakthrough cases that includes a large proportion of
asymptomatic individuals who tested positive for SARS-CoV-2. Petitioner thus applies a
narrower definition of the term “breakthrough case” to a set of cases than CDC has in its
COVID-19 Vaccine Breakthrough Case Investigation.** Petitioner refers to breakthrough cases
in which vaccinated individuals “fall ill and potentially transmit the virus” (Petition at 6) and
states that “CDC reported over 9,000 ‘breakthrough cases’ and 132 COVID-caused deaths
among vaccinated people.” Petition at 6.

CDC’s objective in the COVID-19 Vaccine Breakthrough Case Investigation is to*? ensure the
COVID-19 vaccines are working as expected and to “identify patterns or trends” in:

e Patients’ characteristics, such as age or underlying medical conditions
e The specific vaccine that patients received
e Whether a specific SARS-CoV-2 variant caused the infections”

The objective of this investigation is not simply to count symptomatic COVID-19 cases.
Currently, COVID-19 cases are increasing again in nearly all states. The highest rate of COVID-
19 case spread is in areas with low vaccination rates.*°

Petitioner’s submitted data regarding CDC-reported “breakthrough cases” therefore does not
present new data or information that the Agency has not previously considered regarding the
effectiveness of the Authorized COVID-19 Vaccines. Available data regarding effectiveness of

41 Development and Licensure of Vaccines to Prevent COVID-19, Guidance for Industry, June 2020, at 14,
https://www.fda.gov/media/139638/download.

* CDC, COVID-19 Vaccine Breakthrough Case Investigations and Reporting, https://www.cdc.gov/vaccines/covid-
19/health-departments/breakthrough-cases.html.

*8 CDC, COVID-19 Vaccine Breakthrough Case Investigations and Reporting, https://www.cdc.gov/vaccines/covid-
19/health-departments/breakthrough-cases.html.

“44 CDC, COVID-19 Vaccine Breakthrough Case Investigations and Reporting, https://www.cdc.gov/vaccines/covid-
19/health-departments/breakthrough-cases.html.

4 “As of July 22 [2021], 35% of U.S. counties are experiencing high levels of community transmission. COVID-19
cases are on the rise in nearly 90% of U.S. jurisdictions, and we are seeing outbreaks in parts of the country that
have low vaccination coverage.” CDC, COVID Data Tracker Weekly Review, Interpretive Summary for July 23,
2021, available at https://www.cdc.gov/coronavirus/20 1 9-ncov/covid-data/covidview/index.html.

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the Authorized COVID-19 Vaccines continues to support the conclusion that these vaccines may
be effective in preventing COVID-19. FDA is not aware of any data that changes this
conclusion, nor has Petitioner provided any such data in the Petition. Therefore, the criterion
under section 564(c)(2)(A) continues to be met with respect to the Authorized COVID-19
Vaccines.

3. Benefit-Risk Analysis

Section 564(c)(2)(B) of the FD&C Act requires that, for an EUA to be issued for a medical
product, FDA must conclude “the known and potential benefits of the product, when used to
diagnose, prevent, or treat [the identified serious or life-threatening disease or condition],
outweigh the known and potential risks of the product... .” Petitioner argues that the current
risks of serious adverse events or deaths associated with the Authorized COVID-19 Vaccines
outweigh the benefits of COVID-19 vaccines. This section addresses Petitioner’s arguments
regarding the safety of COVID-19 vaccines and explains why the information submitted by
Petitioner does not change FDA’s analysis regarding the benefits and risks of the Authorized
COVID-19 Vaccines.

FDA issued EUAs for the Authorized COVID-19 Vaccines after reaching a determination
regarding each of these vaccines that, among other things, the known and potential benefits of
the vaccine, when used to prevent COVID-19, outweigh its known and potential risks.4° FDA is
not aware of any data that changes this determination, nor has Petitioner provided any such data
in the Petition. The known and potential benefits of the Authorized COVID-19 Vaccines, when
used to prevent COVID-19, continue to outweigh their known and potential risks, given the risk
of COVID-19 and related, potentially severe, complications.

Petitioner raises numerous concerns regarding safety of the Authorized COVID-19 Vaccines
(Petition at 2-6) and asserts that the EUAs for the Authorized COVID-19 Vaccines should be
revoked due in part to these safety concerns. For reasons explained below, FDA disagrees with
Petitioner’s assertions regarding the safety of the Authorized COVID-19 Vaccines.

As an initial matter, we note that the Petition discusses several assertions made by CDC and
requests that have been directed to CDC. For requests intended for CDC, you should contact
CDC directly.

a. Petitioner’s Claims Regarding
VAERS Data

46 For an extensive discussion of FDA’s analysis of the clinical trial data regarding the risks and benefits of each of
the authorized COVID-19 Vaccines, see FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Decision Memorandum
(Dec. 11, 2020), at 49, https://www.fda.gov/media/144416/download; FDA, Moderna COVID-19 Vaccine EUA
Decision Memorandum (Dec. 18, 2020), at 55, https://www.fda.gov/media/144673/download; FDA, Janssen
COVID-19 Vaccine EUA Decision Memorandum (Feb. 27, 2021), at 59,
https://www.fda.gov/media/146338/download. See also, FDA, Pfizer-BioNTech COVID-19 Vaccine EUA
Amendment Decision Memorandum for Authorization in Individuals 12-15 Years of Age (May 10, 2021), at 38,
https://www.fda.gov/media/148542/download.

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In arguing that the Authorized COVID-19 Vaccines should be revoked due, in part, to safety
concerns, Petitioners assert that “Vaccine Adverse Event Reporting System (VAERS) data reveal
unprecedented levels of deaths and other adverse events since the FDA issued Emergency Use
Authorizations (EUAs) for three COVID vaccines. As of May 10, 2021, VAERS reported 4,434
deaths of people who received at least one COVID vaccination.” As an initial matter, we note
that VAERS is a national passive surveillance vaccine safety database that receives unconfirmed
reports of possible adverse events following the use of a vaccine licensed or authorized in the
United States. VAERS is not designed to assess whether a reported adverse event was caused by
a vaccine. This section explains vaccine safety surveillance, including VAERS, in greater detail
below.

Regarding the number of VAERS reports submitted for the Authorized COVID-19 Vaccines,
this figure can be attributed to multiple factors. First, we note that a large number of COVID-19
vaccine doses have been administered in the United States and that certain adverse event
reporting by vaccination providers is required for the Authorized COVID-19 Vaccines. As of
August 13, 2021, over 353,000,000 doses of the Authorized COVID-19 Vaccines have been
administered.*” We note that the crude number of VAERS reports of death is extremely small
compared to the to the large number of people who have been vaccinated. The VAERS
reporting rate for deaths (which is the number of VAERS death reports received out of the
number of individuals vaccinated) for the Authorized COVID-19 Vaccines is actually very low
(6,490 reports of death out of 346 million doses administered (0.0019%) as of August 2, 2021).*8
Petitioner’s assertion fails to account for this fact.

For licensed vaccines, healthcare providers are legally required under 42 USC 300aa-25 to report
to VAERS two categories of adverse events: “[a]ny adverse event listed in the VAERS Table of
Reportable Events Following Vaccination that occurs within the specified time period after
vaccination [and] [a]n adverse event listed by the vaccine manufacturer as a contraindication to
further doses of the vaccine”*”? Vaccine manufacturers are also required to report to VAERS all
adverse events that come to their attention.~°

Under the EUAs for the Authorized COVID-19 Vaccines, however, vaccination providers are
required to report to VAERS serious adverse events following vaccination with the Authorized
COVID-19 Vaccines, “irrespective of attribution to vaccination” and without a specified time
period after vaccination.°*! Another contributing factor is the v-safe system,°” which is a new
CDC smartphone-based active-surveillance system in which participants who have been

47 CDC, COVID Data Tracker, COVID-19 Vaccinations in the United States, https://covid.cde.gov/covid-data-
tracker/#vaccinations_vacc-total-admin-rate-total.

48 CDC, Selected Adverse Events Reported after COVID-19 Vaccination, https://www.cdc.gov/coronavirus/2019-
ncov/vaccines/safety/adverse-events.html.

49 VAERS, Frequently Asked Questions, https://vaers.hhs.gow/faq.html (emphasis added).

°° 21 CFR 600.80. See also VAERS, Frequently Asked Questions, https://vaers.hhs.gov/faq.html.

>! Section 8, Requirements and Instructions for Reporting Adverse Events and Vaccine Administration Errors,
Pfizer-BioNTech COVID-19 Fact Sheet for Healthcare Providers Administering Vaccine,
https://www.fda.gov/media/144413/download; Section 8, Requirements and Instructions for Reporting Adverse
Events and Vaccine Administration Errors, Moderna COVID-19 Fact Sheet for Healthcare Providers Administering
Vaccine, https://www.fda.gov/media/144637/download; Section 8, Requirements and Instructions for Reporting
Adverse Events and Vaccine Administration Errors, Janssen COVID-19 Fact Sheet for Healthcare Providers
Administering Vaccine, https://www.fda.gov/media/146304/download.

>2 CDC, v-safe Overview, https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/vsafe.html.

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vaccinated may voluntarily enroll. This system was developed for the COVID-19 vaccination
program. V-safe sends text messages and web surveys to participants who can report side effects
following receipt of a COVID-19 vaccine. Ifa participant indicates through the v-safe surveys
that he or she required medical care at any time, CDC calls the participant to complete a report
through VAERS. This system is unique to COVID-19 vaccines and may be contributing to the
number of VAERS reports submitted for the Authorized COVID-19 Vaccines.

Finally, another potential factor is the concept of “stimulated reporting.”°? Because of extensive
media coverage and awareness of the public health emergency — and of the Authorized COVID-
19 Vaccines and their reported side effects —vaccine recipients, health care providers, and others
are more likely to report adverse events for the Authorized COVID-19 Vaccines than for other
vaccines that have been widely available for longer periods of time. Additionally, one of the
articles submitted by Petitioner in support of their argument actually provides support for this
explanation for the number of VAERS reports submitted for the Authorized COVID-19
Vaccines. The article notes “[t]he relatively rapid increase in numbers of reports to VAERS
following the introduction and initial uptake of a new vaccine, an expected occurrence, has been
misinterpreted as actual increases in incidence of adverse events and vaccine related risk.”’~4
Petitioner’s argument regarding VAERS data for the Authorized COVID-19 Vaccines is
unavailing because it fails to account for the factors outlined above.

In addressing Petitioner’s assertion regarding VAERS claims, this section addresses the
extensive vaccine safety surveillance efforts, in addition to VAERS, that are in place for the
Authorized COVID-19 Vaccines.°°> FDA is monitoring the safety of the Authorized COVID-19
Vaccines through both passive and active safety surveillance systems. FDA is doing so in
collaboration with the Centers for Disease Control and Prevention (CDC), the Centers for
Medicare and Medicaid Services (CMS), the Department of Veterans Affairs (VA), and other
academic and large non-government healthcare data systems.

In addition, FDA participates actively in ongoing international pharmacovigilance efforts,
including those organized by the International Coalition of Medicines Regulatory Authorities

°3 We note that an article submitted by Petitioner in support of their arguments regarding VAERS acknowledges this
concept: “Like all spontaneous public health reporting systems, VAERS has limitations. VAERS is subject to
reporting bias, including underreporting of adverse events — especially common, mild ones— and stimulated
reporting, which is elevated reporting that might occur in response to intense media attention and increased public
awareness, such as during the 2009 H1N1 pandemic influenza vaccination program” Shimabukuro et al., Safety
monitoring in the Vaccine Adverse Event Reporting System (VAERS), Vaccine (Nov. 4, 2015),
https:/Awww.ncbi.nlm.nih.gov/pme/articles/PMC4632204/. See also “The number of reports and reporting rate
following 2009-H1N1 vaccination were higher than following 2009-2010 seasonal influenza vaccines for all age
groups. These findings, however, should be interpreted in light of the publicity around the 2009-H1NI1 vaccine and
efforts to increase reporting to VAERS. Heightened public awareness and stimulated reporting likely enhanced
reporting to VAERS. Furthermore, although 2009-H1N1 was licensed similarly to seasonal influenza vaccines, it
was likely perceived as a ‘new’ vaccine by the public and susceptible to the known tendency (1.e., the Weber effect)
for adverse events to be reported more frequently following newly licensed products.” Vellozzi, et al., Adverse
events following influenza A (H1N1) 2009 monovalent vaccines reported to the Vaccine Adverse Event Reporting
System, United States, October 1, 2009—January 31, 2010, Vaccine (Oct. 21, 2010),
https://www.sciencedirect.com/science/article/pii/S0264410X10013319.

>4 Shimabukuro et al., Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS), Vaccine (Nov.
4, 2015), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632204/ (emphasis added).

°> FDA, COVID-19 Vaccine Safety Surveillance, https://www.fda.gov/vaccines-blood-biologics/safety-availability-
biologics/covid-19-vaccine-safety-surveillance.

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(ICMRA) and the World Health Organization (WHO). These efforts are in addition to the
pharmacovigilance efforts being undertaken by the individual manufacturers for authorized
vaccines. A coordinated and overlapping approach using state-of the art technologies has been
implemented. As part of our efforts to be transparent about our COVID-19 vaccine safety

monitoring activities, FDA is posting summaries of the key safety monitoring findings on the
FDA website. °°

i. Vaccine Safety Surveillance

Passive Surveillance

VAERS is a national passive surveillance vaccine safety database that receives unconfirmed
reports of possible adverse events following the use of a vaccine licensed or authorized in the
United States. Passive surveillance is defined as unsolicited reports of adverse events that are
sent to a central database or health authority. In the United States, these are received and entered
into VAERS, which is co-managed by FDA and CDC. In the current pandemic, these reports are
being used to monitor the occurrence of both known and unknown adverse events, as providers
of COVID-19 vaccines are required to report serious adverse events to VAERS.

As part of FDA and CDC's multi-system approach to post-licensure and post-authorization
vaccine safety monitoring, VAERS is designed to rapidly detect unusual or unexpected patterns
of adverse events, also known as “safety signals.” VAERS reports generally cannot be used to
determine if a vaccine caused or contributed to an adverse event or illness. If the VAERS data
suggest a possible link between an adverse event and vaccination, the relationship may be further
studied in a controlled fashion.>’

Anyone can make a report to VAERS, including vaccine manufacturers, private practitioners,
state and local public health clinics, vaccine recipients, and their parents or caregivers.
Surveillance programs like VAERS perform a critical function by generating signals of potential
problems that may warrant further investigation.

VAERS is not designed to assess causality. It is often difficult to determine with certainty if a
vaccine caused an adverse event reported to VAERS. Many events that occur after vaccination
can happen by chance alone. Some adverse events are so rare that their association with a
vaccine is difficult to evaluate. In addition, we often receive reports where there is no clear
clinical diagnosis. FDA draws upon multiple sources of data and medical and scientific
expertise to assess the potential strength of association between a vaccine, including COVID-19
vaccines, and a possible adverse event.

If VAERS monitoring suggests that a vaccine might be causing a health problem, additional
scientifically rigorous studies or investigations can be performed by FDA and CDC. Monitoring
and analysis of VAERS reports typically includes daily in-depth medical review of all serious
reports, statistical data mining techniques, and epidemiological analysis. We look for patterns
and similarities in the onset timing and clinical description. We review published literature to

°6 FDA, COVID-19 Vaccine Safety Surveillance, https://www.fda.gov/vaccines-blood-biologics/safety-availability-
biologics/covid-19-vaccine-safety-surveillance
>7 FDA, VAERS Overview, https://www.fda.gov/vaccines-blood-biologics/vaccine-adverse-events/vaers-overview.

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understand possible biologic hypotheses that could plausibly link the reported adverse event to
the vaccine. We review the pre-licensure or pre-authorization data and any other post-marketing
studies that have been conducted. We also consider “background rate,” meaning the rate at
which a type of adverse event occurs in the unvaccinated general population. When necessary,
we discuss the potential adverse event with our federal and international safety surveillance
partners. We also carefully evaluate unusual or unexpected reports, as well as reports of
“positive re-challenges” (adverse events that occur in the same patient after each dose received).
When there is sufficient evidence for a potential safety concern, we may proceed to conduct
large studies, and we may coordinate with our federal, academic, and private partners to further
assess the potential risk after vaccination. In addition, when potential safety issues arise, they are
often presented to various U.S. government advisory committees, including the Vaccines and
Related Biological Products Advisory Committee, the Advisory Committee on Immunization
Practices (ACIP), and the Advisory Committee on Childhood Vaccines, and are often discussed
with experts from other countries and from the World Health Organization. Federal agencies
that assist in population-based vaccines safety studies include the CDC, Centers for Medicaid
and Medicare (CMS), the Department of Defense (DoD), and the Indian Health Services (IHS).
In addition, we generally communicate and work with international regulatory authorities and
international partners to conduct studies in vaccine safety.

Active Surveillance

Active surveillance involves proactively obtaining and rapidly analyzing information related to
millions of individuals and recorded in large healthcare data systems to verify safety signals
identified through passive surveillance or to detect additional safety signals that may not have
been reported as adverse events to passive surveillance systems. FDA is conducting active
surveillance using the Sentinel BEST (Biologics Effectiveness and Safety) System and the CMS
system, and is also collaborating with other federal and non-federal partners.

BEST

To elaborate further, the BEST system,°* which is part of the Sentinel initiative,-’ comprises
large-scale claims data, electronic health records (EHR), and linked claims-EHR databases with
a data lag of approximately three months. The system makes use of multiple data sources and
enables rapid queries to detect or evaluate adverse events as well as studies to answer specific
safety questions for vaccines. The linked clatms-EHR database makes it possible to study the
safety of vaccines in sub-populations with pre-existing conditions or in pregnant women. The
major partners for BEST currently are Acumen, IBM Federal HealthCare, IQVIA, and Columbia
University and many affiliated partners such as MedStar Health, BlueCross BlueShield of

8 CBER Biologics Effectiveness and Safety (BEST) System, https://www.fda.gov/vaccines-blood-biologics/safety-
availability-biologics/cber-biologics-effectiveness-and-safety-best-system.
°° FDA’s Sentinel Initiative, https://www.fda.gov/safety/fdas-sentinel-initiative.

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America, the Observational Health Data Sciences and Informatics (OHDSI), OneFlorida,
University of California and several others.

Using BEST, CBER plans to monitor about 15 adverse events®! that have been seen with the
deployment of previous vaccines but have yet to be associated with a safety concern for an
authorized COVID-19 vaccine at this time. CBER further plans to use the BEST system to
conduct more in-depth analyses should a safety concern be identified from sources such as
VAERS.

CMS

FDA has worked over the past several years with CMS to develop capabilities for routine and
time-sensitive assessments of the safety of vaccines for people 65 years of age and older using
the Medicare Claims database.” Because it was already in place, this system was immediately
put into use for COVID-19 vaccine surveillance to monitor for adverse events.

During the current pandemic, FDA, CMS, and CDC have already used the Medicare data to
publish a study showing that frailty, comorbidities, and race/ethnicity were strong risk factors of
COVID-19 hospitalization and death among the U.S. elderly.™

VSD

In addition, the Vaccine Safety Datalink (VSD) is a collaborative project between CDC’s
Immunization Safety Office and nine health care organizations. As noted on the CDC’s

°° To confirm the utility of the BEST system for situations such as COVID-19 vaccine surveillance, a test case was
conducted. This study aimed to replicate a previous study by the CDC’s Vaccine Safety Datalink (VSD) (Klein et al.
Pediatrics 2010) that examined the databases and analytic capabilities of the new system. The objective of this study
was to test the new system’s ability to reproduce the increased risk of febrile seizures in children receiving the first
dose of measles-mumps-rubella-varicella (MMRV) vaccine, compared to that of MMR and varicella vaccines
separately but on the same day. The results of the study met the objectives and demonstrated the ability of the BEST
Initiative data network to run a complex study protocol at multiple sites using a distributed data network and the
Observational Medical Outcomes Partnership Common Data Model (organizing disparate data sources into the same
database design using a common format).

6! Background Rates of Adverse Events of Special Interest for COVID-19 Vaccine Safety Monitoring, Draft
Protocol (December 31, 2020), https://www.bestinitiative.org/wp-content/uploads/2021/01/C19-Vaccine-Safety-
AESI-Background-Rate-Protocol-2020.pdf.

62 CMS, Standard Analytical Files (Medicare Claims) — LDS, https://www.cms.gov/Research-Statistics-Data-and-
Systems/Files-for-Order/LimitedDataSets/StandardAnalyticalFiles.

63 As one example of the capabilities of this system, FDA, CMS, and CDC evaluated the risk of Guillain-Barré
syndrome (GBS) following influenza vaccination after CDC’s Vaccine Safety Datalink, identified safety signals
suggesting an increased risk of GBS following high-dose influenza vaccinations and Shingrix vaccinations during
the 2018-2019 influenza season. CBER, CDC, and CMS formed working groups in February 2019 to refine these
safety signals in the CMS data.

4 Hector S Izurieta, David J Graham, Yixin Jiao, Mao Hu, Yun Lu, Yue Wu, Yoganand Chillarige, Michael
Wernecke, Mikhail Menis, Douglas Pratt, Jeffrey Kelman, Richard Forshee, Natural History of Coronavirus Disease
2019: Risk Factors for Hospitalizations and Deaths Among >26 Million US Medicare Beneficiaries, The Journal of
Infectious Diseases, Volume 223, Issue 6, 15 March 2021, Pages 945-956, https://doi.org/10.1093/infdis/jiaa767
https://academic.oup.com/jid/article/223/6/945/6039057.

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webpage, the VSD started in 1990 and continues today in order to monitor safety of vaccines and
conduct studies about rare and serious adverse events following immunization.

The VSD uses electronic health data from each participating site. This includes information on
vaccines: the kind of vaccine given to each patient, date of vaccination, and other vaccinations
given on the same day. The VSD also uses information on medical illnesses that have been
diagnosed at doctors’ offices, urgent care visits, emergency department visits, and hospital stays.
The VSD conducts vaccine safety studies based on questions or concerns raised from the medical
literature and reports to the Vaccine Adverse Event Reporting System (VAERS). When there are
new vaccines that have been recommended for use in the United States or if there are changes in
how a vaccine is recommended, the VSD will monitor the safety of these vaccines.

The VSD has a long history of monitoring and evaluating the safety of vaccines. Since 1990,
investigators from the VSD have published many studies to address vaccine safety concerns.©

In summary, in collaboration and coordination with several different partners, FDA has
assembled passive surveillance systems - including VAERS - and active surveillance systems
that can detect and refine safety findings with the Authorized COVID-19 Vaccines in a relatively
rapid manner. These systems can also potentially be leveraged to assess safety in specific
subpopulations and to assess vaccine effectiveness.

ii. Articles Submitted in Petition
Regarding Vaccine Surveillance

We note at the outset that Petitioner raises concerns regarding the methodology by which CDC
calculated rates of anaphylactic adverse events post-vaccination. Such concerns are best directed
to CDC and are outside the scope of FDA’s Petition response.

Regarding Petitioner’s contention that a low percentage of adverse events have been reported to
VAERS and that therefore “the safety of COVID vaccines is considerably worse than it currently
appears” (Petition at 4), as explained in detail above in this section, VAERS is only one part of a
multi-tiered vaccine safety surveillance system, so the information derived from VAERS reports
does not represent the full extent of vaccine safety information being monitored by FDA and its
federal partners.

Specifically, Petitioner cites to three studies in support of the argument that “[g]iven that only 1
to 13% of adverse reactions have been reported to the FDA and CDC via the VAERS passive
reporting system, according to Lazarus et al., the high number of adverse events and deaths
following COVID vaccines is alarming.” Petition at 5. The articles cited by Petitioner in support
of this contention do not support Petitioner’s position that, due to underreporting of adverse
events, the rate of reported adverse events associated with COVID-19 vaccination is low in
comparison to the actual rate of adverse events. As discussed above in this section, there are
several factors unique to the surveillance of the Authorized COVID-19 Vaccines that have

65 See, e.g., CDC, White Paper on the Safety of the Childhood Immunization Schedule, Vaccine Safety Datalink,
available at https://www.cdc.gov/vaccinesafety/pdf/WhitePaperSafety_WEB.pdf.

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contributed to the number of VAERS reports submitted for these vaccines. Petitioner’s argument
that adverse events associated with the Authorized COVID-19 Vaccines are underreported
because of the figures presented in the articles cited fail to account for any of those factors that
are unique to the Authorized COVID-19 Vaccines.

Petitioner cites to a publication from the Agency for Healthcare Research and Quality (Lazarus
et al.) in support of the argument that deaths and adverse events associated with the Authorized
COVID-19 Vaccines are underreported because “only 1 to 13% of adverse reactions have been
reported to the FDA and CDC via the VAERS passive reporting system” (Petition at 5), and
therefore the actual rate of COVID-19 Vaccine adverse events is significantly higher than
reported. As an initial matter, we note that the language cited from the Lazarus article is
referring to adverse event reporting for drugs and vaccines, not just vaccine adverse events
reported to VAERS.°’ Furthermore, as explained in detail above, several factors have
contributed to the number of VAERS reports submitted for the Authorized COVID-19 Vaccines.
The issues raised in this article regarding underreporting of drug adverse event reporting are not
directly relevant to the claims Petitioner makes regarding adverse event reporting for the
Authorized COVID-19 Vaccines. The article was published in 2010 and does not consider the
numerous factors outlined above regarding reporting of adverse events following COVID-19
vaccination.

Petitioner cites to a journal article in the publication Vaccine® regarding VAERS safety
monitoring in support of their argument that adverse event reports for the Authorized COVID-19
Vaccines are underreported. This article generally discusses the limitations of VAERS and
passive surveillance, which are well-understood by the FDA and which are discussed in this
letter. Additionally, this article notes “[p]erhaps the two most common misconceptions about
VAERS are that temporally associated reports represent true adverse reactions caused by
vaccination, and that VAERS reports equate to rates of adverse events or indicate risk of adverse
events associated with vaccination.”® This statement from the article demonstrates the flaws
underlying Petitioner’s claims that the Authorized COVID-19 Vaccines are unsafe due to the
number of serious adverse events reported to VAERS following administration of these vaccines.
Additionally, the article notes “[t]he relatively rapid increase in numbers of reports to VAERS
following the introduction and initial uptake of a new vaccine, an expected occurrence, has been
misinterpreted as actual increases in incidence of adverse events and vaccine related risk.””°
Thus, the article cited by Petitioner directly contradicts Petitioner’s claims regarding the safety of
the Authorized COVID-19 Vaccines based on the number of VAERS adverse event reports
associated with these vaccines.

6° Lazarus et al., Electronic Support for Public Health- Vaccine Adverse Event Reporting System, Agency for
Healthcare Research and Quality, HHS (Sept. 30, 2010), https://digital.ahrg.gov/ahrgq-funded-projects/electronic-
support-public-health-vaccine-adverse-event-reporting-system.

67 Td. at 6.

68 Shimabukuro et al., Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS), Vaccine (Nov.
4, 2015), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632204/.

69 Td. at 9.

Td.

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Finally, Petitioner also cites to a journal article in the American Journal of Public Health.”! This
article does not raise issues that have not already been addressed in this letter’s discussion of
safety surveillance. For instance, the article notes that passive surveillance has several
limitations, specifically, passive surveillance may involve underreporting of adverse events, and
passive surveillance data is not adequate to determine causation. Additionally, this article notes
that passive surveillance can provide valuable information, “[n]evertheless, if reporting is
reasonably consistent, it may be possible to detect changes in trends of known common adverse
events.”

Therefore, the articles submitted by Petitioner do not present data or information regarding the
Authorized COVID-19 Vaccines that change the Agency’s analysis regarding the benefits and
risks of the Authorized COVID-19 Vaccines.

Petitioner further asserts that extensive safety information regarding vaccines is inaccessible to
the public (“the VAERS database is the only safety database to which the public has access. The
government withholds extensive safety information from the public despite having at least ten
additional data sources and expert consultants to analyze these data....” Petition at 2.). This
contention represents a misunderstanding by Petitioner of the sources of data analyzed by FDA
and its federal partners, and of the types of information available to the public.

As noted above, Petitioner's questions regarding databases operated by other federal partners,
such as DOD, CMS, CDC, VA, should be directed to those federal entities. Regarding FDA’s
BEST system, Petitioner erroneously claims that the public does not have access to the
information on this system. As noted above, the BEST system,” which is part of the Sentinel
initiative,’* comprises large-scale claims data, electronic health records (EHR), and linked
claims-EHR databases with a data lag of approximately three months. The system makes use of
multiple data sources and enables rapid queries to detect or evaluate adverse events as well as
studies to answer specific safety questions for vaccines. The system is not intended to be a
source of raw EHR data. Instead, as explained on FDA’s webpage describing the BEST system,
the purpose of the BEST system is to: (1) build data, analytics, infrastructure for an active, large-
scale, efficient surveillance system for biologic products; and (2) develop innovative methods to
utilize electronic health records (EHR) effectively and establish automated adverse events
reporting, utilizing natural language processing and artificial intelligence. ’° BEST does not have
access to the raw, identifiable data. BEST data partners analyze the raw data per publicly posted
protocols and send the results in aggregated form to BEST for review. The information is
summarized in either final reports, manuscripts or public presentations. BEST publicly posts
study protocols of surveillance activities on the BEST site with open public comments regarding
the protocols, final reports and manuscripts as well as communication on CBER safety site and
public meetings, e.g., VRBPAC, where appropriate. These protocols delineate the scientific
approach to analyzing the raw data, where in the raw form is of limited utility to the public, to

” §. Rosenthal and R. Chen, The reporting sensitivities of two passive surveillance systems for vaccine adverse
events, American Journal of Public Health (Dec. 1995), https://www.ncbi.nlm.nih.gov/pme/articles/PMC1615747/.
? Td.

® CBER Biologics Effectiveness and Safety (BEST) System, https://www.fda.gov/vaccines-blood-biologics/safety-
availability-biologics/cber-biologics-effectiveness-and-safety-best-system.

74 FDA’s Sentinel Initiative, https://www.fda.gov/safety/fdas-sentinel-initiative.

™® CBER Biologics Effectiveness and Safety (BEST) System, https://www.fda.gov/vaccines-blood-biologics/safety-
availability-biologics/cber-biologics-effectiveness-and-safety-best-system.

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generate information on vaccine safety. The final reports and manuscripts summarize the
information and conclusions inferred from well-conducted surveillance studies.

iii. FDA Has Responded to Safety
Signals Related to the Authorized
COVID-19 Vaccines by Extensively
Reviewing Data, Updating the
Authorized Labeling, and
Communicating to the Public

Petitioner further asserts that “FDA and CDC have not responded to these data by issuing any
warnings or restricting the use of these vaccines.” Petition at 2. This assertion is inaccurate. As
explained in detail above, FDA and its federal partners, including CDC, have closely monitored
post-market safety data regarding the Authorized COVID-19 Vaccines. FDA has worked to
identify and investigate serious adverse events occurring in people after receiving the Authorized
COVID-19 Vaccines, and to communicate these risks to the public and revise the authorized
labeling to reflect these risks in a timely fashion.”° The surveillance systems that are in place to
monitor the safety of COVID-19 vaccines authorized for emergency use are working, as
demonstrated by FDA’s and CDC’s work to identify and investigate these serious adverse events
in a timely manner.

Adverse events reported to VAERS following administration of one of the authorized COVID-19
vaccines are reviewed to assess possible safety concerns. Such review of VAERS data regarding
the authorized COVID-19 vaccines has been conducted since these vaccines were authorized.
Such review has prompted the Agency to take action with respect to the currently authorized
COVID-19 vaccines:

e On April 13, 2021, FDA and CDC recommended a pause in the use of the Janssen
COVID-19 vaccine following six VAERS reports in the U.S. of thrombosis with
thrombocytopenia. ’’ The FDA and CDC thoroughly reviewed VAERS and other post-
authorization information and data related to the Janssen COVID-19 vaccine during the
recommended pause. This review included two meetings of ACIP. Following a
thorough safety review, FDA determined that the available data show that the Janssen
COVID-19 vaccine’s known and potential benefits outweigh its known and potential

7 Janssen COVID-19 Vaccine Fact Sheet for Healthcare Providers Administering Vaccine (Vaccination Providers),
Sections 5.2 and 5.3 Warnings and Precautions Regarding Thrombosis with Thrombocytopenia and GBS,
https://www.fda.gov/media/146304/download; Pfizer-BioNTech COVID-19 Vaccine Fact Sheet for Healthcare
Providers Administering Vaccine (Vaccination Providers), Section 5.2, Warning and Precautions Regarding
Myocarditis and Pericarditis, https://www.fda.gov/media/144413/download; Moderna COVID-19 Vaccine Fact
Sheet for Healthcare Providers Administering Vaccine (Vaccination Providers), Section 5.2, Warning and
Precautions Regarding Myocarditis and Pericarditis, https://www.fda.gov/media/144637/download.

7 We note that Petitioner mentions that Denmark, among other nations, has “banned” the Janssen COVID-19
vaccine. To the extent Petitioner relies on this ban as support for Petitioner’s request that FDA revoke the EUA for
this vaccine, we note that Denmark and other nations’ actions with respect to the use of this vaccine are outside
purview of FDA’s work, so we cannot comment on decisions they make under their public health regulatory
framework.

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risks in individuals 18 years of age and older. As a result of this review, the Fact Sheet
for Healthcare Providers Administering Vaccine (Vaccination Providers) was updated to
include a Warning pertaining to the risk of thrombosis with thrombocytopenia. The Fact
Sheet for Recipients and Caregivers was also updated to include information about these
serious adverse events. The FDA and CDC conducted extensive outreach to providers
and clinicians to ensure they were made aware of the potential for these adverse events
and could properly recognize and manage thrombosis with thrombocytopenia in
individuals who receive the Janssen COVID-19 Vaccine.

e On June 25, 2021, following review of VAERS reports, FDA required revisions to the
authorized labeling for the Pfizer-BioNTech COVID-19 vaccine and the Moderna
COVID-19 vaccine to add a warning regarding the suggested increased risks of
myocarditis and pericarditis. This update to the authorized labeling for these vaccines
followed an extensive review of information and the discussion by CDC’s ACIP meeting
on June 23, 2021. As of July 26, 2021, the FDA and the Centers for Disease Control and
Prevention (CDC) have received 1,194 reports of myocarditis or pericarditis occurring
among people ages 30 and younger who received either Moderna or Pfizer-BioNTech
COVID-19 vaccines, particularly following the second dose.’* Through follow-up,
including medical record reviews, the FDA and CDC had confirmed 699 cases of
myocarditis or pericarditis.”

e On July 13, 2021, FDA required revisions to the vaccine recipient and vaccination
provider fact sheets for the Janssen COVID-19 Vaccine to include information pertaining
to a suggested increased risk of Guillain-Barré Syndrome (GBS) during the 42 days
following vaccination. Based on an analysis of Vaccine Adverse Event Reporting
(VAERS) data, at that time, there had been 100 reports of presumptive GBS following
vaccination with the Janssen vaccine after approximately 12.5 million doses
administered. Of these reports, 95 of them were serious and required hospitalization.
There was one reported death. As noted in the Janssen Fact Sheet for Healthcare
Providers Administering Vaccine, because these reactions are reported voluntarily, it is
not always possible to reliably estimate their frequency or establish a causal relationship
to vaccine exposure. Each year in the United States, an estimated 3,000 to 6,000 people
develop GBS. Most people fully recover from the disorder. FDA publicly presented this
issue, and information regarding these 100 reports of presumptive GBS, to the ACIP on
July 22, 2021.°°

During each of these post-authorization reviews and labeling changes, the FDA has evaluated the
available post-authorization information for the authorized COVID-19 Vaccines and continues to
find the known and potential benefits clearly outweigh the known and potential risks.

78 CDC, COVID-19 Reported Adverse Events, https://www.cdc.gov/coronavirus/2019-
ncov/vaccines/safety/adverse-events.html.

1d.

8° FDA, CDC ACIP Meeting Presentation, Guillain-Barré Syndrome (GBS) after Janssen COVID-19 Vaccine:
Vaccine Adverse Event Reporting System (VAERS), July 22, 2021,
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-202 1 -07/02-COVID-Alimchandani-508.pdf.

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iv. Petitioner’s Claims Regarding
Anaphylaxis

Petitioner cites to a study of acute allergic reactions to mRNA COVID-19 vaccines in support of
their argument that adverse event rates for COVID-19 vaccines have been miscalculated by
CDC.*! As stated above, questions relating to CDC are best directed to that Agency. We note,
however, that this journal article states, immediately after the sentence quoted by Petitioner,
“Th]owever, the overall risk of anaphylaxis to an MRNA COVID-19 vaccine remains extremely
low and largely comparable to other common health care exposures. Although cases were
clinically compatible with anaphylaxis, the mechanism of these reactions is unknown.” The
paper further states, in describing the limitations of the study, that “[a] northeastern US cohort
may not be generalizable.” Thus, Petitioner is inappropriately generalizing the results of this
study in an attempt to compare the results to the CDC’s reported data and conclude that the
safety of COVID vaccines is “considerably worse than it currently appears.” Petition at 4.

Additionally, we note that the authorized labeling for all the Authorized COVID-19 vaccines
already contain warnings regarding the risk of anaphylaxis as a potential adverse event. Thus,
the risk of anaphylaxis is a potential safety issue FDA 1s already aware of, and Petitioner’s
argument, and the article submitted in support of this argument, does not change FDA’s
conclusions regarding the safety of the Authorized COVID-19 vaccines.

v. Animal Toxicology and
Pharmacokinetic Studies of COVID-
19 Vaccines

Petitioner raises concerns regarding FDA’s vaccine safety assessment. Specifically, Petitioner
states that other “problems with vaccine safety assessment may exist because of inadequate
animal toxicology and pharmacokinetic studies of COVID vaccines.” Petition at 5; emphasis
added. As an initial matter, we note that Petitioner’s concerns regarding the vaccine safety
assessment for COVID-19 vaccines involves speculation regarding whether problems actually
exist (“problems with vaccine safety assessment may exist .. .”), and Petitioner fails to point to
any specific problems that result or may result from the allegedly inadequate studies.
Regarding Petitioner’s claims, in general, when evaluating the safety data regarding a vaccine,
FDA considers data from animal studies (if such pre-clinical studies were performed) as one part
of the full body of evidence regarding the vaccine. In addition to data from animal studies, if
available, FDA evaluates data from in vitro studies and conducts a safety assessment of data
from clinical studies.

Thus, although Petitioner raises several concerns and cites to several articles regarding risks of
COVID-19 vaccination, FDA is not aware of any information indicating that the known and
potential benefits of the Authorized COVID-19 Vaccines are outweighed by their known and
potential risks, nor has Petitioner provided any such information in the Petition. Therefore, the

8! Blumenthal KG, Robinson LB, Camargo CA, et al., Acute Allergic Reactions to mRNA COVID-19 Vaccines,
JAMA. 2021;325(15):1562—1565. doi:10.1001/jama.2021.3976,
https://jamanetwork.com/journals/jama/fullarticle/2777417.

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criterion under section 564(c)(2)(B) continues to be met with respect to the Authorized COVID-
19 Vaccines.

4. No Alternatives

As noted above, Petitioner requests that “FDA should revoke all EUAs and refrain from
approving any future EUA . . . for any COVID vaccine for all demographic groups because the
current risks of serious adverse events or deaths outweigh the benefits, and because existing,
approved drugs provide highly effective prophylaxis and treatment against COVID, mooting the
EUAs.” Petition at 1. Section 564(c)(3) of the FD&C Act provides one of the required statutory
factors that must be met in order for a product to be granted an EUA. This statutory provision
requires that “there is no adequate, approved, and available alternative to the product for
diagnosing, preventing, or treating [the serious or life-threatening disease or condition].”*” To
the extent Petitioner’s contention can be interpreted as an argument that there are adequate,
approved, available drugs indicated for the prevention of COVID-19 (and that therefore the
requirement in section 564(c)(3) of the FD&C Act that there is no “adequate, approved, and
available alternative to the Authorized COVID-19 Vaccines for preventing COVID-19 is not
met), this argument is erroneous.

As explained in the Decision Review Memoranda for the Authorized COVID-19 Vaccines, at the
time each COVID-19 vaccine EUA was issued, there were no FDA-approved drugs or biological
products indicated to prevent COVID-19 in any population because no vaccine or other medical
product was the subject of an approved marketing application for prevention of COVID-19.®
This is still true today, with the exception of the BLA for BioNTech’s COVID-19 vaccine
(COVID-19 Vaccine, mRNA; Comirnaty), which is now approved for the prevention of
coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2) in individuals 16 years of age and older. The EUA for Pfizer-BioNTech
COVID-19 Vaccine remains in effect. This EUA will continue to cover individuals 12 through
15 years of age, to cover the administration of a third dose to certain immunocompromised
individuals 12 years of age and older, and to cover individuals 16 years of age and older until
sufficient approved vaccine can be manufactured and distributed. Similarly, the EUA for the
Moderna COVID-19 Vaccine and the Janssen COVID-19 Vaccine remain in effect for
individuals 18 years of age and older. Although FDA has approved one new drug application
(NDA) for remdesivir for use in adult and pediatric patients 12 years of age and older and
weighing at least 40 kilograms for the treatment of COVID-19 requiring hospitalization, this
drug is not for prevention of COVID-19. Several other therapies are currently available under
EUA, but not FDA approved, for treatment of COVID-19, and one is available under EVA, but
not FDA approved, for post-exposure prophylaxis in a limited population. These products that
are available under EUA are not considered “approved” products for purposes of section

82 The term “approved,” for purposes of section 564(c) of the FD&C Act, means a product is approved, licensed, or
cleared by FDA under section 505, 510(k), or 515 of the FD&C Act or section 351 of the PHS Act, as applicable,
and this term is indication-specific. See, section 564(a)(2) of the FD&C Act. See also, EUA guidance at 3.

83 FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Decision Memorandum (Dec. 11, 2020), at 8-9,
https://www.fda.gov/media/144416/download; FDA, Moderna COVID-19 Vaccine EUA Decision Memorandum
(Dec. 18, 2020), at 9, https://www.fda.gov/media/144673/download; FDA, Janssen COVID-19 Vaccine EUA
Decision Memorandum (Feb. 27, 2021), at 9, https://www.fda.gov/media/146338/download.

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564(c)(3) because they are not the subject of an approved marketing application (i.e., they are not
approved under an NDA or BLA).

Thus, Petitioner’s assertion that the EUAs for the Authorized COVID-19 Vaccines are “mooted”
by the existence of drugs approved to prevent COVID-19 is incorrect.

5. No Other Circumstances Make A Revision or
Revocation Appropriate to Protect the Public
Health or Safety

As noted above, section 564(g)(2)(C) of the FD&C Act provides that FDA may revise or revoke
an EUA if circumstances justifying its issuance (under section 564(b)(1)) no longer exist, the
criteria for its issuance are no longer met, or other circumstances make a revision or revocation
appropriate to protect the public health or safety. The EUA guidance explains that such other
circumstances may include:

significant adverse inspectional findings (e.g., when an inspection
of the manufacturing site and processes has raised significant
questions regarding the purity, potency, or safety of the EUA
product that materially affect the risk/benefit assessment upon
which the EUA was based); reports of adverse events (number or
severity) linked to, or suspected of being caused by, the EUA
product; product failure; product ineffectiveness (such as newly
emerging data that may contribute to revision of the FDA's initial
conclusion that the product "may be effective" against a particular
CBRN agent); a request from the sponsor to revoke the EUA; a
material change in the risk/benefit assessment based on evolving
understanding of the disease or condition and/or availability of
authorized MCMs; or as provided in section 564(b)(2), a change in
the approval status of the product may make an EUA
unnecessary. *4

As of the date of this writing, FDA has not identified any such circumstances that would make
revocation of any of the Authorized COVID-19 Vaccines appropriate to protect the public health
or safety. As stated previously in this response, FDA determined the EUA standard is met for
the three authorized COVID-19 vaccines because data submitted by the sponsors demonstrated
in a clear and compelling manner that the known and potential benefits of these products, when
used to prevent COVID-19, outweigh the known and potential risks of these products, and that
there is no adequate, approved, and available alternative to the product for diagnosing,
preventing, or treating COVID-19.

As described in detail in section IJ.b.1.1.b above, FDA has identified circumstances that have
made revision of the EUAs for the Authorized COVID-19 Vaccines appropriate, and,

84 RUA Guidance at 29.

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accordingly, has required changes to the authorized labeling for the Authorized COVID-19
Vaccines.*°

Additionally, as explained above, FDA finds no basis in the information submitted in the
Petition, or in any postmarket data regarding the Authorized COVID-19 Vaccines, to support a
revocation of any of these EUAs, nor has Petitioner provided any such information in the
Petition. FDA is not aware of any information indicating that the known and potential benefits
of the Authorized COVID-19 Vaccines are outweighed by their known and potential risks, nor
has Petitioner provided any such information in the Petition. Furthermore, there are no other
circumstances that make a revision or revocation appropriate to protect the public health or
safety, nor has Petitioner provided any information about such circumstances.

FDA therefore sees no justifiable basis upon which to take any action based on Petitioner’s
request with respect to the any of the Authorized COVID-19 Vaccines. Accordingly, as noted
above, we deny Petitioner’s request for FDA to “revoke all EUAs . . . for any COVID vaccine
for all demographic groups because existing, approved drugs provide highly effective
prophylaxis and treatment against COVID, mooting the EUAs.”

2. Petitioner’s Request to Refrain from Granting any Future
EUA for a COVID-19 Vaccine for any Population Because
Approved Drugs Exist for COVID-19 Prevention

Petitioner also requests in the Petition that FDA “refrain from approving any future EUA . . . for
any COVID vaccine for all demographic groups because the current risks of serious adverse
events or deaths outweigh the benefits, and because existing, approved drugs provide highly
effective prophylaxis and treatment against COVID, mooting the EUAs.” *° Petition at 1.

Petitioner has provided no evidence that would provide a basis for FDA to conclude that no
future COVID-19 vaccine candidate could meet the EUA standard. Indeed, FDA is not aware of
any information indicating that the known and potential benefits of the Authorized COVID-19
Vaccines are outweighed by their known and potential risks, nor has Petitioner provided any
such information in the Petition.

Additionally, as explained above in section III.b.i1.1.b. of this letter, to the extent Petitioner’s
contention can be interpreted as an argument that there are FDA-approved drugs indicated for the
prevention of COVID-19 (and that therefore the requirement in section 564(c)(3) of the FD&C
Act that there is no “adequate, approved, and available alternative” could not be met), this

85 FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Amendment Decision Memorandum for Authorization in
Individuals 12 -15 Years of Age (May 10, 2021), Section 4.6, EUA Prescribing Information and Fact Sheets,
https://www.fda.gov/media/148542/download; FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Amendment
Decision Memorandum for Authorization of an Additional Dose in Certain Immunocompromised Individuals
(August 12, 2021), https://www.fda.gov/media/151613/download; FDA, Moderna COVID-19 Vaccine EUA
Amendment Decision Memorandum for Authorization of an Additional Dose in Certain Immunocompromised
Individuals (August 12, 2021), https://www.fda.gov/media/151611/download.

86 FDA authorization of an EUA request is not FDA approval. FDA does not “approve” an EUA request. Rather,
FDA authorizes the emergency use of a product following review of data and information submitted in an EUA
request.

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argument fails. Should FDA receive future requests for EUAs for COVID-19 vaccine
candidates, FDA would consider such requests on a case-by-case basis.*’ Accordingly,
Petitioner’s request is denied.

3. Petitioner’s Request to Refrain from Approving any Future
NDA for any COVID-19 Vaccine for any Population

Petitioner’s request regarding “any future... NDA ... for any COVID Vaccine for all
demographic groups” is moot because vaccines are biological products subject to licensure under
the PHS Act and are not subject to approval under section 505 of the FD&C Act.

4. Petitioner’s Request to Refrain from Licensing any Future
BLA for any COVID-19 Vaccine for any Population

Petitioner requests that FDA “refrain from approving any future... BLA for any COVID
vaccine for all demographic groups because the current risks of serious adverse events or deaths
outweigh the benefits, and because existing, approved drugs provide highly effective prophylaxis
and treatment against COVID, mooting the EUAs.” Petition at 1. To the extent this request can
be interpreted as asserting that the risks of serious adverse events or deaths associated with any
COVID-19 vaccine would necessarily outweigh the benefits of any COVID-19 vaccine and
therefore FDA should refrain from approving any BLA for any COVID-19 vaccine, this section
explains why this argument is unavailing and why we are denying Petitioner’s request.

To the extent this request can be interpreted as also asserting, in addition to the assertion above,
that, because approved drugs provide effective prophylaxis and treatment of COVID-19, the
approval of a BLA for a COVID-19 vaccine would be “moot,” this section explains why such a
position is flawed and why FDA is not granting this request.

a. Petitioner’s Request that FDA Refrain from Approving
any BLA for any COVID-19 Vaccine because the
Current Risks Outweigh the Benefits

Petitioner requests that FDA “refrain from approving any future BLA . . . for any COVID
vaccine for all demographic groups” because the risks of serious adverse events or deaths
associated with any COVID-19 vaccine outweigh the benefits of any COVID-19 vaccine.
Petitioner has provided no evidence that would provide a basis for FDA to conclude that no
COVID-19 vaccine could meet the BLA approval standard, however. Indeed, FDA has now
approved a BLA for BioNTech’s COVID-19 vaccine (COVID-19 Vaccine, mRNA; Comirnaty)
because, among other things, the data and information in the application demonstrated the safety
and effectiveness of the vaccine.** Thus, Petitioner’s request that FDA refrain from approving
any BLAs for COVID-19 vaccines is denied.

87 FDA has issued guidance describing factors the Agency intends to use in determining how to prioritize EUA
requests for COVID-19 vaccine candidates. See October 2020 Guidance at 5 (citing EUA Guidance at 18-20).
88 See FDA's Summary Basis for Regulatory Action (SBRA) for the BioNTech BLA. This memorandum will be
posted on www.fda.gov.

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In Appendix I to this letter, we have provided additional background information about FDA’s
regulatory framework for the review of vaccine BLAs.

b. Petitioner’s Request that FDA Refrain from Approving
any BLA for any COVID-19 Vaccine because the
Current Risks Outweigh the Benefits and because
Currently-Approved Drugs are Effective in Preventing
COVID-19

To the extent Petitioner is arguing that FDA should also refrain from approving a BLA for any
COVID-19 vaccine because of the existence of FDA-approved drugs that are effective in
preventing COVID-19, this argument is unavailing. As described above in section II.b.i.1, there
are no FDA-approved drugs that are effective in preventing COVID-19 (other than
BioNTech’sCOVID-19 vaccine [COVID-19 Vaccine, mRNA; Comirnaty], which is now
approved for the prevention of COVID-19 caused by SARS-CoV-2 in individuals 16 years of
age and older.).

For the reasons outlined in this section, FDA denies Petitioner’s requests to refrain from
licensing any BLAs for a COVID-19 vaccine.

ii. Petitioner’s Requests Regarding COVID-19 Vaccines in Children

1. Request to Immediately Refrain from Allowing COVID-19
Vaccine Trials to Include Pediatric Subjects

In the Petition, Petitioner requests that FDA “immediately refrain from allowing minors to
participate in COVID vaccine trials ....” Petition at 1. To the extent that the Petition can be
interpreted to request that FDA suspend any COVID-19 vaccine clinical trial that includes
pediatric subjects, this section explains why FDA is not at this time ordering that these clinical
trials be suspended.

As explained above in section III.a., with certain exceptions, clinical investigations in which a
drug is administered to human subjects must be conducted under an IND submitted to FDA by
the sponsor. FDA’s review of an IND includes a review of the study protocol which describes,
among other things, the design of the clinical study, including the identified endpoints and
methods for assessing the safety and effectiveness of the investigational product. The Petition
requests that FDA adopt a universal approach toward all clinical trials of COVID-19 vaccines.
Under FDA’s regulations, however, the Agency examines each Investigational New Drug (IND)
Application individually and considers the IND in the context of the standards in the regulation.

The FD&C Act provides a specific mechanism, called a “clinical hold,” for prohibiting sponsors
of clinical investigations from conducting the investigation (section 505(i)(3) of the FD&C Act;
21 U.S.C. 355(4)(3)). FDA’s implementing regulations in 21 CFR 312.42 identify the
circumstances that may justify a clinical hold. In this section of this letter, we explain why, at
this time, FDA has not granted Petitioner’s request to place all proposed or ongoing studies of
COVID-19 vaccines enrolling pediatric subjects on clinical hold under 21 CFR 312.42(b).

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The grounds for placing a proposed or ongoing study, including an ongoing Phase 3 study, on
clinical hold are provided in 21 CFR 312.42(b). Specifically, 21 CFR 312.42(b)(1)(1) through
(b)(1)(v) provides grounds for imposition of a clinical hold of a Phase 1 study. Additionally, as
stated in 21 CFR 312.42(b)(2), FDA may place a proposed or ongoing Phase 2 or 3 investigation
on clinical hold if it finds that: (1) any of the conditions in 21 CFR 312.42(b)(1)(@) through
(b)(1)(v) apply; or (11) the plan or protocol for the investigation is clearly deficient in design to
meet its stated objectives. As indicated in more detail below, at this time, FDA has not granted
Petitioner’s request to place all proposed or ongoing studies of COVID-19 vaccines enrolling
pediatric subjects on clinical hold under 21 CFR 312.42(b).

e 21 CFR 312.42(b)(1)@): Human subjects are or would be exposed to an unreasonable
and significant risk of illness or injury.

FDA continues to evaluate all available information and, based on this evaluation
thus far, does not believe that human subjects in any COVID-19 vaccine study
that includes pediatric subjects are or would be exposed to an unreasonable and
significant risk of illness or injury. The Agency reviews the protocols for
COVID-19 vaccine clinical trials proposing to enroll pediatric subjects when they
are submitted to the IND, in addition to any subsequent protocol amendments. For
those clinical trials that have proceeded to studying COVID-19 vaccines in
pediatric populations, FDA has determined that, based on all information
currently available to FDA, the studies do not expose subjects to unreasonable
risks.

e 21 CFR 312.42(b)(1)(1): The clinical investigators named in the IND are not
qualified by reason of their scientific training and experience to conduct the
investigation described in the IND.

The Petitioner has not provided evidence and FDA is currently aware of no other
information indicating that clinical investigators named in the IND for any
COVID-19 vaccine clinical trial including pediatric subjects are not qualified by
reason of their scientific training and experience to conduct the investigation
described in the INDs.

e 21 CFR 312.42(b)(1)(a11): The investigator brochure is misleading, erroneous, or
materially incomplete.

The Petitioner has not provided evidence and FDA 1s currently aware of no other
information indicating that the investigator brochures for any ongoing COVID-19
vaccine investigation which includes or proposes to include pediatric subjects are
misleading, erroneous, or materially incomplete.

e 21 CFR 312.42(b)(1)(v): The IND does not contain sufficient information required
under 312.23 to assess the risks to subjects of the proposed studies.

The Petitioner has not provided evidence and FDA is currently aware of no other
information indicating that the IND for any ongoing COVID-19 vaccine in which

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pediatric subjects are enrolled contains insufficient information required under 21
CFR 312.23 to assess the risks to pediatric subjects participating in the studies.

e 21 CFR 312.42(b)(1)(v) [provides, in part, that]: The IND is for the study of an
investigational drug intended to treat a life-threatening disease or condition that
affects both genders, and men or women with reproductive potential who have the
disease or condition being studied are excluded from eligibility because of a risk or
potential risk from use of the investigational drug of reproductive toxicity (i.e.,
affecting reproductive organs) or developmental toxicity (i.e., affecting potential
offspring)....

The Petitioner has not provided evidence and FDA 1s currently aware of no other
information indicating that any COVID-19 vaccine studies enrolling pediatric
subjects are excluding from eligibility men or women — including male and
female adolescents and teenagers - with reproductive potential.

e 21 CFR 312.42(b)(2)(11): The plan or protocol for the Phase 2 or Phase 3 investigation
is clearly deficient in design to meet its stated objectives.
The Agency reviewed the protocols for the COVID-19 vaccine investigations
involving pediatric subjects at the time they were submitted to the INDs, as well
as any subsequent amendments as they were submitted, and has determined that
the study designs meets their stated objectives.

At this time, the Agency is aware of no information to indicate that the protocols
for any ongoing clinical investigations of COVID-19 vaccines involving pediatric
subjects are clearly deficient in design to meet their stated objectives.

FDA has reviewed the issues raised in the Petition relating to the request to “immediately refrain
from allowing minors to participate in COVID vaccine trials.” Petition at 1. For the reasons
outlined above, and in light of information currently available to FDA, FDA has determined that
grounds do not exist to grant Petitioner’s request to place all COVID-19 vaccine clinical
investigations involving pediatric subjects on clinical hold pursuant to 21 CFR 312.42.

2. Request that FDA Refrain from Issuing EUA Amendments for
Authorized COVID-19 Vaccines to Include Indications for
Pediatric Populations

The Petition requests, among other things, that “[g]iven the extremely low risk of COVID illness
in children, FDA should . . . immediately refrain from amending EUAs to include children. . . .”
Petition at 1. To the extent that the Petition requests that FDA refrain from issuing EUA
amendments for any of the Authorized COVID-19 Vaccines to include an indication for use in
pediatric populations, this section explains why FDA is not granting this request.

In determining whether to issue an EUA for a product, including an amendment to an EUA in
order to include additional populations within the indication, the FDA evaluates the available
evidence and assesses, among other things, any known or potential risks and any known or
potential benefits. Once a manufacturer submits an EUA request for a COVID-19 vaccine, the
FDA then evaluates the request and determines whether the relevant statutory criteria are met,

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taking into account the totality of the scientific evidence about the vaccine that is available to the
agency.

As noted in Section II.b. above, in the October 2020 Guidance, FDA provided recommendations
that describe key information that would support issuance of an EUA for a vaccine to prevent
COVID-19.* In this guidance, FDA explained that, in the case of such vaccines, any assessment
regarding an EUA will be made on a case-by-case basis considering the target population, the
characteristics of the product, the preclinical and human clinical study data on the product, and
the totality of the available scientific evidence relevant to the product.”” FDA has also stated, in
this guidance, that for a COVID-19 vaccine for which there is adequate manufacturing
information to ensure its quality and consistency, issuance of an EUA would require a
determination by FDA that the vaccine’s benefits outweigh its risks based on data from at least
one well-designed Phase 3 clinical trial that demonstrates the vaccine’s safety and efficacy in a
clear and compelling manner.”!

a. Information Submitted by Petitioner Regarding the Safety
of COVID-19 Vaccines in Pediatric Populations

Petitioner argues that, for children, the risks of COVID-19 vaccines outweigh the benefits
because the risk of severe COVID in children is “extremely low.” Petition at 1. Petitioner cites
to several sources of information in support of this argument (Petition at 12-13), which FDA has
reviewed and considered.

Petitioner cites to CDC data”” regarding death rates of children in the United States due to
COVID-19 and compares the number of children who have died involving COVID-19 to the
number of Americans of all ages who have died of COVID-19. Petitioner’s approach of simply
comparing raw numbers of deaths involving COVID-19 in the U.S. pediatric population against
the raw numbers of deaths involving COVID-19 in the overall U.S. population (all sexes and all
ages), does not provide a sufficient scientific basis upon which to conclude, as Petitioner
contends, that the “relative risk for children due to COVID is very low.” Petition at 12.
Additionally, as discussed in further detail below, based on available data and information, we
have concluded that COVID-19 is a serious or life-threatening disease or condition in the 12-17
age group.

As a preliminary matter, we note that petitioner’s claim that “the death rate following either
vaccination in this age group, assuming these children were trial enrollees, 1s approximately 2 in
2,000 or 0.1%.” (Petition at 13) is erroneous. Our review of the submitted clinical trial data
associated with the Pfizer-BioNTech COVID-19 Vaccine has not identified any deaths among
adolescent or young adult vaccinees.”* Additionally, as described in a NEJM article regarding

8° October 2020 Guidance at 6-7.

°° Td. at 3.

1 Td. at 4.

°*? CDC, National Center for Health Statistics, Weekly Updates by Select Demographic and Geographic
Characteristics, https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm#SexAndAge.

°3 FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Decision Memorandum (Dec. 11, 2020),
https://www.fda.gov/media/144416/download (stating that there were two deaths in vaccine recipients, both >55
years of age). FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Amendment Decision Memorandum for

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the Moderna COVID-19 vaccine, no deaths were reported among vaccine recipients enrolled in
the clinical trial of Moderna COVID-19 Vaccine.” Investigational New Drug (IND) application
sponsors are required to notify FDA in a written safety report of any adverse experience
associated with the use of the drug that is both serious and unexpected.”° Any death that occurs
in a vaccine clinical trial therefore must be reported to FDA and is then thoroughly evaluated by
FDA to determine the cause and whether or not the death is plausibly related to the vaccine.

Additionally, we note that Petitioner raised concerns regarding VAERS reports in arguing that
COVID-19 vaccines should not be authorized for pediatric populations because, Petitioner
argues, “[a]vailable evidence strongly suggests that the vaccine is much more dangerous to
children than the disease.” Petition at 12. VAERS data reviewed to date has not identified risks
related to vaccination that would cause the Agency to change its view that the benefits of
vaccination with the Pfizer-BioNTech COVID-19 vaccine outweigh the risks of vaccination in
individuals 12-17 years of age. VAERS data is evaluated thoroughly, and as described in greater
detail above, FDA acts on safety signals. VAERS reports, however, are not used in isolation to
draw an association between a vaccine and a possible adverse event.

Finally, we note that petitioner cites to an opinion piece published in the British Medical Journal,
which presents the authors’ opinion that the benefits of COVD-19 vaccination are outweighed by
its risks in pediatric populations.”° FDA has reviewed this article and determined it does not
present evidence that the EUA standard could not be met for pediatric populations. Indeed, as
explained in the FDA Decision Memorandum for the Pfizer-BioNTech COVID-19 Vaccine
EUA, based on FDA’s review of all available data regarding the benefits and risks of the use of
the Pfizer-BioNTech COVID-19 vaccine in individuals 12 through 17 years of age, we have
determined that this EUA meets the statutory criteria for individuals in this age range.””

Petitioner has failed to present data demonstrating that, for children, the risks of COVID-19
vaccines outweigh their benefits because the risk of severe COVID in children is “extremely
low.” Petition at 1. As explained in this section, the information submitted by Petitioner does
not support this contention. As explained in further detail below, data reviewed by the Agency
demonstrates that the Pfizer-BioNTech COVID-19 Vaccine, which is authorized for use in
individuals 12 years of age and older, continues to demonstrate that the known and potential
benefits of this vaccine outweigh its known and potential risks in this population. Any other
EUA requests for COVID-19 vaccine candidates for use in pediatric populations will be
reviewed on a case-by-case basis under the applicable statutory standards. Therefore, we deny

Authorization in Individuals 12-15 Years of Age (May 10, 2021), https://www.fda.gov/media/148542/download
(stating that there were no deaths among vaccine recipients 12-15 years of age during the follow-up period).
4K. Ali, et al., Evaluation of mRNA-1273 SARS-CoV-2 Vaccine in Adolescents, NEJM (Aug. 11, 2021), DOT:
10.1056/NEJMoa2109522, https://www.nejm.org/doi/10.1056/NEJMoa2109522.

°5 21 CFR § 312.32(c)(1)(i).

°° W. Pegden, V. Prasad, S. Baral, Covid vaccines for children should not get emergency use authorization, BMJ
(May 7, 2021), https://blogs.bmj.com/bmj/202 1/05/07/covid-vaccines-for-children-should-not-get-emergency-use-
authorization/.

°7 FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Decision Memorandum (Dec. 11, 2020),
https://www.fda.gov/media/144416/download; FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Amendment
Decision Memorandum for Authorization in Individuals 12-15 Years of Age (May 10, 2021),
https://www.fda.gov/media/148542/download.

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Petitioner’s request to refrain from amending any EUA for a COVID-19 vaccine to include a
pediatric indication.

3. Request that FDA Immediately Revoke all EUAs for COVID-
19 Vaccines with Pediatric Indications

Petitioner requests that FDA “immediately revoke all EUAs that permit vaccination of children
under 16 for the Pfizer vaccine and under 18 for other COVID vaccines.” Petition at 1.
Currently, only the Pfizer-BioNTech COVID-19 vaccine is indicated for the prevention of
COVID-19 in pediatric populations. This vaccine is indicated for individuals 12 years of age and
older. As explained in section III.B.i.1.b above, in addressing this request, it is necessary to
consider the EUA revocation standard provided in section 564(g)(2) of the FD&C Act. In this
section, we assess whether any of these statutory conditions under which FDA may revoke an
EUA are met with respect to the pediatric indication for the Pfizer-BioNTech COVID-19
Vaccine EUA and explain why the EUA revocation standard is not met for this vaccine.

a. Standard for Revocation of EUAs is not Met for the
Authorized COVID-19 Vaccines with Pediatric Indications

As explained above in section III.b.1.1.b of this letter, Section 564(g)(2) of the FD&C Act
provides the standard for revocation of an EUA. Under this statutory authority, FDA may revise
or revoke an EUA if:

(A) the circumstances described under [section 564(b)(1) of the FD&C Act] no longer
exist;

(B) the criteria under [section 564(c) of the FD&C Act] for issuance of such authorization
are no longer met; or

As explained above in section II.b., the EUA Guidance notes that once an EUA is issued for a
product, in general, that EUA will remain in effect for the duration of the EUA declaration under
which it was issued, “unless the EUA is revoked because the criteria for issuance . . . are no
longer met or revocation is appropriate to protect public health or safety (section 564(f),(g) [of
the FD&C Act]).”*8

i. Circumstances Continue to Justify the Issuance
of the EUAs for the Authorized COVID-19
Vaccine with Pediatric Indications

As explained in detail above in section HI.b.i.1.b., section 564(b)(2) of the FD&C Act sets forth
the statutory standard for termination of an EUA declaration. This provision provides that an
EUA declaration remains in place until the earlier of: (1) a determination by the HHS Secretary,
in consultation with the Secretary of Defense, that the circumstances that precipitated the
declaration have ceased or (2) a change in the approval status of the product such that the
authorized use(s) of the product are no longer unapproved. Neither of those statutory criteria is

°8 RUA Guidance at 28.

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satisfied with respect to the Authorized COVID-19 Vaccine with a pediatric indication. Thus,
the circumstances described under section 564(b)(1) of the FD&C Act continue to exist. FDA
therefore is not revoking the EUA for the Authorized COVID-19 vaccine with a pediatric
indication under the authority in section 564(g)(2)(A) of the FD&C Act.

1. The Criteria for The Issuance of the
Authorized COVID-19 Vaccine with
Pediatric Indications Continues to Be Met

This section describes in detail why the criteria under section 564(c) of the FD&C Act continue
to be met with respect to the pediatric indication for the Pfizer-BioNTech COVID-19 Vaccine
EUA and why, therefore, FDA may not revoke this EUA under the authority in section
564(g)(2)(B) of the FD&C Act.

a. Serious or life-threatening disease
or condition.

As explained above in section III.b.i.1 of this letter, section 564(c)(1) of the FD&C Act requires
that, for an EUA to be issued for a medical product, “the agent(s) referred to in [the HHS
Secretary’s EUA declaration] can cause a serious or life-threatening disease or condition.” FDA
has concluded that SARS-CoV-2, which is the subject of the EUA declaration, meets this
standard. FDA is not aware of science indicating that there is any change in the ability of the
SARS-CoV-2 virus to cause a serious or life-threatening disease or condition, namely COVID-
19, nor has Petitioner provided any information about such a change.

The SARS-CoV-2 pandemic continues to present an extraordinary challenge to global health
and, as of August 3, 2021, has caused more than 199 million cases of COVID-19 and claimed the
lives of more than 4.2 million people worldwide.” In the United States, more than 34 million
cases and over 611,000 deaths have been reported to the CDC.'°° On January 31, 2020, the U.S.
Secretary of Health and Human Services (HHS) declared a public health emergency related to
COVID-19 and mobilized the Operating Divisions of HHS, and the U.S. President declared a
national emergency in response to COVID-19 on March 13, 2020. Additional background
information on the SARS-CoV-2 virus and COVID-19 pandemic may be found in FDA Decision
Memoranda for the Authorized COVID-19 Vaccines. '°!

Since March 1, 2020, approximately 1.7 million COVID-19 cases in individuals 12 to 17 years
of age have been reported to the Centers for Disease Control and Prevention (CDC). Among
these cases approximately 11,700 resulted in hospitalization, with more than 691 ICU admissions

°° Johns Hopkins University School of Medicine, Coronavirus Resource Center,
https://coronavirus.jhu.edu/map.html.

100 CDC, COVID Data Tracker, https://covid.cde.gov/covid-data-tracker/#trends_dailytrendscases.

101 EDA, Pfizer-BioNTech COVID-19 Vaccine EUA Decision Memorandum (Dec. 11, 2020),
https://www.fda.gov/media/144416/download; FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Amendment
Decision Memorandum for Authorization in Individuals 12-15 Years of Age (May 10, 2021),
https://www.fda.gov/media/148542/download; FDA, Moderna COVID-19 Vaccine EUA Decision Memorandum
(Dec. 18, 2020), https://www.fda.gov/media/144673/download; FDA, Janssen COVID-19 Vaccine EUA Decision
Memorandum (Feb. 27, 2021), https://www.fda.gov/media/146338/download.

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and more than 100 deaths. It is difficult to estimate the incidence of COVID-19 among children
and adolescents because they are frequently asymptomatic and infrequently tested. Children and
adolescents appear less susceptible to SARS-CoV-2 infection and have a milder COVID-19
disease course as compared with adults. However, as with adults, children and adolescents with
underlying conditions such as asthma, chronic lung disease, and cancer are at higher risk than
their heathier counterparts for COVID-19-related hospitalization and death. Of the children who
have developed severe illness from COVID-19, most have had underlying medical conditions.
Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious COVID-19-
associated condition that can present with persistent fever, laboratory markers of inflammation
and heart damage, and, in severe cases, hypotension and shock. As of June 28, 2021, the CDC
received reports of 4196 cases and 37 deaths that met the definition for MIS-C.

Both FDA and CDC have convened advisory committee meetings to discuss the use of COVID-
19 vaccines in pediatric populations. Overall, these advisory committees agreed that there is a
serious risk of severe COVID-19 in the pediatric population. In particular, the June 23, 2021
ACIP meeting discussed the benefits and risks of the use of COVID-19 mRNA vaccines in
adolescents and young adults.'°* This discussion raised the point that adolescents and young
adults have the highest COVID-19 incidence rates, and that these populations are an increasing
proportion of COVID-19 cases reported. COVID-19-associated deaths continue to occur in these
populations; since April 2021, 316 deaths have been reported among persons aged 12-29 years.
Additionally, post-COVID conditions -- such as Multisystem Inflammatory Syndrome in
Children (MIS-C) and Multisystem Inflammatory Syndrome in Adults (MIS-A) -- can occur in
these populations following COVID-19.

Therefore, the criterion under section 564(c)(1) continues to be met with respect to the
Authorized COVID-19 Vaccines with Pediatric Indications.

b. Evidence of Effectiveness

As explained above in section III.b.i.1.b of this letter, Section 564(c)(2)(A) of the FD&C Act
requires that, for an EUA to be issued for a medical product, FDA must conclude “based on the
totality of scientific evidence available to the Secretary, including data from adequate and well-
controlled trials, if available, it is reasonable to believe that the product may be effective to
prevent, diagnose, or treat such serious or life-threatening disease or condition that can be caused
by SARS-CoV-2.” FDA has determined that based on the totality of scientific evidence
available, including data from adequate and well-controlled trials, it is reasonable to believe that
the Pfizer-BioNTech COVID-19 vaccine may be effective to prevent, diagnose, or treat such
serious or life-threatening disease or condition in the 12 through 17 years of age population. !™
The basis for this determination is explained in detail in FDA’s decision memoranda regarding

102 CDC, Megan Wallace and Sara Oliver, CDC ACIP Meeting Presentation, COVID-19 mRNA Vaccines in
Adolescents and Young Adults: Benefit-Risk Discussion, (June 23, 2021),
https:/Awww.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-06/05-COVID-Wallace-508.pdf; CDC, ACIP
Meeting Slides, (June 23, 2021), https://www.cdc.gov/vaccines/acip/meetings/slides-2021-06.html.

103 EDA, Pfizer-BioNTech COVID-19 Vaccine EUA Decision Memorandum (Dec. 11, 2020),
https://www.fda.gov/media/144416/download; FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Amendment
Decision Memorandum for Authorization in Individuals 12-15 Years of Age (May 10, 2021),
https://www.fda.gov/media/148542/download.

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the Pfizer BioNTech COVID-19 Vaccine EUA.'™ Section IIL.b.ii of this letter explains why
Petitioner’s arguments regarding the effectiveness of the Authorized COVID-19 Vaccines, and
the information submitted by Petitioner in support of this argument, does not change FDA’s
analysis regarding the effectiveness of the Pfizer-BioNTech COVID-19 vaccine in individuals 12
through 17 years of age.

Therefore, the criterion under section 564(c)(2)(A) continues to be met with respect to the
Authorized COVID-19 Vaccines.

c. Benefit-Risk Analysis

Section 564(c)(2)(B) of the FD&C Act requires that, for an EUA to be issued for a medical
product, FDA must conclude “the known and potential benefits of the product, when used to
diagnose, prevent, or treat [the identified serious or life-threatening disease or condition],
outweigh the known and potential risks of the product... .” Petitioner argues that the current
risks of serious adverse events or deaths associated with the authorized COVID-19 vaccines
outweigh the benefits of COVID-19 vaccines in the pediatric population. Section II.b.1.1.b.1i
above addresses these arguments insofar as they apply to the Authorized COVID-19 Vaccines
generally and explains why they are unavailing. Section III.b.11 above addresses Petitioner’s
arguments regarding the safety of COVID-19 vaccines in the pediatric population, and explains
why the information submitted by Petitioner does not change FDA’s analysis regarding the
benefits and risks of the authorized COVID-19 vaccines in the pediatric population.

d. No Alternatives

Section 564(c)(3) of the FD&C Act provides one of the required statutory factors that must be
met in order for a product to be granted an EUA. This statutory provision requires that “there is
no adequate, approved, and available alternative to the product for diagnosing, preventing, or
treating [the serious or life-threatening disease or condition].” To the extent Petitioner’s
contention can be interpreted as an argument that there are FDA-approved drugs indicated for the
prevention of COVID-19 in pediatric populations (and that therefore the requirement in section
564(c)(3) of the FD&C Act is not met with respect to the Authorized COVID-19 Vaccine with a
pediatric indication), this argument is erroneous.

As described above in section III.b.i.1.b, there are no FDA-approved drugs or biological products
indicated to prevent COVID-19 in any population, other than the newly-approved BioNTech
COVID-19 vaccine (COVID-19 Vaccine, mRNA; Comirnaty). That vaccine is approved for the
prevention of COVID-19 caused by SARS-CoV-2 in individuals 16 years of age and older.'”
The EUA for Pfizer-BioNTech COVID-19 Vaccine remains in effect to cover those 12 through

104 EDA, Pfizer-BioNTech COVID-19 Vaccine EUA Decision Memorandum (Dec. 11, 2020),
https://www.fda.gov/media/144416/download; FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Amendment
Decision Memorandum for Authorization in Individuals 12-15 Years of Age (May 10, 2021),
https://www.fda.gov/media/148542/download.

105 FDA, Pfizer-BioNTech COVID-19 Vaccine EUA Decision Memorandum (Dec. 11, 2020), at 8-9,
https://www.fda.gov/media/144416/download; FDA, Moderna COVID-19 Vaccine EUA Decision Memorandum
(Dec. 18, 2020), at 9, https://www.fda.gov/media/144673/download; FDA, Janssen COVID-19 Vaccine EUA
Decision Memorandum (Feb. 27, 2021), at 9, https://www.fda.gov/media/146338/download.

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15 years of age, the administration of a third dose to certain immunocompromised individuals 12
years of age and older, and until sufficient approved vaccine can be manufactured and distributed
for use in those 16 years of age and older. Similarly, the EUA for the Moderna COVID-19
Vaccine and the Janssen COVID-19 Vaccine remain in effect for individuals 18 years of age and
older. Therefore, there is no adequate, approved, and available alternative to the Authorized
COVID-19 Vaccines for preventing COVID-19.

ii. No Other Circumstances Make A Revision or
Revocation Appropriate to Protect the Public
Health or Safety

As noted above in section III.b.i.1.b of this letter, section 564(g)(2)(C) of the FD&C Act
provides that FDA may revise or revoke an EUA if circumstances justifying its issuance (under
section 564(b)(1)) no longer exist, the criteria for its issuance are no longer met, or other
circumstances make a revision or revocation appropriate to protect the public health or safety.
The EUA guidance explains that such other circumstances may include:

unnecessary. °°

As of the date of this writing, FDA has not identified any such circumstances that would make
revocation of the pediatric indication for the Pfizer-BioNTech COVID-19 Vaccine EUA
appropriate to protect the public health or safety. As stated previously in this response, FDA
determined the EUA standard is met for the Pfizer-BioNTech COVID-19 Vaccine in individuals
12 through 17 years of age because data submitted by the sponsors demonstrated in a clear and
compelling manner that the known and potential benefits of this vaccine, when used to prevent
COVID-19, outweigh the known and potential risks of this vaccine in individuals 12 through 17
years of age, and that there is no adequate, approved, and available alternative to the product for
diagnosing, preventing, or treating COVID-19 in this population.

As described in detail in section II.b.i.1 above, FDA has identified circumstances that have
made revision of the EUAs for the Authorized COVID-19 Vaccines appropriate, and,

106 BUA Guidance at 29.

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accordingly, has required changes to the authorized labeling for the Authorized COVID-19
Vaccines. !°”

Additionally, as explained above, FDA finds no basis in the information submitted in the
Petition, or in any postmarket data regarding the Pfizer-BioNTech COVID-19 Vaccine, to
support a revocation of the pediatric indication for the Pfizer-BioNTech COVID-19 Vaccine
EUA, nor has Petitioner provided any such information in the Petition. FDA is not aware of any
information indicating that the known and potential benefits of Pfizer-BioNTech COVID-19
Vaccine in the 12-17 years of age population are outweighed by their known and potential risks,
nor has Petitioner provided any such information in the Petition. Furthermore, there are no other
circumstances that make a revision or revocation of the pediatric indication for the Pfizer-
BioNTech COVID-19 Vaccine EUA appropriate to protect the public health or safety, nor has
Petitioner provided any information about such circumstances. FDA therefore sees no justifiable
basis upon which to take any action based on Petitioner’s request with respect to the pediatric
indication for the Pfizer-BioNTech COVID-19 Vaccine EUA. Accordingly, as noted above, we
deny Petitioner’s request that FDA “immediately revoke all EUAs that permit vaccination of
children under 16 for the Pfizer vaccine and under 18 for other COVID vaccines.” Petition at 1.

iii. Petitioner’s Request that FDA Immediately Revoke Tacit Approval that
Pregnant Women may Receive any EUA or Licensed COVID-19
Vaccines and Immediately Issue Public Guidance

Petitioner requests that FDA “immediately revoke tacit approval that pregnant women may
receive any EUA or licensed COVID vaccines and immediately issue public guidance to that
effect.” Petition at 1. Because “tacit approval,” or revocation thereof, is not a concept that exists
in applicable statutes or regulations governing FDA-regulated products, FDA interprets this as a
request that the labeling for the Authorized COVID-19 Vaccines, and any COVID-19 vaccine
that may be licensed in the future, contain a contraindication for use during pregnancy.

In addressing Petitioner’s request for a contraindication, we first discuss the risks posed to
pregnant women by COVID-19. We then provide an explanation of the regulatory framework
for prescription drug labeling for approved and licensed products, including the standard for
inclusion of contraindications in such labeling to inform health care providers of information
such as known hazards in the use of a particular drug as well as the requirements for pregnancy
and lactation information in such labeling. We then discuss labeling for products made available
under an EUA and explain why a contraindication for use in pregnant women was not included
in the labeling for the Authorized COVID-19 Vaccines. This section concludes with an
explanation for why Petitioner’s requests for a contraindication for use during pregnancy in the
labeling for the Authorized COVID-19 Vaccines — and BioNTech’s COVID-19 vaccine
(COVID-19 Vaccine, mRNA; Comirnaty) - is denied.

107 EDA, Pfizer-BioNTech COVID-19 Vaccine EUA Amendment Decision Memorandum for Authorization in
Individuals 12-15 Years of Age (May 10, 2021), https://www.fda.gov/media/148542/download; FDA, Pfizer-
BioNTech COVID-19 Vaccine EUA Amendment Decision Memorandum for Authorization of an Additional Dose
in Certain Immunocompromised Individuals (August 12, 2021), https://www.fda.gov/media/151613/download;
FDA, Moderna COVID-19 Vaccine EUA Amendment Decision Memorandum for Authorization of an Additional
Dose in Certain Immunocompromised Individuals (August 12, 2021),
https://www.fda.gov/media/151611/download; FDA, Janssen COVID-19 Vaccine EVA Decision Memorandum
(Feb. 27, 2021), https://www.fda.gov/media/146338/download.

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1. COVID-19 in Pregnancy

As a preliminary matter, we note that COVID-19 poses significant risks to pregnant women.
CDC explains that “observational data regarding COVID-19 during pregnancy demonstrate that
pregnant people with COVID-19 have an increased risk of severe illness, including illness
resulting in intensive care admission, mechanical ventilation, extracorporeal membrane
oxygenation, or death, though the absolute risk for these outcomes is low. Additionally, they are
at increased risk of preterm birth and might be at an increased risk of adverse pregnancy
complications and outcomes, such as preeclampsia, coagulopathy, and stillbirth.” !°

2. Certain Content and Format Requirements for Prescription
Drug Labeling for Products Approved Under NDAs or BLAs

As FDA explains in the draft guidance for industry, Pregnancy, Lactation, and Reproductive
Potential: Labeling for Human Prescription Drug and Biological Products — Content and Format,
(“Pregnancy and Lactation Guidance’’) “[p]|rescription drug labeling is a communication tool. Its
principal objective is to make available to health care providers the detailed prescribing
information necessary for the safe and effective use of a drug, in a manner that is clear and useful
to providers when prescribing for and counseling patients.”'©’ In order to achieve this objective,
prescription labeling must be based on scientific data, and it must not be inaccurate, false, or
misleading. '!°

FDA regulations govern the content and format of prescription drug labeling for approved drugs
and biological products (see, e.g., §§ 201.56 and 201.57 (21 CFR 201.57); see also 21 CFR
201.100(c)). The regulations are intended to organize labeling information to more effectively
communicate to health care professionals the “information necessary for the safe and effective
use of prescription drugs.”!!! FDA regulations require that the labeling of most prescription drug
products include Highlights of Prescribing Information, which are intended to summarize the
information that is most important for prescribing the drug safely and effectively and to facilitate
access to the more detailed information within product labeling (see § 201.57(a)). FDA
regulations further require that the labeling for most prescription drugs include, among other
information, the following sections: Contraindications; Warnings and Precautions; Adverse

108 CDC, Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States,
Vaccination of Pregnant or Lactating People, https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-
19-vaccines-us.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2F vaccines%2Fcovid-19%2Finfo-by-
product%2Fclinical-considerations.html#pregnant.

109 Pregnancy, Lactation, and Reproductive Potential: Labeling for Human Prescription Drug and Biological
Products - Content and Format Guidance for Industry, Draft Guidance, July 2020, at 2,
https://www.fda.gov/media/90160/download.

"1091 CFR § 201.56(a)(2) “The labeling must be informative and accurate and neither promotional in tone nor false
or misleading in any particular. In accordance with §§ 314.70 and 601.12 of this chapter, the labeling must be
updated when new information becomes available that causes the labeling to become inaccurate, false, or
misleading.”

'!! Preamble to final rule, “Requirements on Content and Format of Labeling for Human Prescription Drug and
Biological Products” (71 FR 3922 at 3928, January 24, 2006) (Physician Labeling Rule). For the content and format
requirements for the labeling of older prescription drug products that are not subject to the labeling requirements in
§ 201.57, see § 201.80 (21 CFR 201.80). The specific labeling requirements for older drug products differ in certain
respects, and generally are not referenced in this response.

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Reactions; and Use in Specific Populations, which includes a subsection on Pregnancy (see §
201.57(c)(1), (5), (6), (7), and (9)(1)).

a. Contraindications

The Contraindications section must describe any situations in which the drug should not be used
because the risk of use “clearly outweighs any possible therapeutic benefit” (§ 201.57(c)(5)).
This section should include observed and anticipated risks, but not theoretical risks.!'* This
could include, for example, a situation where animal data raise substantial concern about the
potential for occurrence of the adverse reaction in humans (e.g., animal data demonstrate that the
drug has teratogenic effects) and those risks do not outweigh any potential benefit of the drug to
any patient.''?

b. Pregnancy

The Pregnancy subsection is located under the Use in Specific Populations section (see §
201.57(c)(9)(i)). On December 4, 2014, FDA issued a final rule amending the regulations on the
requirements for pregnancy and lactation information in prescription drug and biological product
labeling (Pregnancy and Lactation Labeling Rule (PLLR)).'!* The PLLR revisions to the
regulations were intended “to create a consistent format for providing information about the
effects of a drug on pregnancy and lactation that would be useful for decision making by health
care providers and their patients.”'' The labeling content and format requirements in §
201.57(c)(9)(i), as revised by the PLLR, took effect on June 30, 2015, with a phased
implementation schedule for drugs (including biological products) that are the subject of NDAs,
BLAs, and efficacy supplements that had been approved on or after June 30, 2001.'!® The PLLR
also requires for all human prescription drug and biological products, including those for which
an application was approved before June 30, 2001, that the Pregnancy subsection of labeling be
revised to remove the pregnancy letter categories A, B, C, D, and X.!!”

Information in the Pregnancy subsection of labeling may present, in greater detail, a topic that is
briefly summarized in another section of labeling (e.g., Warnings and Precautions).!!’ FDA has
explained that when a topic is discussed in more than one section of labeling, the section
containing the most important information relevant to prescribing should typically include a
succinct description and should cross-reference sections that contain additional detail.!!°

'l2 See § 201.57(c)(5); see also FDA guidance for industry, Warnings and Precautions, Contraindications, and
Boxed Warning Sections of Labeling for Human Prescription Drug and Biological Products - Content and Format;
Guidance for Industry, October 2011 (Warnings Guidance), at 8, https://www.fda.gov/media/71866/download.

13 See Warnings Guidance at 8.

'l4 Final rule, “Content and Format of Labeling for Human Prescription Drug and Biological Products;
Requirements for Pregnancy and Lactation Labeling” (PLLR) (79 FR 72064, December 4, 2014),
https://www.federalregister.gov/documents/2014/12/04/2014-28241/content-and-format-of-labeling-for-human-

prescription-drug-and-biological-products-requirements-for.

5 Td. at 72066.

16 See §§ 201.56(b) and 201.57(c)(9)(i).

"7 §§ 201.57(c)(9) and 201.80; see also 79 FR 72064 at 72095 (December 4, 2014).

18 PLLR, 79 FR 72064 at 72085 (December 4, 2014).

19 See FDA guidance for industry, Labeling for Human Prescription Drug and Biological Products - Implementing
the PLR Content and Format Requirements; Guidance for Industry, February 2013,
https://www.fda.gov/media/71836/download.

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Under current labeling requirements, information in the Pregnancy subsection of labeling is
presented under the following subheadings: Pregnancy Exposure Registry; Risk Summary;

Clinical Considerations; and Data.!*° The labeling for the Authorized COVID-19 Vaccines

includes the Pregnancy Exposure Registry and the Risk Summary subheadings. We briefly

describe these subheadings below.

i. Pregnancy Exposure Registry

If there is a scientifically acceptable pregnancy exposure registry for the drug, the labeling must
state that fact and provide contact information needed for enrolling in or obtaining information
about the registry.

ii. Risk Summary

The Risk Summary subheading is required under the Pregnancy subsection because certain
statements must be included even when no product-specific data are available, given that all
pregnancies have a background risk of birth defect, loss, or other adverse outcomes. '*! The Risk
Summary must contain risk statement(s) that describe for the drug the risk of adverse
developmental outcomes based on all relevant human data, animal data, and/or the drug’s
pharmacology.'*? When multiple data sources are available, the risk statements are required to be
presented in the following order: human, animal, and pharmacologic. '”7

When human data are available that establish the presence or absence of any adverse
developmental outcome(s) associated with maternal use of the drug, a risk statement based on
human data must summarize the specific developmental outcome(s) and include its incidence
and the effects of dose, duration of exposure, and gestational timing of exposure. '** If human
data indicate that there is an increased risk for a specific adverse developmental outcome in
infants born to women exposed to the drug during pregnancy, the risk summary must contain a
quantitative comparison of that risk to the risk for the same outcome in infants born to women
who were not exposed to the drug, but who have the disease or condition for which the drug is
indicated to be used.'*° When risk information is not available for women with the disease or
condition(s) for which the drug is indicated, the risk summary must contain a comparison of the
specific outcome in women exposed to the drug during pregnancy against the rate at which the
outcome occurs in the general population. !”°

When animal data are available, the risk statement based on such data must describe the potential
risk for adverse developmental outcomes in humans and summarize the available data.'?’ This
statement must include: the number and type(s) of species affected; timing of exposure; animal
doses expressed in terms of human dose or exposure equivalents; and outcomes for pregnant
animals and offspring. !”°

20 § 201.57(c)(9)(i).

21 § 201.57(c)(9)(i)(B).
122 Td,

123 Td,

124 § 201.57(c)(9)(i)(B)(1).
125 Tq

126 Id.
127 § 201.57(c)(9)(i)(B)(2).
128 Td.

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With respect to pharmacology, when the drug has a well-understood pharmacologic mechanism
of action that may result in adverse developmental outcomes, the Risk Summary must explain
the mechanism of action and the potential associated risks. !”°

3. Inclusion of Contraindications and Pregnancy Information in
the Labeling for the Authorized COVID-19 Vaccines

For the emergency use of an unapproved product, section 564(e)(1)(A)(1) of the FD&C Act
requires that FDA must—to the extent practicable given the applicable circumstances of the
emergency, and as FDA finds necessary and appropriate to protect the public health—establish
appropriate conditions designed to ensure that health care professionals administering the
authorized product are informed:

¢ That FDA has authorized the emergency use of the product (including the product name

and an explanation of its intended use);

¢ Of the significant known and potential benefits and risks of the emergency use of the

product, and the extent to which such benefits and risks are unknown; and

¢ Of available alternatives and their benefits and risks.

Therefore, as explained in the EUA Guidance, FDA recommends that “a request for an EUA
include a ‘Fact Sheet’ for health care professionals or authorized dispensers that includes
essential information about the product. In addition to the required information, Fact Sheets
should include . . . any contraindications or warnings.” °° The EUA guidance also recommends
that, for unapproved drugs that do not have “FDA-approved labeling for any indication . . . in
addition to the brief summary information found in a Fact Sheet, the sponsor also develop more
detailed information similar to what health care professionals are accustomed to finding in FDA-
approved package inserts.” !3!

The sponsors for all the Authorized COVID-19 Vaccines submitted such prescribing information
in the EUA requests, and FDA reviewed and authorized this labeling. The Fact Sheets for
Healthcare Providers Administering Vaccine for all of the Authorized COVID-19 Vaccines
contain Contraindications and Warnings and Precautions sections because FDA determined that
sufficient data existed for inclusion of such information in the authorized labeling for these
vaccines. |**

FDA did not, however, require inclusion of a contraindication for pregnancy in the authorized
labeling. The authorized COVID-19 vaccines are authorized for use in an age range that includes
women of childbearing age and are not contraindicated for use in pregnant women because FDA

129 § 201.57(c)(9)(i)(B)(3).

130 RUA Guidance at 22.

131 RUA Guidance at 23.

132 Janssen COVID-19 Vaccine Fact Sheet for Healthcare Providers Administering Vaccine (Vaccination Providers),
Sections 5.2 and 5.3 Warnings and Precautions Regarding Thrombosis with Thrombocytopenia and GBS,
https://www.fda.gov/media/146304/download; Pfizer-BioNTech COVID-19 Vaccine Fact Sheet for Healthcare
Providers Administering Vaccine (Vaccination Providers), Section 5.2, Warning and Precautions Regarding
Myocarditis and Pericarditis, https://www.fda.gov/media/144413/download Moderna COVID-19 Vaccine Fact
Sheet for Healthcare Providers Administering Vaccine (Vaccination Providers), Section 5.2, Warning and
Precautions Regarding Myocarditis and Pericarditis, https://www.fda.gov/media/144637/download.

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is not aware of any evidence that suggests the risk of use of the Authorized COVID-19 Vaccines
in pregnant women would clearly outweigh any possible therapeutic benefit.'*? Nor has the
Petitioner presented any such evidence in the Petition. Accordingly, this request is denied.

4. Inclusion of Contraindications and Pregnancy Information in
the Labeling for Licensed COVID-19 Vaccines

With respect to Petitioner’s request that FDA “immediately revoke tacit approval that pregnant
women may receive any EUA or licensed COVID vaccines and immediately issue public
guidance to that effect” (Petition at 1; emphasis added), as explained above in this section, FDA
regulations require the Contraindications section of the labeling for an approved drug or
biological product to describe any situations in which the drug or biological product should not
be used because the risk of use “clearly outweighs any possible therapeutic benefit” (§
201.57(c)(5)). This section should include observed and anticipated risks, but not theoretical
risks. '*4 The approved COVID-19 vaccine (COVID-19 Vaccine, mRNA; Comirnaty) is indicated
for use in an age range that includes women of childbearing age and is not contraindicated for
use in pregnant women because FDA is not aware of any evidence that suggests the risk of use of
BioNTech’s COVID-19 vaccine in pregnant women would clearly outweigh any possible
therapeutic benefit, !*° nor has the Petitioner presented any such evidence in the Petition.

In its review of a BLA for any future COVID-19 vaccine candidate, FDA will apply the
regulatory standards outlined above in determining, on a case-by-case basis, whether to include a
contraindication in pregnancy, or any other contraindications, in the approved labeling for such a
vaccine. Accordingly, Petitioner’s request is denied.

iv. Petitioner’s Request that FDA Immediately Amend its Guidance
regarding Certain Approved Drugs [chloroquine drugs, ivermectin,
“and any other drugs demonstrated to be safe and effective against
COVID”|

Petitioner requests that the Agency “immediately amend its existing guidance for the use of the
chloroquine drugs, tvermectin, and any other drugs demonstrated to be safe and effective against
COVID, to comport with current scientific evidence of safety and efficacy at currently used
doses and immediately issue notifications to all stakeholders of this change.” Petition at 2. FDA
has not issued “guidance for the use of chloroquine drugs, ivermectin, and other drugs

133 FDA’s decision memoranda for the Authorized COVID-19 Vaccines discuss FDA’s analysis of all available data
regarding the use of the Authorized COVID-19 Vaccines in pregnancy. See, FDA, Pfizer-BioNTech COVID-19
Vaccine EUA Decision Memorandum (Dec. 11, 2020), https://www.fda.gov/media/144416/download; FDA,
Moderna COVID-19 Vaccine EUA Decision Memorandum (Dec. 18, 2020),
https://www.fda.gov/media/144673/download; FDA, Janssen COVID-19 Vaccine EUA Decision Memorandum
(Feb. 27, 2021), https://www.fda.gov/media/146338/download.

134 See § 201.57(c)(5); see also Warnings Guidance at 8.

135 See FDA's Summary Basis for Regulatory Action (SBRA) for the BioNTech BLA. This memorandum will be
posted on www.fda.gov.

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demonstrated to be safe and effective against COVID.”'*° FDA has, however, analyzed adverse
event information and made publicly available safety issues regarding the use of
hydroxychloroquine and chloroquine to treat patients with COVID-19.'°7 FDA has also informed
the public that it has received multiple reports of patients who have required medical support and
been hospitalized after self-medicating with ivermectin intended for horses, that taking large
doses of ivermectin can cause serious harm, that ivermectin is not authorized or approved by
FDA to treat COVID-19, and that using any treatment for COVID-19 that is not approved or
authorized by the FDA, unless part of a clinical trial, can cause serious harm.'3* You have not
provided any evidence to suggest that the safety information in these communications is
inaccurate. Thus, to the extent you are requesting that FDA withdraw or revise these previous
safety communications, that request is denied.

v. Petitioner’s Request that FDA Issue Guidance to the Secretary of
Defense and the President

Petitioner requests that FDA “issue guidance to the Secretary of the Defense and the President
not to grant an unprecedented Presidential waiver of prior consent regarding COVID vaccines
for Servicemembers under 10 U.S.C. § 1107(f) or 10 U.S.C. § 1107a.” Petition at 2.

FDA denies this request because FDA, an agency within the U.S. Department of Health and
Human Services, does not issue guidance of the type requested to the President of the United
States or to other Departments in the executive branch of the U.S. federal government.

136 Under FDA’s good guidance practices regulations, a “guidance document” is defined as “documents prepared for
FDA staff, applicants/sponsors, and the public that describe the agency’s interpretation of or policy on a regulatory
issue.” 21 CFR 10.115(a)(b)(1). The regulation provides further that “[g]uidance documents include, but are not
limited to, documents that relate to: The design, production, labeling, promotion, manufacturing, and testing of
regulated products; the processing, content, and evaluation or approval of submissions; and inspection and
enforcement policies.” Importantly, the provision at 21 CFR 10.115(b)(3), excludes from the definition of “guidance
document” general information documents provided to consumers or health professionals, such as those
communications that have been provided to the public regarding the use of hydroxychloroquine, chloroquine, and
ivermectin to treat patients with COVID-19. 21 CFR 10.115(b)(3) states: “[g]uidance documents do not include:
Documents relating to internal FDA procedures, agency reports, general information documents provided to
consumers or health professionals, speeches, journal articles and editorials, media interviews, press materials,
warning letters, memoranda of understanding, or other communications directed to individual persons or firms.”
(Emphasis added.)

137 FDA Drug Safety Communication, FDA cautions against use of hydroxychloroquine or chloroquine for COVID-
19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems, April 24, 2020, updated
June 15, 2020 and July 1, 2020, https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-
hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or; FDA, CDER Office of Surveillance and
Epidemiology Pharmacovigilance Memorandum, May 19, 2020,
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/OSE%20Review_Hydroxychloroquine-
Cholorquine%20-%2019May2020_Redacted.pdf.

138 FDA Consumer Update, Why You Should Not Use Ivermectin to Treat or Prevent COVID-19, March 5, 2021,
https://www.fda.gov/consumers/consumer-updates/why-you-should-not-use-ivermectin-treat-or-prevent-covid-

19; FDA Letter to Stakeholders, Do Not Use Ivermectin Intended for Animals as Treatment for COVID-19 in
Humans, April 10, 2020, https://www.fda.gov/animal-veterinary/product-safety-information/fda-letter-stakeholders-
do-not-use-ivermectin-intended-animals-treatment-covid-19-humans.

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vi. Petitioner’s Request that FDA Issue Guidance to Stakeholders
Regarding the Option to Refuse or Accept Administration of
Investigational COVID-19 Vaccines

Petitioner requests that FDA “issue guidance to all stakeholders in digital and written formats to
affirm that all citizens have the option to accept or refuse administration of investigational
COVID vaccines without adverse work, educational or other non-health related consequences,
under 21 U.S.C. § 360bbb-3(e)(1)(a)(41)(I0) 1 and the informed consent requirements of the
Nuremberg Code.”'*’ We interpret this request to relate to the Authorized COVID-19 Vaccines
and third parties’ decisions with respect to unvaccinated individuals’ participation in certain
activities. Such decisions by third parties with respect to employment, education, and other non-
FDA-regulated activities would not be within FDA’s purview. Accordingly, FDA denies
Petitioner’s request.

vii. Petitioner’s Request that FDA Issue Guidance Regarding Marketing
and Promotion of COVID-19 Vaccines

FDA notes that your Petition discusses statements made by CDC. For requests intended for
CDC, you should contact CDC directly.

As explained above in section III.b.1.1.b of this response, the EUA revocation standard in section
564(g)(2) of the FD&C Act is not met for any of the Authorized COVID-19 Vaccines. With
respect to Petitioner’s request to issue guidance pending revocation of the EUAs for the
Authorized COVID-19 Vaccines, we note that the EUA Guidance contains a section regarding
advertising for EUA products. As explained in the EUA guidance, FDA may, under section
564(e)(1)(B) of the FD&C Act, on a case-by-case basis and to the extent feasible given the
circumstances of a particular public health emergency, establish certain additional conditions that
FDA finds to be necessary or appropriate to protect the public health.'4° The EUA guidance
explains that, under section 564(e)(4) of the FD&C Act, FDA may place conditions on
“advertisements and other promotional descriptive printed matter (e.g., press releases issued by
the EUA sponsor) relating to the use of an EUA product, such as requirements applicable to
prescription drugs under section 502(n) ... .”'4! FDA’s authority under section 564(e)(4)
ordinarily does not extend to statements by third parties who have no direct connection with the
EUA sponsor.

For the Authorized COVID-19 Vaccines, FDA has determined that such conditions are necessary
to protect the public health. Accordingly, the Letter of Authorization for each of the Authorized
COVID-19 Vaccines contains conditions related to printed matter, advertising, and promotion. !
Given the current public health emergency, FDA does not see a need to expend the resources

139 Concerns about potential State vaccine requirements are better directed to the States. FDA does not mandate use
of vaccines.

140 RUA Guidance at 26.

141 Tq. at 27.

12 EDA, Pfizer-BioNTech COVID-19 Vaccine Letter of Authorization (Aug. 12, 2021),
https://www.fda.gov/media/150386/download; FDA, Moderna COVID-19 Vaccine Letter of Authorization (Aug.
12, 2021), https://(www.fda.gov/media/144636/download; FDA, Janssen COVID-19 Vaccine Letter of
Authorization (June 10, 2021), https://www.fda.gov/media/146303/download.

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necessary to develop and issue additional guidance on this topic. Thus, because FDA has already
issued guidance addressing advertising and promotion of EUA products, and because FDA has
established conditions related to printed matter, advertising, and promotion for all of the
Authorized COVID-19 Vaccines, FDA denies Petitioner’s request to issue additional guidance
on this issue.

ec. Conclusion

FDA has considered Petitioner’s requests as they relate to the Authorized COVID-19 Vaccines
and the approved COVID-19 Vaccine. For the reasons given in this letter, FDA denies the
requests in Petitioner’s citizen petition. Therefore, we deny the Petition in its entirety.

Sincerely,

(Prin Menbs

Peter Marks, MD, PhD
Director
Center for Biologics Evaluation and Research

cc: Dockets Management Staff

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Appendix I: Aspects of Vaccine Development and Process for Licensure

A. Vaccines are Biologics and Drugs

Vaccines are both biological products under the Public Health Service Act (PHS Act) (42 U.S.C.
§ 262) and drugs under the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. §
321). The PHS Act defines a “biological product” as including a “vaccine...or analogous
product...applicable to the prevention, treatment, or cure of a disease or condition of human
beings.” 42 U.S.C. § 262(1)(1). The FD&C Act defines drug to include “articles intended for
use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man.” 21 U.S.C. §

321(g)(1)(B).

Under the PHS Act, a biological product may not be introduced or delivered for introduction into
interstate commerce unless a biologics license is in effect for the product. 42 U.S.C. §
262(a)(1)(A).

B. Clinical Investigations of Vaccines

Before a vaccine is licensed (approved) by FDA and can be used by the public, FDA requires
that it undergo a rigorous and extensive development program that includes laboratory research,
animal studies, and human clinical studies to determine the vaccine’s safety and effectiveness.

The PHS Act and the FD&C Act provide FDA with the authority to promulgate regulations that
provide a pathway for the study of unapproved new drugs and biologics. 42 U.S.C. §
262(a)(2)(A) and 21 U.S.C. § 355(i). The regulations on clinical investigations require the
submission of an Investigational New Drug application (IND), which describes the protocol, and,
among other things, assures the safety and rights of human subjects. These regulations are set
out at 21 CFR Part 312. See 21 CFR § 312.2 (explaining that the IND regulations apply to
clinical investigations of both drugs and biologics).

The regulations provide that, once an IND is in effect, the sponsor may conduct a clinical
investigation of the product, with the investigation generally being divided into three phases.
With respect to vaccines, Phase | studies typically enroll fewer than 100 participants and are
designed to look for very common side effects and preliminary evidence of an immune response
to the candidate vaccine. Phase 2 studies may include up to several hundred individuals and are
designed to provide information regarding the incidence of common short-term side effects, such
as redness and swelling at the injection site or fever, and to further describe the immune response
to the investigational vaccine. If an investigational new vaccine progresses past Phase | and
Phase 2 studies, it may progress to Phase 3 studies. For Phase 3 studies, the sample size is often
determined by the number of subjects required to establish the effectiveness of the new vaccine,
which may be in the thousands or tens of thousands of subjects. Phase 3 studies are usually of
sufficient size to detect less common adverse events.

If product development is successful and the clinical data are supportive of the proposed
indication, the completion of all three phases of clinical development can be followed by
submission of a Biologics License Application (BLA) pursuant to the PHS Act (42 U.S.C. §
262(a)), as specified in 21 CFR § 601.2.

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C. Biologics License Applications

A BLA must include data demonstrating that the product is safe, pure, and potent and that the
facility in which the product is manufactured “meets standards designed to assure that the
biological product continues to be safe, pure, and potent.” 42 U.S.C. § 262(a)(2)(C)(i). FDA
does not consider an application to be filed until FDA determines that all pertinent information
and data have been received. 21 CFR § 601.2. FDA’s filing of an application indicates that the
application is complete and ready for review but is not an approval of the application.

Under § 601.2(a), FDA may approve a manufacturer’s application for a biologics license only
after the manufacturer submits an application accompanied by, among other things, “data derived
from nonclinical laboratory and clinical studies which demonstrate that the manufactured
product meets prescribed requirements of safety, purity, and potency.” The BLA must provide
the multidisciplinary FDA reviewer team (medical officers, microbiologists, chemists,
biostatisticians, etc.) with the Chemistry, Manufacturing, and Controls (CMC)!* and clinical
information necessary to make a benefit-risk assessment, and to determine whether “‘the
establishment(s) and the product meet the applicable requirements established in [FDA’s
regulations.” 21 CFR § 601.4(a).

FDA generally conducts a pre-license inspection of the proposed manufacturing facility, during
which production of the vaccine is examined in detail. 42 U.S.C. § 262(c). In addition, FDA
carefully reviews information on the manufacturing process of new vaccines, including the
results of testing performed on individual vaccine lots.

FDA scientists and physicians evaluate all the information contained in a BLA, including the
safety and effectiveness data and the manufacturing information, to determine whether the
application meets the statutory and regulatory requirements. FDA may also convene a meeting
of its advisory committee to seek input from outside, independent, technical experts from various
scientific and public health disciplines that provide input on scientific data and its public health
significance.

As part of FDA’s evaluation of a vaccine as a whole, FDA takes all of a vaccine’s ingredients
into account (including preservatives and adjuvants). FDA licenses a vaccine only after the
Agency has determined that the vaccine is safe and effective for its intended use, in that its
benefits outweigh its potential risks.

143 Also referred to as Pharmaceutical Quality/CMC.

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Exhibit 4
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 139 of 237

Vaccines and Related Biological Products Advisory Committee Meeting
October 26, 2021

FDA Briefing Document

EUA amendment request for Pfizer-BioNTech COVID-19 Vaccine for use

in children 5 through 11 years of age
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 140 of 237

TABLE OF CONTENTS

1 EXECUTIVE SUMMARY ..............:ccc:eeeeeeeeeeeeeeeenneneeeeeeeeeeneeeeaeeeeeeseeeeeeeeeesaaaeeeeeeeeseeeeeeeeeeaeeeeees 4
2 SARS-COV-2 VIRUS AND COVID-19 DISEASE..............ccccccccceeeeeseseeeneeeeeeeeeeeeseeaaeeeeeeeeneeeeeees 6
3 AUTHORIZED AND APPROVED VACCINES AND THERAPIES FOR
COVID~19 o.oo. ceeececcessennneeeeeeeeeeeeeeeaaaaeeeeeeeeeeeeeeaseeaaeseeeeeeeeagaaaaaeeeeeseeesaaseeeeeeaesseeeeeseesseeaaeeeeeennees 8
4 COMIRNATY (COVID-19 VACCINE, MRNA) ..............cc::ceeeceeeeeeeeeeeeeeeeeeeeeeeeseeesneaeeeeeeeeeneenes 10
4.1 Efficacy of a 2-dose primary series of COMIRNATY in individuals 16 years of age and
(0) (0 (=) eee 10
4.2 Safety of a 2-dose primary series of COMIRNATY in individuals 16 years of age and
(0) (0 (= eee 10
4.3 Effectiveness and safety of a 2-dose primary series of Pfizer-BioNTech COVID-19
Vaccine in adolescents 12-15 years Of AQE 0.2... eeeeeeeee eee eeeeeeeteeeeeee eee teeeenaaeeeeeeeeeneneeea 11
4.4 Cases of myocarditis/pericarditis reported in BNT162b2 recipients in ongoing clinical
trials Of BNT162D2 0.0.0... ccccccccccceccceeeeeeeneeeeeeeeeeeeceaaaeeeeeeeeeeccceeeeeaaeeeeeeeeeeeseseneteeeeeeeeeeeeees 12
4.5 Post-EUVA and post-licensure SurveillanCe................::cccccccececeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeaaeeaeeeaee 12

5 EVA AMENDMENT REQUEST FOR THE PFIZER-BIONTECH COVID-19

VACCINE FOR USE IN CHILDREN 5-11 YEARS OF AGE uu... ec cecceeseseeeeeeeeeeeeeeneneeeeeeeeees 14

6 EVA REQUIREMENTS, GUIDANCE AND CONSIDERATIONS PERTAINING
TO COVID-19 VACCINES. ............cccccceeceeeeeeeeeeeeeeeeeeeeeeeeeeeeeeseaeaeeeeeeesesssseaaaeeeeeseeeseeeeeeeeaeaeeeeeees 14
6.1 U.S. requirements to support issuance of an EVA for a biological product .................. 14
6.2 FDA guidance for industry related to COVID-19 VACCINES .......... 2... ccececeeeeeeeeeeeeeeeeeteeetees 15

6.3 Regulatory considerations for clinical development of COVID-19 vaccines in children..15

7 FDA REVIEW OF CLINICAL SAFETY AND EFFECTIVENESS DATA. .........::cccseseeeceeeeeeeees 16
7.1 Overview of study C45910007 ooo... eee cent etter eee ee eaaaaeeeeeeeeeeeeeaaaeeeeeeeeeeeeseeeeeeaeeeeees 16
7.2 Study COSIQN ......... cece eee e eee eee eee eee een naan eter eee teenie aaeeeeeeeeeeeeseggneaeaeeeeeeeeeseeenaaaes 17
7.3 Disposition of Phase 2/3 participants ...........cccccccccccccccceecccececeeeeeeeeeeeeeeeeeeeseeeeeeaeseeeeeeaeeaas 19
7.4 Demographic and baseline CharacteristiCs .......... cc ceeeseeeeeeee tees eeeneeeeeeeeeeeeeeeeeneeeeeeeeees 21
7.5 Immunogenicity results «2.0.2.2... cece eee eee eee eee e eter eee e teeta eae eeeee settee eteeeneeeeeeeeeeeeeneeeeaaaes 22
7.6 Safety reSults «2.0.2... eee eee e eee e eee teeter eee ene ea ee eee e erence eaaaaeeeeeeeeeeeeeaaaaeeeeeeeeeeeeseeeeneeees 24
7.7 Study C4591007 Phase 2/3 SUMMATY ..........::cccceeceee eee eenennteeeeeeeeeeeeeaaaeeeeeeeeeeeeteeeneeeeeeeees 31

8 BENEFIT-RISK ASSESSMENT FOR CHILDREN 5-11 YEARS OF AGE...........::ccccssseeeeeees 32

9 PHARMACOVIGILANCE ACTIVITIES. ........:ccccceceseeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeseeeeeeeeeeeeeeeeeeeneeeeeeeees 34

10 TOPIC FOR VRBPAC DISCUSSION .........cccccceeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeesenneeeeeseenaeeeeeeeeeeeeeeees 36
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 141 of 237

11 REFERENCE. ............cccccsscecceeeeesesseneeeeeeeeeeeeeeseaaaaeeeeeeeeeeeeeeaaaeeeaeeseseeeeesssseaaaeseeeeeseeeeseeeeeaeeas 36
12 APPENDIX: C4591007 PHASE 1 (DOSE RANGING) —- SUMMARY OF

SAFETY AND IMMUNOGENICITY ...........::ccccccceeeeeeeseeneneeeeeeeeeseeneeeeeeeeeeeeeeeeseeeseaaaaeeeeeeeeneeenes 38
List of Tables
Table 1. Emergency Use Authorizations of COVID-19 Vaccines ..................:0eeceee eects eee eeeeeeeeeeeeees 8
Table 2. Emergency Use Authorized Pharmacological Products for Post-exposure Prophylaxis

and/or Treatment Of COVID-19....... ccc ccc cece cece ccc eeeeeeee cece cece eeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeneees 9

Table 3. Study C4591007*: Participants 5-11 Years of Age (10 ug BNT162b2) ........ ee 17

Table 4. Disposition of Immunogenicity Populations, Phase 2/3, Participants 5-11 Years of Age
(Study C4591007 Cohort 1) and Participants 16-25 Years of Age (Study C4591001)....... 20

Table 5. Demographic and Baseline Characteristics, Phase 2/3, Participants 5-11 Years, Safety
Population, Study C4591007 Cohort 1.0.0.0... eee cece cece e eee ee eee eeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeneees 21

Table 6. SARS-CoV-2 Neutralizing GMTs (NT50)? at 1 Month Post-Primary Series in Phase 2/3
BNT162b2 (10 ug) Recipients 5-11 Years of Age and Study C4591001 Phase 2/3 Cohort 1
BNT162b2 (30 ug) Recipients 16-25 Years of Age Without Evidence of SARS-CoV-2
Infection up to 1 Month After Dose 2, Evaluable Immunogenicity Population? ................... 22

Table 7. Seroresponse Rates?” at 1 Month Post-Primary Series in Phase 2/3 BNT162b2 (10 ug)
Recipients 5-11 Years of Age and Study C4591001 Phase 2/3 Cohort 1 BNT162b2 (30 ug)
Recipients 16-25 Years of Age® Without Evidence of SARS-CoV-2 Infection up to 1 Month
After Dose 2, Evaluable Immunogenicity Population©®..............c:cccceeeeeeeeeeeeeeeeteeeeeeeeeeeeenaaaes 23

Table 8. SARS-CoV-2 Neutralizing GMTs? at Pre-Dose 1 and 1 Month Post-Primary Series in
C4591007 Phase 2/3 Cohort 1 Participants 5-11 Years of Age Without Evidence of SARS-
CoV-2 Infection up to 1 Month After Primary Series, Evaluable Immunogenicity Population?

Table 9. Safety Overview, Phase 2/3 Cohorts 1 and 2, Participants 5-11 Years, Safety
Population, Study C4591007 2000.0... cecceecceeeeeeeeeeeeeeeeeeeeeeeeeeeceeeceeeeeeeeeeeeeeeeeeeeseeeeeeeeeeeeeseees 25

Table 10. Frequency of Solicited Local Reactions Within 7 Days After Each Dose, by Severity,
Phase 2/3 Cohort 1 Participants 5-11 Years of Age, Safety Population®, Study C4591007

Table 11. Frequency of Solicited Systemic Reactions Within 7 Days After Dose 2 by Severity,
Phase 2/3 Cohort 1 Participants 5-11 Years of Age, Safety Population, Study C4501007 26

Table 12. Characteristics of Solicited Local and Systemic Adverse Reactions, Phase 2/3 Cohort
1, Participants 5-11 Years, Safety Population, Vaccine Group as Administered, Study
Ooo) 00) eee 27

Table 13. Standard MedDRA Query of Adverse Events by System Organ Class and Preferred
Terms, Phase 2/3, Participants 5-11 Years, Safety Population, Vaccine Group as

Administered, Cohort 1, Study C4591007 ...........cccccccccecceeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeseeeee 30
Table 14. Model-Predicted Benefit-Risk Outcomes of Scenarios 1-6 per One Million Fully
Vaccinated Children 5-11 Years OI... eeeeeeeeee eee e ee eeeeeneeeeeeee eee eeeennaeeeeeeeeeeeeeeaea 34
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 142 of 237

1 EXECUTIVE SUMMARY

On October 6, 2021, Pfizer submitted a request to FDA to amend its Emergency Use
Authorization (EUA) to expand use of Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) for
prevention of COVID-19 caused by SARS-CoV-2 in individuals 5 through 11 years of age
(hereafter 5-11 years of age). The proposed dosing regimen is a 2-dose primary series, 10 ug
mRNA/per dose, administered 3 weeks apart. This EVA request initially included safety data
from 1,518 BNT162b2 recipients and 750 placebo (saline) recipients 5-11 years of age who are
enrolled in the Phase 2/3 portion (Cohort 1) of an ongoing randomized, double-blinded, placebo-
controlled clinical trial, C4591007. Among Cohort 1 participants, 95.1% had safety follow-up 22
months after Dose 2 at the time of the September 6, 2021 data cutoff for this cohort. Safety data
from an additional 1,591 BNT162b2 recipients and 788 placebo recipients enrolled in the Phase
2/3 portion (Cohort 2) of the trial were provided later during FDA’s review of the EUA
amendment request to allow for more robust assessment of serious adverse events and other
adverse events of interest (e.g., myocarditis, pericarditis, anaphylaxis). The median duration of
follow-up in Cohort 2 was 2.4 weeks post Dose 2 at the time of the October 8, 2021 data cutoff
for this cohort. Vaccine effectiveness was inferred by immunobridging SARS-CoV-2 50%
neutralizing antibody titers (NT50, SARS-CoV-2 mNG microneutralization assay). Neutralizing
antibody titers at 1 month post-Dose 2 in children 5-11 years of age were compared to
neutralizing antibody titers 1 month post-Dose 2 among a subset of study participants 16-25
years of age randomly selected from efficacy study C4591001 who had previously received two
doses of 30 ug BNT162b2. A supplemental descriptive analyses of vaccine efficacy (VE) among
Cohort 1 participants (following accrual of 19 total confirmed COVID-19 cases) was also
provided during FDA’s review of the EUA amendment request.

The immunogenicity analyses evaluated neutralizing antibody titers against the USA_WA1/2020
reference strain, as assessed by microneutralization assay, among study participants with no
evidence of prior SARS-CoV-2 infection up to 1 month post-Dose 2. Immunobridging endpoints
and statistical success criteria were as follows:

e SARS-CoV-2 neutralizing antibody GMTs measured at 1 month after Dose 2 in study
C4591007 Phase 2/3 Cohort 1 participants 5-11 years of age vs. GMTs at 1 month after
Dose 2 in a randomly selected subset of study C4591001 Phase 2/3 participants 16-25
years of age, with immunobridging success criteria of >0.67 for the lower bound of the 95%
confidence interval around the GMT ratio (5-11 years of age / 16-25 years of age), anda
point estimate of the GMT ratio 21.0.

e Percentage of participants with seroresponse (24-fold rise from baseline [pre-Dose 1]), with
immunobridging success criterion of >-10% for the lower bound of the 95% confidence
interval around the difference (5-11 years of age minus 16-25 years of age) in seroresponse
rates.

Immunobridging statistical success criteria, as described above, were met. Subgroup analyses
of immunogenicity by age, gender, race and ethnicity, obesity and baseline SARS-CoV-2 status
showed no notable differences as compared with the overall study population, although some
subgroups were too small to draw meaningful conclusions. Descriptive immunogenicity
analyses, based on an exploratory 50% plaque reduction neutralization test (PRNT), showed
that a 10 ug BNT162b2 primary series elicited PRNT neutralizing titers against the reference
strain and B.1.617.2 (Delta) strain in participants 5-11 years of age (34 BNT162b2, 4 placebo)
with no evidence of SARS-CoV-2 infection up to 1 month post-Dose 2.
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 143 of 237

In the supplemental descriptive efficacy analysis, VE against symptomatic COVID-19 after 7
days post Dose 2 up to October 8, 2021 (data cutoff) was 90.7% (2-sided 95% Cl: 67.4%,
98.3%) in participants 5-11 years of age without evidence of prior SARS-CoV-2 infection. Totals
of 3 cases of COVID-19 occurred in the BNT162b2 group and 16 in the placebo group, most of
which occurred during July-August 2021 when the Delta variant was prevalent in the United
States. At the time of the data cutoff, none of these cases met the criteria for severe COVID-19.

Solicited local and systemic adverse reactions (ARs) reported among Cohort 1 participants
generally occurred more frequently after Dose 2, with the most commonly reported solicited ARs
being pain at the injection site (71%), fatigue (39.4%), and headache (28%). Most local and
systemic reactions were mild to moderate in severity, with median onset 2 days post-
vaccination, and most resolved within 1 to 2 days after onset. The most frequently reported
unsolicited adverse event (AE) in Cohort 1 BNT162b2 recipients was lymphadenopathy (n=13;
0.9%). More BNT162b2 recipients (n=14; 0.92%) reported hypersensitivity-related AEs
(primarily skin and subcutaneous disorder including rash and dermatitis) than placebo recipients
(n=4; 0.53%). Overall, from the combined safety database of 3,109 BNT162b2 recipients
(Cohorts 1 and 2), 4 participants reported serious adverse events; all were considered by the
study investigator and FDA as unrelated to vaccination. There were no reports of
myocarditis/pericarditis or anaphylaxis, and no participant deaths. Subgroup safety analyses by
gender, race and ethnicity, obesity and baseline SARS-CoV-2 status showed no notable
differences as compared with the overall study population, although some subgroups were too
small to draw meaningful conclusions.

FDA conducted a quantitative benefit-risk analysis to evaluate predicted numbers of
symptomatic COVID-19 cases, hospitalizations, |CU admissions, and deaths that would be
prevented per million fully vaccinated children 5-11 years of age over a 6-month period, as
compared with predicted numbers of vaccine-associated excess myocarditis cases,
hospitalizations, ICU admissions and deaths per million fully vaccinated children 5-11 years of
age. The model conservatively assumed that the risk of myocarditis/pericarditis associated with
the 10 yg dose in children 5-11 years of age would the same as the estimated risk associated
with the 30 ug dose in adolescents 12-15 years of age from Optum healthcare claims data.
While benefits of vaccination were highly dependent on COVID-19 incidence, the overall
analysis predicted that the numbers of clinically significant COVID-19-related outcomes
prevented would clearly outweigh the numbers of vaccine-associated excess myocarditis cases
over a range of assumptions for COVID-19 incidence. At the lowest evaluated COVID-19
incidence (corresponding to the June 2021 nadir), the predicted number of vaccine-associated
myocarditis cases was greater than the predicted number of COVID-19 hospitalizations
prevented for males and for both sexes combined. However, in consideration of the different
clinical implications of hospitalization for COVID-19 versus hospitalization for vaccine-
associated myocarditis, and benefits related to prevention of non-hospitalized cases of COVID-
19 with significant morbidity, the overall benefits of the vaccine may still outweigh the risks
under this low incidence scenario. If the myocarditis/pericarditis risk in this age group is lower
than the conservative assumption used in the model, the benefit-risk balance would be even
more favorable.

This October 26, 2021 VRPBAC meeting is being held to discuss whether, based on the totality
of scientific evidence available, the benefits of the Pfizer-BioNTech COVID-19 Vaccine when
administered as a 2-dose series (10 ug each dose, 3 weeks apart) outweigh its risks for use in
children 5-11 years of age.
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 144 of 237

2 SARS-COV-2 VIRUS AND COVID-19 DISEASE

SARS-CoV-2 is a zoonotic coronavirus that emerged in late 2019 and was identified in patients
with pneumonia of unknown cause. The virus was named SARS-CoV-2 because of its similarity
to the coronavirus responsible for severe acute respiratory syndrome (SARS-CoV, a lineage B
betacoronavirus). SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA virus
sharing more than 70% of its sequence with SARS-CoV, and ~50% with the coronavirus
responsible for Middle Eastern respiratory syndrome (MERS-CoV). SARS-CoV-2 is the
causative agent of COVID-19, an infectious disease with respiratory and systemic
manifestations. Disease symptoms vary, with many persons presenting with asymptomatic or
mild disease and some progressing to severe respiratory tract disease including pneumonia and
acute respiratory distress syndrome (ARDS), leading to multiorgan failure and death. Symptoms
associated with SARS-CoV-2 infection in individuals less than 18 years of age are similar to
those in adults, but are generally milder, with fever and cough most commonly reported. 1:2
Other symptoms in children include nausea and vomiting, diarrhea, dyspnea, nasal symptoms,
rashes, fatigue and abdominal pain.? Most children with COVID-19 recover within 1 to 2 weeks.
Estimates of asymptomatic infection in children vary from 15 to 50% of infections.*° However,
COVID-19 associated hospitalizations and deaths have occurred in children (see below), and
for some children, COVID-19 symptoms may continue for weeks to months after their initial
illness.®

The SARS-CoV-2 pandemic continues to present a challenge to global health and, as of
October 15, 2021, has caused approximately 239 million cases of COVID-19, including 4.8
million deaths worldwide.’ In the United States, more than 44 million cases have been reported
to the Centers for Disease Control and Prevention (CDC), with over 722,000 deaths. ®° Of the
total COVID-19 cases reported in the United States to date, 22.3% occurred among individuals
<18 years of age, with 8.7% occurring among 5-11-year-olds.'° Following emergency use
authorization of COVID-19 vaccines in December 2020, COVID-19 cases and deaths in the
United States declined sharply during the first half of 2021; however, beginning in late June
2021 a rise in cases was observed, including in children, associated with the highly
transmissible Delta variant that is now predominant in the United States."’ As of the week
ending October 2, 2021, the Delta variant comprised greater than 99% of tested strains in the
United States.'* During the last week in August 2021, new COVID-19 infections in individuals
less than 18 years of age surpassed those in adults 18 to 64 years of age for the first time
during the pandemic." In the United States, COVID-19 cases occurring in children 5-11 years
now constitute 39% of cases in individuals younger than 18 years of age.'* Among cases of
COVID-19 in individuals less than 18 years of age from the COVID-NET network?,
approximately 4,300 have resulted in hospitalization.'* As of October 17, 2021, 691 deaths from
COVID-19 have been reported in the United States in individuals less than 18 years of age, with
146 deaths in the 5-11 year age group. "®

8 COVID-NET covers approximately 10% of the U.S. population; The current network covers nearly 100
counties in the 10 Emerging Infections Program (EIP) states (CA, CO, CT, GA, MD, MN, NM, NY, OR,
and TN) and four additional states through the Influenza Hospitalization Surveillance Project (IA, MI, OH,
and UT); see https:/Awww.cdc.gov/coronavirus/2019-ncov/covid-data/covid-net/purpose-methods.html.
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 145 of 237

conditions, or with congenital heart disease.'” As in the adult population, COVID-19 in children
disproportionally affects underrepresented racial and ethnic groups, with hospitalizations and
deaths more frequent among Native American/Alaskan, Hispanic or Latin American, and non-
Hispanic Black children than among White children. '®:'9

Following observation of an increased incidence of myocarditis in 2020 compared with 2019,
several studies have suggested an association between COVID-19 and myocarditis.2°21 While
the overall incidence of myocarditis following COVID-19 infection is low, persons with COVID-19
have a nearly 16-fold increase in risk for myocarditis, compared to individuals without COVID-
19. The risk is lowest among individuals 25-39 years and higher in persons less than 16 years
and older than 50 years of age.** Myocarditis may also present as part of the Multisystem
inflammatory syndrome in children (MIS-C), usually 3 to 5 weeks after a SARS-CoV-2 infection.
MIS-C is a rare but serious COVID-19-associated condition that occurs in less than 1% of
children with confirmed SARS-CoV-2 infection.2° MIS-C presents with persistent fever,
laboratory evidence of inflammation, and at least 2 affected organs. In severe cases,
hypotension and shock can occur. Most patients have laboratory markers indicating damage to
the heart.*4 During the pandemic, a rise in MIS-C cases has generally lagged behind a rise
observed in COVID-19 infections by several weeks,° with one study demonstrating the peak in
MIS-C cases occurring 31 days following the peak in laboratory-confirmed COVID-19 cases.*6
Between May 2020 and October 4, 2021, the CDC received reports of 5,217 cases and 46
deaths that met the definition for MIS-C; the median age of participants was 9 years with half of
the cases occurring in children ages 5 to 13 years. Males comprised 60% of cases, and 61%
were reported in children who were reported as Hispanic or Black.?’ Up to 66.7% of patients
with MIS-C had cardiac involvement, 7° including left ventricular dysfunction, mitral or tricuspid
regurgitation, coronary artery aneurysms, and/or arrhythmias.*° One study of outcomes in
children with MIS-C followed up to 9 months found that while 76% children with MIS-C required
ICU admission and therapy with inotropes or pressors; most symptoms, including
cardiovascular manifestations, resolved within 1 to 4 weeks.°° Limited data are available on
long-term outcomes in MIS-C.

While children and adolescents appear less susceptible to SARS-CoV-2 infection and generally
have a milder COVID-19 disease course as compared with adults, 31:52 adolescents and adults
have similar SARS-CoV-2 viral loads in their nasopharynx, so adolescents may play a role in
community transmission.**:*4 Transmission of SARS-CoV-2 virus from children can occur in both
household and school settings.*°° In schools, transmission depends on the transmission rates
locally, variants circulating in the community, vaccination rates, and other preventive mitigation
strategies. Transmission between school staff members may be more common than
transmission involving students.*’ There is evidence that SARS-CoV-2 transmission is greater
in secondary and high schools than elementary schools.**:3° Outbreaks of COVID-19 have been
reported in settings where children congregate, such as summer youth camps.441

In addition to morbidity and mortality on an individual level, the continuing spread of SARS-CoV-
2 has caused significant challenges and disruptions in worldwide healthcare systems,
economies, and many aspects of human activity (travel, employment, education). Other impacts
of COVID-19 on children include limited access to basic services such as healthcare and child
protective services, and social isolation due to disruption of school, sports, and social group
gatherings. The emergence of the Delta variant, variable implementation of public health
measures designed to control spread, and continued transmission among unvaccinated
individuals are major factors in the recent resurgence of COVID-19. While recently reported
cases appear to be declining relative to the Delta variant-associated peak globally and in the
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 146 of 237

United States, the longer-term effect of the Delta variant and the potential role of other variants
on the future course of the pandemic is uncertain.

3 AUTHORIZED AND APPROVED VACCINES AND THERAPIES FOR COVID-19

FDA has issued EUAs for three COVID-19 vaccines as shown in Table 1 below. The Pfizer-
BioNTech COVID-19 Vaccine is also FDA approved for use as a 2-dose primary series in
individuals 16 years of age and older, under the trade name COMIRNATY (see Section 4).

Table 1. Emergency Use Authorizations of COVID-19 Vaccines

Date of EUA or

Sponsor Authorized Use (Interval) Indicated Population EUA Amendment
Pfizer- 2-dose primary series (3 Individuals 216 years of age December 11, 2020
BioNTech weeks apart)
Individuals 212 years of age May 10, 2021
Pfizer- 3 primary series dose (at Individuals 212 years of age with August 12, 2021
BioNTech least 1 month after the compromised immune systems
second dose) due to solid organ transplantation
or conditions considered to have
an equivalent level of
immunocompromise
Pfizer- Booster dose (at least 6 e Individuals 65 years of age and September 22, 2021
BioNTech months after completing a older
primary series of e Individuals 18 through 64 years
COMIRNATY and/or Pfizer- of age and at high risk of severe
BioNTech COVID-19 COVID-19
Vaccine) e Individuals 18 through 64 years
of age with frequent institutional
or occupational exposure to
SARS-CoV-2
Moderna 2-dose series (4 weeks 2-dose primary series in adults December 18, 2020
apart) 218 years of age
Moderna 34 dose (at least 1 month Individuals 212 years of age with August 12, 2021
after the second dose) compromised immune systems
due to solid organ transplantation
or conditions considered to have
an equivalent level of
immunocompromise
Moderna Booster dose (at least 6 e Individuals 65 years of age and October 20, 2021
months after completing a older
primary series of Moderna e Individuals 18 through 64 years
COVID-19 Vaccine of age and at high risk of severe
COVID-19
e Individuals 18 through 64 years
of age with frequent institutional
or occupational exposure to
SARS-CoV-2
Janssen Single dose Individuals 218 years of age February 27, 2021
Janssen Booster dose Individuals 218 years of age October 20, 2021
Pfizer, Single heterologous booster Same population(s) as those October 20, 2021
Moderna dose following completion of — eligible to receive a booster dose

and Janssen

primary vaccination with
another authorized or
approved COVID-19

of the vaccine used for primary

vaccination

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Date of EUA or
Sponsor Authorized Use (Interval) Indicated Population EUA Amendment

vaccine (same interval as
authorized for a booster
dose of the vaccine used for
primary vaccination)

Remdesivir is the only product currently approved by the FDA for treatment of COVID-19
requiring hospitalization, and its approved use is limited to individuals 12 years of age and older.
Prior to its approval, remdesivir was authorized for emergency use in adults and pediatric
patients and remains authorized for emergency use in hospitalized pediatric patients who are
not included in the indicated population under licensure.

Emergency use authorizations of COVID-19 pharmacological products for post-exposure
prophylaxis and/or treatment of COVID-19 are as follows:

Table 2. Emergency Use Authorized Pharmacological Products for Post-exposure Prophylaxis
and/or Treatment of COVID-19

Product Date of EUA Authorized Use and Population

SARS-CoV-2-targeting
Monoclonal Antibodies

¢ Bamlanivimab/etesevimab Reissued September 16, All three products are indicated for the
2021 treatment of mild-to-moderate COVID-

¢ Sotrovimab 19 in adults and pediatric patients 12
May 26, 2021 years and older at high risk for

* Casirivimab/imdevimab progressing to severe COVID-19#

Reissued September 9, 2021
Casirivimab/imdevimab is also
authorized for post-exposure prophylaxis
(prevention) for COVID-19 in patients at
high risk for progressing to severe

COVID-19°
Antiviral Drugs
¢ Remdesivir Reissued October 22, 2020 Treatment of COVID-19 in hospitalized
(following FDA approval in pediatric patients weighing at least 3.5
adults and some pediatric kg to <40 kg, or <12 years of age
patients) weighing at least 3.5 kg, or 212 years

and weighing at least 40 kg

Immune Modulators

* Baricitinib Reissued July 29, 2021 Treatment of COVID-19 in hospitalized
patients® receiving systemic
¢ Actemra June 24, 2021 corticosteroids and require

supplemental oxygen, non-invasive or
invasive mechanical ventilation, or

ECMO
COVID-19 Convalescent Reissued March 9, 2021 Treatment of hospitalized patients with
Plasma COVID-19

a Indicated for adults and pediatric patients 12 years of age and older weighing at least 40 kg

b Indicated for adults and pediatric patients 2 years and older

ECMO extracorporeal membrane oxygenation, EUA emergency use authorization

Source: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-
framework/emergency-use-authorization#coviddrugs Accessed August 2, 2021.
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4 COMIRNATY (COVID-19 VACCINE, mRNA)

On August 23, 2021, FDA approved COMIRNATY (COVID-19 Vaccine, mRNA) made by
BioNTech Manufacturing GmbH (in partnership with Pfizer, Inc.). COMIRNATY is a vaccine
indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 16 years of age
and older. The vaccine is administered IM as a series of two doses (0.3 mL each) 3 weeks
apart, with each dose containing 30 ug MRNA. COMIRNATY contains a nucleoside-modified
messenger RNA (mRNA) encoding the viral spike glycoprotein of SARS-CoV-2 that is
formulated in lipid particles. COMIRNATY is the only vaccine or medical product that is FDA
approved for prevention of COVID-19. COMIRNATY is also authorized under EUA for use as a
2-dose primary series in individuals 12 years of age and older, for use as a third primary series
dose in individuals 12 years of age and older with certain immunocompromising conditions, and
for use as a single booster dose administered at least 6 months after completion of a primary
series to individuals 65 years of age and older, individuals 18 through 64 years of age at
increased risk of severe COVID-19, and individuals 18 through 64 years of age with frequent
institutional or occupational exposure to SARS-CoV-2. The vaccine authorized under EUA is
also known as the Pfizer-BioNTech COVID-19 Vaccine. During clinical development, the
vaccine was called BNT162b2.

COMIRNATY is supplied as a concentrated multi-dose liquid formulation (0.45 mL volume)
stored frozen at -90°C to -60°C in a2 mL Type 1 glass vial. A sterile diluent, 0.9% Sodium
Chloride Injection, USP, is supplied separately and is stored at 20°C to 25°C. The COMIRNATY
Multiple Dose Vial is thawed in a refrigerator (2°C to 8°C) for 2 to 3 hours or at room
temperature (up to 25°C) for 30 minutes. Once at room temperature, the COMIRNATY Multiple
Dose Vial is diluted with 1.8 mL of the diluent. After dilution, each vial of COMIRNATY contains
six doses of 0.3 mL of vaccine. COMIRNATY does not contain preservative.

4.1 Efficacy of a 2-dose primary series of COMIRNATY in individuals 16 years of age
and older

Efficacy of BNT162b2 for the prevention of COVID-19 occurring at least 7 days after completion
of a 2-dose primary series was evaluated in an ongoing Phase 3 study, C4591001, in
approximately 44,000 participants randomized 1:1 to receive two doses of either BNT162b2 or
placebo, 3 weeks apart. Participants were enrolled with stratification by age (younger adults: 18
through 55 years of age; older adults: over 55 years of age). The population for the vaccine
efficacy analysis that supported approval of COMIRNATY included participants 16 years of age
and older who had been enrolled from July 27, 2020, and who were followed for the
development of COVID-19 during blinded placebo-controlled follow-up through as late as March
13, 2021. Overall, 60.8% of participants in the BNT162b2 group and 58.7% of participants in the
placebo group had 24 months of follow-up time after the primary series in the blinded placebo-
controlled follow-up period. The overall VE against COVID-19 in subjects without evidence of
prior SARS-CoV-2 infection was 91.1% (95% Cl: 88.8 to 93.1). The overall VE against COVID-
19 in subjects with or without evidence of prior SARS-CoV-2 infection was 90.9% (95% Cl: 88.5
to 92.8).

4.2 Safety of a 2-dose primary series of COMIRNATY in individuals 16 years of age and
older

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(45.5%), chills (41.5%), joint pain (27.5%), fever (17.8%), and injection site swelling (10.6%).
The most commonly reported solicited adverse reactions in BNT162b2 vaccine recipients 56
years of age and older following any dose were pain at the injection site (78.2%), fatigue
(56.9%), headache, (45.9%), muscle pain (32.5%), chills (24.8%), joint pain (21.5%), injection
site swelling (11.8%), fever (11.5%), and injection site redness (10.4%).

Among participants 16 through 55 years of age, SAEs from Dose 1 up to the participant
unblinding date in ongoing follow-up were reported by 0.8% of BNT162b2 recipients and 0.9%
placebo recipients. In a similar analysis, in participants 56 years of age and older serious
adverse events (SAEs) were reported by 1.8% of BNT162b2 recipients and 1.7% of placebo
recipients who received at least 1 dose of BNT162b2 or placebo, respectively. In these
analyses, 58.2% of study participants had at least 4 months of follow-up after the primary series.
There were no notable patterns between treatment groups for specific categories of SAEs
(including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal
relationship to BNT162b2. From Dose 1 through the March 13, 2021 data cutoff date, there
were a total of 38 deaths, 21 in the BNT162b2 group and 17 in the placebo group. None of the
deaths were considered related to vaccination.

4.3 Effectiveness and safety of a 2-dose primary series of Pfizer-BioNTech COVID-19
Vaccine in adolescents 12-15 years of age

On May 10, 2021, FDA authorized the use of Pfizer-BioNTech COVID-19 Vaccine in individuals
12-15 years of age based on safety and effectiveness data from an ongoing Phase 2/3
randomized, double-blinded and placebo-controlled trial of the Pfizer-BioNTech COVID-19
Vaccine in 2,260 participants 12-15 years of age.

Vaccine effectiveness in the adolescent age group was inferred by immunobridging based on a
comparison of SARS-CoV-2 50% neutralization antibody titers (SARS-CoV-2 mNG
microneutralization assay) at 1 month after Dose 2 in participants 12-15 years of age with those
of young adults 16-25 years of age (the most clinically relevant subgroup of the study population
in whom VE has been demonstrated). In the planned immunobridging analysis, the geometric
mean ratio (GMR) of neutralizing antibody titers (adolescents to young adults) was 1.76 (95%
Cl: 1.47, 2.10), meeting the success criterion (lower bound of the 95% Cl for the GMR >0.67). In
a descriptive immunogenicity analysis, seroresponse rates among participants without prior
evidence of SARS-CoV-2 infection were seen in 97.9% of adolescents and 100% of young
adults (difference in seroconversion rates: -2.1%; 95% Cl: -6.0%, 0.9%). Immunogenicity
outcomes were consistent across demographic subgroups, such as baseline SARS-CoV-2
status, comorbidities, ethnicity, race and sex. In the supplemental efficacy analysis, VE after 7
days post Dose 2 was 100% (95% Cl 75.3; 100.0) in participants 12-15 years of age without
prior evidence of SARS-CoV-2 infection and 100% in the group of participants with or without
prior infection. VE between Dose 1 and Dose 2 was 75.0% (95% Cl 7.4; 95.5), with divergence
of cumulative incidence of COVID-19 cases in BNT162b2 vs. placebo groups beginning at
approximately 14 days after Dose 1. Although based on a small number of cases in descriptive
analyses, the supplementary VE data provided compelling direct evidence of clinical benefit in
addition to the immunobridging data.

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muscle pain (42.2%), fever (24.3%), joint pain (20.2%), injection site swelling (9.2%), injection
site redness (8.6%), all of which were generally mild to moderate and lasted a few days. Severe
solicited local and systemic adverse reactions occurred in up to 2.4% of 12-15-year-old
BNT162b2 recipients, were more frequent after Dose 2 (most common: fatigue 1.3%, headache
1.0%, chills 0.4%) than after Dose 1 (most common: fatigue 2.4%, headache 2.0%, chills 1.8%)
and more frequent after any dose in BNT162b2 recipients than age-matched placebo recipients.
Among recipients of BNT162b2, severe solicited adverse reactions/events in 12-15-year-olds
occurred less frequently than in 16-25-year-olds. No deaths were observed in this age group
during the follow-up period. SAEs, while uncommon (<0.5%), represented medical events
expected to occur among individuals in this age group and with the underlying conditions
represented in the study population, and available data do not suggest a causal relationship to
BNT162b2. There were no notable patterns or numerical imbalances between treatment groups
for specific categories of non-serious AEs among study participants 12-15 years of age that
would suggest a causal relationship to BNT162b2 vaccine.

4.4 Cases of myocarditis/pericarditis reported in BNT162b2 recipients in ongoing
clinical trials of BNT162b2

Two cases of myocarditis have been reported in BNT162b2 recipients in study C4591001:

e Amale participant 255 years of age, with no medical history, reported myocarditis 28
days after Dose 2 of BNT162b2; the event was assessed by the investigator as not
related to the study intervention and was ongoing at the time of the data cutoff.

e Amale participant who was randomized to blinded placebo group at age 15 years and
subsequently unblinded and crossed over to open label BNT162b2 at age 16 years was
diagnosed with myopericarditis beginning 2 days after Dose 2 of BNT162b2. He was
hospitalized on Day 3 and treated with IVIG, non-steroidal anti-inflammatory medications
and steroids, and discharged the following day. He was followed by a cardiologist and
seen for follow-up 2 months after vaccination. At that time the cardiologist recommended
limited activity. The investigator concluded that the there was a reasonable possibility
that the myopericarditis was related to vaccine administration due to the plausible
temporal relationship. FDA agrees with this assessment.

4.5 Post-EUA and post-licensure surveillance

As of October 21, 2021, more than 240 million doses of the Pfizer-BioNTech COVID-19 Vaccine
have been administered in the U.S. (CDC COVID Data Tracker, accessed on October 22,
2021). Among all COVID-19 vaccines, 205,046 individuals less than 12 years of age have
received at least one dose and 125,656 are fully vaccinated (CDC COVID Data Tracker,
accessed on October 22, 2021).

The Vaccine Adverse Event Reporting System (VAERS) was queried for adverse event (AE)
reports following administration of the Pfizer-BioNTech COVID-19 Vaccine, and the results are
summarized below. Spontaneous surveillance systems such as VAERS are subject to many
limitations, including underreporting, variable report quality and accuracy, inadequate data
regarding the numbers of doses administered, and lack of direct and unbiased comparison
groups. Reports in VAERS may not be medically confirmed and are not verified by FDA. Also,
there is no certainty that the reported event was actually due to the vaccine.

As of October 18, 2021, VAERS received 442,763 reports (including 270,342 U.S. reports), of
which 854 U.S. reports were in children 5-11 years of age, 9,523 U.S. reports were in children

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12-15 years of age, and 5,821 U.S. reports were in adolescents 16-17 years of age. The top ten
most frequently reported MedDRA preferred terms (PTs) included:

e Overall most frequent PTs: headache, fatigue, pyrexia, SARS-CoV-2 test, dizziness,
pain, nausea, chills, pain in extremity, dyspnoea

e Most frequent PTs in in persons $17 years of age: dizziness, syncope, headache,
pyrexia, nausea, product administered to patient of inappropriate age, chest pain,
fatigue, vomiting, loss of consciousness.

Note that a report may have one or more PTs. An additional query of VAERS for U.S. reports by
dose number retrieved the following: 127,747 reports after Dose 1; 100,730 reports after Dose
2; and 5,223 reports after dose 3 (data as of October 18, 2021).

Safety concerns identified from post-authorization safety surveillance data in VAERS are
summarized below. Anaphylaxis, myocarditis, and pericarditis are existing safety concerns that
have been added to the product Fact Sheets. Review of passive surveillance AE reports and the
Sponsor's periodic safety reports does not indicate any new safety concerns, including in
adolescents. Most AEs are labeled events and consistent with the safety profile for this vaccine.
No unusual frequency, clusters, or other trends for AEs were identified that would suggest a
new safety concern.

Anaphylaxis

Post-authorization surveillance has identified a risk of anaphylaxis, occurring at a rate similar to
reported rates of anaphylaxis following licensed preventive vaccines, primarily in individuals with
history of prior severe allergic reactions to other medications or foods.4243 Anaphylaxis is an
important identified risk in the pharmacovigilance plan (PVP) and included in the Warnings
sections of the vaccine Fact Sheets and Prescribing Information. The estimated crude reporting
rate for anaphylaxis in the U.S. is 6.1 cases per million doses at this time based on the above
VAERS data.

Myocarditis and pericarditis

Post-EUA safety surveillance reports received by FDA and CDC identified increased risks of
myocarditis and pericarditis, particularly within 7 days following administration of the second
dose of the 2-dose primary series. Reporting rates for medical chart-confirmed myocarditis and
pericarditis in VAERS have been higher among males under 40 years of age than among
females and older males and have been highest in males 12 through 17 years of age (~71.5
cases per million second primary series doses among males age 16-17 years and 42.6 cases
per million second primary series doses among males age 12-15 years as per CDC
presentation to the ACIP on August 30, 2021). In an FDA analysis of the Optum healthcare
claims database, the estimated excess risk of myocarditis/pericarditis approached 200 cases
per million fully vaccinated males 16-17 years of age and 180 cases per million fully vaccinated
males 12-15 years of age.*4 Although some cases of vaccine-associated myocarditis/pericarditis
have required intensive care support, available data from short-term follow-up suggest that most
individuals have had resolution of symptoms with conservative management. Information is not
yet available about potential long-term sequelae and outcomes in affected individuals, or
whether the vaccine might be associated initially with subclinical myocarditis (and if so, what are
the long-term sequelae). A mechanism of action by which the vaccine could cause myocarditis
and pericarditis has not been established. Myocarditis and pericarditis were added as important
identified risks in the PVP and included in the Warnings sections of the vaccine Fact Sheets and
Prescribing Information. The Sponsor is conducting additional post-authorization/post-marketing

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studies to assess known serious risks of myocarditis and pericarditis as well as to identify an
unexpected serious risk of subclinical myocarditis.

5 EUA AMENDMENT REQUEST FOR THE PFIZER-BIONTECH COVID-19 VACCINE FOR
USE IN CHILDREN 5-11 YEARS OF AGE

On October 6, 2021, Pfizer and BioNTech submitted a request to amend this EUA to include
use of a 2-dose primary series of the Pfizer-BioNTech COVID-19 Vaccine (10 ug each dose,
administered 3 weeks apart) in individuals 5-11 years of age for active immunization to prevent
COVID-19 caused by severe acute coronavirus 2 (SARS-CoV-2).

The request is accompanied by safety data from 1,518 BNT162b2 and 750 placebo (saline)
Phase 2/3 participants 5-11 years of age in ongoing clinical study, C4591007, of which a total of
1,444 (95.1%) had safety follow-up 22 months after Dose 2 at the time of a September 6, 2021
data cutoff, and data from an additional 1,591 BNT162b2 and 788 placebo participants with a
median duration of follow-up of 2.4 weeks post-Dose 2 at the time of an October 8, 2021 data
cutoff. Vaccine effectiveness in children 5-11 years of age was inferred by immunobridging
SARS-CoV-2 50% neutralizing antibody titers (NT50, as assessed by SARS-CoV-2 mNG
microneutralization assay) among C4591007 study participants 5-11 years of age following
completion of a primary series to antibody titers of those of young adults 16-25 years of age
who received two doses of 30 ug BNT162b2 in study C4591001. Efficacy against COVID-19
disease was assessed descriptively in study C4591007 participants 5-11 years of age.

Vaccine formulation

Authorization is being requested for a modified formulation of the Pfizer-BioNTech COVID-19
Vaccine. Each dose of this formulation contains 10 ug of a nucleoside-modified messenger RNA
(mRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 that is formulated in lipid
particles and supplied as a frozen suspension in multiple dose vials.

To provide a vaccine with an improved stability profile, the Pfizer-BioNTech COVID-19 Vaccine
for use in children 5-11 years of age uses tromethamine (Tris) buffer instead of the phosphate-
buffered saline (PBS) as used in the previous formulation and excludes sodium chloride and
potassium chloride. The packaged vials for the new formulation are stored frozen at -90°C to -
60°C. The frozen vials may be thawed and stored at refrigerator at 2°C to 8°C for up to 10
weeks.

The Pfizer-BioNTech COVID-19 Vaccine does not contain preservative. The vial stoppers are
not made with natural rubber latex. For the 10-ug RNA dose, each 1.3-mL filled via vial must be
diluted with 1.3mL 0.9% sodium chloride for injection to provide 10 doses at 10 ug RNA / 0.2 mL
Injection volume. After dilution, the vials should be stored at 2°C to 25°C and should be used
within 12 hours.

6 EUA REQUIREMENTS, GUIDANCE AND CONSIDERATIONS PERTAINING TO COVID-
19 VACCINES

6.1 U.S. requirements to support issuance of an EUA for a biological product

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living abroad, FDA may issue an EVA after determining that certain statutory requirements are
met (section 564 of the FD&C Act (21 U.S.C. 360bbb-3)).

e The chemical, biological, radiological, or nuclear (CBRN) agent referred to in the March 27,
2020 EUA declaration by the Secretary of HHS (SARS-CoV-2) can cause a serious or life-
threatening disease or condition.

e Based on the totality of scientific evidence available, including data from adequate and well-
controlled trials, if available, it is reasonable to believe that the product may be effective to
prevent, diagnose, or treat such serious or life-threatening disease or condition that can be
caused by SARS-CoV-2, or to mitigate a serious or life-threatening disease or condition
caused by an FDA-regulated product used to diagnose, treat, or prevent a disease or
condition caused by SARS-CoV-2.

e There is no adequate, approved, and available alternative to the product for diagnosing,
preventing, or treating the disease or condition.

If these criteria are met, under an EVA, FDA can allow unapproved medical products (or
unapproved uses of approved medical products) to be used in an emergency to diagnose, treat,
or prevent serious or life-threatening diseases or conditions caused by threat agents. FDA has
been providing regulatory advice to COVID-19 vaccine manufacturers regarding the data
needed to determine that a vaccine’s benefit outweigh its risks. This includes demonstrating that
manufacturing information ensures product quality and consistency.

6.2 FDA guidance for industry related to COVID-19 vaccines

An EVA allowing for rapid and widespread deployment of the vaccine to millions of individuals,
including healthy people, would need to be supported by clear and compelling evidence of
effectiveness and adequate safety follow-up to make a determination of favorable benefit/risk
(see guidance for industry “Emergency Use Authorization for Vaccines to Prevent COVID-19”
February 2021, originally issued October 2020).4° These expectations would apply to age-group
specific data to support an EUA amendment for use of an unapproved COVID-19 vaccine in
children 5-11 years of age. The timing, design, and appropriate endpoints for pediatric studies
are discussed in the context of specific vaccine development programs as described in the
guidance for industry "Development and Licensure of Vaccines to Prevent COVID-19" from
June 2020.*6

6.3. Regulatory considerations for clinical development of COVID-19 vaccines in
children

The Vaccines and Related Biological Products Advisory Committee convened on June 21, 2021
to discuss, in general, the data needed to support authorization and/or licensure of COVID-19
vaccines for use in pediatric populations.

Effectiveness

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available data in humans and animal models, FDA considers neutralizing antibody titers (a
functional measure of the vaccine immune response against SARS-CoV-2) to be clinically
relevant for immunobridging to infer effectiveness of COVID-19 vaccines in pediatric age
groups. Because no specific neutralizing antibody titer has been established to predict
protection against COVID-19, two immunogenicity endpoints (geometric mean titer [GMT] and
seroresponse rate) are considered appropriate for comparing the range of neutralizing antibody
responses elicited by the vaccine in pediatric vs. young adult populations.

Safety

The size of the safety database sufficient to assess risks of COVID-19 vaccines for EVA in
pediatric age groups would generally be the same as for other preventive vaccines for infectious
diseases, provided that no specific safety concern is identified that could reasonably be
evaluated in pre-authorization clinical trials. These safety data would include characterization of
common adverse reactions (reactogenicity, including injection site and systemic adverse
reactions), and less common but medically important adverse reactions. Depending on prior
experience with the vaccine in adults, and prior experience with licensed vaccines based on the
same or similar platforms, FDA has accepted an overall pediatric safety database in the range
of ~500 to ~3,000 trial participants exposed to the age-appropriate dose and regimen intended
for licensure and have at least 6 months of follow-up evaluations after completion of the
vaccination regimen. Since COVID-19 vaccines represent a new class of vaccines, with many of
the lead candidates based on new platform technologies, an appropriate overall pediatric safety
database would approach the upper end of this range, with adequate representation across all
pediatric age groups, in particular younger age groups (e.g., <12 years) that are less
physiologically similar to adults. A control group (ideally placebo control) would be important to
inform interpretation of safety data and to comply with the expectation for adequate and well-
controlled studies to support licensure. If another COVID-19 vaccine is licensed or authorized
for use in the age group(s) enrolled in the trial, recommended by public health authorities, and
widely available such that it is unethical to use a placebo control, the licensed or authorized
COVID-19 vaccine could serve as a control.

Within the overall pre-licensure safety database, solicited reactogenicity could be adequately
characterized among several hundred trial participants in each relevant age group. Additionally,
safety evaluation in all trial participants would include collection of all AEs through at least 1
month after each study vaccination and collection of serious and other medically attended AEs
for the duration of the trial. Although longer-term follow-up (through 1 year or longer post-
vaccination) of trial participants would be important to ongoing assessment of both benefits and
risks, completion of such longer-term follow-up would not be a prerequisite to licensure unless
warranted by a specific safety concern. Post-licensure/post-authorization safety surveillance
and observational studies in pediatric populations would be needed to evaluate for adverse
reactions that occur too rarely to be detected in clinical trials.

7 FDA REVIEW OF CLINICAL SAFETY AND EFFECTIVENESS DATA
7.1 Overview of study C45910007

The EVA amendment request contains safety, immunogenicity, and descriptive efficacy data
from children 5-11 years of age enrolled in C4591007, an ongoing Phase 1/2/3, randomized,
placebo-controlled study. The comparator group for the immunobridging analyses to support
vaccine effectiveness in this age group was a random subset of Phase 2/3 participants 16-25
years of age enrolled in study C4591001, the study in which vaccine efficacy against COVID-19
was established in individuals 16 years of age or older.

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Data from study C4591007

e Phase 2/3: a total of 3,109 BNT162b2 (10 yg) recipients and 1528 placebo recipients 5-11
years of age

- Cohort 1: 1,518 BNT162b2 (10 yg) recipients and 750 placebo recipients, of whom
1,444 (95.1%) and 714 (95.2%), respectively, had at least 2 months of safety follow-up
after completing a 2-dose primary series (data cutoff September 6, 2021). Summary
tables for solicited adverse reactions (ARs) and immunogenicity analyses are based on
this cohort of subjects. A descriptive efficacy analysis was also based on this cohort; at
the time of this Briefing Document was prepared, FDA has not fully verified the
underlying data or Pfizer-BioNTech’s conclusions from this analysis.

-— Cohort 2: A second cohort of 1,591 BNT162b2 (10 ug) recipients and 778 placebo
recipients had a median duration of follow-up of 2.4 weeks post-Dose 2 at the time of
data cutoff (October 8, 2021). Safety data from this cohort were provided for further
assessment of SAEs and AEs of clinical interest. Data verification is in process, but not
yet finished at the time this briefing book was completed.

e Phase 1 data to support dosage selection for Phase 2/3 portion of the study

Table 3. Study C4591007*: Participants 5-11 Years of Age (10 pg BNT162b2)

Study Number! BNT162b2 Placebo (Saline)
Countries Description N N Study Status
C4591007 Phase 1/2/3 Phase 1: 16 Phase 1:0 Ongoing
United States, randomized, placebo- Phase 2/3: 3,109 Phase 2/3: 1,528
Finland, Poland, controlled; to evaluate
and Spain safety, immunogenicity

and efficacy of COVID-

19 vaccine

N=Number of randomized participants as of data cutoff dates July 16, 2021 (all Phase 1 participants), September 6, 2021 (Phase
2/3 Cohort 1: 1,518 BNT162b2, 750 placebo; includes participants starting March 24, 2021) and October 8, 2021 (Phase 2/3 cohort
2: 1,591 BNT162b2, 788 placebo; first subject in this second cohort randomized August 15, 2021).

*First participant, first visit was March 24, 2021.

7.2 Study design

Study C4591007 is an ongoing Phase 1/2/3 randomized, observer-blinded, placebo-controlled
safety, immunogenicity, and efficacy study. This section presents the design for the Phase 2/3
portion of the study in children 5-11 years of age. Please see Appendix 1 for Phase 1 study
design.

Phase 2/3 is being conducted in the United States, Finland, Poland, and Spain. The Phase 2/3
portion of the study did not exclude children with a history of prior SARS-CoV-2 infection or
clinical symptoms/signs of COVID-19, children with known HIV, hepatitis B or hepatitis C, or
stable pre-existing disease (defined as disease not requiring significant change in therapy or
hospitalization for worsening disease during the 6 weeks before enrollment).

Participants were randomized 2:1 to receive two doses of 10 ug BNT162b2 or placebo (saline),
3 weeks apart. Participants who turned 12 years of age during the study would have the
opportunity to receive the EUA-authorized dose level of 30 ug (12-15 years of age) if they
originally received placebo.

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Immunogenicity evaluation

Immunobridging was based on SARS-CoV-2 neutralizing antibody responses in study
C4591007 Phase 2/3 (Cohort 1) participants 5-11 years of age compared to neutralizing
antibody responses in a random subset of study C4591001 participants 16-25 years of age, as
measured by 50% neutralizing antibody titers (NT50, SARS-CoV-2 mNG microneutralization
assay) against the reference strain (USA_WA1/2020) at 1 month after a primary series. The
primary analysis is based on the evaluable immunogenicity population of participants without
evidence of prior SARS-CoV-2 infection up to 1 month after Dose 2.

Primary endpoints and statistical success criteria

e Immunobridging success based on GMT was declared if the lower limit (LL) of the 95% Cl
for the GMT ratio (5-11 years of age / 16-25 years of age) was >0.67, and the point estimate
of the GMT ratio was 21.0.

e Immunobridging success based on the seroresponse rate was declared if the LL of the 95%
Cl for the difference in seroresponse rates (5-11 years of age minus 16-25 years of age)
was >-10%. Seroresponse was defined as a 24-fold rise in SARS-CoV-2 50% neutralizing
titers from before vaccination (pre-Dose 1) to 1 month after Dose 2.

Efficacy evaluation

A secondary objective is to evaluate efficacy of BNT162b2 against laboratory-confirmed
symptomatic COVID-19 occurring from 7 days after Dose 2 in participants without evidence of
prior SARS-CoV-2 infection and in participants with or without evidence of prior SARS-CoV-2
infection. A descriptive analysis was conducted once 19 confirmed cases had accrued.

Safety evaluation
Reactogenicity (solicited local and systemic adverse reactions)

The participants’ parents or participants themselves recorded reactogenicity assessments and
antipyretic/pain medication use from Day 1 through Day 7 after each dose in an e-diary.
Reactogenicity assessments included solicited injection site reactions (pain, redness, swelling)
and systemic AEs (fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle
pain, and new or worsened joint pain).

Unsolicited adverse events

Other safety assessments included: AEs occurring within 30 minutes after each dose, non-
serious unsolicited AEs from Dose 1 through 1 month after Dose 2, and SAEs from Day 1 to 6
months after Dose 2, or the data cutoff date (Phase 1: of July 16, 2021; Phase 2/3: September
6, 2021). AEs were categorized by frequency and maximum severity according to system organ
class (SOC) and preferred term (PT), according to MedDRA, and relationship to the study
intervention was assessed. Deaths are recorded to the end of the study.

Adverse events of clinical interest

The occurrence of certain AEs including lymphadenopathy and myocarditis/pericarditis were
assessed as part of the safety review, as well as additional AEs requested by FDA (including
anaphylaxis, Bell’s palsy, appendicitis, pregnancy exposures and outcomes, and MIS-C cases).
Analysis populations

Pertaining to participants 5-11 years of age

e Safety: All participants who receive at least 1 dose of the study intervention.

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e All-available immunogenicity: All randomized participants who receive at least 1 dose of the
study intervention with at least 1 valid and determinate immunogenicity result after
vaccination.

e Evaluable immunogenicity: All eligible randomized participants who receive two doses of the
vaccine to which they are randomized with Dose 2 received within the predefined window,
have at least 1 valid and determinate immunogenicity result from the blood sample collected
within an appropriate window, and have no other important protocol deviations as
determined by the clinician.

e valuable efficacy: All randomized participants who receive all vaccinations as randomized,
with Dose 2 received within the predefined window (within 19-42 days after Dose 1) and
have no other important protocol deviations as determined by the clinician on or before 7
days after Dose 2.

Data analysis cutoff dates:
e All Phase 1 participants: July 16, 2021
e Phase 2/3 Cohort 1: September 6, 2021; includes participants starting March 24, 2021
e Phase 2/3 Cohort 2: October 8, 2021; first subject in this cohort was randomized August
15, 2021

7.3 Disposition of Phase 2/3 participants

Cohort 1

Cohort 1 was comprised 1,528 BNT162b2 10 ug participants and 757 placebo participants; 11
(0.7%) BNT162b2 and 6 (0.8%) placebo participants did not receive any study agent. Two
BNT162b2 participants (0.1%) and two placebo participants (0.3%) discontinued vaccination
before the 1 month post-Dose 2 follow-up; none resulted from an AE. Three participants turned
12 years of age during the course of the study and became eligible to receive 30 ug BNT162b2
under EUA; two of these participants received two doses of 10 ug BNT162b2 prior to being
unblinded, and the other participant received both doses of placebo before being unblinded and
withdrew to receive a COVID-19 vaccine outside of the study; data from these participants were
included in endpoint analyses up to the point at which they were unblinded.

Safety population: solicited ARs, unsolicited AEs, SAEs and AEs of clinical interest were
assessed in a total of 2,268 (1,518 10 ug BNT162b2, 750 placebo) participants 5-11 years of
age; 95% of participants in each study group completed at least 2 months of safety follow-up
after Dose 2. Five BNT162b2 recipients and six placebo recipients withdrew from the study,
mainly due to voluntary withdrawal.

Comparator group for immunogenicity: The comparator group for immunobridging analyses
consisted of 300 evaluable participants 16-25 years of age who received both doses of
BNT162b2 30 ug and were randomly selected from study C4591001 Phase 2/3.

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Table 4. Disposition of Immunogenicity Populations, Phase 2/3, Participants 5-11 Years of Age
(Study C4591007 Cohort 1) and Participants 16-25 Years of Age (Study C4591001)

5-11 years of age 5-11 years ofage 16-25 years of age

BNT162b2 (10 yg) Placebo BNT162b2 (30 yg)
Disposition n (%) n (%) n (%)
Randomized to receive BNT162b2? 322 (100.0) 163 (100.0) 300 (100.0)
All-available immunogenicity population 311 (96.6) 156 (95.7) 286 (95.3)
Excluded because they did not have at
least 1 valid and determinate 11 (3.4) T (4.3) 13 (4.3)
immunogenicity result after vaccination
Evaluable immunogenicity population 294 (91.3) 147 (90.2) 273 (91.0)
Without evidence of infection up to 1 264 (82.0) 130 (79.8) 253 (84.3)
month after Dose 2°
Subjects excluded from evaluable 28 (8.7) 16 (9.8) 27 (9.0)
immunogenicity population
Reason for exclusion (Subjects may have
been excluded for >1 reason)
Did not receive 2 doses of the vaccine 3 (0.9) 1 (0.6) 0
as randomized
Did not receive Dose 2 within 19 to 42 3 (0.9) 2 (1.2) 3 (1.0)

days after Dose 1

Did not have at least 1 valid and
determinate immunogenicity result 13 (4.0) 14 (8.6) 21 (7.0)
within 28 to 42 days after Dose 2

Did not have blood draw at 1 month

after Dose 2 visit (22) 6 (3.7) 8 (2.7)
1 Month after Dose 2 blood draw

outside of window (28-42 days after 6 (1.9) 8 (4.9) 13 (4.3)
Dose 2)

Had important protocol deviation(s) as 10 (3.1) 0 4 (1.3)

determined by the clinician

%:n/N. n = number of participants with the specified characteristic. N = number of randomized participants in the specified group;

this value is the denominator for the percentage calculations.

a. Participants who had no serological or virological evidence (prior to the 1-month post-Dose 2 blood sample collection) of past
SARS-CoV-2 infection (i.e., N-binding ant body [serum] negative at Visit 1 and Visit 4 (C4591007) or Visit 3 (C4591001), SARS-
CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2, and negative NAAT [nasal swab] result at any unscheduled visit prior
to the 1-month post-Dose 2 blood sample collection) and had no medical history of COVID-19 were included in the analysis.

b. Participants may have been excluded for more than 1 reason.

Cohort 2

In the Phase 2/3 safety expansion, 1,598 participants were randomized to receive BNT162b2
and 796 were randomized to placebo. At the time of the October 8, 2021 cutoff, most
participants (98.7%) had received both Dose 1 and Dose 2. Seven participants in the BNT162b2
group did not receive vaccine, for a Safety Population of 1,591. One participant in the
BNT162b2 group discontinued from the vaccination period due to AEs of pyrexia and
neutropenia that worsened from baseline (see Section 7.6.7, AEs leading to withdrawal). Two
participants (0.1%) in the BNT162b2 group withdrew from the study before the 1 month period.
Neither withdrawal was due to an AE.

Comorbidities at baseline

Comorbidities were defined as described in Kim et al. MMWR 2020.*’ Participants with any
comorbidity, including obesity, constituted 20.6% of the BNT162b2 group and 20.3% of placebo
group. The most common comorbidities at baseline in the Cohort 1 BNT162b2 group were
obesity (11.5%), asthma (7.8%), neurologic disorders (1.3%), and congenital heart disease

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(1.0%). Other comorbidities included diabetes in 2 participants (0.2%), and one participant each
(0.1%) for acute lymphocytic leukemia (immunocompromising conditions), cystic fibrosis, and
sickle cell disease.

Demographic characteristics were similar in Cohort 2 as Cohort 1. Overall, 11.1% of participants
were obese. Comorbidities including obesity were found in 19.9% of participants. As in Cohort
1, the most common comorbidities were asthma, neurologic disorders and congenital heart
disease.

7.4 Demographic and baseline characteristics

Demographic characteristics for the safety population of participants who received BNT162b2
10 ug in Phase 2/3 study C4591007 Cohort 1 are summarized in Table 5 below. Participants
were predominately White, with a mean age of approximately 8 years. Of the BNT162b2
recipients, 11.5% met the definition of obesity, 8.8% had evidence of prior SARS-CoV-2
infection and 20.6% had comorbidities placing them at increased risk of severe COVID-19. More
than 70% of participants were enrolled in the United States.

Table 5. Demographic and Baseline Characteristics, Phase 2/3, Participants 5-11 Years, Safety
Population, Study C4591007 Cohort 1

C4591007 C4591007

BNT162b2 10 yg Placebo

(N#=1518) (N?=750)

Characteristic n° (%) n° (%)
Sex: Male 799 (52.6) 383 (51.1)
Sex: Female 719 (47.4) 367 (48.9)
Race: White 1204 (79.3) 586 (78.1)
Race: Black or African American i (5.9) 58 (7.7)
Race: American Indian or Alaska Native 2 (0.8) 3 (0.4)
Race: Asian 0 (5.9) 47 (6.3)
Race: Multiracial 109 (7.2) 49 (6.5)
Race: Not reported 9 (0.6) 7 (0.9)
Ethnicity: Hispanic or Latino 319 (21.0) 159 (21.2)
Ethnicity: Not Hispanic or Latino a (78.8) 591 (78.8)
Age: Mean years (SD) 2 (1.93) 8.1 (1.97)
Age: Median (years) 8.0 8.0
Obese*: Yes 174 (11.5) 2 (12.3)
Obese®: No 1343 (88.5) 358 (87.7)
Baseline Evidence of Prior SARS-CoV-2 Infection: Negative® 1385 (91.2) 685 (91.3)
Baseline Evidence of Prior SARS-CoV-2 Infection: Positive! 133 (8.8) 65 (8.7)
Comorbidities*: Yes 312 (20.6) 152 (20.3)
Comorbidities*: No 1206 (79.4) = (79.7)
Country: Finland 158 (10.4) 1 (10.8)
Country: Poland 125 (8.2) “0 (8.0)
Country: Spain 162 (10.7) 8 (10.4)
Country: United States 1073 (70.7) 1 (70.8)

Abbreviations: BMI = body mass index; COVID-19 = coronavirus disease 2019; NAAT = nucleic acid amplification test; N-binding =
SARS-CoV-2 nucleoprotein-binding; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

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Demographic and baseline characteristic categories with 0 participants in any treatment group are not shown to avoid inadvertent
unblinding through public disclosure.

a. N=number of participants in the specified group. This value is the denominator for the percentage calculations.

b. n=Number of participants with the specified characteristic.

c. Obese is defined as a body mass index (BMI) at or above the 95" percentile according to the growth chart. Refer to the CDC
growth charts at https:/Awww.cdc.gov/growthcharts/html_charts/bmiagerev.htm.

d. Number of participants who have 1 or more comorbidities that increase the risk of severe COVID-19 disease: defined as
participants who had at least one of the prespecified comorbidities based on MMWR 69(32);1081-1088 and/or obesity (BMI 2 95"
percentile).

e. Negative N-binding antibody result and negative NAAT result at Visit 1 and no medical history of COVID-19.

f. Positive N-binding antibody result at Visit 1, positive NAAT result at Visit 1, or medical history of COVID-19.

Demographic characteristics in Cohort 2 were similar to Cohort 1.
Comparator group for immunogenicity: The 300 participants ages 16-25 years from study

C4591001 were from sites in the United States (64%), Argentina (18%), Brazil (12%), and South
Africa/Turkey/Germany (6% combined total).

Less than 0.8% of participants in either group received non-COVID-19 vaccines during the
study; most were routine pediatric immunizations including diphtheria, pertussis, tetanus, human
papillomavirus vaccine, and meningococcal vaccine.

7.5 Immunogenicity results
7.5.1 Primary immunogenicity objective

Immunogenicity of BNT162b2 was assessed based on analyses of GMTs and seroresponse
rates for neutralizing antibody titers to the reference strain (USA_WA1/2020).

GMTs of neutralizing antibody titers to the reference strain

Among participants in the evaluable immunogenicity population without prior evidence of SARS-
CoV-2 infection up to 1 month after Dose 2, the ratio of SARS-CoV-2 50% neutralizing GMT in
children 5-11 years (10 ug each dose) compared to individuals 16-25 years (30 ug each dose)
was 1.04. (95% Cl: 0.93, 1.18). The lower bound of the 2-sided 95%Cl for GMR was >0.67 and
the point estimate was 21, which met FDA’s requested criteria; see Table 6, below.

Table 6. SARS-CoV-2 Neutralizing GMTs (NT50)? at 1 Month Post-Primary Series in Phase 2/3
BNT162b2 (10 pg) Recipients 5-11 Years of Age and Study C4591001 Phase 2/3 Cohort 1
BNT162b2 (30 ug) Recipients 16-25 Years of Age Without Evidence of SARS-CoV-2 Infection up to
1 Month After Dose 2, Evaluable Immunogenicity Population”

GMT (95% Cl) GMT (95% Cl) . °
5-11 Years of Age 16-25 Years of Age (5-11 ven Rat oon oe Years
Study C4591007 Study C4591001 of Age)!
c= 264 c= 253 g
1197.6 1146.5 1.04
(1106.1, 1296.6) (1045.5, 1257.2) (0.93, 1.18)

a. SARS-CoV-2 mNeonGreen virus microneutralization assay (SARS-CoV-2 mNG NT), reference strain: recombinant
USA_WA1/2020. NT50= 50% neutralizing titer.

b. Evaluable immunogenicity population pertaining to Phase 2/3 BNT162b2 participants 5-11 years of age (study C4591007) and
Phase 2/3 BNT162b2 participants 16-25 years of age (study C4591001).

c. N = Number of Phase 2/3 participants with valid and determinate assay results for the specified assay at the given dose/sampling
time point within specified window.

d. Immunobridging statistical success is declared if the lower limit of the 2-sided 95% Cl for the GMT ratio is greater than 0.67 and
the point estimate of the GMT ratio is 21.0.

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Rates of neutralizing antibody seroresponse to the reference strain

Seroresponse rates among participants without evidence of prior SARS-CoV-2 infection up to 1
month after Dose 2 are displayed in Table 7 below. Children 5-11 years of age had similar
seroresponse (as measured from before vaccination to 1 month after Dose 2) rate as individuals
16-25 years of age. The difference between the two age groups was 0.0% (95% Cl: -2.0%,
2.2%). The lower limit of the 95% Cl for the difference in seroresponse rate was -2.0%, which
was greater than the prespecified margin of -10% and thus immunobridging based on
seroresponse rate was met, see Table 7 below.

Table 7. Seroresponse Rates?” at 1 Month Post-Primary Series in Phase 2/3 BNT162b2 (10 yg)
Recipients 5-11 Years of Age and Study C4591001 Phase 2/3 Cohort 1 BNT162b2 (30 yg)
Recipients 16-25 Years of Age Without Evidence of SARS-CoV-2 Infection up to 1 Month After
Dose 2, Evaluable Immunogenicity Population’

Seroresponse Seroresponse
5-11 Years of Age 16-25 Years of Age % Difference in Seroresponse
Study C4591007 Study C4591001 Rate (Age Group 5-11 Years
%4 %!e minus Age Group 16-25 Years)°
(95% Cl) (95% Cl) (95% Cl)
N= 264 N= 253
99.2 99.2 0
(-2.0, 2.2)
(97.3, 99.9) (97.2, 99.9)

a. SARS-CoV-2 mNeonGreen virus microneutralization assay-NT50, reference strain: recombinant USA_WA1/2020.

b. Seroresponse defined as at least 4-fold rise relative to pre-Dose 1; if the baseline measurement was below LLOQ, a
postvaccination titer of 24 x LLOQ was considered a seroresponse.

c. Evaluable immunogenicity population pertaining to Phase 2/3 BNT162b2 participants 5-11 years of age (study C4591007) and
Phase 2/3 BNT162b2 participants 16-25 years of age (study C4591001).

d. %: n/N. n = number of participants with seroresponse for the given assay at the given dose/sampling time point. N = Number of
subjects with valid and determinate assay results for the specified assay within the specified window for blood samples collected at
baseline (pre-Dose 1) and 1 month after primary series.

e. Immunobridging statistical success is declared if the lower limit of the 2-sided 95% Cl for the difference in percentages of
participants with seroresponse is >-10%.

Subgroup Analyses of Geometric Mean Titers

GMTs of SARS-CoV-2 neutralizing titers and seroresponse rates at 1 month after Dose 2 did
not vary by demographic subgroup, although some subgroups were too small to evaluate by
protocol-specified methods. Specifically, no notable differences in GMTs or seroresponse rates
were observed by age (i.e., 5-6 year-old vs. 7-8 year-old vs. 9-11 year-old), sex, race, ethnicity,
obesity (Y/N), or SARS-CoV-2 status.

In descriptive post hoc analyses of immunogenicity data based on the presence or absence of
comorbidities (defined as described in Kim et al. MMWR 202047), GMT and seroresponse rates
among those with comorbidities were comparable to those without comorbidities.

7.5.2 Exploratory immunogenicity analyses against the Delta Variant

In response to FDA’s request for immunogenicity data to support effectiveness of a 10 yg
BNT162b2 primary series against the Delta variant, Pfizer submitted exploratory descriptive
analyses of data from a randomly selected subset of participants (34 BNT162b2 recipients, 4
placebo recipients) with no evidence of infection up to 1 month post-Dose 2. These data were
generated using non-validated SARS-CoV-2 plaque reduction neutralization assays with the

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reference strain (USA-WA1/2020) and the Delta variant; the relative sensitivity of the two assays
is not known.

Table 8. SARS-CoV-2 Neutralizing GMTs? at Pre-Dose 1 and 1 Month Post-Primary Series in
C4591007 Phase 2/3 Cohort 1 Participants 5-11 Years of Age Without Evidence of SARS-CoV-2
Infection up to 1 Month After Primary Series, Evaluable Immunogenicity Population”

BNT162b2 10 ug Placebo
Assay Target Time Point SMT GMT
(95% Cl) (95% Cl)
Reference strain Pre-Dose 1 (10.0. 10.0) (10.0, 10.0)
1 month post-Dose 2 (79.0. 478.4) (10.0, 10.0)
Delta variant Pre-Dose 1 (10.0. 10.0) (10.0, 10.0)
1 month post-Dose 2 (14.6. 405.3) (10.0. 10.0)

a. SARS-CoV-2 plaque reduction neutralization assay, SARS-CoV-2 strains: recombinant USA_WA1/2020 (reference), B.1.617.2
(Delta).

b. N = number of participants with valid and determinate assay results for the specified assays at the given dose/sampling time point.
Participants with no serological or virological evidence of SARS-CoV-2 infection: defined as N-binding ant body [serum] negative
from pre-Dose 1 to 1 month post-Dose 2, SARS-CoV-2 not detected by NAAT [nasal swab] prior to Dose 1 and Dose 2, and
negative NAAT [nasal swab] result at any unscheduled visit prior to 1-month post-Dose 2, and no medical history of COVID-19.

7.5.3 Efficacy evaluation

Pfizer submitted supplemental, descriptive efficacy data for Phase 2/3 Cohort 1 participants 5-
11 years of age, based on a total of 19 confirmed symptomatic COVID-19 cases occurring at
least 7 days post-Dose 2, accrued up to the data cutoff of October 8, 2021. The evaluable
efficacy population included 1,450 participants randomized to BNT162b2 and 736 participants
randomized to placebo.

In participants 5-11 years of age without evidence of SARS-CoV-2 infection prior to Dose 2, the
observed VE against confirmed COVID-19 occurring at least 7 days after Dose 2 was 90.7%
(95% Cl: 67.4%, 98.3%), with 3 COVID-19 cases in the BNT162b2 group compared to 16 in the
placebo group (2:1 randomization BNT162b2 to placebo). All cases of COVID-19 occurred in
children without prior history of infection. None of these cases met the criteria for severe
infection. Most of the cases occurred in July-August 2021. Comorbidities at baseline (including
obesity) were present in total of 20.1% of cases. No virus sequence analyses were available to
determine whether these cases were caused by the Delta variant or another variant.

7.6 Safety results
Please see the Appendix for Phase 1 study results.
Overview of adverse events: Phase 2/3

In C4591007 Phase 2/3 Cohort 1, e-diary data were collected on 1,511 participants for
reactogenicity (local and systemic reactions). Overall, injection site reactions occurring within 7
days of vaccination with BNT162b2 were common, occurring in approximately 75% of
participants after either Dose 1 or Dose 2. Systemic AEs occurred in approximately 50% of
BNT162b2 recipients.

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No participants withdrew because of AEs, and there were no deaths reported. SAEs occurred in
one participant each from the BNT162b2 and placebo groups, and neither were considered by
the investigator or FDA to be related to the investigational agent. Immediate unsolicited
AEswere rare in this study, occurring in 0.3% or less after either Dose 1 or Dose 2. See Table 9
below.

Table 9. Safety Overview, Phase 2/3 Cohorts 1 and 2, Participants 5-11 Years, Safety Population,
Study C4591007

BNT162b2 10 yg Placebo

Event n/N (%) n/N (%)
Immediate unsolicited AE within 30 minutes after vaccination

Dose #1 3/1518 (0.2) 3/750 (0.4)

Dose #2 4/1515 (0.3) 2/746 (0.3)
Solicited injection site reaction within 7 days

Dose #1 1150/1511 (76.1) — 254/749 (33.9)

Dose #2 1096/1501 (73.0) — 237/741 (32.0)
Solicited systemic AR within 7 days

Dose #1 715/1511 (47.3) 334/749 (44.6)

Dose #2 7771/1501 (51.4) — 272/741 (36.7)
From Dose 1 through 1 month after Dose 2

Any AE 166/1518 (10.9) 69/750 (9.2)

Unsolicited non-serious AE 166/1518 (10.9) 68/750 (9.1)

SAE 0/1518 (<0.1) 1/750 (0.1)
From Dose 1 through cutoff date? or participant unblinding®

Withdrawal due to AEs 1/3109 (<0.1) 0/1538 (0.0)

SAE 4/3109 (0.1) 1/1538 (0.1)

Deaths 0/3109 (0.0) 0/1538 (0.0)

Note: MedDRA (v24.0) coding dictionary applied.

Note: Immediate AE refers to an AE reported in the 30-minute observation period after vaccination.

%:n/N. n = Number of participants with the specified characteristic. N = number of administered participants in the specified group;
this value is the denominator for the percentage calculations.

a. Sept 13, 2021 for 1,518 BNT162b2 and 750 placebo; Oct 8, 2021 for the additional 1,591 BNT162b2 and 788 placebo.

b. Three participants (2 BNT162b2, 1 placebo) turned 12 years of age during the course of the study and elig ble to received 30 ug
BNT162b2 under EUA; for this reason, the participants were unblinded to their treatment assignment.

7.6.1. Immediate AEs

Among the 1,518 Cohort 1 participants who received BNT162b2 Dose 1, a total of 3 reported
any immediate AE, and all were injection site pain. Following Dose 2, 4 participants experienced
an immediate AE, including 1 with nausea, 1 with injection site pain, 1 with injection site
erythema, and 1 with erythema (skin and subcutaneous disorder).

7.6.2 Solicited adverse reactions

Solicited local adverse reactions generally occurred more commonly after Dose 2 and included
pain at the injection site (71%), redness (18.5%) and swelling (15.3%). Systemic adverse
reactions also occurred more frequently after Dose 2 and included fatigue (39.4%), headache
(28%), and muscle pain (11.7%). Most local and systemic reactions were mild to moderate in
severity, with median onset 2 days post-vaccination, and resolved within 1 to 2 days after onset.
Adverse reactions in BNT162b2 recipients that were graded as severe included 4 local
reactions (3 participants with redness, 1 participant with swelling) and 1 systemic reaction (1
participant with muscle pain).

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higher. Systemic adverse reactions such as fever, fatigue, headache, chills, and muscle pain

were generally reported less frequently and were milder in severity in the 5-11 year-old group

compared to individuals 12 years of age or older.

The frequencies of local and systemic adverse reactions within 7 days after each vaccination in
participants with evaluable e-diary data are summarized in Tables 10, 11, and 12 below.

Table 10. Frequency of Solicited Local Reactions Within 7 Days After Each Dose, by Severity,
Phase 2/3 Cohort 1 Participants 5-11 Years of Age, Safety Population’, Study C4591007

BNT162b2 Placebo BNT162b2 Placebo
Dose 1 Dose 1 Dose 2 Dose 2
N=1,511 N=749 N=1,501 N=741
Event % % % %
Pain at the injection site®
Any4 74.1 31.3 71.0 29.5
Mild 58.9 27.3 52.8 25.9
Moderate 14.9 4.0 17.8 3.5
Severe 0.3 0.0 0.3 0.0
Redness°
Any4 14.7 5.7 18.5 5.4
Mild 9.5 49 9.5 4.2
Moderate 5.2 0.8 8.8 1.2
Severe 0.0 0.0 0.2 0.0
Swelling®
Any? 10.5 2.7 15.3 2.7
Mild 5.6 1.7 7.8 2.0
Moderate 4.8 0.9 7.5 0.7
Severe 0.1 0.0 0.0 0.0

%:n/N. n=number of participants in the specified age group with the specified reaction. N=number of participants in the specified

age group reporting at least 1 yes or no response for the specified reaction after the specified dose.
* All participants in the specified age group who received at least 1 dose of the study intervention.
> Mild: does not interfere with activity; moderate: interferes with activity; severe: prevents daily activity.

° Mild: 0.5 to $2.0 cm; moderate: 2.0 to <7.0 cm; severe: >7.0 cm.

¢ Any local reaction: any redness >0.5 cm, any swelling >0.5 cm, or any pain at the injection site.

Table 11. Frequency of Solicited Systemic Reactions Within 7 Days After Dose 2 by Severity,
Phase 2/3 Cohort 1 Participants 5-11 Years of Age, Safety Population, Study C4501007

BNT162b2 Placebo BNT162b2 Placebo

Dose 1 Dose 1 Dose 2 Dose 2

N=1,511 N=749 N=1,501 N=741

Event % % % %
Fever

238.0°C 2.5 1.3 6.5 1.2

238.0°C to 38.4°C 1.5 0.5 3.4 0.7

>38.4°C to 38.9°C 0.8 0.7 2.5 0.4

>38.9°C to 40.0°C 0.2 0.1 0.5 0.1

>40.0°C 0.0 0.0 0.1 0.0

Fatigue?

Any® 33.6 31.3 39.4 24.3
Mild 22.0 20.1 21.4 13.0
Moderate 11.3 11.1 17.3 11.2
Severe 0.3 0.1 0.7 0.1

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BNT162b2 Placebo BNT162b2 Placebo

Dose 1 Dose 1 Dose 2 Dose 2

N=1,511 N=749 N=1,501 N=741

Event % % % %
Headache>

Any® 22.4 24.1 28.0 18.6
Mild 16.5 17.5 18.7 12.6
Moderate 5.8 6.0 9.1 6.1
Severe 0.1 0.5 0.2 0.0

Chills®

Any® 4.6 4.7 9.8 4.3
Mild 3.6 4.0 7.0 3.2
Moderate 1.1 0.7 2.7 0.9
Severe 0.0 0.0 0.1 0.1

Vomiting®

Any® 2.2 1.5 1.9 0.8
Mild 1.7 1.5 1.8 0.8
Moderate 0.5 0.0 0.1 0.0
Severe 0.0 0.0 0.0 0.0

Diarrhea?

Any® 5.9 4.1 5.3 4.7
Mild 5.2 4.1 4.8 4.3
Moderate 0.7 0.0 0.5 0.4
Severe 0.0 0.0 0.0 0.0

New or worsened
muscle pain>

Any® 9.1 6.8 11.7 7.4
Mild 6.4 4.7 7.7 5.1
Moderate 2.6 2.1 3.9 2.3
Severe 0.1 0.0 0.1 0.0

New or worsened
joint pain®

Any® 3.3 5.5 5.2 3.6
Mild 2.3 4.1 3.8 2.7
Moderate 1.1 1.3 1.4 0.9
Severe 0.0 0.0 0.0 0.0

Use of antipyretic or 14.4 8.3 19.7 8.1

pain medication‘
%: n/N. n = Number of participants with the specified reaction. N = Number of participants reporting at least 1 yes or no response
for the specified reaction after the specified dose.
@ All participants in the specified age group who received at least 1 dose of the study intervention.
> Mild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity.
° Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration.
4 Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours.
° Any systemic event: any fever 238.0°C, any fatigue, any vomiting, any chills, any diarrhea, any headache, any new or worsened
muscle pain, or any new or worsened joint pain.
f Severity was not collected for use of antipyretic or pain medication.

Table 12. Characteristics of Solicited Local and Systemic Adverse Reactions, Phase 2/3 Cohort 1,
Participants 5-11 Years, Safety Population, Vaccine Group as Administered, Study C4591007
BNT162b2 10 yg Placebo BNT162b2 10 yg Placebo

Dose 1 Dose 1 Dose 2 Dose 2

Event n@/N° n@/N° n@/N° n@/N°
Any solicited local reaction

Day of onset: median (min, max) 1.0 (1, 6) 1.0 (1, 6) 1.0 (1, 7) 1.0 (1, 7)

Duration: median (min, max) 2.0 (1, 10) 1.0 (1, 10) 2.0 (1, 11) 1.0 (1, 12)

Persisted beyond 7 days 11/1511 9/749 8/1501 5/741

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BNT162b2 10 ug Placebo BNT162b2 10 yg Placebo
Dose 1 Dose 1 Dose 2 Dose 2
Redness
Day of onset: median (min, max) 2.0 (1, 7) 2.0 (1, 5) 2.0 (1, 6) 1.0 (1, 5)
Duration: median (min, max) 1.0 (1, 10) 1.0 (1, 8) 2.0 (1, 10) 1.0 (1, 11)
Persisted beyond 7 days 4/1511 1/749 2/1501 1/741
Swelling
Day of onset: median (min, max) 0 (1, 4) 1.0 (1, 7) 2.0 (1, 4) 1.0 (1, 5)
Duration: median (min, max) 0 (1, 8) 1.0 (1, 9) 2.0 (1, 10) 1.0 (1, 12)
Persisted beyond 7 days 1/1511 1/749 2/1501 2/741
Pain at injection site
Day of onset: median (min, max) 1.0 (1, 6) 1.0 (1, 6) 1.0 (1, 7) 1.0 (1, 7)
Duration: median (min, max) 2.0 (1, 10) 1.0 (1, 10) 2.0 (1, 11) 1.5 (1, 12)
Persisted beyond 7 days 7/1511 8/748 6/1501 5/740
Any solicited systemic reaction
Day of onset: median (min, max) 2.0 (1, 7) 1.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7)
Duration: median (min, max) 1.0 (1, 22) 1.0 (1, 19) 1.0 (1, 51) 1.0 (1, 10)
Persisted beyond 7 days 29/1511 15/749 30/1501 13/741
Fever
Day of onset: median (min, max) é. 0 (2, 7) 2.5 (1, 7) 2.0 (1, 7) 6. 0 (2, 7)
Duration: median (min, max) 1.0 (1, 3) 1.0 (1, 3) 1.0 (1, 5) 1.0 (1, 5)
Persisted beyond 7 days 0 0 0
Fatigue
Day of onset: median (min, max) 2.0 (1, 7) 1.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7)
Duration: median (min, max) 1.0 (1, 21) 2.0 (1, 9) 1.0 (1, 14) 1.0 (1, 10)
Persisted beyond 7 days 16/1511 7/748 17/1501 6/740
Headache
Day of onset: median (min, max) 2.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7)
Duration: median (min, max) 1.0 (1, 22) 1.0 (1, 19) 1.0 (1, 51) 1.0 (1, 9)
Persisted beyond 7 days 12/1511 9/748 10/1501 6/740
Chills
Day of onset: median (min, max) 2.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7)
Duration: median (min, max) 1.0 (1, 10) 1.0 (1, 7) 1.0 (1, 8) 1.0 (1, 8)
Persisted beyond 7 days 3/1511 1/1501 1/740
Vomiting
Day of onset: median (min, max) 4.0 (1, 7) 4.0 (1, 6) 2.0 (1, 6) 3.0 (2, 6)
Duration: median (min, max) 1.0 (1, 5) 1.0 (1, 1) 1.0 (1, 2) 1.0 (1, 5)
Persisted beyond 7 days 0 0 0
Diarrhea
Day of onset: median (min, max) 3.0 (1, 7) 3.0 (1, 7) 3.0 (1, 7) 4.0 (1, 7)
Duration: median (min, max) 1.0 (1, 8) 1.0 (1, 6) 1.0 (1, 28) 1.0 (1, 9)
Persisted beyond 7 days 1/1511 2/1501 2/740
New or worsened joint pain
Day of onset: median (min, max) (1, 6) 2.0 (1, 7) 2.0 (1, 7) (1, 7)
Duration: median (min, max) 1.0 (1, 7) 1.0 (1, 4) 1.0 (1, 18) 1.0 (1, 6)
Persisted beyond 7 days 1/1501

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BNT162b2 10 ug Placebo BNT162b2 10 yg Placebo

Dose 1 Dose 1 Dose 2 Dose 2
New or worsened muscle pain
Day of onset: median (min, max) 2.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7)
Duration: median (min, max) 1.0 (1, 9) 1.0 (1, 8) 1.0 (1, 9) 1.0 (1, 6)
Persisted beyond 7 days 1/1511 1/748 3/1501

a. n= Number of participants with the specified reaction persisted beyond 7 days.
b. N=number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose.

7.6.3 Subgroup analyses of solicited adverse reactions

Subgroup analyses were performed for solicited adverse reactions, comparing BNT162b2 and
placebo groups by sex, race, ethnicity, and baseline SARS-CoV-2 status at baseline. No
notable differences were observed among the study groups, although certain subgroups such
as Black or African American race and Hispanic/Latino ethnicity had too few participants to draw
meaningful conclusions.

7.6.4 Unsolicited adverse events

Information about unsolicited AEs was collected from Dose 1 to 1 month post-Dose 2. No
unsolicited AEs were reported by 21% of participants.

In Cohort 1, the most common unsolicited AE was lymphadenopathy, which was reported in 13
(0.9%) participants in the BNT162b2 group, and 1 participant in the placebo group (0.1%).
Additional unsolicited AEs reported more commonly in the BNT162b2 group than in the placebo
group included otitis externa in 7 participants (0.5%), arthropod bite, nasal congestion,
oropharyngeal pain, and rash in 5 participants (0.3%), each. In BNT162b2 recipients, the
following AEs were considered Grade 3 in severity: 1 tic, 1 rash (bilateral pleomorphic light
eruption on arms). No Grade 4 (life-threatening AEs) were observed in the study. In Cohort 2,
lymphadenopathy was reported in 6 (0.4%) vaccine recipients and 3 placebo recipients (0.4%).

7.6.5 SAEs

In Cohort 1, SAEs occurred at frequency of 0.1% in both BNT162b2 and placebo recipients. For
BNT162b2 recipients, only one SAE was reported, an upper limb fracture. In Cohort 2, 3
BNT162b2 recipients (0.2%) reported a SAE: 1 infection of the knee, 1 foreign body ingestion,
and 1 epiphyseal fracture. All SAEs reported in the study were considered by the study
investigator to be unrelated to vaccination. FDA agrees with this assessment.

Deaths: No deaths have occurred during the study in either Cohort 1 or 2.

7.6.6 AEs of clinical interest

FDA conducted Standardized MedDRA Queries (SMQs) to evaluate for constellations of
unsolicited AEs among recipients 5-11 years of age in study C4591007 Phase 2/3 Cohort 1
through the September 6, 2021 cutoff date. SMQs (narrow and broad in scope) were conducted
on AE Preferred Terms (PTs) that could represent various conditions, including but not limited to
angioedema, arthritis, cardiomyopathy, ischaemic heart disease, cardiac arrhythmia, cardiac
failure, central nervous system (CNS) vascular disorders, convulsions, demyelination, embolic
and thrombotic events, hearing and vestibular disorders, hematopoietic cytopenias,
hypersensitivity, peripheral neuropathy, thrombophlebitis, and vasculitis. For example, the
cardiomyopathy SMQ includes PTs that may be related to myocarditis and pericarditis, such as

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chest pain, palpitations, dyspnea, syncope, troponin elevation, ECG with ST elevation or PR
depression, pericardiac rub, or echocardiographic findings.

with 14 participants in the vaccine group (0.92%) reporting hypersensitivity-related AEs

(primarily skin and subcutaneous disorder including rash and dermatitis) compared with 4
participants in the placebo group (0.53%). See Table 13, below.

As in Cohort 1, SMQ analyses in Cohort 2 showed an imbalance of AEs in the BNT162b2 group
compared to the placebo with respect to hypersensitivity, with 9 participants in the vaccine
group (0.57%) and 4 in the placebo group (0.51%) reporting unsolicited AEs in this category,
primarily skin and subcutaneous disorders of rash and dermatitis. Angioedema was reported in
3 (0.19%) in the vaccine group compared to 1 (0.13%) in the placebo group. These events
included one participant with both angioedema and urticaria, and 3 participants with urticaria.

One participant, a 6-year-old female in the BNT162b2 group, had a non-serious AE of Henoch-
Schonlein purpura which was diagnosed 21 days after Dose 1 and was considered non-serious.

No new or unexpected adverse reactions were identified based on these SMQ results.

Table 13. Standard MedDRA Query of Adverse Events by System Organ Class and Preferred
Terms, Phase 2/3, Participants 5-11 Years, Safety Population, Vaccine Group as Administered,

Cohort 1, Study C4591007

SMQ Overall SMQ BNT162b2 Placebo
System Organ Class 10 ug (N?=750)
Preferred Term (N#=1,518) n® (%)
n? (%)
Any Participants with any unsolicited AEs within SMQ 19 (1.25) 6 (0.80)
Angioedema (SMQ) Any unsolicited AEs within Angioedema (SMQ) 4 (0.26) 3 (0.40)
Eye disorders 0 1 (0.13)
Periorbital oedema 0 1 (0.13)
General disorders and administration site 1 (0.07) 0
conditions
Swelling face 1 (0.07) 0
Skin and subcutaneous tissue disorders 3(0.20) 3 (0.40)
Urticaria 3 (0.20) 3 (0.40)
Arthritis (SMQ) Any unsolicited AEs within Arthritis (SMQ) 1 (0.07) 0
Musculoskeletal and connective tissue disorders _1 (0.07) 0
Synovitis 1 (0.07) 0
Convulsions (SMQ) Any unsolicited AEs within Convulsions (SMQ) 0 0
Demyelination (SMQ) Any unsolicited AEs within Demyelination (SMQ) 0 0
Hypersensitivity (SMQ) Any unsolicited AEs within Hypersensitivity (SMQ) 14 (0.92) 4 (0.53)
Eye disorders 1 (0.07) 1(0.13)
Conjunctivitis allergic 1 (0.07) 1 (0.13)
General disorders and administration site 1 (0.07) 0
conditions
Injection site rash 1 (0.07) 0
Immune system disorders 0 1 (0.13)
Hypersensitivity 0 1 (0.13)
Skin and subcutaneous tissue disorders 12 (0.79) 2 (0.27)
Dermatitis 1 (0.07) 0

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 169 of 237

SMQ Overall SMQ BNT162b2 Placebo
System Organ Class 10 ug (N?=750)
Preferred Term (N7=1,518) n° (%)
n? (%)

Dermatitis allergic 1 (0.07) 0
Dermatitis contact 3 (0.20) 0
Eczema 1 (0.07) 1 (0.13)
Rash 5 (0.33) 0
Rash erythematous 0 1 (0.13)
Rash macular 1 (0.07) 0
Rash pruritic 1 (0.07) 0

Peripheral neuropathy Any unsolicited AEs within Peripheral neuropathy 0 0

(SMQ) (SMQ)

Vasculitis (SMQ) Any unsolicited AEs within Vasculitis (SMQ) 0 0

Note: MedDRA (v24.0) coding dictionary applied.

a. N=number of participants in the specified group. This value is the denominator for the percentage calculations.

b. n=Number of participants reporting at least 1 occurrence of the specified event category. For "any unsolicited AEs within
SMQ," n = the number of participants reporting at least 1 occurrence of any unsolicited AEs within SMQ.

In Cohorts 1 and 2, “chest pain” was reported in a total of 12 participants: 6 assigned to the
BNT162b2 group and 6 assigned to placebo. Chest pain resolved in all participants within 1-2
days of onset. No participants required a cardiac evaluation or ER visit, and none were
hospitalized. In each case the AE was considered to be noncardiac in origin.

7.6.7 AEs leading to study withdrawal

In C4591007 Phase 2/3 Cohort 1, there were no AEs leading to withdrawal. In Cohort 2 with a
follow-up cutoff of October 8, 2021, 1 participant was withdrawn due to AEs of fever 2 days after
Dose 1 and worsening of neutropenia (previously diagnosed as benign transient neutropenia.
Dose 2 was not administered.

7.7 Study C4591007 Phase 2/3 summary

This EVA request included safety data from 1,518 BNT162b2 recipients and 750 placebo
(saline) recipients 5-11 years of age in the Phase 2/3 portion (Cohort 1) of an ongoing clinical
trial, C4591007; Among Cohort 1 participants, 95.1% had safety follow-up 22 months after Dose
2 at the time of the September 6, 2021 data cutoff. Safety data from an additional 1,591
BNT162b2 recipients and 788 placebo recipients from the Phase 2/3 portion of the trial (Cohort
2) were provided for assessment of SAEs and other AEs of interest (e.g., myocarditis,
pericarditis, anaphylaxis); the median duration of follow-up was 2.4 weeks post Dose 2 at the
time of the October 8, 2021 data cutoff for Cohort 2.

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VE against symptomatic COVID-19 after 7 days post Dose 2 as of the October 8, 2021 data
cutoff was 90.7% (2-sided 95% Cl: 67.4%, 98.3%) in participants 5-11 years of age without prior
evidence of SARS-CoV-2 infection; 3 cases of COVID-19 occurred in the BNT162b2 group and
16 in the placebo group. All cases of COVID-19 occurred in participants 5-11 years of age
without prior history of SARS-CoV-2 infection, and most occurred during July-August 2021. At
the time of data cutoff, no cases met the criteria for severe COVID-19 infection.

Solicited local and systemic ARs generally occurred more frequently after Dose 2, and the most
commonly reported solicited ARs were pain at the injection site (71%), fatigue (39.4%), and
headache (28%). Most local and systemic reactions were mild to moderate in severity, with
median onset 2 days post-vaccination, and resolved within 1 to 2 days after onset. The most
frequently reported unsolicited AE in BNT162b2 recipients was lymphadenopathy (n=13; 0.9%).
More BNT162b2 recipients (n=14; 0.92%) reported hypersensitivity-related AEs (primarily rash
and dermatitis) than placebo recipients (n=4; 0.53%). Overall, from the combined safety
database of 3,109 BNT162b2 participants, 4 BNT162b2 participants reported a SAE, and all of
the SAEs were considered unrelated to vaccination. One BNT162b2 recipient withdrew from the
study due to fever (40.1°C) that occurred 2 days after Dose 1 and neutropenia that had
worsened from baseline; the neutropenia was related to a pre-existing condition. There were no
reports of myocarditis/pericarditis or anaphylaxis, and no participant deaths. Subgroup safety
analyses by gender, race and ethnicity, obesity and baseline SARS-CoV-2 status showed no
notable differences compared to the overall study population, although some subgroups were
too small to draw meaningful conclusions.

8 BENEFIT-RISK ASSESSMENT FOR CHILDREN 5-11 YEARS OF AGE

FDA conducted a benefit-risk assessment for use of a Pfizer-BioNTech COVID-19 Vaccine 2-
dose primary series in children 5-11 years of age. The key benefits assessed include
preventable COVID-19 cases, hospitalizations, intensive care unit (ICU) visits and deaths due to
COVID-19. The key risks include excess myocarditis/pericarditis cases, and related
hospitalizations, ICU admissions, and deaths attributable to myocarditis/pericarditis. The
benefits and risks are assessed per million fully vaccinated individuals with and without
stratification by sex, and with comparison to age groups 12-15 years and 16-17 years.

The model assesses the benefits of vaccine protection in a 6-month period after completion of
the primary series. The model assumes vaccine efficacy of 70% against COVID-19 cases and
80% against COVID-19 associated hospitalization based on real-world data for ages 20+ years
during circulation of the Delta variant.*® The incidence rates of COVID-19 cases for the week of
September 11, 2021 are obtained from COVID-NET for all sex/age groups. COVID-NET covers
approximately 10 percent of the U.S. population. Four-week averages of incidence rate for
hospitalizations (week ending on 8/21/2021 to week ending on 9/11/2021) are used due to the
variability in rates given the small numbers of hospitalizations per age/sex group. Estimates for
the percentage of hospitalizations resulting in |CU admission and the percentage of hospitalized
patients who die are based on cumulative rates of hospitalizations, |CU admissions, and deaths
for each sex/age groups reported in COVID-NET since March 2020. The death rate among 5-11
year-olds is lower in COVID-NET than in other national data sources such as the CDC COVID-
19 Data Tracker. This could be due to geographic differences between COVID-NET’s reporting
areas and the recent trajectory of the pandemic. This difference will lead to a conservative
estimate of benefits in the model. The model assumes the incidence rates of COVID-19 cases
and hospitalizations remain constant over the assessment period of 6 months. The estimates for
excess myocarditis/pericarditis among fully vaccinated individuals ages 12-15 years and ages
16-17 years are based on data from Optum health claim database for the period 12/10/2020 —

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07/10/2021, which is a conservative approach that includes non-confirmed cases. For this
analysis the estimate for ages 12-15 years is applied to ages 5-11 years because vaccine-
associated myocarditis/pericarditis data is not available for this age group. The proportions of
vaccine-attributable myocarditis/pericarditis hospitalizations and ICU admissions are obtained
from Vaccine Safety Datalink (12-17 year-old group*’). Some of these hospitalizations and ICU
admissions may be precautionary and therefore not clinically equivalent to COVID-19
hospitalizations and ICU admissions. The dose intended for use in children 5-11 years of age
(10 ug), is lower than the dose used under EVA in adolescents 12-15 years of age (30 yg), and
the observed systemic reactogenicity associated with the respective antigen contents in clinical
trials is lower for children 5-11 years of age as well. Thus, assuming the same rate of vaccine-
associated myocarditis for children 5-11 years of age as has been observed for adolescents 12-
15 years of age in Optum may be a conservative overestimate.

The model results indicate that the benefits of the vaccine are highly dependent on the
incidence of COVID-19. To account for uncertain dynamics of the pandemic, the benefits and
risks were assessed under six scenarios: Scenario 1 with COVID-19 incidence as of September
11, 2021, Scenario 2 with COVID-19 incidence close to the recent peak of the Delta variant
surge at the end of August 2021, Scenario 3 with COVID-19 incidence close to the lowest
recorded incidence in June 2021, Scenario 4 with the same COVID-19 incidence as Scenario 1
and an assumption of 90% vaccine efficacy against cases and 100% efficacy against
hospitalizations based on the preliminary descriptive efficacy analysis from study C4591007
Phase 2/3 Cohort 1, Scenario 5 with a 3x multiple of the death rate to more closely match the
cumulative death rate for 5-11 years old seen in CDC Data Tracker, and Scenario 6 with the
same COVID-19 incidence and assumed vaccine efficacy as Scenario 1 but 50% of the
myocarditis cases as Scenario 1.

The results of the benefit-risk assessment are summarized in Table 14 below. The results
predict that under Scenarios 1 (Sept 11, 2021 Incidence), 2 (Delta surge peak incidence), 4
(high efficacy), and 5 (higher COVID-19 death rate, per the CDC COVID-19 Data Tracker), the
benefits of the Pfizer-BioNTech COVID-19 Vaccine 2-dose primary series clearly outweigh the
risks for ages 5-11 years. Under Scenario 3 (lowest incidence), the model predicts more excess
hospitalizations due to vaccine-related myocarditis/pericarditis compared to prevented
hospitalizations due to COVID-19 in males and in both sexes combined. However, in
consideration of the different clinical implications of hospitalization for COVID-19 versus
hospitalization for vaccine-associated myocarditis/pericarditis, and benefits related to prevention
of non-hospitalized cases of COVID-19 with significant morbidity, the overall benefits of the
vaccine may still outweigh the risks under this lowest incidence scenario. If the
myocarditis/pericarditis risk in this age group is lower than the conservative assumption used in
the model, the benefit-risk balance would be even more favorable.

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Table 14. Model-Predicted Benefit-Risk Outcomes of Scenarios 1-6 per One Million Fully

Vaccinated Children 5-11 Years Old

Benefits Risks
Prevented| Prevented Excess Excess
Prevented; COVID-19] COVID-19/| Prevented Excess | Myocarditis | Myocarditis Excess
Sex COVID-19 | Hospitalizat ICU} COVID-19| Myocarditis | Hospitalizat ICU} Myocarditis
Cases ions | Admissions Deaths Cases ions | Admissions Deaths
Males &
Females
Scenario 1 45,773 192 62 1 106 58 34 0
Scenario 2 54,345 250 80 1 106 58 34 0
Scenario 3 2,639 21 7 0 106 58 34 0
Scenario 4 58,851 241 77 1 106 58 34 0
Scenario 5 45,773 192 62 3 106 58 34 0
Scenario 6 45,773 192 62 1 53 29 17 0
Males only
Scenario 1 44,790 203 67 1 179 98 57 0
Scenario 2 54,345 250 82 1 179 98 57 0
Scenario 3 2,639 21 7 0 179 98 57 0
Scenario 4 57,857 254 83 1 179 98 57 0
Scenario 5 44,790 203 67 3 179 98 57 0
Scenario 6 44,790 203 67 1 89 49 29 0
Females only
Scenario 1 45,063 172 54 1 32 18 10 0
Scenario 2 54,345 250 78 2 32 18 10 0
Scenario 3 2,639 21 7 0 32 18 10 0
Scenario 4 57,938 215 67 2 32 18 10 0
Scenario 5 45,063 172 54 4 32 18 10 0
Scenario 6 45,063 172 54 1 16 9 5 0

Scenario 3: COVID-19 incidence as of nadir in June 2021, VE 70% vs. COVID-19 cases and 80% vs. COVID-19 hospitalization.
Scenario 4: COVID-19 incidence as of September 11, 2021, VE 90% vs. COVID-19 cases and 100% vs. COVID-19 hospitalization.
Scenario 5: COVID-19 case incidence as of September 11, 2021, VE 70% vs. COVID-19 cases and 80% vs. COVID-19.
hospitalization, COVID-19 death rate 300% that of Scenario 1.

Scenario 6: COVID-19 incidence as of September 11, 2021, VE 70% vs. COVID-19 cases and 80% vs. COVID-19 hospitalization,
excess myocarditis cases 50% of Scenario 1.

9 PHARMACOVIGILANCE ACTIVITIES

Pfizer submitted a revised Pharmacovigilance Plan (PVP) to monitor safety concerns that could
be associated with BNT162b2 in individuals 5-11 years of age. The PVP includes the following
safety concerns:

e Important Identified Risks: anaphylaxis, myocarditis, and pericarditis
e Important Potential Risks: Vaccine-associated enhanced disease (VAED), including
vaccine-associated enhanced respiratory disease (VAERD).

Pfizer-BioNTech plans to conduct passive and active surveillance to monitor the post-
authorization safety for the Pfizer-BioNTech COVID-19 Vaccine, including:

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 173 of 237

e Mandatory reporting by the Sponsor under the EUA for the following events to VAERS
within 15 days: SAEs (irrespective of attribution to vaccination); COVID-19 disease resulting
in hospitalization or death; multisystem inflammatory syndrome (MIS)

e Adverse event reporting in accordance with regulatory requirements for the licensed
vaccine, COMIRNATY

e Additionally, following approval of COMIRNATY, the Sponsor was also asked to submit
reports of myocarditis and pericarditis as 15-day reports to VAERS.

e Periodic safety reports containing an aggregate review of safety data including assessment
of AEs; vaccine administration errors, whether or not associated with an AE; and newly
identified safety concerns.

e Post-authorization observational studies, that would be modified to encompass the
evaluation of children 5-11 years of age include active surveillance safety studies using
large health insurance claims and/or electronic health record database(s):

- Study C4591009: A non-interventional post-approval safety study of the Pfizer-BioNTech
COVID-19 mRNA Vaccine in the United States

Objective: To assess the occurrence of safety events of interest, including myocarditis
and pericarditis, in the general U.S. population of all ages, pregnant women, the
immunocompromised, and persons with a prior history of COVID-19 within selected data
sources participating in the U.S. Sentinel System.

— Study C4591021: Post-conditional approval active surveillance study among individuals
in Europe receiving the Pfizer-BioNTech Coronavirus Disease 2019 (COVID-19) Vaccine

Objective: To assess the potential increased risk of AESIs, including
myocarditis/pericarditis, after being vaccinated with at least one dose of the Pfizer-
BioNTech COVID-19 Vaccine.

- Study C4591021 Substudy: Substudy to describe the natural history of myocarditis and
pericarditis following administration of COMIRNATY

Objective: To describe the natural history of post-vaccination myocarditis/pericarditis,
including recovery status, risk factors, and/or identification of serious cardiovascular
outcomes within one year of myocarditis/pericarditis diagnosis among individuals
vaccinated with BNT162b2 as well as individuals not vaccinated with a COVID-19
vaccine.

- Study C4591036: Prospective cohort study with at least 5 years of follow-up for potential
long-term sequelae of myocarditis after vaccination (in collaboration with Pediatric Heart
Network [PHN]). Working title: Myocarditis/pericarditis follow-up study within the
Pediatric Heart Network

Objective: To characterize the clinical course, risk factors, resolution, long-term
sequelae, and quality of life in children and young adults <21 years with acute post-
vaccine myocarditis/pericarditis.

Pfizer-BioNTech also plans to include vaccine effectiveness analyses among individuals 5-11

years of age in Study C4591014 entitled “Pfizer-BioNTech COVID-19 BNT162b2 Vaccine
Effectiveness Study Kaiser Permanente Southern California.”

35
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 174 of 237

10 TOPIC FOR VRBPAC DISCUSSION

The VRBPAC will convene on October 26, 2021, to discuss whether based on the totality of
scientific evidence available, the benefits of the Pfizer-BioNTech COVID-19 Vaccine when
administered as a 2-dose series (10 ug each dose, 3 weeks apart) outweigh its risks for use in
children 5-11 years of age.

11 REFERENCES

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4 Assaker R, Colas A-E, Julien-Marsollier F, et al. Presenting Symptoms of COVID-19 in Children: A
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° Poline J, Gaschignard J, Leblanc C, et al. Systematic Severe Acute Respiratory Syndrome Coronavirus
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2020;ciaa1044.

° Office of National Statistics. Updated estimates of the prevalence of ongoing symptoms following
coronavirus (COVID-19) infection in the UK.
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sets/alldatarelatingtoprevalenceofongoingsymptomsfollowingcoronaviruscovid1 9infectionintheuk.
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8 Centers for Disease Control and Prevention, 2021. COVID Data Tracker (website)
https://covid.cdc.gov/covid-data-tracker/#trends_ dailytrendscases, Accessed October 17, 2021.

° Link-Gelles, Ruth, COVID-19 Vaccine Effectiveness in the United States, the US CDC ACIP Meeting
September 22, 2021. Retrieved from: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-
2021-09-22/04-COVID-Link-Gelles-508.pdf retrieved on October 15, 2021.Centers for Disease Control
and Prevention, 2021. COVID Data Tracker (website) https://covid.cdc.gov/covid-data-
tracker/#demographics. Accessed October 17, 2021.

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https://covid.cdc.gov/covid-data-tracker/#demographics. Accessed October 17, 2021.

™ Centers for Disease Control and Prevention. COVID Data Tracker (website) https://covid.cdc.gov/covid-
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12 Centers for Disease Control and Prevention, 2021. COVID Data Tracker (website)
https://covid.cdc.gov/covid-data-tracker/#nowcasting. Accessed October 9, 2021.

13 Centers for Disease Control and Prevention, 2021. COVID Data Tracker (website)
https://covid.cdc.gov/covid-data-tracker/#trends dailytrendscases and CDC communication

“Centers for Disease Control and Prevention, 2021. COVID Data Tracker (website)
https://covid.cdc.gov/covid-data-tracker/#demographics. Accessed October 17. 2021.

'S Centers for Disease Control and Prevention. COVID Data Tracker (website).Counts of Hospitalizations
by Age from the COVID-NET Network (data downloaded on October 17, 2021.
https://covid.cdc.gov/covid-data-tracker/#covidnet-hospitalization-network. Accessed October 9, 2021.

'6 Centers for Disease Control and Prevention. COVID Data Tracker (website) https://covid.cdc.gov/covid-
data-tracker/#demographics. Accessed October 17, 2021.

'7Centers for Disease Control and Prevention, 2021. COVID Data Tracker (website)
https://covid.cdc.gov/covid-data-tracker/#pediatric-data. Accessed October 9, 2021.

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18 Kim L et al. Hospitalization Rates and Characteristics of Children Aged<18 Years Hospitalized with
Laboratory-Confirmed COVID-19 - COVID-NET, 14 States, March 1-July 25, 2020. MMWR
\2020;69(32):1081. Epub 2020 Aug 14.

19 McCormick DW, Richardson LC, Young PR, et al. Deaths in children and adolescents

associated with COVID-19 and MIS-C in the United States. Pediatrics. 2021; (preprint) doi:
10.1542/peds.2021-052273

0 Diagnosis-wide analysis of COVID-19 complications: an exposure-crossover study

William Murk, Monica Gierada, Michael Fralick, Andrew Weckstein, Reyna Klesh, Jeremy A. Rassen
CMAJ Jan 2021, 193 (1) E10-E18.

1 Daugherty S E, Guo Y, Heath K, DasmariAtas M C, Jubilo K G, Samranvedhya J et al. Risk of clinical
sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study BMJ 2021;
373:n1098.

22 Boehmer, TK et al. Association Between COVID-19 and Myocarditis Using Hospital-Based
Administrative Data — United States, March 2020—January 2021

MMWR September 3, 2021.70(35); 1228-1232

3 Dufort EM et al. COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features,
evaluation, and diagnosis. N Engl J Med. 2020;383(4):347. Epub 2020 Jun 29.

*4 Centers for Disease Control and Prevention. Information for Healthcare Providers about Multisystem
Inflammatory Syndrome in Children (MIS-C). May 20, 2021. https://www.cdc.gov/mis-c/hcp/

25 Centers for Disease Control and Prevention, 2021. COVID Data Tracker (website).
https://covid.cdc.gov/covid-data-tracker/#mis-national-surveillance Graph - Daily MIS-C Cases and
COVID-19 Cases Reported to CDC. Accessed October 17, 2021.

6 Dufort EM et al. Multisystem Inflammatory Syndrome in Children in New York State. N Eng/ J Med.
2020;383:347-58

2’ Centers for Disease Control and Prevention. Health Department-Reported Cases of Multisystem
Inflammatory Syndrome in Children (MIS-C) in the United States. October 17, 2021.
https://covid.cdc.gov/covid-data-tracker/#mis-national-surveillance

6 Feldstein et al. Characteristics and Outcomes of US Children and Adolescents with Mulitsystem
Inflammatory Syndrome in Children (MIS-C) Compared with Severe Acute COVID-19. JAMA
2021;325(11):1074-1087.

2° Farooqi et al. Longitudinal Outcomes for Multisystem Inflammatory Syndrome in Children. Pediatrics.
2021; 148(2):e2021051155

30 Faroogi et al 2021.

31 Viner RM, Mytton OT, Bonell C, et al. Susceptibility to SARS-CoV-2 Infection Among Children and
Adolescents Compared With Adults: A Systematic Review and Meta-analysis. JAMA Pediatr.
2021;175(2):143-156.

32 Leidman E, Duca LM, Omura JD, et al. COVID-19 Trends Among Persons Aged 0-24 Years - United
States, March 1-December 12, 2020. MMWR. 2021;70(3):88-94.

33 Sargent TH, Muller WJ, Zheng X, et al. Age-Related Differences in Nasopharyngeal Severe Acute
Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Levels in Patients With Mild to Moderate
Coronavirus Disease 2019 (COVID-19). JAMA Pediatrics. 2020;174(9):902-903.

34 Yonker LM, Neilan AM, Bartsch Y, et al. Pediatric Severe Acute Respiratory Syndrome Coronavirus 2
(SARS-CoV-2): Clinical Presentation, Infectivity, and Immune Responses. J Pediatr. 2020;227:45-52.e5.
35 Chu VT, Yousaf AR, Chang K, et al. Household Transmission of SARS-CoV-2 from Children and
Adolescents. N Engl J Med. 2021;NEJMc2031915.

36 Centers for Disease control and prevention. Science Brief: Transmission of SARS-CoV-2 in K-12
schools. https://www.cdc.gov/coronavirus/2019-ncov/science/science-

briefs/transmission k 12 schools.html. Accessed October 17, 2021.

37 Ismail SA, Saliba V, Lopez Bernal J, et al. SARS-CoV-2 infection and transmission in educational
settings: a prospective, cross-sectional analysis of infection clusters and outbreaks in England. Lancet
Infect Dis 2021;21(3):344-353. doi:10.1016/s1473-3099(20)30882-3.

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38 Goldstein E, Lipsitch M, Cevik M. On the Effect of Age on the Transmission of SARS-CoV-2 in
Households, Schools, and the Community. J Infect Dis. 2021 Feb 13;223(3):362-369.

3° Larosa E, Djuric O, Cassinadri M, et al. Secondary transmission of COVID-19 in preschool and school
settings in northern Italy after their reopening in September 2020: a population-based study. Euro
Surveill, 2020;25(49):2001911.

40 Tonzel JL, Sokol T. COVID-19 Outbreaks at Youth Summer Camps — Louisiana, June—July 2021.
MMWR 2021;(70):1425-1426.

41 Szablewski CM, Chang KT, Brown MM, et al. SARS-CoV-2 transmission and infection among
attendees of an overnight camp—Georgia, June 2020. MMWR 2020;(69):1023—5.

42 Gee J, Marquez P, Su J, et al. First Month of COVID-19 Vaccine Safety Monitoring — United States,
December 14, 2020—January 13, 2021. MMWR Morb Mortal Wkly Rep 2021;70:283-288.
http://dx.doi.org/10.15585/mmwr.mm7008e3

43 CDC COVID-19 Response Team et al. Allergic Reactions Including Anaphylaxis After Receipt of the
First Dose of Pfizer-BioNTech COVID-19 Vaccine — United States, December 14—23, 2020. MMWR
Morb Mortal Wkly Rep 2021;70:46—51. DOI: http://dx.doi.org/10.15585/mmwr.mm7002e1

“4 EDA. Vaccine approval package: COMIRNATY (COVID-19 Vaccine, mRNA) (Application No 125742).
August 23, 2021. https://www.fda.gov/media/151733/download

45 FDA. Guidance for Industry: Emergency Use Authorization for Vaccines to Prevent COVID-19.
February 2021. httos://www.fda.gov/media/142749/download

46 FDA. Guidance for Industry: Development and Licensure of Vaccines to Prevent COVID-19. June
2020. https://www.fda.gov/requlatory-information/search-fda-quidance-documents/development-and-
licensure-vaccines-prevent-covid-19

47 Kim L, Whitaker M, O'Halloran A, et al. Hospitalization Rates and Characteristics of

Children Aged <18 Years Hospitalized with Laboratory-Confirmed COVID-19 -

COVID-NET, 14 States, March 1-July 25, 2020. MMWR Morb Mortal Wkly Rep.

2020;69(32):1081-88.

48 Link-Gelles, R. COVID-19 Vaccine Effectiveness in the United States, the US CDC ACIP Meeting
September 22, 2021. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-09-22/04-
COVID-Link-Gelles-508.pdf Accessed October 15, 2021.

4° Klein, N. Rapid Cycle Analysis to Monitor the Safety of COVID-19 Vaccines in Near Real-Time within
the Vaccine Safety Datalink: Myocarditis and Anaphylaxis, the US CDC ACIP Meeting August 30, 2021.
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-08-30/04-COVID-Klein-508.pdf
Accessed October 20, 2021.

12 APPENDIX: C4591007 PHASE 1 (DOSE RANGING) —- SUMMARY OF SAFETY AND
IMMUNOGENICITY

During study C4591007 Phase 1, BNT162b2 was evaluated in U.S. children who were not at
high risk of SARS-CoV-2 exposure, did not have medical conditions that represented risk
factors for severe COVID-19, and did not have serologic/virologic evidence of SARS-CoV-2
infection. BNT162b2 dosages of 10 ug, 20 ug, then 30 ug were evaluated sequentially (n=16
participants per dosage) based upon the safety evaluation and recommendation by the internal
review committee (IRC) to either advance to the subsequent dosage or terminate a specific
dosage. Safety evaluation was the same as for Phase 2/3. SARS-CoV-2 50% neutralizing
GMTs (SARS-CoV-2 mNG microneutralization assay) were assessed at 7 days after Dose 2.

Altogether, 48/49 (98%) of participants (assigned to the 10 ug, 20 ug, or 30 ug dosage groups
combined) received two doses of BNT162b2 and completed the 1 month follow-up visit after
Dose 2. One BNT162b2 participant (20 ug dosage group) did not receive study vaccine.
Following safety review of reactogenicity data from the initial 4 participants in the BNT162b2 30
ug dosage group, the IRC recommended to discontinue the 30 ug dosage, due to high
frequencies of solicited ARs, and recommended that the remaining 12 participants receive the

38
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 177 of 237

dosage selected for Phase 2/3 (i.e., 10 ug) at Dose 2. No participants from Phase 1 withdrew or
discontinued from the study.

The frequencies of local and systemic adverse reactions were generally dose number and
dosage dependent. Across dosages, systemic adverse reactions were generally mild and
moderate in severity and resolved within 1 day of onset. No SAEs, deaths or AEs leading to
withdrawal occurred at the time of data cutoff on July 16, 2021, with approximately 3 months of
follow-up. No participants reported anaphylaxis, myocarditis/pericarditis, or MIS-C. One
BNT162b2 (30 ug) recipient reported Grade 1 axillary lymphadenopathy, which started 3 days
after Dose 2 and resolved 17 days later; the AE was considered by the study investigator to be
related to study intervention.

All four participants who received 30 yg for both doses developed mild-moderate redness and
pain at the injection site, and 2 of the 4 participants developed swelling. In addition, all four
subjects reported fevers to 38.9°C with mild to moderate fatigue, and 2 of the 4 developed
muscle pain of moderate severity following the second dose. One participant in the 20 ug group
reported Grade 3 pyrexia (temperature to 39.7° C, also reported as a systemic adverse reaction,
on Day 2 post-Dose 2), which resolved by Day 3. Both 10 and 20 ug dosages elicited similar
immune responses 7 days after Dose 2. In participants 5-11 years of age without evidence of
SARS-CoV-2 infection up to 1 month post-Dose 2, the neutralizing antibody GMTs (NT50) at 1
month after Dose 2 were similar in the BNT162b2 10 ug and 20 ug groups (4163 and 4728,
respectively).

The higher frequencies of solicited adverse reactions in participants receiving the 20 ug and
30 ug dosages, the favorable AE profile at the 10 ug dosage in participants 5-11 years of age
followed for approximately 3 months after Dose 2, and the immunogenicity results
demonstrating similar neutralizing antibody responses at the 10 and 20 ug dosages informed
the Internal Review Committee’s decision to discontinue the 30 ug dosage and proceed to
Phase 2/3 at the 10 ug dosage.

39
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 178 of 237

Exhibit 5
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 179 of 237

Emergency Use Authorization (EUA) for an Unapproved Product

Identifying Information

Review Memorandum

Application Type

EUA (Event-driven EVA request) Amendment

Application Number

EVA 27034, Amendment 324

Sponsor

Pfizer, Inc., on behalf of Pfizer and BioNTech

Submission Date

October 6, 2021

Receipt Date

October 6, 2021

Signatory Authority

Peter Marks, M.D., Ph.D., Director, CBER, and Acting Director,
CBER/OVRR

Review Team

Ramachandra Naik, Ph.D., Chair, OVRR/DVRPA

CAPT Michael Smith, Ph.D., Regulatory Project Manager,
OVRR/DVRPA

Laura Gottschalk, Ph.D., Regulatory Project Manager,
OVRR/DVRPA

Leslie Ball, M.D., Clinical reviewer, OVRR/DVRPA

Ye Yang, Ph.D., Biostatistics reviewer, OBE/DB

Xiao Wang, Ph.D., CMC/Product reviewer, OVRR/DVP

Deborah Thompson, M.D., MSPH, PVP reviewer, OBE/DE

Hong Yang, Ph.D., Benefit-risk assessment reviewer, OBE/ABRA
Osman Yogurtcu, Ph.D., Benefit-risk assessment reviewer,
OBE/ABRA

Patrick Funk, Ph.D., Benefit-risk assessment reviewer, OBE/ABRA
Kathleen Jones, Ph.D., CMC/Facility reviewer, OCBQ/DMPQ
Gregory Price, Ph.D., CMC/Facility reviewer, OCBQ/DMPQ
CAPT Oluchi Elekwachi, PharmD, MPH, Labeling reviewer,
OCBQ/DCM/APLB

Kanaeko Ravenell, MS, SBB, BIMO reviewer, OCBQ/DIS

Review Completion Date

October 29, 2021

Established Name/Other
names used during
development

Pfizer-BioNTech COVID-19 Vaccine/ BNT162b2

Dosage
Forms/Strengths and Route
of Administration

A 0.2 mL suspension (10 ug BNT162b2) for intramuscular injection

Intended Use for EUA

Active immunization to prevent coronavirus disease 2019 (COVID-
19) caused by Severe Acute Respiratory Syndrome Coronavirus 2
(SARS-CoV-2)

Intended Population

ndividuals 5 through 11 years of age

Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 180 of 237

TABLE OF CONTENTS

1 EXECUTIVE SUMMARY ..............:ccc:eeeeeeeeeeeeeeeenneneeeeeeeeeeneeeeaeeeeeeseeeeeeeeeesaaaeeeeeeeeseeeeeeeeeeaeeeeees 5
2 SARS-COV-2 VIRUS AND COVID-19 DISEASE..............ccccccccceeeeeseseeeneeeeeeeeeeeeseeaaeeeeeeeeneeeeeees 7
3 AUTHORIZED AND APPROVED VACCINES AND THERAPIES FOR
COVID~19 o.oo. ceeececcessennneeeeeeeeeeeeeeeaaaaeeeeeeeeeeeeeeaseeaaeseeeeeeeeagaaaaaeeeeeseeesaaseeeeeeaesseeeeeseesseeaaeeeeeennees 9
4 COMIRNATY (COVID-19 VACCINE, MRNA) ..............cc::ceeeceeeeeeeeeeeeeeeeeeeeeeeeseeesneaeeeeeeeeeneenes 11
4.1 Efficacy of a 2-dose primary series of COMIRNATY in individuals 16 years of age and
(0) (0 (=) eee 11
4.2 Safety of a 2-dose primary series of COMIRNATY in individuals 16 years of age and
(0) (0 (= eee 12
4.3 Effectiveness and safety of a 2-dose primary series of Pfizer-BioNTech COVID-19
Vaccine in adolescents 12-15 years Of AQE ........ ee eeeceeeeeee eee eeeeeeeeee eter ee eeeetenaaeeeeeeeeeeeeeea 12
4.4 Cases of myocarditis/pericarditis reported in BNT162b2 recipients in ongoing clinical
trials Of BNT162D2 00.0... ecccccccccceccceeeeeeeneeeeeeeeeeeeceeaaeeeeeeeeeececeneseeeeeeeeeeeeseeesiteeeeeeeeseneees 13
4.5 Post-EVA and post-licensure Surveillance ................::ccccccsccceeeeeeceeeeeeeeeeaeeeaeeaeeeeeeeaaeeaaaeaes 13

5 EVA AMENDMENT REQUEST FOR THE PFIZER-BIONTECH COVID-19

VACCINE FOR USE IN CHILDREN 5-11 YEARS OF AGE ...0.......ceeceeeseeeeeeeeeeeeeeseeeeeeeeeeeeees 15

6 EVA REQUIREMENTS, GUIDANCE AND CONSIDERATIONS PERTAINING
TO COVID-19 VACCINES. ............cccccccceeeeeeeeeeeeeeeeeeeeeeeeeeeeeesseaeaeeeeeeeeesesaaaaeseeeeeeeeseeeeeeeaeeeeeseess 16
6.1 U.S. requirements to support issuance of an EVA for a biological product .................. 16
6.2 FDA guidance for industry related to COVID-19 VACCINES. ..............ccccecceceeeeeeeeeeteeeeeteeetees 16

6.3 Regulatory considerations for clinical development of COVID-19 vaccines in children ..16

7 FDA REVIEW OF CLINICAL SAFETY AND EFFECTIVENESS DATA..........::ccccsseeeeceeeeeeees 18
7.1 Overview of study C45910007 ooo... cece etree rete eeaaaeeeeeeeeeeeetaaaaeeeeeeeeeeeeseneneneeeeees 18
7.2 Study COSIQN ......... cece cece ee eee enna ae ieee eee teen naa nee eeeeee seen eeeggeeaeeeeeeeeeeeneeeeaaaes 18
7.3 Disposition of Phase 2/3 participants ...........cccccccccccccccceecececeeeeceeeeeeeeeeeeeeeeeeeeeeeeeeseeeeeeeeeas 20
7.4 Demographic and baseline CharacteristiCs .......... ccc eeseeeeeee eee eeeeeeneneeeeeeeeeeeeeeneneeeeeeeeees 22
7.5 Immunogenicity results «2.0.2.2... cece eee eee ee eee eee tees eee e teen ea aaeeeeeeeeeeeeeeeeneaeeeeeeeeeeeneeeeaaaaes 23
7.6 Efficacy reSUItS........ eee cece e ee ee eee e eee eter erent e ee ee ee ee etree ence eaaaaaeeeeeeeeeeeeecaaaeeeeeeeeeeeeeeeeeeeeees 25
7.7 Safety reSults «2.00.0... eee tenner teeter nna ee etree erent naaaaeeeeeeeeeeeeeaaaaeeeeeeeeeeeeeeeeeeeeees 26
7.8 Study C4591007 Phase 2/3 SUMMATY .........c cc ccececeeee eee eennnneeeeeeeeeeeeeaaaaeeeeeeeeeeeeeeneneeaeeeeees 32

8 FDA REVIEW OF OTHER INFORMATION SUBMITTED. ...........::ccccseeeeeeeeeeeeeeeeeeeeeeeeeeeeneeees 33
8.1 Chemistry, Manufacturing, and Control (CMC) information ..............c:ccceeeeeeeeeeereteeeeeees 33
8.2 Pharmacovigilance Activities ....... eee etree eee eeenaeeeeeeeee eee tegeeeeeeeeeeeeeeneeenaaaeees 35
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 181 of 237

8.3 Clinical assay iNfOrMatiONn ........... cece eect eect eter eee ee teeta aaeeeeeeeeeeeeeeeeeneeeeeeeeeeeeeneeenaaaaes 36

8.4 Inspection of clinical StUdYy SItCS 00.0... een ee eee eee e ee eene eee ee teeter ete aaeeeeeeeeeeeeeeneenaaaaees 36

8.5 EVA prescribing information and fact Sheets ..............cceceeeeeeceeeeeeeeeeneeeeeeeeeeeeeeeeneneeeeeeeeees 37
9 BENEFIT/RISK IN THE CONTEXT OF THE PROPOSED EUA FOR PFIZER-

BIONTECH COVID-19 VACCINE IN CHILDREN 5-11 YEARS OF AGE ...........::ssseeeeeeeeeeees 37
9.1 Known and potential benefits ...... 2... cece cece cece cece eee eeeceeeeeeeeeeeeeeeeeeeeeeeeeeeesaeeeeeeesaeeeaeeaas 37
9.2 Data gaps related to DenefitS «0. eee eee e ee ee etna aaae ener ee eeeeeeaaaeeeeeeeeeeeeseeeeeeeeeeees 38
9.3 Known and potential riSkS ......... cece eee e cece ecee eens eeeaeeeaeeeaeeeaaeeaaeeaaeeaaeeaaaeeaaeaaeeaaeese 38
9.4 Data gaps related to riSKkS ........ eee eee cece ee enenne eter ee ee eee eaaaeeeeeeeeeeeetegeneeaeeeeeeeeeeeeeennaaeees 39
9.5 Quantitative benefit-risk assessment for children 5-11 years Of AGE ...........eeeeeeeeeeeeeeeeees 39

10 VRBPAC SUMMARY .........ccccceeseeeeeeeeeeeeeeeeeeeeeeeeeeeaeneeeeeeaaeeeeeeeeaeseeeeeeeeeseseeeeeeeeseseeeeeeeseeneees 41
11 OVERALL SUMMARY AND RECOMMENDATIONS .....0.....ccceccceeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeneeeeeees 42
12 REFERENCEG.........ccccccceeeeeceeeeeeeeeeeeeeeeeeeeeeeneeeeeeeeaaeeeeeseaaaeeeeeeaaaeseeeeeaeseeeeeaeseseseeeeeeeeeeeeeeeeeees 43
13 APPENDIX 1: C4591007 PHASE 1 (DOSE RANGING) —- SUMMARY OF

SAFETY AND IMMUNOGENICITY ....000...ceccceceeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeseeeeeeeeseeeeeeeeesneeeeeees 46
14 APPENDIX 2: COVID-19 AND SEVERE COVID-19 CASE DEFINITIONS ............::::cseeeeee 47
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 182 of 237

List of Tables

Table 1. Emergency Use Authorizations of COVID-19 Vaccines ........... ccc cccceccceeeeeeeeeeeeeeeteeeeteeees i)

Table 2. Emergency Use Authorized Pharmacological Products for Post-exposure Prophylaxis
and/or Treatment Of COVID-19........ cc ccc cccccccccccccecc cece eceeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeecaeeseeeseeeeseeenaeeaas 10

Table 3. Study C4591007*: Participants 5-11 Years of Age (10 ug BNT162b2) ........ ee 18

Table 4. Disposition of Immunogenicity Populations, Phase 2/3, Participants 5-11 Years of Age
(Study C4591007 Cohort 1) and Participants 16-25 Years of Age (Study C4591001)....... 21

Table 5. Demographic and Baseline Characteristics, Phase 2/3, Participants 5-11 Years, Safety
Population, Study C4591007 Cohort 1.0.0.0... eee eceee cece cece eee eeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeees 22

Table 7. Seroresponse Rates” at 1 Month Post-Primary Series in Phase 2/3 BNT162b2 (10 ug)
Recipients 5-11 Years of Age and Study C4591001 Phase 2/3 Cohort 1 BNT162b2 (30 ug)
Recipients 16-25 Years of Age Without Evidence of SARS-CoV-2 Infection up to 1 Month
After Dose 2, Evaluable Immunogenicity Population®..............c:ccceeeeeeeeeeeeeeeeeteeeeeeeeeeeeenaaaes 24

Table 8. SARS-CoV-2 Neutralizing GMTs?@ at Pre-Dose 1 and 1 Month Post-Primary Series in

C4591007 Phase 2/3 Cohort 1 Participants 5-11 Years of Age Without Evidence of SARS-
CoV-2 Infection up to 1 Month After Primary Series, Evaluable Immunogenicity Population?

Table 9. Safety Overview, Phase 2/3 Cohorts 1 and 2, Participants 5-11 Years, Safety
Population, Study C4591007 .00........ecceeeceeeseeeeeeeeceee cece eeeeeeeeeeeeeeeeeeeeegeseeeeeeeeeeeeeeeeeeeeeeeeeeeees 26

Table 10. Frequency of Solicited Local Reactions Within 7 Days After Each Dose, by Severity,
Phase 2/3 Cohort 1 Participants 5-11 Years of Age, Safety Population®, Study C4591007

Table 11. Frequency of Solicited Systemic Reactions Within 7 Days After Dose 2 by Severity,
Phase 2/3 Cohort 1 Participants 5-11 Years of Age, Safety Population, Study C4501007 28

Table 12. Characteristics of Solicited Local and Systemic Adverse Reactions, Phase 2/3 Cohort
1, Participants 5-11 Years, Safety Population, Vaccine Group as Administered, Study

C4591 007 ooo eee cecee cece cece eee cette eee ee eter reece eset eens eee ecneeeeeeeceaeeeeesecaaeeeeeseaeeeeessnaaeeeeeseiaaeeeenees 29
Table 13. Model-Predicted Benefit-Risk Outcomes of Scenarios 1-6 per One Million Fully
Vaccinated Children 5-11 Years OI «0.22... cece cee ceeeeeeeeeeaeeeaeeeaeeeaaeeaaeeeaeeaaaeeaaeeaaeaaes 41
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 183 of 237

1 EXECUTIVE SUMMARY

On October 6, 2021, Pfizer submitted a request to FDA to amend its emergency use
authorization (EVA) to expand use of Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) for
prevention of COVID-19 caused by SARS-CoV-2 in individuals 5 through 11 years of age
(hereafter 5-11 years of age). The proposed dosing regimen is a 2-dose primary series, 10 ug
mRNA/per dose, administered 3 weeks apart. To provide a vaccine with an improved stability
profile and greater ease of use at vaccine distribution sites, authorization was also requested for
a modified formulation of the Pfizer-BioNTech COVID-19 Vaccine that uses a tromethamine
(Tris)/Sucrose buffer instead of the phosphate-buffered saline (PBS)/Sucrose buffer as used in
the previous formulation. Analytical comparability assessment, which uses laboratory testing to
demonstrate that a change in product formulation is not expected to impact safety or
effectiveness of the product, demonstrated that the Tris/Sucrose formulation is comparable to
the previously authorized/ approved BNT162b2 PBS/Sucrose formulation.

Pfizer's EVA request includes safety data from 5-11-year-old participants in the Phase 2/3
portion of the ongoing randomized, observer-blinded, placebo-controlled clinical trial C4591007.
The request initially included safety data from 1,518 recipients of BNT162b2 and 750 recipients
of saline placebo, over 95% of whom had 22 months of safety follow-up after Dose 2 (Cohort 1;
data cut-off September 6, 2021). To allow for more robust assessment of serious adverse
events and adverse events of interest (e.g., myocarditis, pericarditis, anaphylaxis), Pfizer
subsequently provided safety data from an additional 1,591 BNT162b2 recipients and 788
placebo recipients who were enrolled into the trial later and whose median duration of follow-up
was 2.4 weeks post-Dose 2 (Cohort 2; data cut-off October 8, 2021).

Vaccine effectiveness was inferred by immunobridging SARS-CoV-2 50% neutralizing antibody
titers (NT50, SARS-CoV-2 mNG microneutralization assay) among study participants 5-11
years of age (Phase 2/3 Cohort 1 of study C4591007) compared to those among a randomly
selected subset of study participants 16-25 years of age (Phase 2/3 of study C4591001). The
immunogenicity analyses evaluated neutralizing antibody titers against the USA_WA1/2020
reference strain, as assessed by microneutralization assay, among study participants with no
evidence of prior SARS-CoV-2 infection up to 1 month post-Dose 2. Immunobridging endpoints
and statistical success criteria were as follows:

e SARS-CoV-2 neutralizing antibody geometric mean titers (GMTs) measured 1 month after
Dose 2, with immunobridging success criteria of >0.67 for the lower bound of the 95%
confidence interval around the GMT ratio (5-11 years of age / 16-25 years of age), anda
point estimate of the GMT ratio 21.0.

Immunobridging statistical success criteria, as described above, were met. Subgroup analyses
of immunogenicity by age, gender, race and ethnicity, obesity and baseline SARS-CoV-2 status
showed no notable differences as compared with the overall study population, although some
subgroups were too small to draw meaningful conclusions. Descriptive immunogenicity
analyses, based on an exploratory 50% plaque reduction neutralization test (PRNT), showed
that a 10 ug BNT162b2 primary series elicited PRNT neutralizing titers against the reference
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 184 of 237

strain and B.1.617.2 (Delta) strain in participants 5-11 years of age (34 BNT162b2, 4 placebo)
with no evidence of SARS-CoV-2 infection up to 1 month post-Dose 2.

In a supplemental descriptive efficacy analysis, vaccine efficacy (VE) against symptomatic
COVID-19 after 7 days post-Dose 2 up to October 8, 2021 (data cut-off) was 90.7% (2-sided
95% Cl: 67.7%, 98.3%) in participants 5-11 years of age without evidence of prior SARS-CoV-2
infection. Totals of 3 cases of COVID-19 occurred in the BNT162b2 group and 16 in the placebo
group, most of which occurred during July-August 2021 when the Delta variant was prevalent in
the United States. At the time of the data cut-off, none of these cases met the criteria for severe
COVID-19.

Solicited local and systemic adverse reactions (ARs) were more frequently reported after Dose
2. The most commonly reported solicited ARs following administration of any primary series
dose were pain at the injection site (84.3%), fatigue (51.7%), and headache (38.2%). Most local
and systemic reactions were mild to moderate in severity, with median onset 2 days post-
vaccination, and most resolved within 1 to 2 days after onset. The most frequently reported
unsolicited adverse event (AE) in Cohort 1, lymphadenopathy was reported in 13 BNT162b2
recipients (0.9%); in Cohort 2, lymphadenopathy was reported in 6 BNT162b2 recipients (0.4%).
In Cohort 1, more BNT162b2 recipients (n=14; 0.92%) reported hypersensitivity-related AEs
(primarily skin and subcutaneous disorder including rash and dermatitis) than placebo recipients
(n=4; 0.53%). For Cohort 2, hypersensitivity reactions were reported in 9 participants (0.6%) in
the BNT162b2 group; events included a Type IV hypersensitivity reaction and other rashes.
Regarding serious adverse events (SAEs), one event (fracture) was reported in Cohort 1 and 3
events (infective arthritis, foreign body ingestion, and epiphyseal fracture) were reported in
Cohort 2; all were considered by the study investigator and FDA as unrelated to vaccination.
There were no reports of myocarditis/pericarditis or anaphylaxis, and no deaths. Subgroup
safety analyses by gender, race and ethnicity, obesity and baseline SARS-CoV-2 status showed
no notable differences as compared with the overall study population, although some subgroups
were too small to draw meaningful conclusions.

FDA conducted a quantitative benefit-risk analysis to evaluate predicted numbers of
symptomatic COVID-19 cases, hospitalizations, ICU admissions, and deaths that would be
prevented per million fully vaccinated children 5-11 years of age over a 6-month period, as
compared with predicted numbers of vaccine-associated excess myocarditis cases,
hospitalizations, ICU admissions and deaths per million fully vaccinated children 5-11 years of
age. The model conservatively assumed that the risk of myocarditis/pericarditis associated with
the 10 ug dose in children 5-11 years of age would the same as the estimated risk associated
with the 30 ug dose in adolescents 12-15 years of age from Optum healthcare claims data.
While benefits of vaccination were highly dependent on COVID-19 incidence, the overall
analysis predicted that the numbers of clinically significant COVID-19-related outcomes
prevented would clearly outweigh the numbers of vaccine-associated excess myocarditis cases
over a range of assumptions for COVID-19 incidence. At the lowest evaluated COVID-19
incidence (corresponding to the June 2021 nadir), the predicted number of vaccine-associated
myocarditis cases was greater than the predicted number of COVID-19 hospitalizations
prevented for males and for both sexes combined. However, in consideration of the different
clinical implications of hospitalization for COVID-19 versus hospitalization for vaccine-
associated myocarditis, and benefits related to prevention of non-hospitalized cases of COVID-
19 with significant morbidity, the overall benefits of the vaccine may still outweigh the risks even
under this low incidence scenario, which incorporates very conservative assumptions. If the
myocarditis/pericarditis risk in this age group is lower than the conservative assumption used in
the model, the benefit-risk balance would be even more favorable.
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 185 of 237

At the VRBPAC meeting held on October 26, 2021, the Committee discussed and then voted on
whether, based on the totality of scientific evidence available, the benefits of the Pfizer-
BioNTech COVID-19 Vaccine when administered as a 2-dose series (10 ug each dose, 3 weeks
apart) outweigh its risks for use in children 5-11 years of age. The vote was 17-0 in favor of the
authorization, with 1 abstention.

Based on the totality of the scientific evidence available at this time to support the conclusion
that the Pfizer-BioNTech COVID-19 vaccine may be effective, and that the known and potential
benefits outweigh the known and potential risks associated with the vaccine when used for
active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 5-11 years of
age, the review team recommends authorization of the Pfizer-BioNTech COVID-19 vaccine
under EUA for use as a 2-dose series (10 ug each dose, 3 weeks apart) in children 5-11 years
of age.

2 SARS-COV-2 VIRUS AND COVID-19 DISEASE

SARS-CoV-2 is a zoonotic coronavirus that emerged in late 2019 and was identified in patients
with pneumonia of unknown cause. The virus was named SARS-CoV-2 because of its similarity
to the coronavirus responsible for severe acute respiratory syndrome (SARS-CoV, a lineage B
betacoronavirus). SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA virus
sharing more than 70% of its sequence with SARS-CoV, and ~50% with the coronavirus
responsible for Middle Eastern respiratory syndrome (MERS-CoV). SARS-CoV-2 is the
causative agent of COVID-19, an infectious disease with respiratory and systemic
manifestations. Disease symptoms vary, with many persons presenting with asymptomatic or
mild disease and some progressing to severe respiratory tract disease including pneumonia and
acute respiratory distress syndrome (ARDS), leading to multiorgan failure and death. Symptoms
associated with SARS-CoV-2 infection in individuals less than 18 years of age are similar to
those in adults, but are generally milder, with fever and cough most commonly reported. ':2
Other symptoms in children include nausea and vomiting, diarrhea, dyspnea, nasal symptoms,
rashes, fatigue and abdominal pain.* Most children with COVID-19 recover within 1 to 2 weeks.
Estimates of asymptomatic infection in children vary from 15 to 50% of infections.*° However,
COVID-19 associated hospitalizations and deaths have occurred in children (see below), and
for some children, COVID-19 symptoms may continue for weeks to months after their initial
illness.®

The SARS-CoV-2 pandemic continues to present a challenge to global health and, as of
October 15, 2021, has caused approximately 239 million cases of COVID-19, including 4.8
million deaths worldwide.’ In the United States, more than 44 million cases have been reported
to the Centers for Disease Control and Prevention (CDC), with over 722,000 deaths. ®° Of the
total COVID-19 cases reported in the United States to date, 22.3% occurred among individuals
<18 years of age, with 8.7% occurring among 5-11-year-olds.'° Following emergency use
authorization of COVID-19 vaccines in December 2020, COVID-19 cases and deaths in the
United States declined sharply during the first half of 2021; however, beginning in late June
2021 a rise in cases was observed, including in children, associated with the highly
transmissible Delta variant that is now predominant in the United States.'’ As of the week
ending October 2, 2021, the Delta variant comprised greater than 99% of tested strains in the
United States.'? During the last week in August 2021, new COVID-19 infections in individuals
less than 18 years of age surpassed those in adults 18 to 64 years of age for the first time
during the pandemic. In the United States, COVID-19 cases occurring in children 5-11 years
now constitute 39% of cases in individuals younger than 18 years of age.'* Among cases of
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COVID-19 in individuals less than 18 years of age from the COVID-NET network?,
approximately 4,300 have resulted in hospitalization. '* As of October 17, 2021, 691 deaths from
COVID-19 have been reported in the United States in individuals less than 18 years of age, with
146 deaths in the 5-11 year age group. '®

The most common underlying medical conditions among hospitalized children were chronic lung
disease (29%), obesity (25%) and neurologic disorders (23%). A total of 68% of hospitalized
children had more than one underlying condition. Obesity and feeding tube dependence were
associated with increased risk of severe disease. Available evidence suggests that highest risk
groups include children with special healthcare needs, including genetic, neurologic, metabolic
conditions, or with congenital heart disease."” As in the adult population, COVID-19 in children
disproportionally affects underrepresented racial and ethnic groups, with hospitalizations and
deaths more frequent among Native American/Alaskan, Hispanic or Latin American, and non-
Hispanic Black children than among White children. '*:19

Following observation of an increased incidence of myocarditis in 2020 compared with 2019,
several studies have suggested an association between COVID-19 and myocarditis.2°21 While
the overall incidence of myocarditis following COVID-19 infection is low, persons with COVID-19
have a nearly 16-fold increase in risk for myocarditis, compared to individuals without COVID-
19. The risk is lowest among individuals 25-39 years and higher in persons less than 16 years
and older than 50 years of age.** Myocarditis may also present as part of the multisystem
inflammatory syndrome in children (MIS-C), usually 3 to 5 weeks after a SARS-CoV-2 infection.
MIS-C is a rare but serious COVID-19-associated condition that occurs in less than 1% of
children with confirmed SARS-CoV-2 infection.2° MIS-C presents with persistent fever,
laboratory evidence of inflammation, and at least 2 affected organs. In severe cases,
hypotension and shock can occur. Most patients have laboratory markers indicating damage to
the heart.*4 During the pandemic, a rise in MIS-C cases has generally lagged behind a rise
observed in COVID-19 infections by several weeks,*° with one study demonstrating the peak in
MIS-C cases occurring 31 days following the peak in laboratory-confirmed COVID-19 cases.*6
Between May 2020 and October 4, 2021, the CDC received reports of 5,217 cases and 46
deaths that met the definition for MIS-C; the median age of participants was 9 years with half of
the cases occurring in children ages 5 to 13 years. Males comprised 60% of cases, and 61%
were reported in children who were reported as Hispanic or Black.*’ Up to 66.7% of patients
with MIS-C had cardiac involvement, 7° including left ventricular dysfunction, mitral or tricuspid
regurgitation, coronary artery aneurysms, and/or arrhythmias.29 One study of outcomes in
children with MIS-C followed up to 9 months found that while 76% children with MIS-C required
ICU admission and therapy with inotropes or pressors; most symptoms, including
cardiovascular manifestations, resolved within 1 to 4 weeks.°° Limited data are available on
long-term outcomes in MIS-C.

While children and adolescents appear less susceptible to SARS-CoV-2 infection and generally
have a milder COVID-19 disease course as compared with adults, 31:2 adolescents and adults
have similar SARS-CoV-2 viral loads in their nasopharynx, so adolescents may play a role in
community transmission.**:34 Transmission of SARS-CoV-2 virus from children can occur in both
household and school settings.*°° In schools, transmission depends on the transmission rates
locally, variants circulating in the community, vaccination rates, and other preventive mitigation

strategies. Transmission between school staff members may be more common than
transmission involving students.*’ There is evidence that SARS-CoV-2 transmission is greater
in secondary and high schools than elementary schools.*°:°° Outbreaks of COVID-19 have been
reported in settings where children congregate, such as summer youth camps.441

In addition to morbidity and mortality on an individual level, the continuing spread of SARS-CoV-
2 has caused significant challenges and disruptions in worldwide healthcare systems,
economies, and many aspects of human activity (travel, employment, education). Other impacts
of COVID-19 on children include limited access to basic services such as healthcare and child
protective services, and social isolation due to disruption of school, sports, and social group
gatherings. The emergence of the Delta variant, variable implementation of public health
measures designed to control spread, and continued transmission among unvaccinated
individuals are major factors in the recent resurgence of COVID-19. While recently reported
cases appear to be declining relative to the Delta variant-associated peak globally and in the
United States, the longer-term effect of the Delta variant and the potential role of other variants
on the future course of the pandemic is uncertain.

3 AUTHORIZED AND APPROVED VACCINES AND THERAPIES FOR COVID-19

Table 1. Emergency Use Authorizations of COVID-19 Vaccines

Date of EUA or

or conditions considered to have
an equivalent level of
immunocompromise

Pfizer- Booster dose (at least 6 e Individuals 65 years of age and September 22, 2021
BioNTech months after completing a older

primary series of e Individuals 18 through 64 years

COMIRNATY and/or Pfizer- of age and at high risk of severe

BioNTech COVID-19 COVID-19

Vaccine) e Individuals 18 through 64 years

of age with frequent institutional
or occupational exposure to

SARS-CoV-2
Moderna 2-dose series (4 weeks 2-dose primary series in adults December 18, 2020
apart) 218 years of age
Moderna 34 dose (at least 1 month Individuals 212 years of age with August 12, 2021
after the second dose) compromised immune systems

due to solid organ transplantation
or conditions considered to have
an equivalent level of
immunocompromise

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Date of EUA or

Sponsor Authorized Use (Interval) Indicated Population EUA Amendment
Moderna Booster dose (at least 6 e Individuals 65 years of age and October 20, 2021
months after completing a older
primary series of Moderna e Individuals 18 through 64 years
COVID-19 Vaccine of age and at high risk of severe
COVID-19

e Individuals 18 through 64 years
of age with frequent institutional
or occupational exposure to

SARS-CoV-2
Janssen Single dose Individuals 218 years of age February 27, 2021
Janssen Booster dose Individuals 218 years of age October 20, 2021
Pfizer, Single heterologous booster Same population(s) as those October 20, 2021
Moderna dose following completion of — eligible to receive a booster dose
and Janssen _ primary vaccination with of the vaccine used for primary
another authorized or vaccination

approved COVID-19
vaccine (same interval as
authorized for a booster
dose of the vaccine used for
primary vaccination)

Emergency use authorizations of COVID-19 pharmacological products for post-exposure
prophylaxis and/or treatment of COVID-19 are as follows:

Table 2. Emergency Use Authorized Pharmacological Products for Post-exposure Prophylaxis
and/or Treatment of COVID-19

Product Date of EUA Authorized Use and Population

SARS-CoV-2-targeting
Monoclonal Antibodies

¢ Bamlanivimab/etesevimab Reissued September 16, All three products are indicated for the
2021 treatment of mild-to-moderate COVID-

¢ Sotrovimab 19 in adults and pediatric patients 12
May 26, 2021 years and older at high risk for

* Casirivimab/imdevimab progressing to severe COVID-19?

Reissued September 9, 2021
Casirivimab/imdevimab is also
authorized for post-exposure prophylaxis
(prevention) for COVID-19 in patients at
high risk for progressing to severe

and weighing at least 40 kg

10
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Product Date of EUA Authorized Use and Population

Immune Modulators

* Baricitinib Reissued July 29, 2021 Treatment of COVID-19 in hospitalized
patients’ receiving systemic

¢ Actemra June 24, 2021 corticosteroids and require

supplemental oxygen, non-invasive or
invasive mechanical ventilation, or

ECMO
COVID-19 Convalescent Reissued March 9, 2021 Treatment of hospitalized patients with
Plasma COVID-19

a Indicated for adults and pediatric patients 12 years of age and older weighing at least 40 kg

b Indicated for adults and pediatric patients 2 years and older

ECMO extracorporeal membrane oxygenation, EUA emergency use authorization

Source: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-
framework/emergency-use-authorization#coviddrugs Accessed August 2, 2021.

4 COMIRNATY (COVID-19 VACCINE, mRNA)

COMIRNATY is supplied as a concentrated multi-dose liquid formulation (0.45 mL volume)
stored frozen at -90°C to -60°C in a 2 mL Type 1 glass vial. A sterile diluent, 0.9% Sodium
Chloride Injection, USP, is supplied separately and is stored at 20°C to 25°C. The COMIRNATY
Multiple Dose Vial is thawed in a refrigerator (2°C to 8°C) for 2 to 3 hours or at room
temperature (up to 25°C) for 30 minutes. Once at room temperature, the COMIRNATY Multiple
Dose Vial is diluted with 1.8 mL of the diluent. After dilution, each vial of COMIRNATY contains
six doses of 0.3 mL of vaccine. COMIRNATY does not contain preservative.

4.1 Efficacy of a 2-dose primary series of COMIRNATY in individuals 16 years of age and
older

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had been enrolled from July 27, 2020, and who were followed for the development of COVID-19
during blinded placebo-controlled follow-up through as late as March 13, 2021. Overall, 60.8%
of participants in the BNT162b2 group and 58.7% of participants in the placebo group had 24
months of follow-up time after the primary series in the blinded placebo-controlled follow-up
period. The overall VE against COVID-19 in subjects without evidence of prior SARS-CoV-2
infection was 91.1% (95% Cl: 88.8 to 93.1). The overall VE against COVID-19 in subjects with
or without evidence of prior SARS-CoV-2 infection was 90.9% (95% Cl: 88.5 to 92.8).

4.2 Safety of a 2-dose primary series of COMIRNATY in individuals 16 years of age and older

In study C4591001, the most commonly reported solicited adverse reactions (occurring in 210%
of participants) among BNT162b2 vaccine recipients 16 through 55 years of age following any
dose were pain at the injection site (88.6%), fatigue (70.1%), headache (64.9%), muscle pain
(45.5%), chills (41.5%), joint pain (27.5%), fever (17.8%), and injection site swelling (10.6%).
The most commonly reported solicited adverse reactions in BNT162b2 vaccine recipients 56
years of age and older following any dose were pain at the injection site (78.2%), fatigue
(56.9%), headache, (45.9%), muscle pain (32.5%), chills (24.8%), joint pain (21.5%), injection
site swelling (11.8%), fever (11.5%), and injection site redness (10.4%).

Among participants 16 through 55 years of age, SAEs from Dose 1 up to the participant
unblinding date in ongoing follow-up were reported by 0.8% of BNT162b2 recipients and 0.9%
placebo recipients. In a similar analysis, in participants 56 years of age and older serious
adverse events (SAEs) were reported by 1.8% of BNT162b2 recipients and 1.7% of placebo
recipients who received at least 1 dose of BNT162b2 or placebo, respectively. In these
analyses, 58.2% of study participants had at least 4 months of follow-up after the primary series.
There were no notable patterns between treatment groups for specific categories of SAEs
(including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal
relationship to BNT162b2. From Dose 1 through the March 13, 2021 data cut-off date, there
were a total of 38 deaths, 21 in the BNT162b2 group and 17 in the placebo group. None of the
deaths were considered related to vaccination.

4.3 Effectiveness and safety of a 2-dose primary series of Pfizer-BioNTech COVID-19
Vaccine in adolescents 12-15 years of age

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days post-Dose 2 was 100% (95% Cl 75.3; 100.0) in participants 12-15 years of age without
prior evidence of SARS-CoV-2 infection and 100% in the group of participants with or without
prior infection. VE between Dose 1 and Dose 2 was 75.0% (95% Cl 7.4; 95.5), with divergence
of cumulative incidence of COVID-19 cases in BNT162b2 vs. placebo groups beginning at
approximately 14 days after Dose 1. Although based on a small number of cases in descriptive
analyses, the supplementary VE data provided compelling direct evidence of clinical benefit in
addition to the immunobridging data.

Safety data from a total of 2,260 adolescents 12-15 years of age randomized to receive vaccine
(N=1,131) or placebo (N=1,129) with a median of greater than 2 months of follow-up after the
second dose suggest a favorable safety profile, with no specific safety concerns identified that
would preclude issuance of an EVA. The most common solicited adverse reactions after any
dose included injection site pain (90.5%), fatigue (77.5%), headache (75.5%), chills (49.2%),
muscle pain (42.2%), fever (24.3%), joint pain (20.2%), injection site swelling (9.2%), injection
site redness (8.6%), all of which were generally mild to moderate and lasted a few days. Severe
solicited local and systemic adverse reactions occurred in up to 2.4% of 12-15-year-old
BNT162b2 recipients, were more frequent after Dose 2 (most common: fatigue 1.3%, headache
1.0%, chills 0.4%) than after Dose 1 (most common: fatigue 2.4%, headache 2.0%, chills 1.8%)
and more frequent after any dose in BNT162b2 recipients than age-matched placebo recipients.
Among recipients of BNT162b2, severe solicited adverse reactions/events in 12-15-year-olds
occurred less frequently than in 16-25-year-olds. No deaths were observed in this age group
during the follow-up period. SAEs, while uncommon (<0.5%), represented medical events
expected to occur among individuals in this age group and with the underlying conditions
represented in the study population, and available data do not suggest a causal relationship to
BNT162b2. There were no notable patterns or numerical imbalances between treatment groups
for specific categories of non-serious AEs among study participants 12-15 years of age that
would suggest a causal relationship to BNT162b2 vaccine.

4.4 Cases of myocarditis/pericarditis reported in BNT162b2 recipients in ongoing clinical trials
of BNT162b2

Pericarditis and myopericarditis have been reported in BNT162b2 recipients in study C4591001:

e Amale participant 255 years of age, with no medical history, reported pericarditis 28
days after Dose 2 of BNT162b2; the event was assessed by the investigator and FDA as
not related to the study intervention and was ongoing at the time of the data cut-off.

e Amale participant who was randomized to blinded placebo group at age 15 years and
subsequently unblinded and crossed over to open label BNT162b2 at age 16 years was
diagnosed with myopericarditis beginning 2 days after Dose 2 of BNT162b2. He was
hospitalized on Day 3 and treated with IVIG, non-steroidal anti-inflammatory medications
and steroids, and discharged the following day. He was followed by a cardiologist and
seen for follow up 2 months after vaccination. At that time the cardiologist recommended
limited activity. The investigator concluded that the there was a reasonable possibility
that the myopericarditis was related to vaccine administration due to the plausible
temporal relationship. FDA agrees with this assessment.

4.5 Post-EUA and post-licensure surveillance

As of October 21, 2021, more than 244 million doses of the Pfizer-BioNTech COVID-19 Vaccine
have been administered in the U.S. According to the CDC COVID Data Tracker, 205,046
individuals less than 12 years of age have received at least one dose of the Pfizer-BioNTech

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COVID-19 Vaccine, and 125,656 have received two doses. It is not known what proportions of
these numbers represent unauthorized use of the vaccine and what proportions might reflect
errors in reporting of the recipients’ ages.

As of October 18, 2021, VAERS received 442,763 reports (including 270,342 U.S. reports), of
which 854 U.S. reports were described as involving children 5-11 years of age, 9,523 U.S.
reports were in children 12-15 years of age, and 5,821 U.S. reports were in adolescents 16-17
years of age. The top ten most frequently reported MedDRA Preferred Terms (PTs) included:

e Overall, most frequent PTs: headache, fatigue, pyrexia, SARS-CoV-2 test, dizziness,
pain, nausea, chills, pain in extremity, dyspnoea

Safety concerns identified from post-authorization safety surveillance data in VAERS are
summarized below. Anaphylaxis, myocarditis, and pericarditis are existing safety concerns that
have been added to the product Fact Sheets. Review of passive surveillance AE reports and the
Sponsor's periodic safety reports did not indicate any new safety concerns, including in
adolescents. Most AEs are labeled events and consistent with the safety profile for this vaccine.
No unusual frequency, clusters, or other trends for AEs were identified that would suggest a
new safety concern, including among the reports described as involving children 5-11 years of
age.

Anaphylaxis

Post-authorization surveillance has identified a risk of anaphylaxis, occurring at a rate similar to
reported rates of anaphylaxis following licensed preventive vaccines, primarily in individuals with
history of prior severe allergic reactions to other medications or foods.4?49 Anaphylaxis is an
important identified risk in the pharmacovigilance plan and included in the Warnings sections of
the vaccine Fact Sheets and Prescribing Information. The estimated crude reporting rate for
anaphylaxis in the U.S. is 6.1 cases per million doses at this time based on the above VAERS
data.

Myocarditis and pericarditis

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females and older males and have been highest in males 12 through 17 years of age (~71.5
cases per million second primary series doses among males age 16-17 years and 42.6 cases
per million second primary series doses among males age 12-15 years as per CDC
presentation to the ACIP on August 30, 2021). In an FDA analysis of the Optum healthcare
claims database, the estimated excess risk of myocarditis/pericarditis approached 200 cases
per million fully vaccinated males 16-17 years of age and 180 cases per million fully vaccinated
males 12-15 years of age.*4 Although some cases of vaccine-associated myocarditis/pericarditis
have required intensive care support, available data from short-term follow-up suggest that most
individuals have had resolution of symptoms with conservative management. Information is not
yet available about potential long-term sequelae and outcomes in affected individuals, or
whether the vaccine might be associated initially with subclinical myocarditis (and if so, what are
the long-term sequelae). A mechanism of action by which the vaccine could cause myocarditis
and pericarditis has not been established. Myocarditis and pericarditis were added as important
identified risks in the pharmacovigilance plan and included in the Warnings sections of the
vaccine Fact Sheets and Prescribing Information. The Sponsor is conducting additional post-
authorization/post-marketing studies to assess known serious risks of myocarditis and
pericarditis as well as to identify an unexpected serious risk of subclinical myocarditis.

5 EUA AMENDMENT REQUEST FOR THE PFIZER-BIONTECH COVID-19 VACCINE FOR
USE IN CHILDREN 5-11 YEARS OF AGE

The request is accompanied by safety data from the Phase 2/3 portions of study C459100771.
This data includes 518 BNT162b2 recipients and 750 placebo (saline) recipients 5-11 years of
age, of whom over 95% of participants in each group had 22 months of safety follow up after
Dose 2 (Cohort 1, September 6, 2021 data cut-off), and data from an additional 1,591
BNT162b2 and 788 placebo recipients who were enrolled into the trial later and whose median
duration of follow-up was 2.4 weeks post-Dose 2 (Cohort 2; October 8, 2021 data cut-off).
Vaccine effectiveness in children 5-11 years of age was inferred by immunobridging SARS-
CoV-2 50% neutralizing antibody titers (NT50, as assessed by SARS-CoV-2 mNG
microneutralization assay) among C4591007 study participants 5-11 years of age following
completion of a primary series to antibody titers of those of young adults 16-25 years of age
who received two doses of 30 ug BNT162b2 in study C4591001. Efficacy against COVID-19
disease was assessed descriptively in study C4591007 participants 5-11 years of age.

Vaccine formulation

Authorization is being requested for a modified formulation of the Pfizer-BioNTech COVID-19
Vaccine. To provide an improved stability profile to the vaccine, the Pfizer-BioNTech COVID-19
Vaccine for use in children 5-11 years of age uses tromethamine (Tris) buffer instead of the
phosphate-buffered saline (PBS) as used in the previous formulation. The packaged vials for
the new formulation are also stored frozen at -90°C to -60°C; however, the frozen vials may be
thawed and stored at refrigerator at 2°C to 8°C for up to 10 weeks. For the 10-ug mRNA dose,
each 1.3-mL filled vial must be diluted with 1.3 mL 0.9% sodium chloride for injection to provide
10 doses at 10 ug RNA/ 0.2 mL Injection volume. After dilution, the vials should be stored at
2°C to 25°C and should be used within 12 hours. See Section 8.1 Chemistry, Manufacturing,
and Controls (CMC) information, for details.

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6 EUA REQUIREMENTS, GUIDANCE AND CONSIDERATIONS PERTAINING TO COVID-
19 VACCINES

6.1 U.S. requirements to support issuance of an EVA for a biological product

Based on the declaration by the Secretary of the U.S. Department of Health and Human
Services (HHS) that the COVID-19 pandemic constitutes a public health emergency with a
significant potential to affect national security or the health and security of United States citizens
living abroad, FDA may issue an EVA after determining that certain statutory requirements are
met (section 564 of the FD&C Act (21 U.S.C. 360bbb-3)).

e There is no adequate, approved, and available alternative to the product for diagnosing,
preventing, or treating the disease or condition.

6.2 FDA guidance for industry related to COVID-19 vaccines

6.3 Regulatory considerations for clinical develooment of COVID-19 vaccines in children

The Vaccines and Related Biological Products Advisory Committee convened on June 21,
2021, to discuss, in general, the data needed to support authorization and/or licensure of
COVID-19 vaccines for use in pediatric populations.

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Effectiveness

Regulatory precedent with other preventive vaccines provides a basis for inference of vaccine
effectiveness in pediatric populations based on immunobridging to a young adult population in
which clinical disease endpoint vaccine efficacy has been demonstrated for the same prototype
vaccine. The immune marker(s) used for immunobridging do not need to be scientifically
established to predict protection but should be clinically relevant to the disease. Based on
available data in humans and animal models, FDA considers neutralizing antibody titers (a
functional measure of the vaccine immune response against SARS-CoV-2) to be clinically
relevant for immunobridging to infer effectiveness of COVID-19 vaccines in pediatric age
groups. Because no specific neutralizing antibody titer has been established to predict
protection against COVID-19, two immunogenicity endpoints (geometric mean titer [GMT] and
seroresponse rate) are considered appropriate for comparing the range of neutralizing antibody
responses elicited by the vaccine in pediatric vs. young adult populations.

Safety

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7 FDA REVIEW OF CLINICAL SAFETY AND EFFECTIVENESS DATA
7.1. Overview of study C45910007

The EVA amendment request contains safety, immunogenicity, and descriptive efficacy data
from children 5-11 years of age enrolled in C4591007, an ongoing Phase 1/2/3, randomized,
placebo-controlled study. The comparator group for the immunobridging analyses to support
vaccine effectiveness in this age group was a random subset of Phase 2/3 participants 16-25
years of age enrolled in study C4591001, the study in which VE against COVID-19 was
established in individuals 16 years of age or older.

Data from study C4591007

e Phase 2/3: a total of 3,109 BNT162b2 (10 yg) recipients and 1538 placebo recipients 5-11
years of age

— Cohort 1: 1,518 BNT162b2 (10 ug) recipients and 750 placebo recipients, of whom
1,444 (95.1%) and 714 (95.2%), respectively, had at least 2 months of safety follow-up
after completing a 2-dose primary series (data cut-off September 6, 2021). Summary
tables for solicited adverse reactions (ARs) and immunogenicity analyses are based on
this cohort of subjects. A descriptive efficacy analysis was also based on this cohort.

— Cohort 2: A second cohort of 1,591 BNT162b2 (10 ug) recipients and 7878 placebo
recipients had a median duration of follow up of 2.4 weeks post-Dose 2 at the time of
data cut-off (October 8, 2021). Safety data from this cohort were provided for further
assessment of SAEs and AEs of clinical interest.

e Phase 1 data to support dosage selection for Phase 2/3 portion of the study

Table 3. Study C4591007*: Participants 5-11 Years of Age (10 pg BNT162b2)

Study Number! BNT162b2 Placebo (Saline)
Countries Description N N Study Status
C4591007 Phase 1/2/3 Phase 1: 16 Phase 1:0 Ongoing
United States, randomized, placebo- Phase 2/3: 3,109 Phase 2/3: 1,538
Finland, Poland, controlled; to evaluate
and Spain safety, immunogenicity

and efficacy of COVID-

19 vaccine

N=Number of randomized participants as of data cut-off dates July 16, 2021 (all Phase 1 participants), September 6, 2021 (Phase
2/3 cohort 1: 1,518 BNT162b2, 750 placebo; enrollment started June 7, 2021) and October 8, 2021 (Phase 2/3 cohort 2: 1,591
BNT162b2, 788 placebo; enrollment started August 26, 2021).

*First participant, first visit was March 24, 2021 (Phase 1).

7.2. Study design

Phase 2/3 is being conducted in the United States, Finland, Poland, and Spain. The Phase 2/3

portion of the study did not exclude children with a history of prior SARS-CoV-2 infection or
clinical symptoms/signs of COVID-19, children with known HIV, hepatitis B or hepatitis C, or

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stable pre-existing disease (defined as disease not requiring significant change in therapy or
hospitalization for worsening disease during the 6 weeks before enrollment).

Immunogenicity evaluation

Primary endpoints and statistical success criteria

Efficacy evaluation

A secondary objective is to evaluate efficacy of BNT162b2 against laboratory-confirmed
symptomatic COVID-19 occurring from 7 days after Dose 2 in participants without evidence of
prior SARS CoV-2 infection and in participants with or without evidence of prior SARS CoV-2
infection. A descriptive analysis was conducted once 19 confirmed cases had accrued. COVID-
19 and severe COVID-19 case definitions are included in Appendix 2.

Safety evaluation

Reactogenicity (solicited local and systemic adverse reactions)

Unsolicited adverse events

Other safety assessments included: AEs occurring within 30 minutes after each dose, non-
serious unsolicited AEs from Dose 1 through 1 month after Dose 2, and SAEs from Day 1 to 6
months after Dose 2, or the data cut-off date (Phase 1: July 16, 2021; Phase 2/3: September 6,
2021). AEs were categorized by frequency and maximum severity according to MedDRA
System Organ Class and PT, and relationship to the study intervention was assessed. Deaths
are recorded to the end of the study.

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Adverse events of clinical interest

Analysis populations

Pertaining to participants 5-11 years of age

e Safety: All participants who receive at least 1 dose of the study intervention.

e All-available immunogenicity: All randomized participants who receive at least 1 dose of the
study intervention with at least 1 valid and determinate immunogenicity result after
vaccination.

Data analysis cut-off dates:
e All Phase 1 participants: July 16, 2021
e Phase 2/3 Cohort 1 (initial): September 6, 2021 (enrollment started June 7, 2021)
e Phase 2/3 Cohort 2: October 8, 2021 (enrollment started August 26, 2021)

7.3 Disposition of Phase 2/3 participants

Cohort 1 (initial enrollment)

Cohort 1 was comprised 1,538 BNT162b2 10 yg participants and 757 placebo participants; 11
(0.7%) BNT162b2 and 6 (0.8%) placebo participants did not receive any study agent. Two
BNT162b2 participants (0.1%) and two placebo participants (0.3%) discontinued vaccination
before the 1 month post-Dose 2 follow up; none resulted from an AE. Three participants turned
12 years of age during the course of the study and became eligible to receive 30 ug BNT162b2
under EUA; two of these participants received two doses of 10 ug BNT162b2 prior to being
unblinded, and the other participant received both doses of placebo before being unblinded and
withdrew to receive a COVID-19 vaccine outside of the study; data from these participants were
included in endpoint analyses up to the point at which they were unblinded.

Safety population: solicited ARs, unsolicited AEs, SAEs and AEs of clinical interest were
assessed in a total of 2,268 (1,518 10 ug BNT162b2, 750 placebo) participants 5-11 years of
age; over 95% of participants in each study group completed at least 2 months of safety follow-
up after Dose 2. Five BNT162b2 recipients and six placebo recipients withdrew from the study,
mainly due to voluntary withdrawal.

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Table 4. Disposition of Immunogenicity Populations, Phase 2/3, Participants 5-11 Years of Age
(Study C4591007 Cohort 1) and Participants 16-25 Years of Age (Study C4591001)

5-11 years of age 5-11 years ofage 16-25 years of age

BNT162b2 (10 wg) Placebo BNT162b2 (30 yg)
Disposition n (%) n (%) n (%)
Randomized to receive BNT162b2? 322 (100.0) 163 (100.0) 300 (100.0)
All-available immunogenicity population 311 (96.6) 156 (95.7) 286 (95.3)
Excluded because they did not have at
least 1 valid and determinate 11 (3.4) T (4.3) 13 (4.3)
immunogenicity result after vaccination
Evaluable immunogenicity population 294 (91.3) 147 (90.2) 273 (91.0)
Without evidence of infection up to 1
month after Dose 2° 264 (82.0) 130 (79.8) 253 (84.3)
Subjects excluded from evaluable 28 (8.7) 16 (9.8) 27 (9.0)
immunogenicity population
Reason for exclusion (Subjects may have
been excluded for >1 reason)
Did not receive 2 doses of the vaccine 3 (0.9) 1 (0.6) 0
as randomized
Did not receive Dose 2 within 19 to 42 3 (0.9) 2 (1.2) 3 (1.0)

days after Dose 1

Did not have at least 1 valid and
determinate immunogenicity result 13 (4.0) 14 (8.6) 21 (7.0)
within 28 to 42 days after Dose 2

Did not have blood draw at 1 month

after Dose 2 visit (22) 6 (3.7) 8 (2.7)
1 Month after Dose 2 blood draw

outside of window (28-42 days after 6 (1.9) 8 (4.9) 13 (4.3)
Dose 2)

Had important protocol deviation(s) as 10 (3.1) 0 4 (1.3)

determined by the clinician

%:n/N. n = number of participants with the specified characteristic. N = number of randomized participants in the specified group;

this value is the denominator for the percentage calculations.

a. Participants who had no serological or virological evidence (prior to the 1-month post-Dose 2 blood sample collection) of past
SARS-CoV-2 infection (i.e., N-binding ant body [serum] negative at pre-Dose 1 and at 1 month post-Dose 2, SARS-CoV-2 not
detected by NAAT [nasal swab] at pre-Dose 1 and pre-Dose 2, and negative NAAT [nasal swab] result at any unscheduled visit
prior to the 1-month post-Dose 2 blood sample collection) and had no medical history of COVID-19 were included in the analysis.

b. Participants may have been excluded for more than 1 reason.

Efficacy population

Of 2186 participants (1450 BNT162b2 and 736 placebo) in the evaluable efficacy population,
1305 BNT162b2 and 663 placebo participants did not have evidence of SARS-CoV-2 infection
from pre-Dose 1 to 7 days post-Dose 2.

Cohort 2 (expansion)

In the Phase 2/3 safety expansion, 1,598 participants were randomized to receive BNT162b2
and 796 were randomized to placebo. At the time of the October 8, 2021, cut-off, most
participants (98.7%) had received both Dose 1 and Dose 2. Seven of the randomized
BNT162b2 participants did not receive vaccine. One participant in the BNT162b2 group
discontinued from the vaccination period due to AEs of pyrexia and neutropenia that worsened
from baseline (see Section 7.7.7, AEs leading to withdrawal). Two participants (0.1%) in the
BNT162b2 group withdrew from the study before the 1-month period. Neither withdrawal was
due to an AE.

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Comorbidities at baseline

(0.1%) for acute lymphocytic leukemia (immunocompromising conditions), cystic fibrosis, and

sickle cell disease.

disease.

7.4 Demographic and baseline characteristics

Demographic characteristics for the Phase 2/3 study C4591007 Cohort 1 safety population are
summarized in Table 5 below. Overall, participants were predominately White, with a mean age
of approximately 8 years. Of the BNT162b2 recipients, 11.5% were obese, 8.8% had evidence

of prior SARS-CoV-2 infection and 20.6% had comorbidities placing them at increased risk of

severe COVID-19. More than 70% of participants were enrolled in the United States.

Table 5. Demographic and Baseline Characteristics, Phase 2/3, Participants 5-11 Years, Safety

Population, Study C4591007 Cohort 1

C4591007 C4591007

BNT162b2 10 ug Placebo

(N?=1518) (N?=750)

Characteristic n° (%) n° (%)
Sex: Male 799 (52.6) 383 (51.1)
Sex: Female 719 (47.4) 367 (48.9)
Race: White 1204 (79.3) 586 (78.1)
Race: Black or African American 89 (5.9) 58 (7.7)
Race: American Indian or Alaska Native 12 (0.8) 3 (0.4)
Race: Asian 90 (5.9) 47 (6.3)
Race: Native Hawaiian or other Pacific Islander <1% <1%
Race: Multiracial 109 (7.2) 49 (6.5)
Race: Not reported 9 (0.6) 7 (0.9)
Ethnicity: Hispanic or Latino 319 (21.0) 159 (21.2)
Ethnicity: Not Hispanic or Latino 1196 (78.8) 591 (78.8)
Ethnicity: Not reported <1% <1%
Age: Mean years (SD) 8.2 (1.93) 8.1 (1.97)
Age: Median (years) 8.0 8.0
Obese*: Yes 174 (11.5) 92 (12.3)
Obese*: No 1343 (88.5) 658 (87.7)
Obese*: Missing <1% <1%
Baseline Evidence of Prior SARS-CoV-2 Infection: Negative® 1385 (91.2) 685 (91.3)
Baseline Evidence of Prior SARS-CoV-2 Infection: Positive’ 133 (8.8) 65 (8.7)
Comorbidities*: Yes 312 (20.6) 152 (20.3)
Comorbidities*: No 1206 (79.4) = (79.7)
Country: Finland 158 (10.4) 1 (10.8)
Country: Poland 125 (8.2) “0 (8.0)
Country: Spain 162 (10.7) 8 (10.4)

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C4591007 C4591007

BNT162b2 10 ug Placebo

(N?=1518) (N?=750)

Characteristic n° (%) n° (%)
Country: United States 1073 (70.7) 531 (70.8)

a. N = number of participants in the specified group. This value is the denominator for the percentage calculations.

b. n = Number of participants with the specified characteristic.

e. Negative N-binding antibody result and negative NAAT result at pre-Dose 1 and no medical history of COVID-19.

f. Positive N-binding antibody result at pre-Dose 1, positive NAAT result at pre-Dose 1, or medical history of COVID-19.

The demographic and baseline characteristics of the evaluable immunogenicity and efficacy
populations without baseline evidence of SARS-CoV-2 infection were similar to the overall
characteristics of Cohort 1 population.

Demographic characteristics in Cohort 2 were similar to Cohort 1.
Comparator group for immunogenicity: The 300 participants ages 16-25 years from study

C4591001 were from sites in the United States (64%), Argentina (18%), Brazil (12%), and South
Africa/Turkey/Germany (6% combined total).

7.5 Immunogenicity results
7.5.1 Primary immunogenicity objective

Immunogenicity of BNT162b2 was assessed based on analyses of GMTs and seroresponse
rates for neutralizing antibody titers to the reference strain (USA_WA1/2020).

GMTs of neutralizing antibody titers to the reference strain

Among participants in the evaluable immunogenicity population without prior evidence of SARS-
CoV-2 infection up to 1 month after Dose 2, the ratio of SARS-CoV-2 50% neutralizing GMT in
children 5-11 years (10 ug each dose) compared to individuals 16-25 years (30 ug each dose)
was 1.04 (95% Cl: 0.93, 1.18). The lower bound of the 2-sided 95%Cl for GMR was >0.67 and
the point estimate was 21, which met FDA’s requested criteria; see Table 6, below.

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GMT (95% Cl) GMT (95% Cl) one
5-11 Years of Age 16-25 Years of Age (5-11 ven Rat oon oe Years
Study C4591007 Study C4591001 of Age)!
Nc = 264 Nc= 253 g
1197.6 1146.5 1.04
(1106.1, 1296.6) (1045.5, 1257.2) (0.93, 1.18)

a. SARS-CoV-2 mNeonGreen virus microneutralization assay (SARS-CoV-2 mNG NT), reference strain: recombinant
USA_WA1/2020. NT50= 50% neutralizing titer.

b. Evaluable immunogenicity population pertaining to Phase 2/3 BNT162b2 participants 5-11 years of age (study C4591007) and
Phase 2/3 BNT162b2 participants 16-25 years of age (study C45910071).

c. N = Number of Phase 2/3 participants with valid and determinate assay results for the specified assay at the given dose/sampling
time point within specified window.

d. Immunobridging statistical success is declared if the lower limit of the 2-sided 95% Cl for the GMT ratio is greater than 0.67 and
the point estimate of the GMT ratio is 21.0.

Rates of neutralizing antibody seroresponse to the reference strain

a. SARS-CoV-2 mNeonGreen virus microneutralization assay-NT50, reference strain: recombinant USA_WA1/2020.

b. Seroresponse defined as at least 4-fold rise relative to pre-Dose 1; if the baseline measurement was below LLOQ, a
postvaccination titer of 24 x LLOQ was considered a seroresponse.

c. Evaluable immunogenicity population pertaining to Phase 2/3 BNT162b2 participants 5-11 years of age (study C4591007) and
Phase 2/3 BNT162b2 participants 16-25 years of age (study C4591001).

e. Immunobridging statistical success is declared if the lower limit of the 2-sided 95% Cl for the difference in percentages of
participants with seroresponse is >-10%.

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Subgroup Analyses of Geometric Mean Titers

GMTs of SARS-CoV-2 neutralizing titers and seroresponse rates at 1 month after Dose 2 did
not vary by demographic subgroup, although some subgroups were too small to evaluate by
protocol-specified methods. Specifically, no notable differences in GMTs or seroresponse rates
were observed by age (i.e., 5-6 years vs. 7-8 years vs. 9-11 years), sex, race, ethnicity, obesity
(Y/N), or SARS-CoV-2 status.

In descriptive post hoc analyses of immunogenicity data based on the presence or absence of
comorbidities (defined as described in Kim et al. MMWR 20204’), GMT and seroresponse rates
among those with comorbidities were comparable to those without comorbidities.

7.5.2 Exploratory immunogenicity analyses against the Delta Variant

Table 8. SARS-CoV-2 Neutralizing GMTs? at Pre-Dose 1 and 1 Month Post-Primary Series in
C4591007 Phase 2/3 Cohort 1 Participants 5-11 Years of Age Without Evidence of SARS-CoV-2
Infection up to 1 Month After Primary Series, Evaluable Immunogenicity Population”

a. SARS-CoV-2 plaque reduction neutralization assay, SARS-CoV-2 strains: recombinant USA_WA1/2020 (reference), B.1.617.2
(Delta).

7.6 Efficacy results

Pfizer submitted supplemental, descriptive efficacy data for Phase 2/3 Cohort 1 participants 5-
11 years of age, based on a total of 19 confirmed symptomatic COVID-19 cases occurring at
least 7 days post-Dose 2, accrued up to the data cut-off of October 8, 2021. The evaluable
efficacy population included 1,450 participants randomized to BNT162b2 and 736 participants
randomized to placebo, of whom 1305 BNT162b2 and 663 placebo participants did not have
evidence of SARS-CoV-2 infection from pre-Dose 1 to 7 days after Dose 2.

In participants 5-11 years of age without evidence of SARS-CoV-2 infection prior to Dose 2, the
observed VE against confirmed COVID-19 occurring at least 7 days after Dose 2 was 90.7%

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(95% Cl: 67.7%, 98.3%), with 3 COVID-19 cases in the BNT162b2 group compared to 16 in the
placebo group (2:1 randomization BNT162b2 to placebo). All cases of COVID-19 occurred in
children without prior history of infection. None of these cases met the criteria for severe
infection. Most of the cases occurred in July-August 2021. Comorbidities at baseline (including
obesity) were present in total of 20.1% of cases. No virus sequence analyses were available to
determine whether these cases were caused by the Delta variant or another variant.

7.7 Safety results
Please see the Appendix 1 for Phase 1 study results.

Overview of adverse events: Phase 2/3

In C4591007 Phase 2/3 Cohort 1, e-diary data were collected from 1,511 BNT162b2 recipients
and 749 placebo recipients for reactogenicity (local and systemic reactions). Overall, injection
site reactions occurring within 7 days of vaccination with BNT162b2 were common, occurring in
approximately 75% of participants after either Dose 1 or Dose 2. Systemic AEs occurred in
approximately 50% of BNT162b2 recipients.

No Cohort 1 participants withdrew because of AEs, and there were no deaths reported. SAEs
occurred in one participant each from the BNT162b2 and placebo groups, and neither were
considered by the investigator or FDA to be related to the investigational agent. Immediate
unsolicited AEs were rare in this study, occurring in 0.3% or less after either Dose 1 or Dose 2.
See Table 9 below.

Table 9. Safety Overview, Phase 2/3 Cohorts 1 and 2, Participants 5-11 Years, Safety Population,
Study C4591007

BNT162b2 10 yg Placebo

Event n/N (%) n/N (%)
Immediate unsolicited AE within 30 minutes after vaccination

Dose #1 3/1518 (0.2) 3/750 (0.4)

Dose #2 4/1515 (0.3) 2/746 (0.3)
Solicited injection site reaction within 7 days

Dose #1 1150/1511 (76.1) — 254/749 (33.9)

Dose #2 1096/1501 (73.0) — 237/741 (32.0)
Solicited systemic AR within 7 days

Dose #1 715/1511 (47.3) 334/749 (44.6)

Dose #2 7771/1501 (51.4) — 272/741 (36.7)
From Dose 1 through 1 month after Dose 2 (cohort 1)?

Any AE 166/1518 (10.9) 69/750 (9.2)

Unsolicited non-serious AE
From Dose 1 through 1 month after Dose 2 (cohort 2)?

166/1518 (10.9) 68/750 (9.1)

Any AE

115/1591 (7.2)

50/788 (6.3)

Unsolicited non-serious AE

113/1591 (7.1)

50/788 (6.3)

From Dose 1 through cut-off date® or participant unblinding®

Withdrawal due to AEs

1/3109 (<0.1)

0/1538 (0.0)

SAE

4/3109 (0.1)

1/1538 (0.1)

Deaths

0/3109 (0.0)

0/1538 (0.0)

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Note: MedDRA (v24.0) coding dictionary applied.

Note: Immediate AE refers to an AE reported in the 30-minute observation period after vaccination.

%:n/N. n = Number of participants with the specified characteristic. N = number of administered participants in the specified group;
this value is the denominator for the percentage calculations.

a. For cohort 1, 95% of participants had at least 2 months follow-up. For cohort 2, 71% of participants had at least 2 weeks follow-
up.

b. Oct 8, 2021 for all participants (cohort 1 and cohort 2), N=3109 is the total N for BNT162

c. Three participants (2 BNT162b2, 1 placebo) turned 12 years of age during the course of the study and eligible to received 30 ug
BNT162b2 under EUA; for this reason, the participants were unblinded to their treatment assignment.

7.7.1. Immediate AEs

7.7.2 Solicited adverse reactions

Rates of local and systemic adverse reactions in children 5-11 years of age were generally
similar to those in individuals 12 years of age or older enrolled in study C4591001, with pain at
the injection site slightly lower in the 5-11 year-old group, but redness and swelling slightly
higher. Systemic adverse reactions such as fever, fatigue, headache, chills, and muscle pain
were generally reported less frequently and were milder in severity in the 5-11 year-old group
compared to individuals 12 years of age or older.

The frequencies of local and systemic adverse reactions within 7 days after each vaccination in
participants with evaluable e-diary data are summarized in Tables 10, 11, and 12 below.

Table 10. Frequency of Solicited Local Reactions Within 7 Days After Each Dose, by Severity,
Phase 2/3 Cohort 1 Participants 5-11 Years of Age, Safety Population’, Study C4591007

BNT162b2 10ug Placebo BNT162b2 10ug Placebo

Dose 1 Dose 1 Dose 2 Dose 2

N=1,511 N=748 N=1,501 N=740

Event % % % %
Pain at the injection site®

Any? 74.1 31.3 71.0 29.5

Mild 58.9 27.3 52.8 25.9

Moderate 14.9 4.0 17.8 3.5

Severe 0.3 0.0 0.3 0.0

Redness°

Any4 14.7 5.7 18.5 5.4

Mild 9.5 4.9 9.5 4.2

Moderate 5.2 0.8 8.8 1.2

Severe 0.0 0.0 0.2 0.0

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BNT162b2 10ug Placebo BNT162b2 10ug Placebo

Dose 1 Dose 1 Dose 2 Dose 2

N=1,511 N=748 N=1,501 N=740

Event % % % %
Swelling®

Any4 10.5 2.7 15.3 2.7

Mild 5.6 1.7 7.8 2.0

Moderate 4.8 0.9 7.5 0.7

Severe 0.1 0.0 0.0 0.0

%:n/N. n=number of participants in the specified age group with the specified reaction. N=number of participants in the specified
age group reporting at least 1 yes or no response for the specified reaction after the specified dose; the N used in the
percentage calculations for redness and swelling were 749 after Dose 1 and 741 after Dose 2 in the placebo group, due to an e-

diary error.

a. Randomized participants in the specified age group who received at least 1 dose of the study intervention.

b. Mild: does not interfere with activity; moderate: interferes with activity; severe: prevents daily activity.

c. Mild: 0.5 to $2.0 cm; moderate: 2.0 to <7.0 cm; severe: >7.0 cm.

d. Any local reaction: any redness >0.5 cm, any swelling >0.5 cm, or any pain at the injection site.

Table 11. Frequency of Solicited Systemic Reactions Within 7 Days After Dose 2 by Severity,

Phase 2/3 Cohort 1 Participants 5-11 Years of Age, Safety Population, Study C4501007

BNT162b2 10ug Placebo BNT162b2 10ug Placebo

Dose 1 Dose 1 Dose 2 Dose 2

N=1,511 N=748 N=1,501 N=740

Event % % % %
Fever

238.0°C 2.5 1.3 6.5 1.2

238.0°C to 38.4°C 1.5 0.5 3.4 0.7

>38.4°C to 38.9°C 0.8 0.7 2.5 0.4

>38.9°C to 40.0°C 0.2 0.1 0.5 0.1

>40.0°C 0.0 0.0 0.1 0.0

Fatigue?

Any® 33.6 31.3 39.4 24.3
Mild 22.0 20.1 21.4 13.0
Moderate 11.3 11.1 17.3 11.2
Severe 0.3 0.1 0.7 0.1

Headache>

Any® 22.4 24.1 28.0 18.6
Mild 16.5 17.5 18.7 12.6
Moderate 5.8 6.0 9.1 6.1
Severe 0.1 0.5 0.2 0.0

Chills®

Any® 4.6 4.7 9.8 4.3
Mild 3.6 4.0 7.0 3.2
Moderate 1.1 0.7 2.7 0.9
Severe 0.0 0.0 0.1 0.1

Vomiting®

Any® 2.2 1.5 1.9 0.8
Mild 1.7 1.5 1.8 0.8
Moderate 0.5 0.0 0.1 0.0
Severe 0.0 0.0 0.0 0.0

Diarrhea?

Any® 5.9 4.1 5.3 4.7
Mild 5.2 4.1 4.8 4.3
Moderate 0.7 0.0 0.5 0.4
Severe 0.0 0.0 0.0 0.0

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BNT162b2 10ug Placebo BNT162b2 10ug Placebo
Dose 1 Dose 1 Dose 2 Dose 2
N=1,511 N=748 N=1,501 N=740
Event % % % %
New or worsened
muscle pain®
Any® 9.1 6.8 11.7 7.4
Mild 6.4 4.7 7.7 5.1
Moderate 2.6 2.1 3.9 2.3
Severe 0.1 0.0 0.1 0.0
New or worsened
joint pain®
Any® 3.3 5.5 5.2 3.6
Mild 2.3 4.1 3.8 2.7
Moderate 1.1 1.3 1.4 0.9
Severe 0.0 0.0 0.0 0.0
Use of antipyretic or 14.4 8.3 197 8.1

pain medication‘
%: n/N. n = Number of participants with the specified reaction. N = Number of participants reporting at least 1 yes or no response
for the specified reaction after the specified dose; the N used in the percentage calculations for fever and use of antipyretic or pain
medication were 749 after Dose 1 and 741 after Dose 2 in the placebo group, due to an e-diary error.
a. All participants in the specified age group who received at least 1 dose of the study intervention.
b. Mild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity.
c. Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration.
d. Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours.
e. Any systemic event: any fever 238.0°C, any fatigue, any vomiting, any chills, any diarrhea, any headache, any new or worsened
muscle pain, or any new or worsened joint pain.
f. Severity was not collected for use of antipyretic or pain medication.

Dose 1 Dose 1 Dose 2 Dose 2

Event n@/N° n@/N° n@/N° n@/N°
Any solicited local reaction

Day of onset: median (min, max) 1.0 (1, 6) 1.0 (1, 6) 1.0 (1, 7) 1.0 (1, 7)

Duration: median (min, max) 2.0 (1, 10) 1.0 (1, 10) 2.0 (1, 11) 1.0 (1, 12)

Persisted beyond 7 days 11/1511 9/749 8/1501 5/741
Redness

Day of onset: median (min, max) 2.0 (1, 7) 2.0 (1, 5) 2.0 (1, 6) 1.0 (1, 5)

Duration: median (min, max) 1.0 (1, 10) 1.0 (1, 8) 2.0 (1, 10) 1.0 (1, 11)

Persisted beyond 7 days 4/1511 1/749 2/1501 1/741
Swelling

Day of onset: median (min, max) 2.0 (1, 4) 1.0 (1, 7) 2.0 (1, 4) 1.0 (1, 5)

Duration: median (min, max) .O (1, 8) 1.0 (1, 9) 2.0 (1, 10) 1.0 (1, 12)

Persisted beyond 7 days 1/1511 1/749 2/1501 2/741
Pain at injection site

Day of onset: median (min, max) 1.0 (1, 6) 1.0 (1, 6) 1.0 (1, 7) 1.0 (1, 7)

Duration: median (min, max) 2.0 (1, 10) 1.0 (1, 10) 2.0 (1, 11) 1.5 (1, 12)

Persisted beyond 7 days 7/1511 8/748 6/1501 5/740
Any solicited systemic reaction

Day of onset: median (min, max) 2.0 (1, 7) 1.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7)

Duration: median (min, max) 1.0 (1, 22) 1.0 (1, 19) 1.0 (1, 51) 1.0 (1, 10)

Persisted beyond 7 days 29/1511 15/749 30/1501 13/741

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BNT162b2 10 ug Placebo BNT162b2 10 yg Placebo

Dose 1 Dose 1 Dose 2 Dose 2

Fever

Day of onset: median (min, max) é. 0 (2, 7) 2.5 (1, 7) 2.0 (1, 7) 6. 0 (2, 7)

Duration: median (min, max) 1.0 (1, 3) 1.0 (1, 3) 1.0 (1, 5) 1.0 (1, 5)

Persisted beyond 7 days 0 0 0 0
Fatigue

Day of onset: median (min, max) 2.0 (1, 7) 1.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7)

Duration: median (min, max) 1.0 (1, 21) 2.0 (1, 9) 1.0 (1, 14) 1.0 (1, 10)

Persisted beyond 7 days 16/1511 7/748 17/1501 6/740
Headache

Day of onset: median (min, max) 2.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7)

Duration: median (min, max) 1.0 (1, 22) 1.0 (1, 19) 1.0 (1, 51) 1.0 (1, 9)

Persisted beyond 7 days 12/1511 9/748 10/1501 6/740
Chills

Day of onset: median (min, max) 2.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7)

Duration: median (min, max) 1.0 (1, 10) 1.0 (1, 7) 1.0 (1, 8) 1.0 (1, 8)

Persisted beyond 7 days 3/1511 0 1/1501 1/740
Vomiting

Day of onset: median (min, max) 4.0 (1, 7) 4.0 (1, 6) 2.0 (1, 6) 3.0 (2, 6)

Duration: median (min, max) 1.0 (1, 5) 1.0 (1, 1) 1.0 (1, 2) 1.0 (1, 5)

Persisted beyond 7 days 0 0 0 0
Diarrhea

Day of onset: median (min, max) 3.0 (1, 7) 3.0 (1, 7) 3.0 (1, 7) 4.0 (1, 7)

Duration: median (min, max) 1.0 (1, 8) 1.0 (1, 6) 1.0 (1, 28) 1.0 (1, 9)

Persisted beyond 7 days 1/1511 0 2/1501 2/740
New or worsened joint pain

Day of onset: median (min, max) 2.0 (1, 6) 2.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7)

Duration: median (min, max) 1.0 (1, 7) 1.0 (1, 4) 1.0 (1, 18) 1.0 (1, 6)

Persisted beyond 7 days 0 0 1/1501
New or worsened muscle pain

Day of onset: median (min, max) 2.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7) 2.0 (1, 7)

Duration: median (min, max) 1.0 (1, 9) 1.0 (1, 8) 1.0 (1, 9) 1.0 (1, 6)

Persisted beyond 7 days 1/1511 1/748 3/1501 0

a. n = Number of participants with the specified reaction persisted beyond 7 days.
b. N = number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose.

7.7.3. Subgroup analyses of solicited adverse reactions

7.7.4 Unsolicited adverse events

In 1 group of participants (cohort 1; initial enrollment cohort), non-serious adverse events from
Dose 1 through up to 30 days after Dose 2 up to the cut-off date of September 06, 2021, in
ongoing follow up were reported by 10.9% of Pfizer BioNTech COVID-19 Vaccine (10 mcg
modRNA) recipients and by 9.1% of placebo recipients. In this group of participants, >99% had
follow-up 30 days post Dose 2. In a second group of participants (cohort 2; expansion cohort)
for which the median follow-up was 2.4 weeks (range 0 — 3.7 weeks), non-serious adverse

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events from Dose 1 through the cut-off date of October 8, 2021, were reported by 7.1% of Pfizer
BioNTech COVID-19 Vaccine (10 mcg modRNA) recipients and by 6.3% of placebo recipients.

In the initial enrollment cohort, from Dose 1 through 30 days after Dose 2, lymphadenopathy
was reported in 13 (0.9%) participants in the Pfizer BioNTech COVID-19 Vaccine (10 mcg
modRNA) group vs. 1 (0.1%) in the placebo group. In the expansion cohort, from Dose 1
through the cut-off date, lymphadenopathy was reported in 6 (0.4%) participants in the Pfizer
BioNTech COVID-19 Vaccine (10 mcg modRNA) group vs. 3 (0.4%) in the placebo group.
There were no other notable patterns between treatment groups for specific categories of non-
serious adverse events that would suggest a causal relationship to Pfizer BioNTech COVID 19
Vaccine.

7.7.5 SAEs

In Cohort 1 (median of 2.3 months follow-up post Dose 2), SAEs occurred at frequency of 0.1%
in both BNT162b2 and placebo recipients. For BNT162b2 recipients, only one SAE was
reported, an upper limb fracture. In Cohort 2 (median of 2.4 weeks follow-up post Dose 2), 3
BNT162b2 recipients (0.2%) reported a SAE: 1 infection of the knee, 1 foreign body ingestion,
and 1 epiphyseal fracture. All SAEs reported in the study were considered by the study
investigator to be unrelated to vaccination. FDA agrees with this assessment.

Deaths: No deaths have occurred during the study in either Cohort 1 or 2.

7.7.6 AEs of clinical interest

FDA conducted Standardized MedDRA Queries (SMQs) to evaluate for constellations of
unsolicited AEs among recipients 5-11 years of age in study C4591007 Phase 2/3 Cohort 1
through the September 6, 2021, cut-off date. SMQs (narrow and broad in scope) were
conducted on AE Preferred Terms (PTs) that could represent various conditions, including but
not limited to angioedema, arthritis, cardiomyopathy, ischaemic heart disease, cardiac
arrhythmia, cardiac failure, central nervous system vascular disorders, convulsions,
demyelination, embolic and thrombotic events, hearing and vestibular disorders, hematopoietic
cytopenias, hypersensitivity, peripheral neuropathy, thrombophlebitis, and vasculitis. For
example, the cardiomyopathy SMQ includes PTs that may be related to myocarditis and
pericarditis, such as chest pain, palpitations, dyspnea, syncope, troponin elevation, ECG with
ST elevation or PR depression, pericardiac rub, or echocardiographic findings.

For Cohort 1, the SMQ analyses resulted in identification of 19 participants with AEs of interest
in the SMQs (narrow and broad in scope) in the BNT162b2 group and 6 in the placebo group.
The SMQ analyses revealed an imbalance of AEs potentially representing allergic reactions,
with 14 participants in the vaccine group (0.92%) reporting hypersensitivity-related AEs
(primarily skin and subcutaneous disorder including rash and dermatitis) compared with 4
participants in the placebo group (0.53%).

For Cohort 2, the SMQ analyses with respect to hypersensitivity identified 9 participants in the
vaccine group (0.57%) and 4 in the placebo group (0.51%) reporting unsolicited AEs in this
category, primarily skin and subcutaneous disorders of rash and dermatitis. The SMQ for
angioedema was reported in 3 (0.19%) in the vaccine group compared to 1 (0.13%) in the
placebo group. These events included one participant with both angioedema and urticaria, and
3 participants with urticaria.

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One participant, a 6-year-old female in the BNT162b2 group, had a non-serious AE of Henoch-
Schonlein purpura which was diagnosed 21 days after Dose 1 and was considered non-serious.

No new or unexpected adverse reactions were identified based on these SMQ results.

7.7.7 AEs leading to study withdrawal

In C4591007 Phase 2/3 Cohort 1, there were no AEs leading to withdrawal. In Cohort 2 with a
follow up cut-off of October 8, 2021, 1 participant was withdrawn due to AEs of fever 2 days
after Dose 1 and worsening of neutropenia (previously diagnosed as benign transient
neutropenia. Dose 2 was not administered.

7.8 Study C4591007 Phase 2/3 summary

This EVA request included safety data from 1,518 BNT162b2 recipients and 750 placebo
(saline) recipients 5-11 years of age in the Phase 2/3 portion (Cohort 1) of an ongoing clinical
trial, C4591007; Among Cohort 1 participants, 95.1% had safety follow up 22 months after Dose
2 at the time of the September 6, 2021, data cut-off. Safety data from an additional 1,591
BNT162b2 recipients and 788 placebo recipients from the Phase 2/3 portion of the trial (Cohort
2) were provided for assessment of SAEs and other AEs of interest (e.g., myocarditis,
pericarditis, anaphylaxis); the median duration of follow-up was 2.4 weeks post-Dose 2 at the
time of the October 8, 2021, data cut-off for Cohort 2.

Immunobridging success criteria were met for geometric mean neutralizing antibody titers and
seroresponse rates at 1 month post-Dose 2 against the USA_WA1/2020 reference strain, as
assessed by 50% mNG microneutralization assay, among children 5-11 years of age in study
C4591007 Cohort 1 compared to study participants 16-25 years of age randomly selected from
study C4591001. Subgroup immunogenicity analyses by age, gender, race and ethnicity,
obesity and baseline SARS-CoV-2 status showed no notable differences compared to the
overall study population, although some subgroups were too small to draw meaningful
conclusions. Descriptive immunogenicity analyses, based on 50% plaque reduction
neutralization test (PRNT), showed that a 10 ug BNT162b2 primary series elicited PRNT
neutralizing titers against the reference strain and B.1.617.2 (Delta) strain in participants 5-11
years of age (34 BNT162b2, 4 placebo). Lastly, in a supplemental descriptive efficacy analysis,
VE against symptomatic COVID-19 after 7 days post-Dose 2 as of the October 8, 2021, data
cut-off was 90.7% (2-sided 95% Cl: 67.7%, 98.3%) in participants 5-11 years of age without
prior evidence of SARS-CoV-2 infection; 3 cases of COVID-19 occurred in the BNT162b2 group
and 16 in the placebo group. All cases of COVID-19 occurred in participants 5-11 years of age
without prior history of SARS-CoV-2 infection, and most occurred during July-August 2021. At
the time of data cut-off, no cases met the criteria for severe COVID-19 infection.

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in 13 BNT162b2 recipients (0.9%); in Cohort 2, lymphadenopathy was reported in 6 BNT162b2
recipients (0.4%). In Cohort 1, more BNT162b2 recipients (n=14; 0.92%) reported
hypersensitivity-related AEs (primarily skin and subcutaneous disorder including rash and
dermatitis) than placebo recipients (n=4; 0.53%). For Cohort 2, hypersensitivity reactions were
reported in 9 participants (0.6%) in the BNT162b2 group; events included a Type IV
hypersensitivity reaction and other rashes. Overall, from the combined safety database of 3,109
BNT162b2 participants, 4 BNT162b2 participants reported a SAE, and all of the SAEs were
considered unrelated to vaccination. One BNT162b2 recipient withdrew from the study due to
fever (40.1°C) that occurred 2 days after Dose 1 and neutropenia that had worsened from
baseline; the neutropenia was related to a pre-existing condition. There were no reports of
myocarditis/pericarditis or anaphylaxis, and no participant deaths. Subgroup safety analyses by
gender, race and ethnicity, obesity and baseline SARS-CoV-2 status showed no notable
differences compared to the overall study population, although some subgroups were too small
to draw meaningful conclusions.

8 FDA REVIEW OF OTHER INFORMATION SUBMITTED
8.1 Chemistry, Manufacturing, and Control (CMC) information

The currently authorized/approved Pfizer-BioNTech COVID-19 vaccine, MRNA (BNT162b2), is
formulated in phosphate-buffer saline (PBS) containing sodium chloride and potassium chloride
(referred to as PBS/Sucrose formulation), and this formulation was used in Study C4591007. To
provide a vaccine with an improved stability profile and greater ease of use at vaccine
distribution sites, Pfizer/BioNTech have developed a new drug product (DP) formulation using
tromethamine (Tris) buffer (referred to as Tris/Sucrose formulation). The new formulation no
longer contains sodium chloride and potassium chloride. The BNT162b2 Tris/Sucrose vaccine
product is formulated at 0.1 mg/mL of mRNA in 10 mM Tris, 300 mM sucrose, pH 7.4. For use
in children 5-11 years of age, the Tris/Sucrose DP is filled at 1.3 mL fill volume in glass vials and
requires dilution with 1.3 mL 0.9% sodium chloride for injection prior to administration. After
dilution, each vial provides a total of 10 doses of 10-ug MRNA, each in 0.2 mL injection volume.

The Tris/Sucrose DP is currently manufactured using facilities already authorized or approved
for the manufacture of the PBS/Sucrose DP. The manufacturing process for the Tris/Sucrose
DP uses the same drug substance (DS) and the same lipids and has the same initial steps as

for the current PBS/Sucrose formulation, including the steps of (b) (4) and
(b) (4) Changes are implemented in the formulation buffer (from PBS to Tris) during the
(b) (4) DP formulation unit operations. Subsequent steps

of sterile filtration, aseptic filling, labeling and freezing for storage are essentially the same
between the two formulations with only adjustments to reflect the different fill volumes. The
Tris/Sucrose DP manufacturing process was validated by process-performance qualification
(PPQ) execution, including production of 3 PPQ lots filled at 2.25 mL, supporting the 30-ug
mRNA dose, and two PPQ lots filled at 1.3 mL, supporting the 10-ug mRNA dose. The
validation results demonstrated that with a well-defined process protocol, consistent
manufacturing of the BNT162b2 Tris/Sucrose DP can be achieved for both fill volumes.

Analytical comparability was demonstrated for the Tris/Sucrose DP when compared with the
currently authorized/approved PBS/sucrose DP based on in-process test results, final DP
release test results and characterization test results. Analytical comparability uses laboratory
testing to demonstrate that a change in product formulation does not impact a product's safety
or effectiveness. In the case of a lipid nanoparticle containing mRNA such as BNT162b2
multiple different release parameters are evaluated, ranging from product appearance to size of

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the lipid-nanoparticle to the integrity of the mRNA in the product. Release and characterization
tests include tests for purity, composition, and critical attributes of mRNA associated with the
activity of the vaccine

In this case, analytical comparability to the current PBS/Sucrose formulation was demonstrated
for the Tris/Sucrose DP through a combination of release and characterization testing.
Comparability was established for the three PPQ Tris/Sucrose DP lots manufactured at
production scale and filled at a volume of 2.25 mL.

The manufacturing specifications for the Tris/Sucrose DP are based on those established for
the authorized/approved PBS/Sucrose DP and are not affected by the change from the
PBS/Sucrose to the Tris/Sucrose buffer. The analytical procedures for Tris/Sucrose DP release
and stability testing are identical to the corresponding PBS/Sucrose procedures with the
exception of an update to include minor modifications in sample preparations to account for the
difference in MRNA concentration between the two formulations. Validation of each assay
method for the Tris/Sucrose DP was performed and the validation results have demonstrated
that all the analytical procedures are suitable for their intended use.

Based on the available stability data for the Tris/Sucrose DP and the established 9-month expiry
for the PBS/Sucrose DP, the initial shelf-life for the BNT162b2 Tris/Sucrose vaccine product is 6
months when stored frozen between -90°C to -60°C. The available stability data also support
storage at 2-8°C for up to 10 weeks once the frozen Tris/Sucrose vaccine has been thawed. At
the vaccine administration sites, the 10 ug Tris/Sucrose DP vials can be stored at 2°C to 25°C
for up to 24 hours. However, after the first puncture, the vaccines must be used within 12 hours.
This proposed in-use shelf-life is supported by compatibility assessment and microbial in-use
challenge studies.

Taken together, the analytical comparability assessment demonstrated that the Tris/Sucrose DP
lots are comparable to the previously authorized/approved BNT162b2 PBS/Sucrose DP. The
results further support the capability of the commercial manufacturing process to produce a
consistent Tris/Sucrose DP with acceptable quality.

The manufacture of the Pfizer-BioNTech COVID-19 Vaccine is performed at a number of
facilities. For each of these facilities, FDA requested and reviewed information on equipment,
facilities, quality systems and controls, container closure systems as well as other information
as per the guidance, “Emergency Use Authorization for Vaccines to Prevent COVID-19,
February 2021”, to ensure that there is adequate control of the manufacturing processes and
facilities.

In particular, the following information was assessed:

e Facilities appear to be adequately designed and maintained and manufacturing process,
personnel, air direction and waste flow are suitable for manufacturing.

e Multiple product manufacturing areas and equipment used to manufacture the COVID-
19 vaccine were assessed and cleaning and changeover procedures were evaluated
and appear adequate. Cross-contamination controls appear suitable to mitigate risk of
cross contamination.

e The successful qualification of critical equipment for drug substance and drug product
manufacturing was verified.

e Aseptic process information and validation studies were assessed and appear
acceptable.

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e Drug product solution sterilization by filtration was reviewed and appears acceptable.

e Sterilization and depyrogenation of pertinent equipment and materials, including
container/closure components, description and validation studies appear acceptable.

e Utilities qualification studies including HVAC systems, appear adequate. Air cleanliness
of the manufacturing cleanrooms were adequately controlled and maintained.

e Container/closure integrity studies to ensure sterility of drug product in the final container
were conducted and appear adequate.

FDA also performed inspections at two facilities, reviewed the inspectional histories of all
applicable facilities and all available information to ascertain whether each facility meets current
good manufacturing practice requirements. We find that all the facilities are adequate to support
the use of the Pfizer-BioNTech COVID-19 Vaccine under EVA for individuals five years of age
and older.

8.2 Pharmacovigilance activities

Pfizer submitted a revised pharmacovigilance plan to monitor safety concerns that could be
associated with BNT162b2 in individuals 5-11 years of age. The plan includes the following
safety concerns:

e Important Identified Risks: anaphylaxis, myocarditis, and pericarditis
e Important Potential Risks: Vaccine-associated enhanced disease, including vaccine-
associated enhanced respiratory disease.

Pfizer-BioNTech plans to conduct passive and active surveillance to monitor the post-
authorization safety for the Pfizer-BioNTech COVID-19 Vaccine, including:

e Adverse event reporting in accordance with regulatory requirements for the licensed
vaccine, COMIRNATY

e Additionally, following approval of COMIRNATY, the Sponsor was also asked to submit
reports of myocarditis and pericarditis as 15-day reports to VAERS.

- Study C4591009: A non-interventional post-approval safety study of the Pfizer-BioNTech
COVID-19 mRNA Vaccine in the United States

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— Study C4591021: Post-conditional approval active surveillance study among individuals
in Europe receiving the Pfizer-BioNTech Coronavirus Disease 2019 (COVID-19) Vaccine

Objective: To assess the potential increased risk of events of interest, including
myocarditis/pericarditis, after being vaccinated with at least one dose of the Pfizer-
BioNTech COVID-19 Vaccine.

- Study C4591021 Substudy: Substudy to describe the natural history of myocarditis and
pericarditis following administration of COMIRNATY

Pfizer-BioNTech also plans to include vaccine effectiveness analyses among individuals 5-11
years of age in Study C4591014 entitled “Pfizer-BioNTech COVID-19 BNT162b2 Vaccine
Effectiveness Study Kaiser Permanente Southern California.”

8.3 Clinical assay information

The SARS-CoV-2 mNG microneutralization assay used in the Phase 2/3 clinical study
C4591007 measures neutralizing antibodies (50% inhibition titers) against SARS-CoV-2 using
Vero cell monolayers in a 96-well plate format. The SARS-CoV-2 mNG virus is derived from the
USA_WA1/2020 strain that had been rescued by reverse genetics and engineered to express a
fluorescent reporter gene (mNeonGreen) upon productive infection of cells. The validation
protocol (that includes evaluation of dilutional linearity, precision, limits of quantification, and
limit of detection) and the results of the validation study, executed at Pfizer Hackensack
Meridian Health Center (Nutley, New Jersey), were submitted to support the suitability of the
assay for neutralizing antibody assessment against the USA_WA1/2020 strain.

Additionally, a plaque reduction neutralization test (PRNT) was used to determine neutralizing
titers against the reference USA_WA1/2020 strain and the SARS-CoV-2 virus Delta variant (a
recombinant virus with Delta variant spike gene on the USA_WA1/2020 genetic background).
The PRNT is a non-validated assay and was used for exploratory purposes only.

8.4 Inspection of clinical study sites

The review team decided that Bioresearch Monitoring (BIMO) inspections are not needed to
support the review of this EUA amendment. Sites under this study had been previously
inspected.

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8.5 EUA prescribing information and fact sheets

The Full EUA Prescribing Information, Fact Sheet for Health Care Providers Administering
Vaccine (Vaccination Providers), and Vaccine Information Fact Sheet for Recipients and
Caregivers were reviewed, and suggested revisions were sent to the Sponsor. The revised Fact
Sheets are accurate, not misleading, and appropriate for the proposed use of the product under
EUA.

For the Fact Sheets applicable for the 12 years and older population, certain information has
been updated to reflect changes made to the scope of the October 29, 2021 authorization. For
example, certain portions of the fact sheets have been revised to: refer to the use of different
color caps; identify the availability of the new formulation; clarify the new age groups for whom
the vaccine is authorized; and explain which dosage may be used for individuals who receive
their first dose at age 11 and turn 12 years old before their second dose. In addition, we made
additional changes to address the potential that the previous versions of the fact sheets created
confusion. For example, we removed a sentence from the fact sheets stating that COMIRNATY
and the Pfizer-BioNTech COVID-19 Vaccine are “legally distinct with certain differences that do
not impact safety or effectiveness.” Communicating the legal relationship of the different
products did not appear relevant to the target audience of these fact sheets, as the more
relevant information for them is that when prepared according to their respective instructions for
use, the FDA-approved COMIRNATY and the two EUA-authorized formulations of Pfizer-
BioNTech COVID-19 Vaccine for ages 12 years of age and older can be used interchangeably
without presenting any safety or effectiveness concerns. We continue to explain in the Letter of
Authorization that the original formulation of the Pfizer-BioNTech COVID-19 Vaccine and
COMIRNATY are legally distinct with certain differences that do not impact safety or
effectiveness.

9 BENEFIT/RISK IN THE CONTEXT OF THE PROPOSED EUA FOR PFIZER-BIONTECH
COVID-19 VACCINE IN CHILDREN 5-11 YEARS OF AGE

9.1 Known and potential benefits

Available data support the effectiveness of the Pfizer-BioNTech COVID-19 Vaccine in
preventing symptomatic COVID-19 among children 5-11 years of age. The immunobridging
analyses from study C4591007 met pre-specified success criteria that allow for inference of
vaccine effectiveness in this age group. Furthermore, direct evidence for clinical benefit is
provided by a preliminary descriptive analysis of VE against symptomatic COVID-19 of any
severity, with a VE point estimate of 90.7% (2-sided 95% Cl: 67.7%, 98.3%) compared with
placebo. This VE point estimate is similar to the estimated VE among adults in enrolled in the
Phase 3 placebo-controlled efficacy trial that supported the original EUA authorization as well as
VE estimates in adults from real-world observational studies. While no cases of severe COVID-
19 were accrued during study follow-up to date, it is highly likely that vaccine effectiveness
against severe COVID-19 among children 5-11 years of age will be even higher than vaccine
effectiveness against non-severe COVID-19, as is the case in adults. Prevention of symptomatic
COVID-19 will also likely result in prevention of sequelae such as post-COVID symptoms (also
known as “long COVID”) and MIS-C. Since the overall burden of COVID-19 is lower in children
5-11 years of age compared with adults, the individual-level and population-level benefits of the
vaccine, in particular among healthy vaccine recipients at low risk of severe COVID-19, are
expected to be lower in children 5-11 years of age than in adults and will depend largely on the
incidence of COVID-19 (see Section 9.5). Nonetheless, given the uncertainty of the COVID-19
pandemic and likelihood of continued SARS-CoV-2 transmission during over the ensuing

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months, widespread deployment of the vaccine for use among children 5-11 years of age will
likely have a substantial effect on COVID-19 associated morbidity and mortality in this age
group. The impact of measures currently in place to mitigate against SARS-CoV-2 transmission
in settings where children congregate with other children and with adults also contributes to
consideration of vaccine benefits in this age group. If these measures were relaxed, the
potential benefits of vaccination in this age group would be even greater.

9.2 Data gaps related to benefits

The data gaps associated with benefits of the Pfizer-BioNTech COVID-19 vaccine when used in
children 5-11 years of age include the following:

e Duration of protection and potential need for booster doses.

Effectiveness in certain populations at high risk of severe COVID-19, including highly
immunocompromised children.

e Benefits (and in particular the need for a 2-dose primary series) in children previously
infected with SARS-CoV-2 relative to those who have not been previously infected;
despite these uncertainties, however, available data support that previously infected
individuals are susceptible to re-infection.

e Future vaccine effectiveness as influenced by characteristics of the pandemic, including
emergence of new variants.

e Vaccine effectiveness against asymptomatic infection.

e Vaccine effectiveness against transmission of SARS-CoV-2.

9.3 Known and potential risks

In children 5-11 years of age, there were higher rates of solicited local and systemic adverse
reactions, lymphadenopathy, and hypersensitivity reactions in vaccine recipients than placebo
recipients. Overall, the rates of these adverse reactions reported among children 5-11 years of
age were lower than those reported among older age groups and likely reflect the lower vaccine
mRNA content evaluated in children 5-11 years of age. In considering unsolicited adverse
events reported among children 5-11 years of age, the available safety data from a total
database of over 3,000 vaccine recipients do not suggest any new safety concerns compared
with the safety profile described in older age groups.

Anaphylaxis, primarily among individuals with a history of severe allergic reactions to other
medications or foods, has been documented to occur at a rate of approximately 6 cases per
million doses among vaccine recipients 16 years of age and older (similar in magnitude to
reported rates of anaphylaxis following licensed preventive vaccines). Risk of allergic reactions,
including the potential for severe allergic reactions and the need for vaccine providers to be able
to manage them should they occur and a contraindication for use in individuals with known
allergy to any component of the vaccine, are described in the vaccine Fact Sheets and
Prescribing Information. Additionally, risk of anaphylaxis/severe allergic reactions will be further
evaluated as part of the pharmacovigilance plan for the vaccine.

Myocarditis/pericarditis, in particular in the first week following Dose 2, is a known risk
associated with the Pfizer-BioNTech COVID-19 Vaccine and is greatest among adolescent
males 16-17 years of age compared with both younger and older age groups. In contrast to
myocarditis in the pre-COVID era, most reported cases of vaccine-associated myocarditis have
involved rapid resolution of symptoms with conservative management; however, the long-term
sequelae of vaccine-associated myocarditis, if any, remain to be determined. The risk of vaccine
associated myocarditis/pericarditis among children 5-11 years of age is unknown at this time.

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No cases of myocarditis or pericarditis were reported among over 3,000 vaccine recipients in
the clinical trial, most of whom had at least 2 weeks of follow-up post-Dose 2. However, this
safety database is not large enough to quantify the frequency of this uncommon adverse
reaction. Data supporting that the risk of vaccine-associated myocarditis may be lower among
children 5-11 years of age compared with adolescents 16-17 years of age include a lower rate
of vaccine-associated myocarditis among adolescents 12-15 years of age compared with
adolescents 16-17 years of age, a lower incidence of myocarditis in the pre-COVID era among
children 5-11 years of age compared with adolescents, and lower rates of systemic
reactogenicity in children 5-11 years of age associated with the lower vaccine mRNA content
intended for use in this age group.

9.4 Data gaps related to risks

The data gaps associated with risks of the Pfizer-BioNTech COVID-19 vaccine when used in
children 5-11 years of age include the following:

e Risk of myocarditis/pericarditis, as described in detail in Section 9.3 above.

e Safety in certain subpopulations: available data are insufficient to make conclusions
about the safety of the vaccine in certain subpopulations such as immunocompromised
children. Safety data in children previously infected with SARS-CoV-2 are limited;
however, available data do not suggest increased reactogenicity or other safety
concerns among previously infected children.

e Adverse reactions that are very uncommon or that require longer follow-up to be
detected. Active and passive safety surveillance will continue during the post
authorization period to detect new safety signals.

9.5 Quantitative benefit-risk assessment for children 5-11 years of age

FDA conducted a quantitative benefit-risk assessment for use of a Pfizer-BioNTech COVID-19
Vaccine 2-dose primary series in children 5-11 years of age. The key benefits assessed include
preventable COVID-19 cases, hospitalizations, intensive care unit (ICU) admissions and deaths
due to COVID-19. The key risks include excess myocarditis/pericarditis cases, and related
hospitalizations, ICU admissions, and deaths attributable to myocarditis/pericarditis. The
benefits and risks are assessed per million fully vaccinated individuals with and without
stratification by sex, and with comparison to age groups 12-15 years and 16-17 years.

The model assesses the benefits of vaccine protection in a 6-month period after completion of
the primary series. The model assumes VE of 70% against COVID-19 cases and 80% against
COVID-19 associated hospitalization based on a CDC vaccine effectiveness study for ages 20+
years during circulation of the Delta variant.*® The incidence rates of COVID-19 cases for the
week of September 11, 2021, are obtained from COVID-NET for all sex/age groups. COVID-
NET covers approximately 10 percent of the U.S. population. Four-week averages of incidence
rate for hospitalizations (week ending on 8/21/2021 to week ending on 9/11/2021) are used due
to the variability in rates given the small numbers of hospitalizations per age/sex group.
Estimates for the percentage of hospitalizations resulting in ICU admission and the percentage
of hospitalized patients who die are based on cumulative rates of hospitalizations, ICU
admissions, and deaths for each sex/age groups reported in COVID-NET since March 2020.
The death rate among 5-11 year-olds is lower in COVID-NET than in other national data
sources such as the CDC COVID-19 Data Tracker. This could be due to geographic differences
in case reporting and the recent trajectory of the pandemic. This difference will lead to a
conservative estimate of benefits in the model. The model assumes that incidence rates of
COVID-19 cases and hospitalizations remain constant over the assessment period of 6 months.

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The estimates for excess myocarditis/pericarditis among fully vaccinated individuals ages 12-15
years and ages 16-17 years are based on Optum healthcare claims data for the period
12/10/2020 to 07/10/2021, which is a conservative approach that includes non-confirmed cases.
For this analysis the estimate for ages 12-15 years is applied to ages 5-11 years because
vaccine-associated myocarditis/pericarditis data are not available for this age group. The
proportions of vaccine-attributable myocarditis/pericarditis hospitalizations and ICU admissions
are obtained from Vaccine Safety Datalink (12-17 year-old group’). Some of these
hospitalizations and ICU admissions may be precautionary and therefore not clinically
equivalent to COVID-19 hospitalizations and ICU admissions. The dose intended for use in
children 5-11 years of age (10 ug), is lower than the dose used under EVA in adolescents 12-15
years of age (30 ug), and the observed systemic reactogenicity associated with the respective
antigen contents in clinical trials is lower for children 5-11 years of age as well. Thus, assuming
the same rate of vaccine-associated myocarditis for children 5-11 years of age as has been
observed for adolescents 12-15 years of age in Optum claims data may be a conservative
overestimate.

The model inputs described above were used to develop “Scenario 1,” a base model from which
five alternative scenarios were derived to address key uncertainties associated with model
inputs. The model’s results indicate that the incidence of COVID-19 is highly influential to the
benefits of the vaccine. To account for uncertain dynamics of the pandemic, FDA assesses the
benefits and risks under Scenario 2 with COVID-19 incidence close to recent peak, and
Scenario 3 with COVID-19 incidence close to the lowest recorded incidence since the beginning
of the pandemic. These two scenarios provide likely bounds for potential future states of the
pandemic. Scenario 4 (90% vaccine efficacy against cases and 100% efficacy against
hospitalizations) tests the impact on benefits and risks of potentially higher vaccine efficacy
suggested by the Sponsor’s newly submitted descriptive efficacy analysis (see Section 7.6).
Scenario 5 with a 3x multiple of the death rate is used to match the cumulative death rate for 5-
11 year-olds seen in CDC Data Tracker. Scenario 6 uses a 50% lower rate of attributable
myocarditis than Scenario 1 to address the uncertainty associated with the rate of vaccine-
attributable myocarditis in children 5-11 years, for whom the data is not available.

The results of the benefit-risk assessment are summarized in Table 13 below. The results
predict that under Scenarios 1 (base), 2 (peak COVID incidence), 4 (high efficacy), and 5 (high
COVID death rate), and 6 (low attributable myocarditis rate) the benefits of the Pfizer-BioNTech
COVID-19 Vaccine 2-dose primary series outweigh the risks for ages 5-11 years. Under
Scenario 3 (low incidence), the model predicts more excess hospitalizations due to vaccine-
related myocarditis/pericarditis compared to prevented hospitalizations due to COVID-19 in
males and in both sexes combined. However, in consideration of the different clinical
implications of hospitalization for COVID-19 versus hospitalization for vaccine-associated
myocarditis/pericarditis, and benefits related to prevention of non-hospitalized cases of COVID-
19 with significant morbidity, the overall benefits of the vaccine may still outweigh the risks
under this low incidence scenario. If the myocarditis/pericarditis risk in this age group is lower
than the conservative assumption used in the model, the benefit-risk balance would be even
more favorable.

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Table 13. Model-Predicted Benefit-Risk Outcomes of Scenarios 1-6 per One Million Fully
Vaccinated Children 5-11 Years Old

Benefit: Benefit: Benefit: Benefit: Risk: Risk: Risk: Risk:
Prevented |Prevented |Prevented |Prevented |Excess Excess Excess Excess
COVID-19 |COVID-19 |COVID-19 |COVID-19 |Myocarditis |Myocarditis |Myocarditis |Myocarditis
Sex Cases Hospitaliza- |ICU Deaths Cases Hospitaliza- |ICU Deaths
tions Admissions tions Admissions
Males &
Females
Scenario 1 45,773 192 62 1 106 92 34 0
Scenario 2 54,345 250 80 1 106 92 34 0
Scenario 3 2,639 21 7 0 106 92 34 0
Scenario 4 58,851 241 77 1 106 92 34 0
Scenario 5 45,773 192 62 3 106 92 34 0
Scenario 6 45,773 192 62 1 53 46 17 0
Males only
Scenario 1 44,790 203 67 1 179 156 57 0
Scenario 2 54,345 250 82 1 179 156 57 0
Scenario 3 2,639 21 7 0 179 156 57 0
Scenario 4 57,857 254 83 1 179 156 57 0
Scenario 5 44,790 203 67 3 179 156 57 0
Scenario 6 44,790 203 67 1 89 78 29 0
Females
only
Scenario 1 45,063 172 54 1 32 28 10 0
Scenario 2 54,345 250 78 2 32 28 10 0
Scenario 3 2,639 21 7 0 32 28 10 0
Scenario 4 57,938 215 67 2 32 28 10 0
Scenario 5 45,063 172 54 4 32 28 10 0
Scenario 6 45,063 172 54 1 16 14 5 0

Scenario 1: COVID-19 incidence as of September 11, 2021, VE 70% vs. COVID-19 cases and 80% vs. COVID-19 hospitalization.
Scenario 2: COVID-19 incidence at peak of U.S. Delta variant surge at end of August 2021, VE 70% vs. COVID-19 cases and 80%
vs. COVID-19 hospitalization.
Scenario 3: COVID-19 incidence as of nadir in June 2021, VE 70% vs. COVID-19 cases and 80% vs. COVID-19 hospitalization.
Scenario 4: COVID-19 incidence as of September 11, 2021, VE 90% vs. COVID-19 cases and 100% vs. COVID-19 hospitalization.
Scenario 5: COVID-19 case incidence as of September 11, 2021, VE 70% vs. COVID-19 cases and 80% vs. COVID-19.
hospitalization, COVID-19 death rate 300% that of Scenario 1.
Scenario 6: COVID-19 incidence as of September 11, 2021, VE 70% vs. COVID-19 cases and 80% vs. COVID-19 hospitalization,

excess myocarditis cases 50% of Scenario 1.

10 VRBPAC SUMMARY

The 170th meeting of the VRBPAC was held on October 26, 2021, to discuss the data
submitted by Pfizer in support of the EUA amendment request and other data to inform benefits
and risks of the Pfizer-BioNTech COVID-19 Vaccine in children 5-11 years of age. In addition to
presentations from the Center for Disease Control and Prevention on the epidemiology of
COVID-19 in children and on known safety signals, Pfizer and the FDA presented data from
Study C4591007, and the FDA also presented a benefit-risk analysis modeling use of the
vaccine in the intended population. The Committee’s discussion focused on the benefits and
risks of the vaccine, and associated uncertainties, taking into account the current trend of the
pandemic. There was concern expressed that some populations, such as those with
comorbidities, might benefit more from the vaccine than healthy children who are generally at
low risk of serious complications of COVID-19, in particular those who have previously been
infected with SARS-CoV-2 and may already benefit from natural immunity against currently

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circulating variants. The voting question presented to the Committee was “Based on the totality
of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine when
administered as a 2-dose series (10 ug each dose, 3 weeks apart) outweigh its risks for use in
children 5-11 years of age.” The vote was 17 yes, 0 no, and 1 abstain. Several of those voting
yes explained that they wanted to make the option of vaccination available to this age group
based on individual considerations. In explaining their votes a few of the committee members
noted their concern that the vaccine might be mandated at this time, given the uncertainties
around benefit and risk balance in the setting of decreasing COVID-19 incidence and increasing
SARS-CoV-2 seroprevalence in this age group. FDA representatives explained that FDA does
not mandate vaccines for the general public and that vaccine mandates are outside the scope of
FDA's decision making process. Some members also noted the importance of safety
monitoring as well as the importance of obtaining more experience with the vaccine. A few other
members noted that the availability of the vaccine will help children directly and potentially help
reduce transmission of SARS-CoV-2.

11 OVERALL SUMMARY AND RECOMMENDATIONS

Following review of information submitted in support of the EUA request, the review team
concludes that:

e As summarized in Section 6 of this review, the CBRN agent referred to in the March 27,
2020 EUA declaration by the Secretary of HHS (SARS-CoV-2) can cause a serious or life-
threatening disease or condition.

e Based on the totality of scientific evidence available, including data from adequate and well-
controlled trials described in Section 7 of this review, Pfizer-BioNTech COVID-19 Vaccine,
when administered as a 2-dose primary series in children 5 -11 years of age, may be
effective in preventing serious or life-threatening disease or condition that can be caused by
SARS-CoV-2. Vaccine effectiveness was inferred by immunobridging based on a
comparison of SARS-CoV-2 50% neutralizing antibody titers at one month after dose 2 in
participants 5-11 years of age with those of young adults 16 to 25 years of age, the most
clinically relevant subgroup of the study population in whom VE has been demonstrated. In
the planned immunobridging analysis, the GMT ratio of neutralizing antibody titers (children
to young adults) was 1.04% (95% Cl: 0.93, 1.18) meeting the success criterion (lower bound
of the 95% Cl for the GMT ratio > 0.67 and the point estimate 21). In a descriptive
immunogenicity analysis, seroresponse rates among participants without prior evidence of
SAR-Co-V2 infection were seen in 99.2% percent of children and 99.2% percent of young
adults, with a difference in seroconversion rates of 0 (95% Cl -2.0, 2,2), meeting the
prespecified success criteria of the lower limit of the 95% Cl for the difference in
seroresponse of greater than -10%. immunogenicity outcomes were consistent across
demographic subgroups. Descriptive analyses from a randomly selected subset of
participants (34 BNT162b2 recipients, 4 placebo recipients) with no evidence of infection up
to 1 month post-Dose 2 demonstrated that a 10 ug primary series elicited PRNT neutralizing
titers against both the reference strain and the Delta variant. In a supplemental efficacy
analysis, VE after 7 days post-Dose 2 was 90.7% (95% Cl: 67.7%, 98.3%); 3 cases of
COVID-19 occurred in participants 5-11 years of age without prior history of SARS-CoV-2
infection, and most occurred during July-August 2021. Although based on a small number of
cases and descriptive analysis, the supplemental VE data provide compelling direct
evidence of clinical benefit in addition to the immunobridging data.

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e Based on the data summarized in Section 7 and benefits and risks in Section 9 of this
review, the known and potential benefits of the vaccine outweigh the known and potential
risks when used for active immunization to prevent COVID-19 caused by SARS-CoV-2 in
individuals 5-11 years of age. Known and potential benefits include reduction in the risk of
symptomatic COVID-19 and associated serious sequelae. Potential benefits that could be
further evaluated but are not necessary to support an EVA include prevention of COVID-19
in individuals with previous SARS-CoV-2 infection, reduction in asymptomatic SARS-CoV-2
infection and reduction of SARS-CoV-2 transmission. Known and potential risks include
common local and systemic adverse reactions (notably injection site reactions, fatigue,
headache, muscle pain, chills, fever and joint pain), less commonly lymphadenopathy, and
hypersensitivity reactions (e.g., rash, pruritis, urticaria, angioedema), and rarely anaphylaxis
and myocarditis/pericarditis (based on experience in Pfizer-BioNTech COVID-19 vaccine
recipients 12 years of age and older). Risks that should be further evaluated include
quantifying the rate of vaccine-associated myocarditis/pericarditis in this age group and
surveillance for other adverse reactions that may become apparent with more widespread
use of the vaccine and with longer duration of follow-up. Acknowledging the current
uncertainties around benefits and risks, a quantitative analysis using conservative
assumptions predicts that overall benefits of vaccination outweigh risks in children 5-11
years of age.

e COMIRNATY is the only FDA approved vaccine indicated for active immunization for
prevention of COVID-19 caused by SARS-CoV-2. It is licensed as a 2-dose primary series
given 3 weeks apart in individuals 16 years. The Pfizer-BioNTech COVID-19 vaccine is
authorized as a 2-dose primary series given weeks apart in adolescents 12-15 years of age.
A third dose is authorized for use, as part of the primary series, in immunocompromised
individuals 12 years and older. A booster dose administered at least 6 months after
completing a primary series is authorized for in use in individuals 65 years of age and older,
individuals at high risk of severe COVID-19, and individuals 18-64 years of age with frequent
institutional or occupational exposure to SARS-CoV-2. The Pfizer-BioNTech COVID-19
vaccine is authorized for use as a single heterologous booster dose following completion of
primary vaccination with another authorized or approved COVID-19 vaccine. No COVID-19
vaccine is currently available for use in children 5-11 years of age.

Based on the considerations outlined above, the review team recommends authorization of the
Pfizer-BioNTech COVID-19 Vaccine under EVA for use as a 2-dose primary series (10 ug each
dose, 3 weeks apart) in children 5-11 years of age.

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13 APPENDIX 1: C4591007 PHASE 1 (DOSE RANGING) —- SUMMARY OF SAFETY AND
IMMUNOGENICITY

During study C4591007 Phase 1, BNT162b2 was evaluated in U.S. children who were not at
high risk of SARS-CoV-2 exposure, did not have medical conditions that represented risk
factors for severe COVID-19, and did not have serologic/virologic evidence of SARS-CoV-2
infection. BNT162b2 dosages of 10 ug, 20 yg, then 30 ug were evaluated sequentially (n=16
participants per dosage) based upon the safety evaluation and recommendation by the internal
review committee (IRC) to either advance to the subsequent dosage or terminate a specific
dosage. Safety evaluation was the same as for Phase 2/3. SARS-CoV-2 50% neutralizing
GMTs (SARS-CoV-2 mNG microneutralization assay) were assessed at 7 days after Dose 2.

Altogether, 48/49 (98%) of participants (assigned to the 10 ug, 20 ug, or 30 ug dosage groups
combined) received two doses of BNT162b2 and completed the 1 month follow up visit after
Dose 2. One BNT162b2 participant (20 ug dosage group) did not receive study vaccine.
Following safety review of reactogenicity data from the initial 4 participants in the BNT162b2 30
ug dosage group, the IRC recommended to discontinue the 30 ug dosage, due to high
frequencies of solicited ARs, and recommended that the remaining 12 participants receive the
dosage selected for Phase 2/3 (i.e., 10 ug) at Dose 2. No participants from Phase 1 withdrew or
discontinued from the study.

The frequencies of local and systemic adverse reactions were generally dose number and
dosage dependent. Across dosages, systemic adverse reactions were generally mild and
moderate in severity and resolved within 1 day of onset. No SAEs, deaths or AEs leading to
withdrawal occurred at the time of data cut-off on July 16, 2021, with approximately 3 months of
follow up. No participants reported anaphylaxis, myocarditis/pericarditis, or MIS-C. One
BNT162b2 (30 yg) recipient reported Grade 1 axillary lymphadenopathy, which started 3 days
after Dose 2 and resolved 17 days later; the AE was considered by the study investigator to be
related to study intervention.

All four participants who received 30 ug for both doses developed mild-moderate redness and
pain at the injection site, and 2 of the 4 participants developed swelling. In addition, all four
subjects reported fevers to 38.9°C with mild to moderate fatigue, and 2 of the 4 developed
muscle pain of moderate severity following the second dose. One participant in the 20-ug group
reported Grade 3 pyrexia (temperature to 39.7° C, also reported as a systemic adverse reaction,
on Day 2 post-Dose 2), which resolved by Day 3. Both 10 and 20 ug dosages elicited similar

46
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 225 of 237

immune responses 7 days after Dose 2. In participants 5-11 years of age without evidence of
SARS-CoV-2 infection up to 1 month post-Dose 2, the neutralizing antibody GMTs (NT50) at 1
month after Dose 2 were similar in the BNT162b2 10 ug and 20 ug groups (4163 and 4728,
respectively).

The higher frequencies of solicited adverse reactions in participants receiving the 20 ug and
30 ug dosages, the favorable AE profile at the 10-ug dosage in participants 5-11 years of age
followed for approximately 3 months after Dose 2, and the immunogenicity results
demonstrating similar neutralizing antibody responses at the 10 and 20 ug dosages informed
the IRC’s decision to discontinue the 30-ug dosage and proceed to Phase 2/3 at the 10-ug
dosage.

14 APPENDIX 2: COVID-19 AND SEVERE COVID-19 CASE DEFINITIONS
COVID-19

Presence of at least 1 of the following symptoms and SARS-CoV-2 NAAT positive during, or
within 4 days before or after, the symptomatic period, either at the central laboratory or at a local
testing facility (Using an acceptable test), which triggered a potential COVID-19 illness visit:

e Fever, new or increased cough, new or increased shortness of breath, chills, new or
increased muscle pain, new loss of taste or smell, sore throat, diarrhea as defined by 23
loose stools/day, vomiting

Severe COVID-19

Confirmed COVID-19 plus at least one of the following symptoms:

e Clinical signs at rest indicative of severe systemic illness:
— Respiratory rate and heart rate outside normal range
- S§pO2 <92% on room air, >50% FiO2 to maintain 292%, or PaO2/Fi02 <300 mm Hg

e Respiratory failure: defined as needing high-flow oxygen, including CPaP, BiPaP,
noninvasive ventilation, mechanical ventilation, or ECMO

e Evidence of shock or cardiac failure:

— SBP (mm Hg); <70 + (age in years x 2) for age up to 10 years, <90 for age 210
years
— Requiring vasoactive drugs to maintain blood pressure in the normal range

e Significant acute renal failure (serum creatinine 22 times ULN for age or 2-fold increase
in baseline creatinine)

e Significant gastrointestinal/hepatic failure (total bilirubin 24 mg/dL or ALT 2 times ULN
for age)

e Significant neurological dysfunction (Glasgow Coma Scale score <11, or acute change
in mental status with a decrease in Glasgow Coma Scale score 23 points from abnormal
baseline)

e ICU admission
Death

47
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 226 of 237

Exhibit 6
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 227 of 237

(¢ ZN U.S. FOOD & DRUG
~ ADMINISTRATION

Our STN: BL 125742/0 BLA APPROVAL
BioNTech Manufacturing GmbH August 23, 2021
Attention: Amit Patel

Pfizer Inc.

235 East 42nd Street
New York, NY 10017

Dear Mr. Patel:

Please refer to your Biologics License Application (BLA) submitted and received on
May 18, 2021, under section 351(a) of the Public Health Service Act (PHS Act) for
COVID-19 Vaccine, MRNA.

LICENSING

We are issuing Department of Health and Human Services U.S. License No. 2229 to
BioNTech Manufacturing GmbH, Mainz, Germany, under the provisions of section
351(a) of the PHS Act controlling the manufacture and sale of biological products. The
license authorizes you to introduce or deliver for introduction into interstate commerce,
those products for which your company has demonstrated compliance with
establishment and product standards.

Under this license, you are authorized to manufacture the product, COVID-19 Vaccine,
mRNA, which is indicated for active immunization to prevent coronavirus disease 2019
(COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
in individuals 16 years of age and older.

The review of this product was associated with the following National Clinical Trial
(NCT) numbers: NCT04368728 and NCT04380701.

MANUFACTURING LOCATIONS

Under this license, you are approved to manufacture COVID-19 Vaccine, mRNA drug
substance at Wyeth BioPharma Division of Wyeth Pharmaceuticals LLC, 1 Burtt Road,
Andover, Massachusetts. The final formulated product will be manufactured, filled,
labeled and packaged at Pfizer Manufacturing Belgium NV, Rijksweg 12, Puurs,
Belgium and at Pharmacia & Upjohn Company LLC, 7000 Portage Road, Kalamazoo,
Michigan. The diluent, 0.9% Sodium Chloride Injection, USP, will be manufactured at
Hospira, Inc., (b) (4) and at Fresenius Kabi
USA, LLC, (b) (4) .

U.S. Food & Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993

w ww.fda.gov
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 228 of 237
Page 2 — STN BL 125742/0 — Elisa Harkins

You may label your product with the proprietary name, COMIRNATY, and market it in
2.0 mL glass vials, in packages of 25 and 195 vials.

We did not refer your application to the Vaccines and Related Biological Products
Advisory Committee because our review of information submitted in your BLA, including
the clinical study design and trial results, did not raise concerns or controversial issues
that would have benefited from an advisory committee discussion.

DATING PERIOD

The dating period for COVID-19 Vaccine, MRNA shall be 9 months from the date of
manufacture when stored between -90°C to -60°C (-130°F to -76°F). The date of
manufacture shall be no later than the date of final sterile filtration of the formulated
drug product (at Pharmacia & Upjohn Company LLC in Kalamazoo, Michigan, the date
of manufacture is defined as the date of sterile filtration for the final drug product; at
Pfizer Manufacturing Belgium NV in Puurs, Belgium, it is defined as the date of the ®®

Following the final sterile filtration, (D) (4)

, no
reprocessing/reworking is allowed without prior approval from the Agency. The dating
period for your drug substance shall be (D) (4) when stored at (b) (4) We have
approved the stability protocols in your license application for the purpose of extending
the expiration dating period of your drug substance and drug product under 21 CFR
601.12.

FDA LOT RELEASE

Please submit final container samples of the product in final containers together with
protocols showing results of all applicable tests. You may not distribute any lots of
product until you receive a notification of release from the Director, Center for Biologics
Evaluation and Research (CBER).

BIOLOGICAL PRODUCT DEVIATIONS

You must submit reports of biological product deviations under 21 CFR 600.14. You
should identify and investigate all manufacturing deviations promptly, including those
associated with processing, testing, packaging, labeling, storage, holding and
distribution. If the deviation involves a distributed product, may affect the safety, purity,
or potency of the product, and meets the other criteria in the regulation, you must
submit a report on Form FDA 3486 to the Director, Office of Compliance and Biologics
Quality, electronically through the eBPDR web application or at the address below.
Links for the instructions on completing the electronic form (eBPDR) may be found on
CBER's web site at https://www.fda.gov/vaccines-blood-biologics/report-problem-center-
biologics-evaluation-research/biological-product-deviations:

Food and Drug Administration
Center for Biologics Evaluation and Research
Document Control Center
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 229 of 237
Page 3 — STN BL 125742/0 — Elisa Harkins

10903 New Hampshire Ave.
WO71-G112
Silver Spring, MD 20993-0002

MANUFACTURING CHANGES

You must submit information to your BLA for our review and written approval under 21
CFR 601.12 for any changes in, including but not limited to, the manufacturing, testing,
packaging or labeling of COVID-19 Vaccine, mRNA, or in the manufacturing facilities.

LABELING

We hereby approve the draft content of labeling including Package Insert, submitted
under amendment 74, dated August 21, 2021, and the draft carton and container labels
submitted under amendment 63, dated August 19, 2021.

CONTENT OF LABELING

As soon as possible, but no later than 14 days from the date of this letter, please submit
the final content of labeling (21 CFR 601.14) in Structured Product Labeling (SPL)
format via the FDA automated drug registration and listing system, (eLIST) as described
at http://www.fda.gov/Forlndustry/DataStandards/StructuredProductLabeling/
default.htm. Content of labeling must be identical to the Package Insert submitted on
August 21, 2021. Information on submitting SPL files using eLIST may be found in the
guidance for industry SPL Standard for Content of Labeling Technical Qs and As at
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRequlatoryInformation/Guida
nces/UCM072392.pdf.

The SPL will be accessible via publicly available labeling repositories.
CARTON AND CONTAINER LABELS

Please electronically submit final printed carton and container labels identical to the
carton and container labels submitted on August 19, 2021, according to the guidance
for industry Providing Regulatory Submissions in Electronic Format — Certain Human
Pharmaceutical Product Applications and Related Submissions Using the eCTD
Specifications at https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/providing-requlatory-submissions-electronic-format-certain-human-
pharmaceutical-product-applications.

All final labeling should be submitted as Product Correspondence to this BLA STN BL
125742 at the time of use and include implementation information on Form FDA 356h.

ADVERTISING AND PROMOTIONAL LABELING
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 230 of 237
Page 4 -— STN BL 125742/0 — Elisa Harkins

You may submit two draft copies of the proposed introductory advertising and
promotional labeling with Form FDA 2253 to the Advertising and Promotional Labeling
Branch at the following address:

Food and Drug Administration

Center for Biologics Evaluation and Research

Document Control Center

10903 New Hampshire Ave.

WO71-G112

Silver Spring, MD 20993-0002

You must submit copies of your final advertising and promotional labeling at the time of
initial dissemination or publication, accompanied by Form FDA 2253 (21 CFR
601.12(f)(4)).

All promotional claims must be consistent with and not contrary to approved labeling.
You should not make a comparative promotional claim or claim of superiority over other
products unless you have substantial evidence or substantial clinical experience to
support such claims (21 CFR 202.1(e)(6)).

ADVERSE EVENT REPORTING

You must submit adverse experience reports in accordance with the adverse
experience reporting requirements for licensed biological products (21 CFR 600.80),
and you must submit distribution reports at monthly intervals as described in 21 CFR
600.81. For information on adverse experience reporting, please refer to the guidance
for industry Providing Submissions in Electronic Format —Postmarketing Safety
Reports for Vaccines at https://www.fda.gov/requlatory-information/search-fda-
guidance-documents/providing-submissions-electronic-format-postmarketing-safety-
reports-vaccines. For information on distribution reporting, please refer to the guidance
for industry Electronic Submission of Lot Distribution Reports at
http:/Awww.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRequlatoryInformation
/Post-MarketActivities/LotReleases/ucm061966.htm.

PEDIATRIC REQUIREMENTS

Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
new active ingredients, new indications, new dosage forms, new dosing regimens, or

new routes of administration are required to contain an assessment of the safety and

effectiveness of the product for the claimed indication in pediatric patients unless this

requirement is waived, deferred, or inapplicable.

We are deferring submission of your pediatric studies for ages younger than 16 years
for this application because this product is ready for approval for use in individuals 16
years of age and older, and the pediatric studies for younger ages have not been
completed.
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 231 of 237
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Your deferred pediatric studies required under section 505B(a) of the Federal Food,
Drug, and Cosmetic Act (FDCA) are required postmarketing studies. The status of
these postmarketing studies must be reported according to 21 CFR 601.28 and section
505B(a)(4)(C) of the FDCA. In addition, section 506B of the FDCA and 21 CFR 601.70
require you to report annually on the status of any postmarketing commitments or
required studies or clinical trials.

Label your annual report as an “Annual Status Report of Postmarketing Study
Requirement/Commitments’” and submit it to the FDA each year within 60 calendar
days of the anniversary date of this letter until all Requirements and Commitments
subject to the reporting requirements under section 506B of the FDCA are released or
fulfilled. These required studies are listed below:

1. Deferred pediatric Study C4591001 to evaluate the safety and effectiveness of
COMIRNATY in children 12 years through 15 years of age.

Final Protocol Submission: October 7, 2020
Study Completion: May 31, 2023
Final Report Submission: October 31, 2023

2. Deferred pediatric Study C4591007 to evaluate the safety and effectiveness of
COMIRNATY in infants and children 6 months to <12 years of age.

Final Protocol Submission: February 8, 2021
Study Completion: November 30, 2023
Final Report Submission: May 31, 2024

3. Deferred pediatric Study C4591023 to evaluate the safety and effectiveness of
COMIRNATY in infants <6 months of age.

Final Protocol Submission: January 31, 2022
Study Completion: July 31, 2024
Final Report Submission: October 31, 2024

Submit the protocols to your IND 19736, with a cross-reference letter to this BLA STN
BL 125742 explaining that these protocols were submitted to the IND. Please refer to
the PMR sequential number for each study/clinical trial and the submission number as
shown in this letter.

Submit final study reports to this BLA STN BL 125742. In order for your PREA PMRs to
be considered fulfilled, you must submit and receive approval of an efficacy or a labeling
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 232 of 237
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supplement. For administrative purposes, all submissions related to these required
pediatric postmarketing studies must be clearly designated as:

e Required Pediatric Assessment(s)

We note that you have fulfilled the pediatric study requirement for ages 16 through 17
years for this application.

POSTMARKETING REQUIREMENTS UNDER SECTION 505(0)

Section 505(0) of the Federal Food, Drug, and Cosmetic Act (FDCA) authorizes FDA to
require holders of approved drug and biological product applications to conduct
postmarketing studies and clinical trials for certain purposes, if FDA makes certain
findings required by the statute (section 505(0)(3)(A), 21 U.S.C. 355(0)(3)(A)).

We have determined that an analysis of spontaneous postmarketing adverse events
reported under section 505(k)(1) of the FDCA will not be sufficient to assess known
serious risks of myocarditis and pericarditis and identify an unexpected serious risk of
subclinical myocarditis.

Furthermore, the pharmacovigilance system that FDA is required to maintain under
section 505(k)(3) of the FDCA is not sufficient to assess these serious risks.

Therefore, based on appropriate scientific data, we have determined that you are
required to conduct the following studies:

4. Study C4591009, entitled “A Non-Interventional Post-Approval Safety Study of
the Pfizer-BioNTech COVID-19 mRNA Vaccine in the United States,” to evaluate
the occurrence of myocarditis and pericarditis following administration of
COMIRNATY.

We acknowledge the timetable you submitted on August 21, 2021, which states
that you will conduct this study according to the following schedule:

Final Protocol Submission: August 31, 2021
Monitoring Report Submission: October 31, 2022
Interim Report Submission: October 31, 2023
Study Completion: June 30, 2025

Final Report Submission: October 31, 2025

5. Study C4591021, entitled “Post Conditional Approval Active Surveillance Study
Among Individuals in Europe Receiving the Pfizer-BioNTech Coronavirus
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Disease 2019 (COVID-19) Vaccine,” to evaluate the occurrence of myocarditis
and pericarditis following administration of COMIRNATY.

We acknowledge the timetable you submitted on August 21, 2021, which states
that you will conduct this study according to the following schedule:

Final Protocol Submission: August 11, 2021
Progress Report Submission: September 30, 2021
Interim Report 1 Submission: March 31, 2022
Interim Report 2 Submission: September 30, 2022
Interim Report 3 Submission: March 31, 2023
Interim Report 4 Submission: September 30, 2023
Interim Report 5 Submission: March 31, 2024
Study Completion: March 31, 2024

Final Report Submission: September 30, 2024

6. Study C4591021 substudy to describe the natural history of myocarditis and
pericarditis following administration of COMIRNATY.

We acknowledge the timetable you submitted on August 21, 2021, which states
that you will conduct this study according to the following schedule:

Final Protocol Submission: January 31, 2022
Study Completion: March 31, 2024
Final Report Submission: September 30, 2024
7. Study C4591036, a prospective cohort study with at least 5 years of follow-up for
potential long-term sequelae of myocarditis after vaccination (in collaboration

with Pediatric Heart Network).

We acknowledge the timetable you submitted on August 21, 2021, which states
that you will conduct this study according to the following schedule:

Final Protocol Submission: November 30, 2021

Study Completion: December 31, 2026
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Final Report Submission: May 31, 2027

8. Study C4591007 substudy to prospectively assess the incidence of subclinical
myocarditis following administration of the second dose of COMIRNATY ina
subset of participants 5 through 15 years of age.

We acknowledge the timetable you submitted on August 21, 2021, which states
that you will conduct this assessment according to the following schedule:

Final Protocol Submission: September 30, 2021
Study Completion: November 30, 2023
Final Report Submission: May 31, 2024

9. Study C4591031 substudy to prospectively assess the incidence of subclinical
myocarditis following administration of a third dose of COMIRNATY in a subset of
participants 16 to 30 years of age.

We acknowledge the timetable you submitted on August 21, 2021, which states
that you will conduct this study according to the following schedule:

Final Protocol Submission: November 30, 2021
Study Completion: June 30, 2022
Final Report Submission: December 31, 2022

Please submit the protocols to your IND 19736, with a cross-reference letter to this BLA
STN BL 125742 explaining that these protocols were submitted to the IND. Please refer
to the PMR sequential number for each study/clinical trial and the submission number
as shown in this letter.

Please submit final study reports to the BLA. If the information in the final study report
supports a change in the label, the final study report must be submitted as a
supplement to this BLA STN BL 125742. For administrative purposes, all submissions
related to these postmarketing studies required under section 505(0) must be submitted
to this BLA and be clearly designated as:

e Required Postmarketing Correspondence under Section 505(o0)

e Required Postmarketing Final Report under Section 505(o0)

e Supplement contains Required Postmarketing Final Report under Section
505(0)

Section 505(0)(3)(E)(ii) of the FDCA requires you to report periodically on the status of
any study or clinical trial required under this section. This section also requires you to
periodically report to FDA on the status of any study or clinical trial otherwise
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 235 of 237
Page 9— STN BL 125742/0 — Elisa Harkins

undertaken to investigate a safety issue. In addition, section 506B of the FDCA and 21
CFR 601.70 require you to report annually on the status of any postmarketing
commitments or required studies or clinical trials.

You must describe the status in an annual report on postmarketing studies for this
product. Label your annual report as an Annual Status Report of Postmarketing
Requirements/Commitments and submit it to the FDA each year within 60 calendar
days of the anniversary date of this letter until all Requirements and Commitments
subject to the reporting requirements of section 506B of the FDCA are fulfilled or
released. The status report for each study should include:

the sequential number for each study as shown in this letter;

information to identify and describe the postmarketing requirement;

the original milestone schedule for the requirement;

the revised milestone schedule for the requirement, if appropriate;

the current status of the requirement (i.e., pending, ongoing, delayed, terminated,
or submitted); and,

e an explanation of the status for the study or clinical trial. The explanation should
include how the study is progressing in reference to the original projected
schedule, including, the patient accrual rate (i.e., number enrolled to date and the
total planned enrollment).

As described in 21 CFR 601.70(e), we may publicly disclose information regarding
these postmarketing studies on our website at http://www.fda.gov/Drugs/Guidance
ComplianceRequlatoryInformation/Post-marketingPhaselVCommitments/default.htm.

We will consider the submission of your annual report under section 506B of the FDCA
and 21 CFR 601.70 to satisfy the periodic reporting requirement under section
505(0)(3)(E)(ii) provided that you include the elements listed in section 505(0) and 21
CFR 601.70. We remind you that to comply with section 505(0), your annual report
must also include a report on the status of any study or clinical trial otherwise
undertaken to investigate a safety issue. Failure to periodically report on the status of
studies or clinical trials required under section 505(0) may be a violation of FDCA
section 505(0)(3)(E)(ii) and could result in regulatory action.

POSTMARKETING COMMITMENTS SUBJECT TO REPORTING REQUIREMENTS
UNDER SECTION 506B

We acknowledge your written commitments as described in your letter of
August 21, 2021 as outlined below:

10.Study C4591022, entitled “Pfizer-BioNTech COVID-19 Vaccine Exposure during
Pregnancy: A Non-Interventional Post-Approval Safety Study of Pregnancy and
Infant Outcomes in the Organization of Teratology Information Specialists
(OTIS)/MotherToBaby Pregnancy Registry.”

Final Protocol Submission: July 1, 2021
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Page 10 — STN BL 125742/0 — Elisa Harkins

Study Completion: June 30, 2025
Final Report Submission: December 31, 2025

11. Study C4591007 substudy to evaluate the immunogenicity and safety of lower
dose levels of COMIRNATY in individuals 12 through <30 years of age.

Final Protocol Submission: September 30, 2021
Study Completion: November 30, 2023
Final Report Submission: May 31, 2024

12. Study C4591012, entitled “Post-emergency Use Authorization Active Safety
Surveillance Study Among Individuals in the Veteran’s Affairs Health System
Receiving Pfizer-BioNTech Coronavirus Disease 2019 (COVID-19) Vaccine.”
Final Protocol Submission: January 29, 2021
Study Completion: June 30, 2023
Final Report Submission: December 31, 2023

13. Study C4591014, entitled “Pfizer-BioNTech COVID-19 BNT162b2 Vaccine
Effectiveness Study - Kaiser Permanente Southern California.”

Final Protocol Submission: March 22, 2021
Study Completion: December 31, 2022
Final Report Submission: June 30, 2023

Please submit clinical protocols to your IND 19736, and a cross-reference letter to this
BLA STN BL 125742 explaining that these protocols were submitted to the IND. Please
refer to the PMC sequential number for each study/clinical trial and the submission
number as shown in this letter.

If the information in the final study report supports a change in the label, the final study
report must be submitted as a supplement. Please use the following designators to
prominently label all submissions, including supplements, relating to these
postmarketing study commitments as appropriate:

e Postmarketing Commitment — Correspondence Study Update
e Postmarketing Commitment — Final Study Report
e Supplement contains Postmarketing Commitment — Final Study Report
Case 6:22-cv-00093-ADA-JCM Document1 Filed 01/24/22 Page 237 of 237
Page 11 —STN BL 125742/0 — Elisa Harkins

For each postmarketing study subject to the reporting requirements of 21 CFR 601.70,
you must describe the status in an annual report on postmarketing studies for this
product. Label your annual report as an Annual Status Report of Postmarketing
Requirements/Commitments and submit it to the FDA each year within 60 calendar
days of the anniversary date of this letter until all Requirements and Commitments
subject to the reporting requirements of section 506B of the FDCA are fulfilled or
released. The status report for each study should include:

the sequential number for each study as shown in this letter;

information to identify and describe the postmarketing commitment;

the original schedule for the commitment;

the status of the commitment (i.e., pending, ongoing, delayed, terminated, or
submitted); and,

e an explanation of the status including, for clinical studies, the patient accrual rate
(i.e., number enrolled to date and the total planned enrollment).

POST APPROVAL FEEDBACK MEETING

New biological products qualify for a post approval feedback meeting. Such meetings
are used to discuss the quality of the application and to evaluate the communication
process during drug development and marketing application review. The purpose is to
learn from successful aspects of the review process and to identify areas that could
benefit from improvement. If you would like to have such a meeting with us, please
contact the Regulatory Project Manager for this application.

Sincerely,
Mary A. Malarkey Marion F. Gruber, PhD
Director Director
Office of Compliance Office of Vaccines

and Biologics Quality Research and Review
Center for Biologics Center for Biologics

Evaluation and Research Evaluation and Research

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