Burk Declaration
- Date
- 2021-12-17
Summary
Exhibit 11 to the Burk Declaration, filed December 17, 2021 as Document 40-11 in Case 2:21-cv-00702-CLM in the U.S. District Court, N.D. of Alabama. The exhibit is an FDA review memorandum dated October 20, 2021 from CBER on EUA 27034 for the Pfizer-BioNTech COVID-19 Vaccine. It reviews an NIH request to amend the authorization to allow a single heterologous booster dose after primary vaccination with another authorized or approved COVID-19 vaccine, summarizing a Phase 1/2 open-label trial of 458 individuals and the October 15, 2021 advisory committee discussion. The memorandum reports that neutralizing antibody titers increased between 4.2 and 75.9 fold and no new safety concerns were identified, and it recommends authorization of the heterologous booster dose.
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Case 2:21-cv-00702-CLM Document 40-11 Filed 12/17/21 Page 1 of 7 FILED
2021 Dec-17 PM 01:27
U.S. DISTRICT COURT
N.D. OF ALABAMA
Burk Declaration
Exhibit 11
Case 2:21-cv-00702-CLM Document 40-11 Filed 12/17/21 Page 2 of 7
Review Memorandum
Date: October 20, 2021
To: The File
From: David Cho, PhD (CBER/OD)
Through: Peter Marks, MD, PhD (CBER/OD)
Applicant name: Pfizer
Application Number: EUA 27034
Product: Pfizer-BioNTech COVID-19 Vaccine
Subject: EUA amendment to support use of a Pfizer-BioNTech COVID-19
Vaccine heterologous booster dose following primary vaccination
with other authorized COVID-19 vaccines.
This memorandum provides a summary, review, and recommendation on the request by the National
National Institute for Allergy and Infectious Diseases of the National Institutes of Health (further referred
to as NIH) that FDA amend the existing Emergency Use Authorization (EUA) for the Pfizer-BioNTech
COVID-19 Vaccine to include its use as a single heterologous booster dose following completion of
primary vaccination with other currently authorized COVID-19 vaccines. The requested authorization is as
follows:
A single booster dose of the Pfizer-BioNTech COVID-19 Vaccine 1 (0.3 mL) may be administered as a
heterologous booster dose following completion of primary vaccination with another authorized or
approved COVID-19 vaccine. The eligible population(s) and dosing interval for the heterologous booster
dose are the same as those authorized for a booster dose of the vaccine used for primary vaccination.
Executive Summary
NIH has proposed amending EUA 27034 to allow a single dose of the Pfizer-BioNTech COVID-19
Vaccine to be used as a heterologous booster dose following completion of primary vaccination with
another authorized or approved COVID-19 vaccine. To support this request, NIH has provided information
from a 3 x 3 matrixed booster study that evaluated the three currently authorized or approved COVID-19
vaccines and documented that booster administration of each of the vaccines resulted in a booster response,
regardless of the primary vaccination. These data were presented at the FDA’s Vaccines and Related
1
References to Pfizer-BioNTech COVID‑19 Vaccine in this memo also apply to COMIRNATY (COVID-19 Vaccine, mRNA).
1
Case 2:21-cv-00702-CLM Document 40-11 Filed 12/17/21 Page 3 of 7
Biologics Products Advisory Committee (VRBPAC) meeting on October 15th, 2021, and the advisors
endorsed implementing an allowance for heterologous boosting of the currently authorized and approved
COVID-19 vaccines.
Review
The NIH data submitted data that is available as a preprint on line:
Atmar RL, Lyke, RE, Deming, ME, et al. Heterologous SARS-CoV-2 Booster Vaccinations –
Preliminary Report. 2021; medRxiv preprint doi: https://doi.org/10.1101/2021.10.10.21264827.
This is a Phase 1/2 open-label clinical trial being conducted at 10 sites in the United States. In this study,
adults who had completed primary vaccination with a Moderna COVID-19 Vaccine 2-dose series (N=151),
a Janssen COVID-19 Vaccine single dose (N=156), or a Pfizer-BioNTech COVID-19 Vaccine 2-dose
series (N=151) at least 12 weeks prior to enrollment and who reported no history of SARS-CoV-2 infection
were randomized 1:1:1 to receive a booster dose of one of three vaccines: Moderna COVID-19 Vaccine,
Janssen COVID-19 Vaccine, or Pfizer-BioNTech COVID-19 Vaccine. The dose volume and antigen
content used for the booster dose of each of the vaccines was the same as that authorized for the primary
vaccination. Adverse events were assessed through 28 days after the booster dose. Neutralizing antibody
titers, as measured by a pseudovirus neutralization assay using a lentivirus expressing the SARS-CoV-2
Spike protein with D614G mutation, were assessed on Day 1 prior to administration of the booster dose and
on Day 15 after the booster dose.
The following table from the preprint summarizes patient enrollment into the trial:
2
Case 2:21-cv-00702-CLM Document 40-11 Filed 12/17/21 Page 4 of 7
An overall review of adverse reactions reported following the Pfizer-BioNTech COVID-19 Vaccine
heterologous booster dose did not identify any new safety concerns, as compared with adverse reactions
reported following Pfizer-BioNTech COVID-19 Vaccine primary series doses or homologous booster dose.
The following figure summarizes the reactogenicity reported in the study:
3
Case 2:21-cv-00702-CLM Document 40-11 Filed 12/17/21 Page 5 of 7
Two serious adverse events were reported in this trial (rhabdomyoslysis following a fall and acute
cholecystitis). Neither was judged to be related to booster vaccine administration.
The following table summarizes the neutralizing antibody responses to homologous and heterologous
boosting in this study. Geometric mean neutralizing antibody titers to SARS-CoV-2 D614G increased
4
Case 2:21-cv-00702-CLM Document 40-11 Filed 12/17/21 Page 6 of 7
between 4.2 and 75.9 fold from pre-booster baseline to 15 days post-booster. The data support that the
Pfizer-BioNTech COVID-19 Vaccine booster dose elicited a booster response regardless of the vaccine
received for primary vaccination.
Following presentation of the data from the heterologous booster dose study to the VRBPAC on October
15, 2021, the committee discussed the nature of the study and its implications. Although the relatively
small sizes of the populations were noted, and no formal vote was taken, the consensus of the committee
was that the presented analyses would support use of the authorized or approved COVID-19 vaccines as
heterologous booster doses.
Recommendation
The data from the NIH Heterologous SARS-CoV-2 Booster Vaccination study indicate that each of the
three currently authorized or approved COVID-19 vaccines (Moderna, Janssen, Pfizer) are capable of
generating a booster response when administered to indiviuals who completed primary vaccination with
another authorized or approved COVID-19 vaccine. Geometric mean neutralizing antibody titers to SARS-
CoV-2 D614G increased between 4.2 and 75.9 fold from pre-booster baseline to 15 days post-booster.
While some differences in reactogenicity following the booster dose were apparent, depending on the
primary vaccination and/or the booster vaccination, no new safety concerns were identified as compared
with the characterized safety profiles of the vaccines when used for primary vaccination or for homologous
boosting. A limitation of the study is its relatively small size, with a total of 458 individuals (approximately
50 individuals each in 9 arms). Although boosting of neutralizing antibody titers was documented for each
of the nine combinations of primary vaccination and booster dose, because of the limited sample size and
5
Case 2:21-cv-00702-CLM Document 40-11 Filed 12/17/21 Page 7 of 7
short duration of follow-up, it is not possible at this time to determine if there is a preferred strategy for use
of heterologous COVID-19 vaccine booster doses.
In considering the appropriate populations that would be eligible for a heterologous booster dose and the
appropriate interval between primary vaccination and a heterologous booster dose, the need for a booster
dose is determined by immunity elicited by the primary vaccination. Thus, the eligible population(s) and
dosing interval for a Pfizer-BioNTech COVID-19 Vaccine heterologous booster dose that would be
supported by available data would be the same as those authorized for a homologous booster dose of the
vaccine used for primary vaccination. 2
Based on the totality of the data submitted by NIH, the Pfizer-BioNTech COVID-19 vaccine, when
administered as a heterologous booster dose following completion of primary vaccination with another
authorized COVID-19 vaccine may be effective in improving protection against serious outcomes of
COVID-19 among individuals in whom immunity elicited by primary vaccination has waned. Additionally,
the known and potential benefits outweigh the known and potential risks for use of a booster dose of the
Pfizer-BioNTech COVID-19 Vaccine when given following completion of primary vaccination with
another authorized COVID-19 Vaccine, following the eligible population(s) and interval authorized for a
homologous booster dose of that vaccine.
We therefore recommend authorization of the Pfizer-BioNTech COVID-19 Vaccine for a heterologous
booster dose following completion of primary vaccination with another authorized COVID-19 vaccine.
2
CBER’s review and analysis of the use of homologous booster doses, including the eligible population(s) and dosing interval
for a homologous booster, is documented in separate review memoranda. Those three review memoranda, Emergency Use
Authorization (EUA) Amendments for an Unapproved Product Review Memorandum: EUA 27073 (Amendment 250) for the
Moderna COVID-19 Vaccine; Emergency Use Authorization (EUA) Amendments for an Unapproved Product Review
Memorandum: EUA 27205 (Amendment 194) for the Janssen COVID-19 Vaccine; and Emergency Use Authorization (EUA)
Amendments for an Unapproved Product Review Memorandum: EUA 27034 (Amendment 305) for the Pfizer-BioNTech
COVID-19 Vaccine, are incorporated here by reference.
6
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