Federal Efforts Accelerate Vaccine and Therapeutic Development, but More Transparency Needed on Emergency Use Authorizations (GAO-21-207)
Summary
A GAO report to congressional addressees, GAO-21-207, dated November 2020, on COVID-19 vaccine and therapeutic development. It notes that the U.S. had about 10.3 million cumulative reported cases and about 224,000 reported deaths as of November 12, 2020. It describes Operation Warp Speed, a partnership between the Department of Health and Human Services and the Department of Defense, which seeks to accelerate a vaccine development process that can take approximately 10 years or longer by completing key steps simultaneously. Its title states that federal efforts accelerate development but that more transparency is needed on emergency use authorizations.
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United States Government Accountability Office
Report to Congressional Addressees
COVID-19
November 2020
Federal Efforts
Accelerate Vaccine
and Therapeutic
Development, but
More Transparency
Needed on
Emergency Use
Authorizations
GAO-21-207
November 2020
COVID-19
Federal Efforts Accelerate Vaccine and Therapeutic
Development, but More Transparency Needed on
Highlights of GAO-21-207, a report to
Emergency Use Authorizations
congressional addressees
Why GAO Did This Study What GAO Found
The U.S. had about 10.3 million Through Operation Warp Speed—a partnership between the Department of
cumulative reported cases of COVID- Health and Human Services (HHS) and the Department of Defense (DOD)—the
19 and about 224,000 reported deaths federal government is accelerating efforts to develop vaccines and therapeutics
as of November 12, 2020. Given this for COVID-19. A typical vaccine development process can take approximately 10
catastrophic loss of life as well as the years or longer, but efforts under Operation Warp Speed seek to greatly
pandemic’s effects on the U.S. accelerate this process by completing key steps simultaneously (see figure). As
economy, effective and safe vaccines of October 15, 2020, Operation Warp Speed publicly announced financial
and therapeutics are more important support for the development or manufacturing of six COVID-19 vaccine
than ever.
candidates totaling more than $10 billion in obligations. It has also announced
The CARES Act includes a provision financial support for the development of therapeutics, such as a $450 million
for GAO to report on its ongoing award to manufacture a monoclonal antibody treatment (a treatment that uses
monitoring and oversight efforts related laboratory-made antibodies, which also may be able to serve as a prevention
to the COVID-19 pandemic. This report option).
examines, (1) efforts of Operation
Warp Speed to accelerate COVID-19 Operation Warp Speed Timeline for a Potential Vaccine Candidate
vaccine and therapeutic development;
and (2) FDA’s use of EUAs for COVID-
19 therapeutics and vaccines, among
other objectives.
GAO reviewed federal laws and
agency documents, including HHS and
DOD information on vaccine and
therapeutic development and EUAs as
of November 2020. GAO interviewed
or received written responses from
HHS and DOD officials, and
interviewed representatives from
vaccine developers and
manufacturers, as well as select public
health stakeholders and provider
groups covering a range of provider
types. Note: An Emergency Use Authorization allows for emergency use of medical products without FDA
approval or licensure during a declared emergency, provided certain statutory criteria are met.
What GAO Recommends
FDA should identify ways to uniformly The Food and Drug Administration (FDA) may temporarily allow the use of
disclose to the public the information unlicensed or unapproved COVID-19 vaccines and therapeutics through
from its scientific review of safety and emergency use authorizations (EUA), provided there is evidence that the
effectiveness data when issuing EUAs products may be effective and that known and potential benefits outweigh known
for therapeutics and vaccines. HHS and potential risks. For vaccines, FDA issued guidance in October 2020 to
neither agreed nor disagreed with the provide vaccine sponsors with recommendations regarding the evidence FDA
recommendation, but said it shared needed to support issuance of an EUA. For therapeutics, FDA has issued four
GAO’s goal of transparency and would EUAs as of November 9, 2020. The evidence to support FDA’s COVID-19
explore approaches to achieve this therapeutic authorization decisions has not always been transparent, in part
goal. because FDA does not uniformly disclose its scientific review of safety and
effectiveness data for EUAs, as it does for approvals for new drugs and biologics.
View GAO-21-207. For more information,
contact Mary Denigan-Macauley at (202) 512-
Given the gravity of the pandemic, it is important that FDA identify ways to
7114 or deniganmacauleym@gao.gov, or uniformly disclose this information to the public. By doing so, FDA could help
Alyssa M. Hundrup at (202) 512-7114 or improve the transparency of, and ensure public trust in, its EUA decisions.
hundrupa@gao.gov
United States Government Accountability Office
Contents
Letter 1
Background 5
Operation Warp Speed Partnership Leads Federal Efforts to
Accelerate Developing and Manufacturing COVID-19 Vaccines
and Therapeutics 12
FDA Clarified Expected Evidence for COVID-19 Vaccine EUAs,
but the Evidence to Support Its COVID-19 Therapeutic EUA
Decisions Is Not Always Transparent 20
Stakeholders Indicate Initial Planning Documents Are Helpful, but
Seek Additional Information on Federal Plans for Vaccine
Distribution 31
Conclusions 39
Recommendation for Executive Action 39
Agency Comments and Our Evaluation 39
Appendix I Comments from the Department of Health and Human Services 43
Appendix II GAO Contacts and Staff Acknowledgments 45
Related GAO Products 46
Table
Table 1: Statutory Criteria Required for an Emergency Use
Authorization (EUA) 11
Figures
Figure 1: Traditional Vaccine Development Timeline Compared to
Potential Operation Warp Speed Timeline 7
Figure 2: Reported Operation Warp Speed Leadership Structure,
as of November 2020 9
Figure 3: Overview of the Four Vaccine Platform Technologies
Considered by Operation Warp Speed, as of October
2020 15
Page i GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Figure 4: Timeline of Emergency Use Authorizations for
COVID-19 Therapeutics, as of November 9, 2020 24
Figure 5: Data Cited to Support Issuance of Emergency Use
Authorizations (EUA) for Therapeutics for COVID-19, as
of November 9, 2020 27
Abbreviations
ASPR Assistant Secretary for Preparedness and Response
BARDA Biomedical Advanced Research and Development
Authority
CDC Centers for Disease Control and Prevention
COVID-19 Coronavirus Disease 2019
DOD Department of Defense
EUA Emergency Use Authorization
HHS Department of Health and Human Services
FDA Food and Drug Administration
NIH National Institutes of Health
VTrckS Vaccine Tracking System
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Page ii GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Letter
441 G St. N.W.
Washington, DC 20548
November 17, 2020
Congressional Addressees
The U.S. has had about 10.3 million cumulative reported cases of
Coronavirus Disease 2019 (COVID-19) and about 224,000 reported
deaths as of November 12, 2020. Given this catastrophic loss of life as
well the pandemic’s effects on the U.S. economy, safe and effective
vaccines to prevent the disease and therapeutics to treat those made ill
by its effects are more important than ever.
Since June 2020, we have cited the critical importance of planning for the
quick and flexible development, manufacturing, distribution, and
administration of COVID-19 vaccine(s) and therapeutics. In addition, we
have recommended that federal plans for vaccine distribution outline how
efforts will be coordinated across federal agencies and nonfederal
entities. We have also noted the importance of timely, clear, and
consistent communication to state and local health officials, stakeholders,
and the public about vaccine and therapeutic availability, efficacy, and
safety to ensure public confidence and trust, which in turn could
encourage vaccine and therapeutic use. 1
Efforts to develop, manufacture, and distribute COVID-19 vaccines and
therapeutics involve multiple federal agencies, the private sector, and
state and local governments. These federal efforts include Operation
Warp Speed, a partnership between the Department of Defense (DOD)
and the Department of Health and Human Services (HHS) that aims to
accelerate the development, manufacturing, and distribution of COVID-19
vaccines and therapeutics, with the goal of producing 300 million doses of
a COVID-19 vaccine, with initial doses available by January 2021.
HHS’s Food and Drug Administration (FDA) is responsible for licensing
and approving vaccines and therapeutics. As of November 9, 2020, no
vaccines were available to prevent COVID-19, though several candidates
were under development. Regarding therapeutics, the agency has
approved one therapeutic and made certain others available through
1GAO, COVID-19: Opportunities to Improve Federal Response and Recovery Efforts,
GAO-20-625 (Washington, D.C.: June. 25, 2020) and GAO, COVID-19: Federal Efforts
Could Be Strengthened by Timely and Concerted Actions, GAO-20-701 (Washington,
D.C.: Sept. 21, 2020).
Page 1 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Emergency Use Authorizations (EUA), which allows for emergency use of
medical products without FDA approval or licensure, provided certain
statutory criteria are met. 2 An FDA official has stated that the agency also
likely will review COVID-19 vaccine candidates through the EUA
process. 3
The CARES Act includes a provision for GAO to report on its ongoing
monitoring and oversight efforts related to the COVID-19 pandemic. 4 This
report is part of our body of work in response to the CARES Act and
focuses on the federal government’s efforts related to COVID-19 vaccines
and therapeutics. Specifically, in this report, we
1. describe the efforts of Operation Warp Speed to accelerate the
development and manufacturing of COVID-19 vaccines and
therapeutics, 5
2. examine FDA’s potential use of EUAs for COVID-19 vaccines, as well
as its use of EUAs for COVID-19 therapeutics, and
3. describe the actions the federal government has taken to plan for the
distribution of any authorized or licensed COVID-19 vaccine, and
initial perspectives of public health officials and providers on these
efforts.
To describe the efforts of Operation Warp Speed to accelerate the
development and manufacturing of COVID-19 vaccines and therapeutics,
we reviewed relevant agency documents, including HHS’s and DOD’s
Operation Warp Speed fact sheet, clinical trial protocols for Operation
Warp Speed COVID-19 vaccine candidates, FDA’s guidance for clinical
trials, and the Operation Warp Speed memorandum of understanding
between HHS and DOD. We also analyzed data on obligations for
contracts and other acquisition vehicles available in the Federal
Procurement Data System-Next Generation through October 15, 2020.
2See 21 U.S.C. § 360bbb-3.
3Vaccine sponsors may also submit biologics license applications for licensure of vaccine
candidates. FDA guidance indicates that licensure is the goal for COVID-19 vaccine
candidates, including those that first receive an EUA.
4Pub. L. No. 116-136, § 19010, 134 Stat. 281, 579-81 (2020). This report also responds,
in part, to a bipartisan request from the House Select Subcommittee on the Coronavirus
Crisis for GAO to examine Operation Warp Speed.
5In this report, we describe Operation Warp Speed’s initial activities as of October 2020.
We will continue to review and evaluate Operation Warp Speed’s efforts to accelerate
COVID-19 vaccine and therapeutic development and manufacturing in future work.
Page 2 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
We assessed the reliability of this data by reviewing existing information
about the system and the data it collects—specifically, the data dictionary
and data validation rules—and performed electronic testing. We
determined the data were sufficiently reliable for the purposes of
describing agencies’ reported Operation Warp Speed obligations. To help
identify key challenges in scaling up manufacturing for COVID-19
vaccines and therapeutics, we conducted a literature review and reviewed
reports and journal articles about vaccine and therapeutics
manufacturing. We interviewed or received written responses from HHS
and DOD officials, including officials working within the Operation Warp
Speed partnership. We also interviewed vaccine and therapeutic
manufacturing experts and representatives from vaccine developers and
manufacturers working with Operation Warp Speed for additional
perspectives on vaccine and therapeutic development and manufacturing
activities.
To examine FDA’s potential use of EUAs for COVID-19 vaccines and its
use of EUAs for COVID-19 therapeutics, we reviewed relevant federal
laws and agency documents, including FDA’s guidance for EUAs, FDA’s
guidance for COVID-19 vaccines, and FDA’s guidance for EUAs for
COVID-19 vaccines. 6 We also reviewed publicly available EUA
documentation on FDA’s website as of November 9, 2020, including
authorization letters for COVID-19 therapeutics and related fact sheets to
health care providers, and decision memos, as well as an EUA revocation
letter and related documentation. We interviewed FDA officials, as well as
received written responses to questions from FDA officials. We also
interviewed a public health association and nine provider associations.
We selected provider associations based on their involvement on the
front lines of responding to the COVID-19 pandemic, as well as to ensure
we spoke with associations covering a broad range of specialty health
care providers, non-specialty health care providers, and hospitals. We
also spoke with an infectious disease expert from a prominent research
institution, as well as observed presentations of FDA officials. 7 We
6FDA, Emergency Use Authorization of Medical Products and Related Authorities:
Guidance for Industry and Other Stakeholders, (January 2017); Development and
Licensure of Vaccines to Prevent COVID-19: Guidance for Industry, (June 2020); and
Emergency Use Authorization for Vaccines to Prevent COVID-19: Guidance for Industry,
(October 2020).
7We reviewed, for example, presentations from the Journal of the American Medical
Association, the Center for Infectious Disease Research and Policy at the University of
Minnesota, and the Duke-Margolis Center for Health Policy.
Page 3 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
assessed FDA’s potential use of EUAs for COVID-19 vaccines and its
use of EUAs for COVID-19 therapeutics against Standards for Internal
Control in the Federal Government for information and communication, as
well as our past work on lessons learned during public health
emergencies and the PanCAP—generally the operative plan for the
federal response to COVID-19. 8
To describe the activities the federal government has taken to plan for the
distribution and administration of any authorized or licensed COVID-19
vaccine and initial perspectives on these efforts, we reviewed documents
related to federal plans, including the Centers for Disease Control and
Prevention’s (CDC) COVID-19 Vaccination Program Interim Playbook
Jurisdiction Operations and HHS’s and DOD’s Operation Warp Strategy
for Distributing a COVID-19 Vaccine, issued in September 2020 as well
as the updated interim playbook issued in October 2020. 9 We interviewed
or received written responses from HHS and DOD officials, including
Operation Warp Speed officials, about federal vaccine distribution plans.
We also interviewed representatives from stakeholder groups
representing state and local public health officials, including the
Association of Immunization Managers, Association of State and
Territorial Health Officials, National Governor’s Association, and provider
associations for their initial perspectives on the available information on
the federal government’s plans for vaccine distribution and administration,
including communication plans.
We conducted this performance audit from June 2020 to November 2020
in accordance with generally accepted government auditing standards.
Those standards require that we plan and perform the audit to obtain
sufficient, appropriate evidence to provide a reasonable basis for our
8GAO, Standards for Internal Control in the Federal Government, GAO-14-704G
(Washington, D.C.: Sept. 10, 2014). Internal control is a process effected by an entity’s
oversight body, management, and other personnel that provides reasonable assurance
that the objective of an entity will be achieved.
9In this report, we are presenting initial observations about these vaccine distribution
documents. We will continue to evaluate these and any additional vaccine-related
planning documents, as well as federal agencies’ implementation of those plans. In
September 2020, we recommended that the Secretary of Health and Human Services,
with support from the Secretary of Defense, establish a time frame for documenting and
sharing a national plan for distributing and administering COVID-19 vaccine and that it
ensure such a plan was consistent with best practices for project planning and scheduling
and outlined an approach for how efforts would be coordinated across federal agencies
and nonfederal entities. GAO, COVID-19: Federal Efforts Could Be Strengthened by
Timely and Concerted Actions, GAO-20-701 (Washington, D.C.: Sept. 21, 2020).
Page 4 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
findings and conclusions based on our audit objectives. We believe that
the evidence obtained provides a reasonable basis for our findings and
conclusions based on our audit objectives.
Background
FDA Approval and Typically, before a drug, biologic, or other medical product can be
Licensure Process and marketed in the U.S., it must be approved or licensed by FDA. 10 While the
Operation Warp Speed process varies by product type, the process for drugs and biologics—
which include vaccines—generally includes FDA’s review of evidence
submitted by a product’s sponsor to determine whether the new product
is safe and effective for its intended use or uses, including whether the
product’s known benefits outweigh the known risks. For drugs or
biologics, it typically takes years of research and development to collect
sufficient clinical evidence for FDA review.
Before a drug or biologic is approved or licensed, it will have gone
through preclinical research, which includes in vitro and testing on
animals for toxicity, and typically three phases of clinical trials to test
safety and efficacy in humans. 11
• Phase 1. Clinical trials in phase 1 generally test the safety of a
product with a small group of healthy volunteers (usually less than
100). The goal of this phase is to determine the product’s most
frequent side effects and how it is metabolized and excreted.
• Phase 2. In phase 2, the product is given to a larger group of
volunteers (usually a few dozen to hundreds) to see if it is safe and
effective for a particular use. For vaccines, phase 2 trials look at
questions such as the maximum tolerated dose, the optimal schedule
for giving the product (how many doses and at what time intervals),
10FDA approves chemically derived drugs through a review of new drug applications; it
licenses biologically derived products, such as vaccines, through review of biologics
license applications.
11According to FDA officials, in some cases when a new product is being tested for a life-
threatening condition, the development process may be expedited by going through only
one or two phases of clinical trials before an application is submitted to FDA for marketing
approval. In addition, postmarket studies are required for some products that FDA has
approved for marketing. For vaccines, FDA’s Vaccine and Related Biological Products
Advisory Committee reviews and evaluates data concerning the safety, effectiveness, and
appropriate use of vaccines and related biological products which are intended for use in
the prevention, treatment, or diagnosis of human diseases and makes appropriate
recommendations to the Commissioner of Food and Drugs.
Page 5 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
and whether the immune system of a person taking the vaccine is
having the desired responses.
• Phase 3. In phase 3, the product is given to still larger groups of
volunteers (usually many thousands) than in phase 2. Researchers
confirm its effectiveness, monitor side effects, compare it to commonly
used treatments, and collect information that will allow the product to
be used safely. For vaccines, this phase examines things such as
whether the product prevents new infections or, if people become
infected, if the product helps control the infections so they do not
become severe.
The vaccine development process has typically taken approximately 10
years or longer according to some studies, with many candidates failing,
according to another study. 12 With Operation Warp Speed, the federal
government aims to accelerate this process for the development of a
COVID-19 vaccine (see fig. 1). To help accelerate the process, the
federal government is taking on financial risk to develop and manufacture
selected vaccines before their safety and efficacy is fully known so that
any candidates receiving FDA authorization and/or licensure can be
distributed as soon as possible.
12See for example, E.S. Pronker et al., “Risk in Vaccine Research and Development
Quantified,” PLOS One, vol. 8, no. 3 (2013); and Pharmaceutical Research and
Manufacturers of America, “2017 State of Vaccines,” (Washington, D.C. November 8,
2017). For a study on success rates for clinical trials, see A. Lo et al., “Estimation of
clinical trial success rates and related parameters,” Biostatistics, vol. 20, no. 2 (2019).
Page 6 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Figure 1: Traditional Vaccine Development Timeline Compared to Potential Operation Warp Speed Timeline
Notes: The timelines for vaccine development depicted in this figure are not drawn to scale. These
timelines depict examples, and the specific development steps and timelines for a given vaccine may
vary from this example.
a
Phase 1 clinical trials generally test the safety of a product with a small group of healthy volunteers
(usually less than 100). The goal of this phase is to determine the product’s most frequent side effects
and how it is metabolized and excreted.
Phase 2 clinical trials look at questions such as the maximum tolerated dose, the optimal schedule for
giving the product (how many doses and at what time intervals), and whether the immune system of a
person taking the vaccine is having the desired responses. These trials are conducted with a
medium-size population of volunteers (usually a few dozen to hundreds).
Phase 3 clinical trials look at things like whether the product prevents new infections or, if people
become infected, if the product helps control the infections so they do not become severe. These
trials involve many thousands of volunteers, usually including participants who are at increased risk
for infection. According to FDA officials, these clinical trial phases may overlap.
b
According to FDA, manufacturing processes are reviewed as part of the vaccine licensure process.
Thus, even under a traditional vaccine timeline, some initial manufacturing occurs during
development, so the manufacturing processes can be adequately validated. According to an
Operation Warp Speed fact sheet, the federal government is taking on the financial risk to enable
large-scale manufacturing to start while clinical trials are ongoing, with the goal of having millions of
doses available for distribution upon authorization or licensure of a COVID-19 vaccine.
Page 7 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
c
The Operation Warp Speed timeline depicts an example of a potential accelerated timeline for
COVID-19 vaccine development. However, the development process of any given Operation Warp
Speed vaccine candidate may vary from this example. As of November 2020, approximately 10
months have elapsed since exploratory and preclinical research began in January 2020, after the first
U.S. cases of COVID-19 were reported, and as of October 14, 2020, four of the six Operation Warp
Speed candidates have begun phase 3 clinical trials. The timing for any remaining steps have yet to
be determined as of this report. According to Operation Warp Speed documentation, certain steps
may overlap or be shortened to accelerate the development of a COVID-19 vaccine.
d
During an emergency, as declared by the Secretary of Health and Human Services under 21 U.S.C.
§ 360bbb-3(b), FDA may temporarily authorize unapproved medical products or unapproved uses of
approved medical products through an Emergency Use Authorization (EUA), provided certain
statutory criteria are met. FDA has indicated that issuance of an EUA for a COVID-19 vaccine for
which there is adequate manufacturing information would require the submission of certain clinical
trial information from Phase 3 clinical trials that demonstrate the safety and effectiveness of the
vaccine in a clear and compelling manner, among other things. Any COVID-19 vaccine that initially
receives an EUA from FDA is expected to ultimately be reviewed and receive licensure through a
biologics license application, according to FDA guidance.
The Operation Warp Speed HHS and DOD partnership also has engaged
with private industry, including vaccine and therapeutic developers and
manufacturers, and other federal partners, such as the Department of
Veterans Affairs, to help achieve its goal of producing 300 million doses
of a safe and effective COVID-19 vaccine with initial doses available by
January 2021. 13 The Secretary of Health and Human Services and the
Secretary of Defense co-chair an Operation Warp Speed Executive
Board, which provides guidance on initiatives and receives updates on
progress toward milestones, according to Operation Warp Speed officials.
See figure 2 for Operation Warp Speed’s leadership structure, as outlined
by officials.
13Multiple HHS components are involved in Operation Warp Speed, including the
Biomedical Advanced Research and Development Authority (BARDA) within the Office of
the Assistant Secretary for Preparedness and Response (ASPR); CDC; and the National
Institutes of Health (NIH). The Department of Veterans Affairs is primarily involved in
Operation Warp Speed through its participation in clinical trials for vaccine candidates
supported by Operation Warp Speed. For example, as of September 2020, 19 Department
of Veterans Affairs facilities were participating in clinical trials for three Operation Warp
Speed supported vaccine candidates. Outside of Operation Warp Speed, DOD is also
pursuing medical research and development projects for COVID-19 vaccines,
therapeutics, and diagnostics as part of its efforts to protect servicemembers from COVID-
19.
Page 8 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Figure 2: Reported Operation Warp Speed Leadership Structure, as of November
2020
Operation Warp Speed has five areas of focus outlined in a memorandum
of understanding between HHS and DOD: (1) vaccines; (2) therapeutics;
(3) diagnostics; (4) supply, production, and distribution; and (5) security
assurance. Its senior leadership team—which, according to Operation
Warp Speed officials includes the directors of these five areas of focus,
the Chief Advisor, the Chief Operating Officer, and an HHS senior official
(the Deputy Chief of Staff for Policy)—provides information, advice, and
Page 9 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
recommendations to the Executive Board to inform the board’s decision-
making.
Funding to Support the The CARES Act and the Coronavirus Preparedness and Response
Development of COVID-19 Supplemental Appropriations Act, 2020, appropriated funding for HHS
activities to support the development of vaccines and therapeutics for
Vaccines and
COVID-19. This included appropriations to FDA, the National Institutes of
Therapeutics Health (NIH), and the Public Health and Social Services Emergency Fund
for activities that include, but are not limited to, developing
countermeasures and vaccines and purchasing vaccines and
therapeutics. 14 As of October 31, 2020, HHS reported it had obligated
about $13.3 billion and expended about $1.3 billion for vaccines, and it
obligated about $2.8 billion and expended about $622 million for
therapeutics.
The CARES Act includes a number of provisions related to federal
contracting efforts to facilitate agencies’ response to the pandemic. We
have reported previously that a variety of contracting flexibilities are
available to agencies to facilitate contract awards and the obligation of
funds in response to the pandemic including the use of “other transaction
authority,” which enables federal agencies to negotiate terms and
conditions specific to a project without requiring them to comply with
certain federal regulations. 15
Emergency Use The Secretary of Health and Human Services may declare that
Authorization General circumstances, prescribed by statute, exist justifying the emergency use
of certain medical products. 16 Once a declaration has been made, FDA
Statutory Criteria and
may temporarily allow use of unapproved medical products or
Guidance unapproved uses of approved medical products through an EUA,
14See CARES Act, Pub. L. No. 116-136, div. B., tits. I, VIII, 134 Stat. 281, 509, 555-56,
560-61 (2020); Coronavirus Preparedness and Response Supplemental Appropriations
Act, 2020, Pub. L. No. 116-123, div. A., tits. I, III, 134 Stat. 146, 148, 149-50. The Public
Health and Social Services Emergency Fund is an account through which funding is
provided to certain HHS offices, such as ASPR.
15See GAO, COVID-19 Contracting: Observations on Federal Contracting in Response to
the Pandemic, GAO-20-632, (Washington, D.C.: July 29, 2020).
16See 21 U.S.C. § 360bbb-3(b)(1). Drugs approved by FDA for uses other than COVID-19
and without an EUA for COVID-19, such as dexamethasone, have also been used by
some physicians to treat the disease as part of research studies.
Page 10 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
provided certain statutory criteria are met. 17 One of these criteria—
evidence that the product may be effective—requires less certainty of
effectiveness than is required to approve therapeutics or license
vaccines. For example, a request for an EUA may be submitted and FDA
may authorize the product before all of the preclinical research and
clinical studies that would be needed to support full approval are
necessarily completed. See table 1 for a description of certain statutory
criteria. 18
Table 1: Statutory Criteria Required for an Emergency Use Authorization (EUA)
Criteria Explanation
Serious or life threatening The chemical, biological, radiological, or nuclear threat agent referred to in the Secretary of Health and
disease or condition Human Services’ emergency declaration must be capable of causing a serious or life-threatening
disease or condition.
Evidence the product may Based on the totality of the scientific evidence available, including data from adequate and well-
be effective controlled clinical trials, if available, it must be reasonable to believe that the medical product may be
effective in diagnosing, treating, or preventing the disease or condition.a
Risk-benefit analysis Based on the totality of the scientific evidence available, it must be reasonable to believe that the
known and potential benefits of the product, when used to diagnose, prevent, or treat the identified
disease or condition, outweigh the known and potential risks of the product.
No alternatives There must be no adequate, approved, and available alternative to the candidate product for
diagnosing, preventing, or treating the disease or condition.b
Source: GAO summary of 21 U.S.C. § 360bbb-3(c) and FDA guidance. | GAO-21-207
Note: All criteria in this table must be met in order for a medical product to receive an EUA, in addition
to further statutory criteria set forth in 21 U.S.C. § 360bbb-3(c).
a
The “may be effective” standard for EUAs requires less certainty of effectiveness than is required to
approve drugs or license biologics.
b
A potential alternative product may be considered “unavailable” if there are insufficient supplies of
the approved alternative to fully meet the emergency need. A potential alternative product may be
considered “inadequate” if, for example, there are contraindicating data for special circumstances of
populations.
FDA may revise or revoke an EUA if the circumstances giving rise to the
emergency declaration no longer exist, the above criteria for issuance are
no longer met, or revocation is appropriate to protect public health or
safety. For example, an EUA may be revoked if new data become
17The FDA Commissioner may issue EUAs under delegated authority from the Secretary
of Health and Human Services. See 85 Fed. Reg. 7,316 (Feb. 7, 2020).
18The law also directs FDA to impose certain required conditions in an EUA as necessary
or appropriate to protect public health and allows the agency discretion to impose
additional conditions. See 21 U.S.C. § 360bbb-3(e). For example, with respect to the
emergency use of an unapproved product, FDA must establish appropriate conditions for
the monitoring and reporting of adverse events associated with the product and for
recordkeeping and reporting by the manufacturer.
Page 11 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
available indicating that the product is not effective or safe. In general,
unless it is revoked, an EUA will remain in effect for the duration of the
emergency declaration.
FDA issued guidance in January 2017 for industry and stakeholders
regarding FDA’s general recommendations and procedures applicable to
all EUAs. The guidance recommends that product sponsors submit any
available relevant scientific evidence regarding preclinical testing data
and evidence from human experience regarding product efficacy. 19 Given
the variety of medical products, the guidance states that the type and
amount of data needed to support an EUA may vary and does not specify
the minimum number or types of studies needed to meet the statutory
criteria to authorize a product. Instead, FDA states that it will assess the
sufficiency of the effectiveness data and the risk-benefit profile of each
candidate product on a case-by-case basis.
Operation Warp
Speed Partnership
Leads Federal Efforts
to Accelerate
Developing and
Manufacturing
COVID-19 Vaccines
and Therapeutics
19FDA recommends the EUA request include any available relevant scientific evidence
regarding the mechanism of action (i.e., how the medical product produces an effect in the
body); preclinical research, such as in vitro and animal toxicology data; data on activity or
effectiveness in animals that would contribute to understanding potential effects in
humans; data on human experience such as from published case reports, uncontrolled
trials, and controlled trials; and information to support dosing for the intended use. See
FDA, Emergency Use Authorization of Medical Products and Related Authorities:
Guidance for Industry and Other Stakeholders, January 2017.
Page 12 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Operation Warp Speed is As of October 15, 2020, Operation Warp Speed had publicly announced
Accelerating the financial support for the development and manufacturing of six vaccine
candidates for COVID-19. 20 In selecting vaccine candidates, Operation
Development and
Warp Speed officials said that they focused on candidates that had initial
Manufacturing of Six data on clinical safety and efficacy and the ability to enter late stage
Vaccines clinical trials by fall 2020, and the ability to rapidly scale up
manufacturing. 21 Through our reviews of federal procurement data and
clinical trial protocols, among other information, and interviews with
Operation Warp Speed officials and representatives from vaccine
developers and manufacturers, we have found the following about
Operation Warp Speed’s support of COVID-19 vaccine development.
The federal government has announced awards for six Operation
Warp Speed vaccine candidates. Through HHS and DOD, Operation
Warp Speed has announced contract awards with obligations totaling at
least $10 billion and a total potential estimated value of at least $18
billion. 22 Awarded contracts for the six vaccine candidates include at least
$2 billion obligated using Federal Acquisition Regulation-based contracts
and at least $8 billion obligated using other transaction authority, which
enables federal agencies to negotiate terms and conditions specific to a
project without requiring them to comply with certain federal regulations.
20The federal government has obligated funding for awards and/or modifications to each
company with a product considered an Operation Warp Speed COVID-19 vaccine
candidate for different types of activities. For example, for some vaccine candidates,
Operation Warp Speed has publicly announced support for both clinical development and
manufacturing activities; while for other candidates, it has only announced support for the
manufacturing or purchase of initial vaccine doses.
21According to a New England Journal of Medicine article co-authored by Operation Warp
Speed’s Chief Advisor (Dr. Moncef Slaoui) and its Director of Vaccines (Dr. Matthew
Hepburn), Operation Warp Speed prioritized candidates that 1) had robust preclinical data
or early-stage clinical trial data supporting their potential for clinical safety and efficacy; 2)
could enter phase 3 clinical trials during summer or fall 2020; and 3) were based on
vaccine-platform technologies permitting fast manufacturing and had developers with the
ability to produce more than 100 million doses by mid-2021. See M. Slaoui and M.
Hepburn. “Developing Safe and Effective COVID Vaccines — Operation Warp Speed’s
Strategy and Approach,” New England Journal of Medicine, Aug. 26, 2020. Our analysis
of acquisition documents associated with Operation Warp Speed vaccine candidates
remains ongoing, and the criteria that officials have outlined for selecting Operation Warp
Speed candidates may differ from the source selection criteria for specific acquisitions.
22The six vaccine candidates are considered to be part of Operation Warp Speed, but the
awards to the candidates were made by offices within HHS and DOD, including BARDA
and the Army Contracting Command on behalf of the Joint Program Executive Office for
Chemical, Biological, Radiological and Nuclear Defense, respectively. Total potential
estimated value is based on all contracts being definitized and options being exercised.
Page 13 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
In prior work, we have noted that other transactions can enable agencies
to attract companies that have not typically done business with the
government, in part through the ability to negotiate intellectual property
provisions that are tailored to each party’s needs. 23 We also have noted
challenges with the use of other transactions in terms of a risk of reduced
accountability and transparency, in part because such transactions are
exempt from the Federal Acquisition Regulation and related controls and
oversight mechanisms that apply to government procurement contracts.
Operation Warp Speed is supporting multiple vaccine candidates to
mitigate uncertainties associated with safety or efficacy, among
other factors. Regarding potential vaccines, Operation Warp Speed
officials said their intent was to select vaccine candidates that utilize
various technologies. Specifically, they said they identified four vaccine
platform technologies that would be most likely to yield a safe and
effective vaccine: the mRNA platform, the replication-defective live-vector
platform, the recombinant-subunit-adjuvanted protein platform, and the
attenuated replicating live-vector platform (see fig. 3). 24 According to
Operation Warp Speed officials, their strategy includes selecting different
platform technologies to mitigate the risk that any one platform or specific
vaccine could fail because of problems with safety, efficacy, industrial
manufacturability, or scheduling factors. As of October 2020, Operation
Warp Speed has publicly announced support for vaccine candidates
using three of the four vaccine platform technologies.
23GAO, Defense Acquisitions: DOD’s Use of Other Transactions for Prototype Projects
Has Increased, GAO-20-84 (Washington, D.C.: Nov. 22, 2019); and Federal Acquisitions:
Use of ‘Other Transaction’ Agreements Limited and Mostly for Research and
Development Activities, GAO-16-209 (Washington, D.C.: Jan. 7, 2016).
24When referring to vaccine platform technologies, we are referring to the underlying
technology used as the basis of the vaccine.
Page 14 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Figure 3: Overview of the Four Vaccine Platform Technologies Considered by Operation Warp Speed, as of October 2020
Notes: In parentheses next to the name of the company are details about the most advanced clinical
trial phase of that company’s COVID-19 vaccine candidate, according to the Biomedical Advanced
Research and Development Authority’s website, MedicalCountermeasures.gov as of October 15,
2020.
The federal government has obligated funding for awards and/or modifications to each company with
a product considered an Operation Warp Speed COVID-19 vaccine candidate for different types of
activities, such as clinical development, manufacturing, or purchase of initial vaccine doses.
SARS-CoV-2 is the virus that causes COVID-19.
Phase 1 clinical trials generally test the safety of a product with a small group of healthy volunteers
(usually less than 100). The goal of this phase is to determine the product’s most frequent side effects
and how it is metabolized and excreted.
Phase 2 clinical trials look at questions such as the maximum tolerated dose, the optimal schedule for
giving the product (how many doses and at what time intervals), and whether the immune system of a
person taking the vaccine is having the desired responses. These trials are conducted with a
medium-size population of volunteers (usually a few dozen to hundreds).
Phase 3 clinical trials look at things like whether the product prevents new infections or, if people
become infected, if the product helps control the infections so they do not become severe. These
Page 15 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
trials involve many thousands of volunteers, usually including participants who are at increased risk
for infection. According to FDA officials, these clinical trial phases may overlap.
Four vaccine candidates in phase 3 clinical trials follow typical
clinical trial design by enrolling mostly healthy non-pregnant adults.
Four of the six Operation Warp Speed supported vaccine candidates had
begun phase 3 clinical trials in the United States, as of October 2020. 25
The developers of these four vaccine candidates released their phase 3
clinical trial protocols to the public in September 2020. 26 These protocols
explain how the developers will test each vaccine in humans for safety
and effectiveness through the phase 3 trials. 27
Through our review of the four vaccine candidates’ protocols, we found
that they generally appeared to follow a typical clinical trial design by
enrolling mostly healthy non-pregnant adult populations and excluding
other groups such as children, pregnant women, and those with certain
comorbid or unstable conditions. 28 Excluding these groups in the initial
phase 3 trials is not unusual, but a potential consequence is that the data
on vaccine safety and effectiveness may not apply to these excluded
populations. Whether FDA will consider authorizing or licensing these
vaccine candidates for such excluded populations, including for people
with certain comorbid or unstable conditions, is currently unknown. How
and when testing for vaccine safety and efficacy would be conducted for
these groups also is presently unknown.
25On September 24, 2020, a fifth candidate, Novavax, announced that it had initiated
phase 3 trials in the United Kingdom (U.K.). On September 9, 2020, AstraZeneca paused
the phase 3 trial for its COVID-19 vaccine after a trial participant in the U.K. experienced
an unexplained illness in the phase 3 trial. As of October 23 2020, AstraZeneca’s trials
have resumed, including in the United States. On October 12, 2020, Janssen announced
that it paused the phase 3 trial for its COVID-19 vaccine after a trial participant
experienced an unexplained illness, but on October 23, 2020 Janssen announced that
preparations were underway to resume the trial.
26We reviewed the clinical trial protocols that AstraZeneca, Janssen, Moderna, and Pfizer
released in September 2020.
27On November 9, 2020, Pfizer publicly announced findings from its first interim efficacy
analysis from phase 3 clinical trials of its COVID-19 vaccine candidate and stated plans to
share additional data on safety and efficacy for this candidate in the coming weeks.
28Three of the four companies set a minimum enrollment age of 18 years for their phase 3
clinical trials, while one company (Pfizer) planned to enroll people as young as 16 years
old. In October 2020, Pfizer announced on its website that it received permission from
FDA to enroll children as young as 12 years old.
Page 16 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
We also found that the four candidates’ clinical trial protocols provide
limited details on how the vaccine developers will analyze their safety and
efficacy data, specifically for population subgroups (e.g., the elderly,
people with comorbidities, or racial/ethnic groups) or sample sizes
needed for such subgroup analyses. Unless vaccine developers collect
sufficient data for a subgroup analysis, it may not be possible to identify
the potential for different safety or efficacy results for one or more
subgroups, even if vaccine candidates are found safe and effective in the
aggregate for the general population. The protocols reference separate
analysis plan documents that may contain more information on their
methodologies and planned analyses. We intend to request and review
these plans in future work.
Operation Warp Speed documents emphasize the importance of ensuring
that participation in clinical trials for COVID-19 vaccines includes those
disproportionately affected by COVID-19, such as people in racial and
ethnic minority groups. Moreover, FDA’s June 2020 guidance on the
development and licensure of COVID-19 vaccines encourages the
inclusion of diverse populations in all phases of vaccine clinical
development. 29 In this guidance, FDA strongly encourages the enrollment
of populations most affected by COVID-19, specifically citing racial and
ethnic minorities. Several stakeholders we interviewed noted that, at a
minimum, clinical trials for COVID-19 vaccines should include the same
percentage of persons from racial and ethnic minority groups as the
overall population, particularly in light of the disparities found in indicators
of COVID-19, including testing, cases, hospitalizations, and deaths. 30
Efforts to Develop COVID- To support the development of therapeutics for COVID-19, Operation
19 Therapeutics through Warp Speed is using criteria similar to those used to select candidate
vaccines. In particular, it is focusing its funding support on candidate
Operation Warp Speed
therapeutics that are (1) advanced enough to enter clinical trials in the
Also Underway short term (i.e., by early fall 2020), (2) have the potential for FDA
authorization or approval by the end of 2020, and (3) are able to be
29FDA, Development and Licensure of Vaccines to Prevent COVID-19: Guidance for
Industry, June 2020.
30See GAO-20-701, 186; and the Department of Health and Human Services, Centers for
Disease Control and Prevention, Report to Congress on Paycheck Protection Program
and Health Care Enhancement Act Disaggregated Data on U.S. Coronavirus Disease
2019 (COVID-19) Testing, 5th 30-Day Update & COVID-19 Diagnosis, Hospitalizations,
and Deaths (October 2020).
Page 17 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
rapidly manufactured at scale, according to a journal article written by
Operation Warp Speed officials. 31
For example, in July 2020, Operation Warp Speed announced a DOD
award of $450 million to support the large-scale manufacturing of
Regeneron’s monoclonal antibody treatment. In October 2020, it also
announced an agreement with Eli Lilly and Company for the federal
government to purchase initial doses of the company’s antibody
therapeutic treatment subject to FDA authorization or licensure of the
treatment. 32 According to Operation Warp Speed officials, they are also
evaluating whether to support clinical trials that would repurpose certain
existing antiviral drugs for the treatment of COVID-19. Further, Operation
Warp Speed is supporting clinical trials of various anticoagulation
regimens for the treatment of patients with COVID-19 in various clinical
settings, according to officials. 33
Operation Warp Speed’s There is the potential for challenges to arise in the scaled up production
Efforts to Scale Up of COVID-19 vaccines and therapeutics through Operation Warp Speed.
Such challenges include:
Production May Face
Challenges • Limited manufacturing capacity. Before the COVID-19 pandemic,
most existing vaccine manufacturing capacity was already in use,
according to experts we interviewed. Therefore, new capacity has had
31M. Slaoui, S.E. Green and J. Woodcock. “Bridging the Gap at Warp Speed — Delivering
Options for Preventing and Treating Covid-19,” New England Journal of Medicine, Sept.
15, 2020. In this article, officials explained that the short time frame means that in certain
cases, Operation Warp Speed is focusing on drugs that are already approved by FDA or
in human trials for other indications because these drugs can be rapidly evaluated for use
for COVID-19 and further developed if clinical activity is detected. Our analysis of
acquisition documents associated with Operation Warp Speed candidate therapeutics
remains ongoing, and the criteria that officials have outlined for selecting Operation Warp
Speed candidates may differ from the source selection criteria for specific acquisitions.
32Monoclonal antibodies are laboratory-made antibodies that may be able to serve as
another prevention option until a vaccine becomes available. They usually only last for a
few months, thus potentially requiring people to get multiple infusions or injections on a
regular schedule for them to remain effective. Regeneron and Eli Lilly submitted EUA
requests for their monoclonal antibody treatments in early October 2020. On November 9,
2020, FDA issued an EUA for Eli Lilly’s treatment (bamlanivimab).
33NIH announced these clinical trials on September 10, 2020. According to the NIH press
release, these trials will evaluate the safety and effectiveness of varying types of blood
thinners (i.e., anti-coagulants) in treating adults diagnosed with COVID-19 by preventing
or reducing the formation of blood clots. These trials, which are being conducted with
inpatients and outpatients and will be conducted with patients discharged from the hospital
are also part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines
initiative.
Page 18 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
to be created, or production shifted from other products. Additionally,
once bulk quantities of vaccines or therapeutics are produced, they
must be sealed into sterile containers, such as vials or syringes, in a
process known as fill-finish manufacturing. Experts from three
pharmaceutical industry groups we interviewed said there is a
shortage of facilities with capacity to handle fill-finish manufacturing,
which could lead to production bottlenecks.
• Disruptions to manufacturing supply chains. Vaccine
manufacturing supply chains may be strained by disruptions caused
by the global pandemic, including changes in the labor market,
increases or decreases in the demand for certain goods, or as one
DOD official noted, export restrictions implemented by some
countries. For example, officials at one COVID-19 vaccine
manufacturing facility told us that they have experienced challenges
obtaining materials, including disposable reactor bags, reagents, and
certain chemicals. They also said that due to global demand, they
sometimes must wait 4-12 weeks for items that before the pandemic
were typically available for shipment within one week. One expert we
interviewed also told us that the supply of the materials used in fill-
finish manufacturing, such as glass vials and pre-filled syringes, is
limited.
• Difficult technology transfer processes. According to literature we
reviewed, scaling up manufacturing requires transferring knowledge of
how to produce COVID-19 vaccines and therapeutics across multiple
manufacturing sites, often involving the use of subcontractors. This
knowledge transfer is a complex process, and one expert we
interviewed told us that it is especially difficult for new technologies
such as RNA vaccines, where there is little experience in scaling up
production—going from making a small amount of vaccine in a
laboratory setting to commercial scale production of hundreds of
millions of vaccine doses. Additionally, there has been at least one
instance in which the technology transfer process for a COVID-19
vaccine has been hampered by disagreements over ownership of
intellectual property rights related to manufacturing technology.
• Gaps in available workforce. The ability to hire and train personnel
with the specialized skills needed to run vaccine manufacturing
processes may be a challenge for even experienced manufacturers.
For example, we heard from representatives at a COVID-19 vaccine
manufacturing facility that filling open positions for mid- to upper
management positions had been a challenge. These positions are
significant because manufacturing managers function as the technical
points of contact for production questions and are responsible for
Page 19 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
managing safety, quality, and compliance with current good
manufacturing practices.
Through Operation Warp Speed, federal agencies and vaccine
manufacturers said they are working together to mitigate these
challenges. For example:
• Operation Warp Speed has announced HHS and DOD awards to
enhance domestic manufacturing capacity, including fill-finish
manufacturing.
• Representatives from a COVID-19 vaccine manufacturing facility told
us that they are in frequent communication with officials from
Operation Warp Speed to coordinate and that DOD is assisting them
with expediting procurement and delivery of critical manufacturing
equipment.
• Officials from BARDA said that agency subject matter experts worked
with each of the six Operation Warp Speed vaccine developers to
create a list of critical supply needs that are common across the
vaccine candidates. BARDA has been working with suppliers to
increase production capacity for the materials identified as critical
needs, according to officials.
We will continue to examine the federal government’s efforts to develop
and manufacture COVID-19 vaccines and therapeutics, including
Operation Warp Speed’s activities and any further actions it may take to
mitigate potential challenges.
EUAs are an important tool for quickly making vaccines and therapeutics
FDA Clarified available in time of emergency, when speed and flexibility are needed.
Expected Evidence For COVID-19 vaccines, FDA issued guidance in October 2020 to provide
vaccine sponsors with recommendations regarding the evidence—that is,
for COVID-19 Vaccine data and information—needed to support issuance of an EUA. For
EUAs, but the therapeutics, FDA has issued four EUAs as of November 9, 2020.
However, the evidence to support FDA’s COVID-19 therapeutic EUA
Evidence to Support decisions has not always been transparent, because the agency has not
Its COVID-19 uniformly disclosed information from its scientific review of the safety and
effectiveness data at the time of each authorization. Further, EUAs can
Therapeutic EUA be beneficial in bringing vaccines and therapeutics quickly to market
Decisions Is Not during an emergency, but there can be some unintended consequences
to consider.
Always Transparent
Page 20 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
New Guidance for COVID- In October 2020, FDA issued additional EUA guidance specific to COVID-
19 Vaccine EUAs 19 vaccines that recommends minimum evidence for vaccine sponsors to
submit with EUA requests for vaccines to FDA. 34 FDA has indicated
Recommends Minimum
through guidance that vaccine sponsors will likely submit requests for
Data and Information for EUAs, once clinical data are ready, as a means to get any vaccine to
Vaccine Sponsors to market more quickly. Specifically, FDA’s October guidance includes
Submit with EUA recommendations regarding the manufacturing, safety, and effectiveness
Requests data and information needed to support the issuance of an EUA for a
COVID-19 vaccine.
According to an FDA official, the risk-benefit analysis that it must conduct
before issuing an EUA should be based on certain, minimum evidence, in
part because any COVID-19 vaccine will be administered to healthy
individuals, raising the standard for what it considers allowable risk. The
October 2020 guidance states that FDA does not expect to be able to
issue an EUA without certain data from phase 3 clinical trials. 35 It also
reiterates that any vaccine candidate should follow the recommendations
set forth in COVID-19 vaccine guidance that the agency published in
June 2020, including that any vaccine should reduce the risk of infection
or of serious illness by at least 50 percent over a placebo group. 36
The October 2020 EUA guidance also states that, prior to authorization,
FDA expects developers to have a median follow-up duration of at least 2
months after completion of the full vaccine regimen, to help provide
adequate information to assess the vaccine candidate’s risk-benefit
profile. This is in contrast to the 6 months of safety data usually submitted
for FDA licensure of a vaccine, according to an FDA official. An FDA
official said the agency is working with CDC and vaccine sponsors to
create plans to collect safety information from any individuals who receive
a vaccine under an EUA so that they can continue to monitor these data.
34FDA, Emergency Use Authorization for Vaccines to Prevent COVID-19: Guidance for
Industry, October 2020.
35On November 9, 2020, Pfizer announced that its first interim efficacy analysis from
phase 3 clinical trials of its COVID-19 vaccine candidate had found that the vaccine was
more than 90 percent effective in preventing COVID-19 in participants who did not have
evidence of a prior infection. Pfizer announced that it plans to submit an EUA request for
this vaccine candidate in late November 2020.
36FDA, Development and Licensure of Vaccines to Prevent COVID-19: Guidance for
Industry, June 2020. The June 2020 guidance applies to any vaccine candidate submitted
to FDA, whether for an EUA or licensure, according to officials.
Page 21 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
The October EUA guidance also states that any EUA request for COVID-
19 vaccine should include a plan for active follow-up for safety.
FDA’s Support for Its FDA has issued four EUAs for COVID-19 therapeutics as of November 9,
COVID-19 Therapeutic 2020, but the evidence to support these authorization decisions has not
always been transparent. Since March 24, 2020, when the Secretary of
EUA Decisions Is Not
Health and Human Services declared that circumstances existed
Always Transparent justifying emergency use of drugs and biologics during the COVID-19
pandemic, FDA has issued four EUAs for therapeutics: 37
• one for a new use for two existing drugs—chloroquine and
hydroxychloroquine—on March 28, 2020, 38
• one for a new drug—remdesivir—on May 1, 2020,
• one for a new biologic—COVID-19 convalescent plasma—on August
23, 2020, 39 and
• one for another new biologic—bamlanivimab, a monoclonal
antibody—on November 9, 2020.
After reviewing additional scientific evidence, about 2.5 months after its
authorization (on June 15, 2020), FDA revoked the EUA for chloroquine
and hydroxychloroquine. FDA’s revocation letter states that based on
continued review of scientific evidence including a randomized controlled
trial and adverse event reporting (including adverse cardiac events), it
determined the drugs were unlikely to be effective in treating COVID-19
and that the known and potential benefits no longer outweighed the
known and potential risks for the authorized use.
37See 85 Fed. Reg. 18,250 (Apr. 1, 2020). FDA also issued three EUAs for drugs and
blood products that we do not consider therapeutics for the purpose of this report because
they support other existing treatments—one drug for maintaining sedation and two fluids
for continuous renal replacement therapy. These other products are 1) REGIOCIT
replacement solution, 2) Fresenius Kabi Propoven 2%, and 3) Fresenius Medical,
multiFiltrate PRO System and multiBic/multiPlus Solutions. Our review focused on the four
EUAs FDA issued for drugs or biologics to treat COVID-19—hydroxychloroquine and
chloroquine, remdesivir, COVID-19 convalescent plasma, and bamlanivimab.
38The EUA was for oral formulations of chloroquine phosphate and hydroxychloroquine
sulfate to treat adults and certain adolescents who are hospitalized with COVID-19 when
participation in a clinical trial is not available or feasible. We refer to these products as
chloroquine and hydroxychloroquine in this report. These products are approved for other
uses, such as to treat lupus.
39Plasma is the liquid portion of blood that contains antibodies.
Page 22 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Additionally, FDA revised the EUA for remdesivir to broaden the scope of
its authorized uses about 4 months after initial authorization (on August
28, 2020). 40 Then, on October 22, 2020, FDA approved remdesivir,
through the new drug approval process, to treat COVID-19 in adult and
pediatric patients (12 years of age and older weighing at least 40 kg)
requiring hospitalization. On the same day, the agency revised the EUA
for remdesivir for use to treat COVID-19 in hospitalized pediatric patients
less than 12 years of age weighing at least 3.5 kg.
As of November 9, 2020, three therapeutics—remdesivir, COVID-19
convalescent plasma, and bamlanivimab—remain authorized for
emergency use for COVID-19, of the four FDA has authorized to date.
See figure 4 for a timeline of EUAs for COVID-19 therapeutics.
40FDA first authorized the use of remdesivir on May 1, 2020, to treat hospitalized adult
and pediatric patients with severe COVID-19 disease, defined as patients with low blood
oxygen levels or needing oxygen therapy or more intensive breathing support such as a
mechanical ventilator.
Page 23 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Figure 4: Timeline of Emergency Use Authorizations for COVID-19 Therapeutics, as of November 9, 2020
Page 24 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Although FDA’s COVID-19 therapeutic EUA decisions are articulated
through authorization letters and other publicly available supporting
documents, the evidence to support FDA’s authorization decisions has
not always been transparent. This is because FDA has not uniformly
disclosed to the public information from its scientific review of each
therapeutic’s safety and effectiveness data, at the time of its
authorization. For example:
• For all four EUAs it has authorized so far, FDA released fact sheets
for health care providers, but they contained different levels of
information. For example, the fact sheets for chloroquine and
hydroxychloroquine and COVID-19 convalescent plasma were silent
on the evidence supporting the EUA, whereas the fact sheets for
remdesivir and bamlanivimab included a section entitled, “Clinical
Trial Results and Supporting Data for EUA,” with detailed information
on the studies, including subjects enrolled, dosing used, and end point
results.
• FDA released a clinical decision memo in August 2020 along with the
COVID-19 convalescent plasma authorization letter, summarizing the
literature it reviewed to inform its decision that the product may be
effective to treat hospitalized patients with COVID-19. Specifically, the
convalescent plasma decision memo contained a detailed summary of
the preclinical and clinical studies reviewed in support of the EUA,
including subjects enrolled and other information, as well as FDA’s
summary of the evidence of effectiveness and risk-benefit analysis. In
contrast, FDA did not release decision memos with the chloroquine
and hydroxychloroquine, remdesivir, or bamlanivimab authorization
letters. 41
• It was not until the chloroquine and hydroxychloroquine EUA
revocation letter was publicly released on June 15, 2020, that further
details on the evidence used to support the March 28, 2020, EUA
were published; these details were in a memo attached to the
revocation letter.
41FDA released a number of additional documents for chloroquine and
hydroxychloroquine and remdesivir under the Freedom of Information Act, which requires
federal agencies to provide the public access to certain government records and
information. See 5 U.S.C. § 552. About 3 months after its initial authorization of remdesivir
and 3 months after authorization of chloroquine and hydroxychloroquine, the agency
disclosed review summaries containing information about its review of the products,
including detailed information about the preclinical and clinical data reviewed to support
efficacy and safety.
Page 25 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Moreover, there has been considerable variation in the type and amount
of data and information FDA cited in its authorization letters and available
supporting documentation, compounding the lack of transparency
surrounding the evidence supporting FDA’s EUA decisions. For example,
stakeholders, including three of nine provider associations, a public health
association, and an infectious disease expert we interviewed about EUAs,
as well as several former FDA officials, have expressed concern
regarding the threshold of evidence FDA cited for authorization of some
COVID-19 therapeutics. 42 FDA officials noted that the statute requires
FDA to consider the totality of information available in its EUA reviews,
and the evidence for each product can vary. The following are examples
of variation in evidence:
• The evidence cited to support the EUAs for both remdesivir and
bamlanivimab included randomized, placebo-controlled clinical trials—
considered the gold standard for determining effectiveness—while the
evidence cited to support the EUA for chloroquine and
hydroxychloroquine included no clinical trial data.
• FDA initially authorized remdesivir to treat a limited hospitalized group
though it cited more data and information about the drug’s safety and
effectiveness in treating COVID-19 than for other therapeutic EUAs.
By comparison, it authorized chloroquine and hydroxychloroquine to
treat any hospitalized patient with confirmed COVID-19 when
participation in a clinical trial was not available or feasible and it
authorized COVID-19 convalescent plasma for treating any
hospitalized patient.
It is understandable that FDA might expect different types of data and
information to support issuance of EUAs for different products. For
example, FDA could expect different data for an EUA for a drug that has
not previously been approved for any use than it could for a drug that is
already on the market, but has been approved for other uses. However,
absent communication about FDA’s review of evidence, the basis upon
which it has issued EUAs is not transparent. See figure 5 for the evidence
cited by FDA as the basis for its EUA decisions.
42See Congressional Research Service, The U.S. Blood Supply and the COVID-19
Response: In Brief (August 2020) and Congressional Research Service, Treatment of
COVID-19: Hydroxychloroquine and Chloroquine (May 2020).
Page 26 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Figure 5: Data Cited to Support Issuance of Emergency Use Authorizations (EUA) for Therapeutics for COVID-19, as of
November 9, 2020
Notes:
We reviewed supporting documentation made publicly available by FDA, including authorization
letters, revocation letters, fact sheets for providers, and decision memos.
a
Prior to receiving an EUA for COVID-19 treatment, the product was approved for uses unrelated to
COVID-19.
b
The National Institutes of Health considers the “gold standard” for testing interventions in humans to
be randomized, placebo-controlled clinical trials—meaning volunteers are randomly assigned either
to a test group receiving the experimental intervention or to a control group receiving a placebo or
standard care. Human testing can also involve clinical trials that do not adhere to all of these
practices; for example, not using a placebo. Preclinical studies are conducted to test products in
animals and in the laboratory.
c
FDA subsequently revoked the EUA for chloroquine and hydroxychloroquine. Based on continued
review of scientific evidence including a randomized controlled trial and adverse event reporting
(including adverse cardiac events), FDA determined that chloroquine phosphate and
hydroxychloroquine sulfate were unlikely to be effective in treating COVID-19 and that the known and
potential benefits no longer outweighed the known and potential risks for the authorized use. Clinical
trial data were referenced in the revocation letter, but not the initial EUA authorization letter, which
stated that the clinical data were anecdotal.
d
FDA first authorized the use of remdesivir on May 1, 2020, to treat hospitalized adult and pediatric
patients with severe COVID-19, defined as patients with low blood oxygen levels or needing oxygen
therapy or more intensive breathing support such as a mechanical ventilator. The data reported in the
table reference data cited in FDA’s initial May 1 authorization letter, including a randomized, placebo-
controlled clinical trial. On August 28, 2020, FDA revised the EUA for remdesivir to broaden the
scope of its authorized uses to treat all hospitalized COVID-19 patients based on review of an
additional randomly controlled trial without placebo. On October 22, 2020, FDA approved remdesivir,
through the new drug approval process, to treat COVID-19 in adult and pediatric patients (12 years of
Page 27 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
age and older weighing at least 40 kg) requiring hospitalization. On the same day, the agency revised
the EUA for remdesivir for use to treat COVID-19 in hospitalized pediatric patients less than 12 years
of age and weighing at least 3.5 kg.
e
We refer to “limited studies” to include instances of FDA characterizing the studies as limited, studies
in which the data were anecdotal only, or studies that were still ongoing at the time of authorization.
f
According to the FDA authorization letter for COVID-19 convalescent plasma, the EUA was issued
based on review of historical evidence using convalescent plasma in prior outbreaks of respiratory
viruses, certain preclinical evidence, results from small clinical trials of convalescent plasma
conducted during the current outbreak, and data obtained from the ongoing National Convalescent
Plasma Expanded Access Protocol, but without the presence of data from prospective, well-controlled
randomized clinical trials.
g
According to the authorization letter, the EUA was issued based on review of the topline data from
the planned interim analysis of an ongoing randomized, double-blinded, placebo-controlled, phase 2
dose finding trial of bamlanivimab in outpatients with mild to moderate COVID-19. The provider fact
sheet provided additional detail on the findings from this study. There are additional clinical trials for
bamlanivimab, at least one of which was for a different indication to treat hospitalized patients, but
these studies were not explicitly cited by FDA as support for the EUA.
Because the type and amount of data needed to support authorization of
a therapeutic can vary, it is especially important for FDA to uniformly
disclose the evidence supporting its EUA decisions. Doing so would
enhance transparency and be consistent with federal internal control
standards for information and communication. These standards specify
that agencies should obtain quality data from reliable sources and
communicate quality information to external stakeholders, including the
public, to achieve objectives, such as maintaining the public’s trust in
agency decision-making. 43 Further, it would be consistent with our past
work, as well as with the PanCAP—the general operative plan for the
federal response to COVID-19—which both highlight the importance of
clear communication during a crisis. 44 In addition, the FDA Commissioner
has cited the paramount importance of ensuring public trust in FDA during
this crisis.
43According to federal internal control standards for information and communication,
management should use quality information to achieve the entity’s objectives and
externally communicate the necessary quality information to achieve the entity’s
objectives. GAO-14-704G.
44See, for example, our June 2020 report on the federal government’s response to the
pandemic, which states that in the midst of a nationwide emergency, clear and consistent
communication—among all levels of government, with health care providers, and to the
public—is key. GAO, COVID-19: Opportunities to Improve Federal Response and
Recovery Efforts, GAO-20-625 (Washington, D.C.: June 25, 2020). The PanCAP also
stresses the importance of clear, concise, accurate, and accessible critical public health
messages. See Department of Health and Human Services, U.S. Government COVID-19
Response Plan (Mar. 13, 2020).
Page 28 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
FDA officials we spoke with agreed that improved transparency is
important. These officials stated that the agency has tried to improve
transparency about their EUA decisions by publicly issuing a decision
memo with each authorization, as they did with the COVID-19
convalescent plasma authorization. However, FDA officials told us that
the agency may not be able to uniformly disclose the same information
from its scientific review of the safety and effectiveness data for each
COVID-19 therapeutic EUA because of federal laws protecting certain
information from public disclosure without the sponsor’s consent—such
as confidential commercial information and trade secrets. 45 Officials noted
that for new drugs and biologics, the agency publishes drug approval
packages. These packages include summary review memos that contain
detailed information about the preclinical and clinical data reviewed to
support effectiveness and safety for each product, including clinical
statistical efficacy trials as well as conclusions about those trials. 46
Officials indicated that consistently publishing this information for EUA
decisions would be beneficial.
We understand FDA’s reported constraints. However, in light of the
gravity of the pandemic and the need for a high degree of public
confidence in FDA’s decisions, the agency should identify ways to
uniformly disclose the information from its scientific review of safety and
effectiveness data when issuing EUAs for therapeutics and vaccines,
and, if necessary, seek the authority to publicly disclose such information.
This could be achieved, for example, by seeking authority to more
uniformly disclose information from its clinical review memorandum
supporting the issuance of an EUA for a therapeutic or vaccine product,
similar to the summary of safety and effectiveness data that FDA
discloses from approval packages for new drugs and biologics. Improving
the transparency of its therapeutic decisions could, in turn, bolster public
trust in those decisions.
45See 21 U.S.C. § 360bbb-3(h)(2) (referring to 18 U.S.C. § 1905 and 5 U.S.C. §
552(b)(4)).
46FDA is required to publish the approval package for new drugs and biologics on FDA’s
website. Among other things, each package is to include a summary review that
documents conclusions from all reviewing disciplines about the approved product, noting
any critical issues and disagreements with the applicant and within the review team and
how they were resolved, recommendations for action, and an explanation of any
nonconcurrence with review conclusions. 21 U.S.C. § 355(l). FDA officials noted that the
documents in these packages may also be redacted for certain information such as trade
secrets.
Page 29 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
EUAs Can Result in While EUAs can be beneficial in bringing medical products quickly to
Unintended market during an emergency, there can be some unintended
consequences, according to FDA officials and stakeholder groups we
Consequences
interviewed.
Potential decrease in clinical trial participation. A therapeutic or
vaccine made widely available to the public under an EUA can affect the
ability of product sponsors to enroll participants in clinical trials and may
even incentivize clinical trial participants to withdraw from the trial,
according to an FDA official and two stakeholder groups we interviewed.
Three stakeholder groups told us the public seems to interpret an EUA for
a COVID-19 therapeutic to be the “standard of care” recommended for
treatment, even though that is not the intent of an EUA. Such
interpretations may decrease public willingness to enroll in clinical trials
for other therapeutics that may have more efficacy potential, according to
one of the stakeholder groups. For example, the EUA for COVID-19
convalescent plasma has generated concern about the ability to stand up
clinical trials for potentially more promising, specific therapies, such as
monoclonal antibodies, according to one of the stakeholder groups.
FDA officials have stated that this unintended consequence is especially
important to consider for vaccines, since the first authorized or licensed
vaccine may not be as effective as candidates still in development, for
example. FDA’s October 2020 EUA guidance specifies that FDA expects
a vaccine sponsor to continue to collect placebo-controlled data to work
toward submission of a biologics license application. Specifically, the
guidance states that an EUA request for COVID-19 vaccine should
include strategies that will be implemented to ensure that ongoing clinical
trials of the vaccine are able to assess long-term safety and efficacy in
sufficient numbers of subjects to support vaccine licensure through a
biologics license application. Further, the Director of the Office of
Vaccines Research and Review at FDA’s Center for Biologics Evaluation
and Research stated that FDA is actively holding internal discussions
about ways to address this trial participation challenge. According to this
official, when an EUA is first issued, the vaccine may not be widely
deployable so phase 3 clinical trials may be able to continue with
participants receiving vaccine or a placebo.
Vaccine hesitancy. FDA officials and stakeholder groups have noted
that, if there is public concern that an EUA will be issued for a vaccine
with less certainty of effectiveness than is required to license a vaccine, it
may result in the public being hesitant about getting the vaccine, affecting
vaccine uptake. FDA’s October 2020 EUA guidance is one effort to
Page 30 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
combat this risk and help the public feel confident about an EUA decision.
Further, FDA officials have stated, and the agency’s October EUA
guidance reiterates, that any vaccine under consideration for an EUA will
go to a public meeting of its Vaccines and Related Biological Products
Advisory Committee. The public will be able to view the briefing package,
the committee discussion and deliberations, and FDA’s recommendation,
according to FDA officials. 47
Drug shortages. An EUA for additional uses of existing therapeutics can
increase demand for a drug, which can in turn create shortages of that
drug. Such shortages occurred when hydroxychloroquine and chloroquine
were authorized for emergency use for COVID-19. Several versions of
hydroxychloroquine and chloroquine are approved by FDA for other uses,
such as prophylaxis and treatment of malaria. After the EUA for
chloroquine and hydroxychloroquine was issued in March 2020, FDA
reported shortages of these drugs, limiting their availability for individuals
who use the drugs for these approved conditions.
In September 2020, we recommended that the Secretary of Health and
Stakeholders Indicate Human Services with support from the Secretary of Defense, establish a
Initial Planning time frame for documenting and sharing a national plan for distributing
and administering COVID-19 vaccine; ensure that such a plan is
Documents Are consistent with best practices for project planning and scheduling; and
Helpful, but Seek that it outlines an approach for how efforts would be coordinated across
federal agencies and nonfederal entities. As discussed below, HHS and
Additional Information DOD have released initial planning documents for the distribution and
on Federal Plans for administration of potential COVID-19 vaccines. Stakeholders we
interviewed said these documents were helpful, but would like to see
Vaccine Distribution additional information as planning for vaccine distribution continues. We
will continue to examine the federal government’s vaccine distribution
planning efforts in future work.
47According to FDA officials, the Vaccines and Related Biological Products Advisory
Committee will make a recommendation to FDA and FDA will consider that
recommendation in deciding whether to issue an EUA.
Page 31 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Federal Government HHS with support from DOD has begun to develop plans for how any
Released Interim Planning authorized or licensed COVID-19 vaccine will be distributed, including
which groups may have priority and how it might be allocated and
Documents for the
administered. On September 16, 2020, HHS and DOD released two
Distribution of Potential documents—CDC’s COVID-19 Vaccination Program Interim Playbook for
COVID-19 Vaccines and Jurisdiction Operations and HHS’s and DOD’s From the Factory to the
Plans to Identify Priority Frontlines: The Operation Warp Speed Strategy for Distributing a COVID-
Groups for Initial Allocation 19 Vaccine—outlining a strategy for the distribution and administration of
any COVID-19 vaccine. 48 HHS and DOD subsequently released an
updated version of CDC’s COVID-19 Vaccination Program Interim
Playbook for Jurisdiction Operations on October 29, 2020. 49
CDC’s COVID-19 Vaccination Program Interim Playbook for Jurisdiction
Operations is intended to assist state, territorial, and local public health
programs and their partners plan and operationalize local vaccination
response to COVID-19. 50 The interim playbook notes that it is not yet
known which vaccines may be available, in what volumes, at what time,
with what efficacy, and with what storage and handling requirements, all
of which could impact the distribution and administration of a vaccine.
CDC stated that it intends to update its interim playbook over time as
more information about any COVID-19 vaccines becomes available. 51
The September release of the interim playbook set a deadline of October
16, 2020, for 64 jurisdictions to submit interim COVID-19 vaccination
48Department of Health and Human Services, Centers for Disease Control and
Prevention, COVID-19 Vaccination Program Interim Playbook for Jurisdiction Operations
(Washington, D.C.: Sept. 16, 2020) and Department of Defense and Department of Health
and Human Services, From the Factory to the Frontlines: The Operation Warp Speed
Strategy for Distributing a COVID-19 Vaccine (Washington, D.C.: Sept. 16, 2020).
49Department of Health and Human Services, Centers for Disease Control and
Prevention, COVID-19 Vaccination Program Interim Playbook for Jurisdiction Operations,
version 2.0 (Washington, D.C.: Oct. 29, 2020).
50According to the interim playbook, jurisdictions may include state, local, territorial, and
tribal governments. The interim playbook notes that CDC is working directly with the
Indian Health Service at the federal level.
51The October 29, 2020, updated interim playbook provides new details on distribution,
storage, and handling of any COVID-19 vaccine, such as which federal entities CDC will
coordinate with in allocating available vaccine and updated hypothetical vaccination
scenarios for planning purposes. Such scenarios contain more details on potential vaccine
storage and handling requirements.
Page 32 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
plans that address requirements outlined in the playbook. 52 All 64
jurisdictions submitted their interim COVID-19 vaccination plans to CDC,
according to the updated interim playbook released in late October. CDC
provided feedback to the jurisdictions on their plans in late October, and
posted executive summaries of each jurisdiction’s interim plan on the
CDC website. 53
CDC’s Advisory Committee on Immunization Practices established a
COVID-19 vaccine work group to consider options for priority groups for
vaccination. 54 This work group intends to collect, analyze, and prepare
information related to COVID-19 vaccines for presentation, discussion,
deliberation, and vote by the advisory committee. 55 According to CDC, the
advisory committee, including its COVID-19 vaccine work group, will
review evidence on COVID-19 epidemiology and burden, vaccine safety,
vaccine efficacy, evidence quality, and implementation issues to inform
recommendations for COVID-19 vaccine policy, including priority groups
for vaccination. The Advisory Committee on Immunization Practices met
at the end of October 2020 and discussed an ethical framework for early
COVID-19 vaccine allocation, among other things. The advisory
52The 64 jurisdictions include the 50 states, the District of Columbia, American Samoa,
Guam, Republic of the Marshall Islands, Federated States of Micronesia, Commonwealth
of the Northern Mariana Islands, Republic of Palau, Puerto Rico, the U.S. Virgin Islands,
Chicago, Houston, New York City, Philadelphia, and San Antonio. These jurisdictions are
CDC Immunization and Vaccines for Children Cooperative Agreement funding recipients.
53See Department of Health and Human Services, Centers for Disease Control and
Prevention, COVID-19 Vaccination Program Operational Guidance: The COVID-19
Vaccination Program Interim Operational Guidance for Jurisdictions Playbook,
https://www.cdc.gov/vaccines/covid-19/covid-19-vaccination-guidance.html for the posted
executive summaries, updated as of Nov. 5, 2020.
54The Advisory Committee on Immunization Practices is comprised of medical and public
health experts who make recommendations on the use of vaccines in the civilian
population of the United States. Its recommendations serve as public health guidance for
safe use of vaccines and other related products. Advisory Committee on Immunization
Practices work groups are subgroups of the larger advisory committee that review relevant
information and develop recommendations for presentation to the advisory committee.
55According to CDC, the COVID-19 vaccine work group has 41 members, including
advisory committee voting members, liaisons, ex-officios, and consultants with expertise in
epidemiology, vaccine safety, vaccinology, immunology, general medicine, geriatrics,
pediatrics, obstetrics and gynecology, immunocompromised hosts, vaccine administration
and delivery, public health and surveillance, ethics, health equity, communications, and
emergency preparedness.
Page 33 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
committee has not made recommendations on priority groups for any
COVID-19 vaccine, as of November 10, 2020.
Vaccine prioritization policies are formulated by recommendations from
the advisory committee and approved by the CDC Director. The Director’s
recommendations are then shared with the Secretary of Health and
Human Services, according to CDC officials. The officials said the
recommendations will also be provided to the National Security Council
for interagency staffing for executive decision-making, and Operation
Warp Speed is to distribute available vaccine in accordance with these
recommendations and decisions.
In addition, CDC and NIH sponsored an expert committee that the
National Academies of Sciences, Engineering, and Medicine convened to
make recommendations about the allocation of any COVID-19 vaccine.
On October 2, 2020, the expert committee issued its final report,
Framework for Equitable Allocation of a COVID-19 Vaccine. 56 In the
report, the committee recommended that any vaccine for COVID-19 be
allocated under a phased approach. The first phase would prioritize
health care personnel and first responders, people at significantly higher
risk for severe illness based on comorbid or underlying conditions, and
older adults living in congregate settings. The committee noted that its
report can inform the recommendations of CDC’s Advisory Committee on
Immunization Practices and also includes additional recommendations for
HHS, such as to create and appropriately fund a COVID-19 vaccination
risk communication and community engagement program to support
state, tribal, local and territorial authorities in its engaging with
community-based organizations and communicating about any COVID-19
vaccine.
56See National Academies of Sciences, Engineering, and Medicine 2020. Framework for
Equitable Allocation of COVID-19 Vaccine. Washington, DC: The National Academies
Press. https://doi.org/10.17226/25917 (accessed Oct. 13, 2020).
Page 34 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
State and Local Public Representatives of state and local public health officials and health care
Health Officials and providers said that the federal government’s planning efforts to date have
been helpful, and they have heard that additional information is
Providers Seek Additional
forthcoming. They also noted several areas where additional information
Information about Vaccine and assistance may be necessary. For example, in an October 2020
IT Systems, Allocation public letter to the administration, the National Governors Association
Plans, Handling and noted that additional guidance and clarification is needed on the roles and
Storage, and expectations of states in distributing any COVID-19 vaccine. In another
letter, the association had questions about funding for vaccine
Communication Efforts administration, the formula for allocation of vaccine, and what information
would be shared publicly on each vaccine. 57 Associations representing
state and territorial health officials, including immunization managers,
stated the need for $8.4 billion in additional resources to support COVID-
19 vaccine distribution activities, including workforce recruitment and
training, and communication outreach. 58
Representatives of state and local public health officials and health care
providers we interviewed identified the following examples of additional
information they are seeking:
57National Governors Association, “NGA Leadership Letter Requesting White House
Meeting on Vaccine Distribution,” October 15, 2020, accessed on Oct. 19, 2020,
https://www.nga.org/advocacy-communications/letters-nga/executive-committee/nga-
leadership-letter-requesting-white-house-meeting-on-vaccine-distribution/ and National
Governor’s Association, “Working Together For Vaccine Distribution”, October 19, 2020,
accessed Oct. 23, 2020
https://www.nga.org/advocacy-communications/working-together-vaccine-distribution/.
HHS responded to the questions from the October 19, 2020 letter from the National
Governors Association, stating that CDC intends to award an additional $140 million for
COVID-19 vaccine readiness by December 15, 2020, but stated that states should
recognize that most of the major costs of a vaccine campaign are already being covered
by the federal government. HHS’s response also provided additional details on distribution
plans, initial allocation of the COVID-19 vaccine, and public messaging, among other
topics. Department of Health and Human Services, “Readout from the Trump
Administration’s 40th Governors Briefing on COVID-19 Response and Vaccine Distribution
Best Practices,” October 30, 2020, accessed on November 6, 2020.
https://www.hhs.gov/about/news/2020/10/30/readout-from-trump-administrations-40th-gov
ernors-briefing-covid-19-response-vaccine-distribution-best-practices.html.
58Association of State and Territorial Health Officials and Association of Immunization
Managers, “ASTHO and AIM Letter to Congressional Leadership Requesting Funds for
COVID-19 Vaccination Distribution and Seasonal Influenza,” October 15, 2020, accessed
on Oct. 20, 2020,
https://www.astho.org/Federal-Government-Relations/Correspondence/ASTHO-AIM-Fund
s-for-Vaccination-Distribution-Letter/
Page 35 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Specific information on IT systems and reporting requirements.
Additional information is needed on the IT systems providers will be
required to use and how they will be required to track and report certain
information. Providers will be required to record and report information
within 24 hours of administration in their jurisdiction’s current
Immunization Information System or an alternative federal system if their
current system does not meet CDC’s data reporting requirements,
according to the updated interim playbook. 59 The updated interim
playbook also stated that additional information on these data
requirements is forthcoming. Representatives from one provider group
and one group representing state officials we spoke with stated that some
providers are not adequately prepared for any new IT systems.
Providers enrolled in the federal COVID-19 Vaccination Program will
order and monitor vaccines and ancillary supplies at no cost through new
and existing IT systems, according to the interim playbook. 60 Specifically,
CDC recommended jurisdictions use its existing Vaccine Tracking
System (VTrckS) for this purpose, but indicated that it may also develop a
new IT system to supplement VTrckS. 61 The updated interim playbook
also specifies that providers will be required to update their vaccine
inventory daily in VaccineFinder, which the public can check online to find
COVID-19 vaccination clinics. 62 Several provider groups supported the
use of existing IT infrastructure rather than the implementation of a new
system to reduce any potential reporting or ordering problems that may
come with learning and using a new system.
Method for allocating available vaccine to jurisdictions. As noted
above, CDC is working to identify groups to have priority for receiving
initial COVID-19 vaccine doses, but HHS has not specified how it will
59Immunization Information Systems, sometimes known as “vaccine registries,” are
confidential, population-based, computerized databases that record all immunization
doses administered by participating providers to persons residing within a given
jurisdiction. According to the interim playbook, required data elements may include the
type of vaccine administered, administration date, and administration location.
60According to the interim playbook, the COVID-19 Vaccination Program encompasses all
plans for the allocation and deployment of COVID-19 vaccines to state, local, territorial,
and tribal governments, as well as any communication plans. Providers must enroll in the
COVID-19 Vaccination Program to administer the vaccine to patients, which will be
coordinated by their local governments.
61VTrckS is CDC’s information management system that allows providers and public
health departments to order and manage publicly funded vaccines.
62VaccineFinder is a public website at which patients can search for locations and/or
providers that have vaccinations by location. See https://vaccinefinder.org/.
Page 36 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
allocate available vaccines to individual jurisdictions, which will be
important to ensure that all individuals in identified priority groups are
reached. In the interim playbook, CDC states that early in the vaccination
program, there is likely to be a limited supply of any available vaccine,
and it provides hypothetical scenarios for state and local jurisdictions to
use to develop operational plans for early COVID-19 vaccination while
supplies are limited. Also, knowing how allocation decisions will be made
will allow public health officials to plan for vaccine distribution and
administration, as well as prepare public messaging for patients,
according to representatives from two stakeholder groups we interviewed.
Guidance on handling and storing any ultra-cold or large lots of
vaccine. Some COVID-19 vaccines under development may require
storage at ultra-cold temperatures. 63 CDC has indicated that it will use a
current centralized distribution contract with a private distributor to fulfill
orders for most COVID-19 vaccine products. However, any vaccines that
require ultra-cold temperatures will be shipped directly from the vaccine
manufacturer instead of the distributor, according to the interim playbook.
Additionally, ultra-cold vaccines could have specific handling
requirements. For example, according to a presentation at an August
2020 CDC Advisory Committee on Immunization Practices meeting, the
thermal shipping container for one Operation Warp Speed vaccine
candidate should not be opened more than twice a day and should be
closed within one minute or less after opening. 64 Two provider groups
said that many providers and their offices do not have freezers that can
store an ultra-cold vaccine, and another indicated in a letter that they may
need additional funds from the federal government to procure supplies,
such as the necessary equipment to store any ultra-cold vaccine, to
safely and efficiently administer COVID-19 vaccines.
The updated interim playbook also notes that any ultra-cold vaccine
would likely be shipped in 975 dose increments, which is larger than the
100 dose orders used for other COVID-19 vaccines. Our prior work on
distribution of the H1N1 vaccine found that receiving vaccine lots in 100
63According to CDC’s interim playbook, storage and handling requirements for each
COVID-19 vaccine product will vary from refrigerated (2°C to 8°C) to frozen (-15°C to -
25°C) to ultra-cold (-60°C to -80°C) temperatures. According to CDC, vaccines must be
stored properly from the time they are manufactured until they are administered otherwise
they may be less effective or unusable.
64Brian Gleeson, “BNT162b2: Storage, handling and administration” (presentation shown
at the August 2020 CDC Advisory Committee on Immunization Practices meeting, Atlanta,
Ga., August 2020).
Page 37 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
dose minimum amounts was a challenge for states because those 100-
dose lots had to be broken down further before being sent to providers,
leading to delays in some providers receiving the vaccines. 65 Two
stakeholders expressed concern that vaccine doses could be wasted if
vaccine that requires ultra-cold storage is mishandled or if the large
number of doses in one shipment are thawed, but are not administered
within the time frame that they would be usable.
In an October 2020 letter, the National Governor’s Association stated that
if ultra-cold storage vaccines come in shipments with a large number of
doses as indicated by the federal government, states will likely need to
distribute them further in rural areas, and asked for guidance on
redistribution of ultra-cold storage vaccines without compromising the
vaccine. In response, HHS indicated that it plans to issue further
guidance on ultra-cold vaccines as plans are developed and that there is
ongoing work to develop smaller package sizes for ultra-cold vaccine
shipments.
Additional information on public messaging. Representatives from
three groups representing providers and state and local public health
officials told us that public messaging and clear communications are key
to effective deployment of COVID-19 vaccines, and one said that they
would like to see a federal communication plan or strategy. CDC has
noted the importance of clear and effective communication to promote
public uptake of any COVID-19 vaccine, and that messaging should be
tailored for each audience to ensure communication is effective. CDC
shared its COVID-19 vaccination communication objectives, such as
ensuring public confidence in the safety and efficacy of COVID-19
vaccines, in the interim playbook. 66 Agency officials said they plan to
develop additional communication resources for jurisdictions and tribal
organizations to use so that entities can tailor messages for special
populations in their communities. The interim playbook indicated this
information will be available on a website that is under development, but
did not provide a planned date for its completion and availability.
65GAO, Influenza Pandemic: Lessons from the H1N1 Pandemic Should Be Incorporated
into Future Planning, GAO-11-632 (Washington, D.C.: June 27, 2011).
66COVID-19 vaccine communication objectives included in the interim playbook include
educating the public about the development, authorization, distribution, and execution of
COVID-19 vaccines, ensuring public confidence in the safety and efficacy of COVID-19
vaccines, helping the public to understand key differences between EUAs and vaccine
licensure, and tracking and monitoring public receptiveness to COVID-19 vaccination
messaging, among other objectives.
Page 38 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
The Operation Warp Speed partnership has enabled the federal
Conclusions government—in concert with private industry—to move at an unusually
fast pace to address the complex challenge of developing COVID-19
vaccine and therapeutic candidates, while at the same time ramping up
manufacturing so that once such vaccines and therapeutics are
authorized, licensed, or approved, they can be mass-produced. We are
continuing to conduct work examining Operation Warp Speed’s efforts to
support COVID-19 vaccine and therapeutic development and
manufacturing, including steps it has taken to address challenges in
achieving its goal of quickly developing safe and effective vaccines and
therapeutics.
FDA has issued EUAs for four therapeutics, but the evidence to support
its authorization decisions was not always transparent. As more potential
COVID-19 therapeutics are developed through Operation Warp Speed
and through other efforts, FDA has an opportunity to improve
transparency. It can do this by identifying ways to uniformly disclose
information from its scientific review of safety and effectiveness data—
similar to the agency’s public disclosure of such data supporting the
approval of new drugs and biologics—when it issues an EUA for a
therapeutic or vaccine. FDA officials agreed that more transparency in
these decisions is needed, but noted that federal law may restrict the type
of information the agency can disclose for EUAs absent the sponsor’s
consent. If needed, FDA could seek authority to make such information
available. Doing so could help increase the public’s confidence in FDA’s
EUA decisions.
We are making the following recommendation to FDA:
Recommendation for
Executive Action The Secretary of Health and Human Services should direct the FDA
Commissioner to identify ways to uniformly disclose to the public the
information from FDA’s scientific review of safety and effectiveness
data—similar to the public disclosure of the summary safety and
effectiveness data supporting the approval of new drugs and biologics—
when issuing EUAs for therapeutics and vaccines, and, if necessary, seek
the authority to publicly disclose such information. (Recommendation 1)
We provided a draft of this report to HHS and DOD for review and
Agency Comments comment. HHS provided general comments, which are reproduced in
and Our Evaluation appendix I. HHS neither agreed nor disagreed with our recommendation;
however, in commenting on the draft, FDA stated that the agency shared
GAO’s goal of transparency, believed that disclosing information from its
Page 39 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
review of safety and effectiveness data would contribute to public
confidence in the agency’s reviews, and that it will explore approaches for
greater transparency in this area, including considering whether additional
authorities are needed. Both departments also provided technical
comments, which we incorporated as appropriate.
We are sending copies of this report to the appropriate congressional
committees, the Secretary of Health and Human Services, the Acting
Secretary of Defense, and other interested parties. In addition, the report
is available at no charge on the GAO website at http://www.gao.gov.
If you or your staff have any questions about this report, please contact
Mary Denigan-Macauley at 202-512-7114 or
deniganmacauleym@gao.gov or Alyssa M. Hundrup at (202) 512-7114 or
hundrupa@gao.gov. Contact points for our Offices of Congressional
Relations and Public Affairs may be found on the last page of this report.
GAO staff who made major contributions to this report are listed in
appendix II.
Mary Denigan-Macauley
Director, Health Care
Alyssa M. Hundrup
Acting Director, Health Care
Page 40 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
List of Addressees
The Honorable Richard C. Shelby
Chairman
The Honorable Patrick J. Leahy
Vice Chairman
Committee on Appropriations
United States Senate
The Honorable Lamar Alexander
Chairman
The Honorable Patty Murray
Ranking Member
Committee on Health, Education, Labor, and Pensions
United States Senate
The Honorable Ron Johnson
Chairman
The Honorable Gary C. Peters
Ranking Member
Committee on Homeland Security and Governmental Affairs
United States Senate
The Honorable Nita M. Lowey
Chairwoman
The Honorable Kay Granger
Ranking Member
Committee on Appropriations
House of Representatives
The Honorable Frank Pallone, Jr.
Chairman
The Honorable Greg Walden
Republican Leader
Committee on Energy and Commerce
House of Representatives
Page 41 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
The Honorable Bennie Thompson
Chairman
The Honorable Mike D. Rogers
Ranking Member
Committee on Homeland Security
House of Representatives
The Honorable Carolyn B. Maloney
Chairwoman
The Honorable James R. Comer
Ranking Member
Committee on Oversight and Reform
House of Representatives
The Honorable James E. Clyburn
Chairman
Select Subcommittee on the Coronavirus Crisis
Committee on Oversight and Reform
House of Representatives
The Honorable Bill Foster
House of Representatives
The Honorable Mark E. Green, MD
House of Representatives
Page 42 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Appendix I: Comments from the Department
Appendix I: Comments from the Department of
Health and Human Services
of Health and Human Services
Page 43 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Appendix I: Comments from the Department of
Health and Human Services
Page 44 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Appendix II: GAO Contacts and Staff
Appendix II: GAO Contacts and Staff
Acknowledgments
Acknowledgments
Mary Denigan-Macauley, 202-512-7114 deniganmacauleym@gao.gov;
GAO Contacts Alyssa M. Hundrup, (202) 512-7114, hundrupa@gao.gov
In addition to the contacts named above Deirdre Brown (Assistant
Staff Director), Kelly DeMots (Assistant Director), Rebecca Abela (Analyst-in-
Acknowledgments Charge), Alison Goetsch (Analyst-in-Charge), Jennie Apter, Justin Cubilo,
Kaitlin Farquharson, Sandra George, Haden Huang, and Ethiene
Salgado-Rodriguez made key contributions to this report. Other staff
contributing include, Nora Adkins, Darnita Akers, Mariel Alper, Mike
Dickens, Maya Dru, Lorraine Ettaro, Cory Gerlach, Ryan Han, Nicolaus
Heun, Laura Holliday, Katheryn Hubbell, Anna Irvine, Julia Kennon, Gay
Hee Lee, Christopher Murray, Angie Nichols-Friedman, John Ortiz,
Miranda Riemer, Meghan Shrewsbury, Amber Sinclair, and Sirin
Yaemsiri.
Page 45 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
Related GAO Products
Related GAO Products
COVID-19: Federal Efforts Could Be Strengthened by Timely and
Concerted Actions. GAO-20-701. Washington, D.C.: September 21, 2020.
COVID-19 Contracting: Observations on Federal Contracting in
Response to the Pandemic. GAO-20-632. Washington, D.C.: July 29,
2020.
COVID-19: Opportunities to Improve Federal Response and Recovery
Efforts. GAO-20-625. Washington, D.C.: June 25, 2020.
Defense Acquisitions: DOD’s Use of Other Transactions for Prototype
Projects Has Increased. GAO-20-84. Washington, D.C.: November 22,
2019.
Federal Acquisitions: Use of ‘Other Transaction’ Agreements Limited and
Mostly for Research and Development Activities. GAO-16-209.
Washington, D.C.: January 7, 2016.
Influenza Pandemic: Lessons from the H1N1 Pandemic Should Be
Incorporated into Future Planning. GAO-11-632. Washington, D.C.: June
27, 2011.
(104575)
Page 46 GAO-21-207 COVID-19 Vaccine and Therapeutic Efforts
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