COVID-19: Legal Considerations for Bringing a New Vaccine to Market

COVID-19: Legal Considerations for Bringing a New Vaccine to Market

Legal Sidebari

COVID-19: Legal Considerations for Bringing
a New Vaccine to Market
March 24, 2020
As the number of confirmed COVID-19 cases increases at an accelerating rate, interest has grown in
developing a COVID-19 vaccine as an avenue for addressing the pandemic. Media reports indicate that a
number of countries and companies are working on developing a vaccine. The National Institute of
Allergy and Infectious Diseases (NIAID) and the biotechnology company Moderna, Inc., recently
initiated the first clinical trials of a potential vaccine in the United States at a hospital in Seattle. However,
developing a new vaccine and obtaining approval to market it can take a long time. This Sidebar discusses
the licensure (i.e., approval) process for vaccines under the Public Health Service Act (PHS Act) and the
federal Food, Drug, and Cosmetic Act (FD&C Act), as well as potential legal avenues for expediting that
process to bring a new vaccine to market sooner.
FDA Approval of New Vaccines
Vaccines are intended to prevent diseases and generally work by introducing pathogens to the human
body (usually by injection) to trigger an immune response to the disease (i.e., producing antibodies to the
pathogen). Vaccines are biological products approved and regulated by the U.S. Food and Drug
Administration’s (FDA’s) Center for Biologics Evaluation and Research (CBER) under Section 351 of
the Public Health Service Act. A biologic such as a vaccine generally cannot be introduced into commerce
unless FDA approves it. To be approved, FDA must determine that the vaccine is safe, potent, and pure
based on data from laboratory studies and clinical trials. In general, this requirement means that the
vaccine must achieve the desired effect (i.e., prevents the targeted disease or condition) and that the risk
of adverse side effects is outweighed by the expected benefits.
Developing a new vaccine, or any other drug or biological product, begins in a laboratory. When a
company (i.e., sponsor) is ready to test its new vaccine on humans in clinical trials, the sponsor submits
an investigational new drug application (IND) to FDA. The IND contains information known about the
vaccine so far and the sponsor’s plan for the clinical studies, including the investigational plan and
protocols for the studies. FDA uses the IND to ensure that clinical trials will protect the safety and rights
of the participants and yield data with enough scientific integrity to evaluate the safety and effectiveness
of the vaccine. The sponsor generally cannot begin clinical trials until FDA approves the IND.
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If the clinical trials are successful, the sponsor may seek FDA approval to market its new vaccine. FDA
approves new vaccines through biologics license applications (BLAs) reviewed by CBER. BLAs contain
data from the laboratory and clinical studies and information about how and where the biologic will be
manufactured. As courts have recognized, FDA exercises its scientific judgment when deciding whether
to license vaccines based on such studies. Biologics that are approved through a BLA receive 12 years of
regulatory exclusivity, during which time FDA cannot approve any biosimilars (i.e., abbreviated
applications for the same biologic that depend on the clinical data in the BLA to demonstrate safety,
potency, and purity). (These exclusivity rights and separate patent rights raise potential intellectual
property questions that are discussed in more detail in this Sidebar.)
Options for Bringing a New Vaccine to Market Faster
The process of developing and testing a new vaccine to the point where it meets the safety, purity, and
potency standard can be a lengthy process. The FD&C Act provides several options that may allow a
sponsor to bring a new vaccine to market faster. Generally, these options use one of two approaches. First,
FDA can direct more of its resources to the product to accelerate the development and/or review processes
(e.g., fast track product designation, breakthrough therapy designation, and priority review). Second, FDA
can modify how it evaluates the risks and benefits of the vaccine before allowing its use, either by relying
on different types of evidence (e.g., the accelerated approval process) or lowering the evidentiary standard
in emergency situations (e.g., emergency use authorization). (For ease of reference, this section uses the
general term “biologic” because vaccines are biological products, but the pathways discussed below are
also available for traditional small molecule drugs.)
Shortening the Development and Review Processes
Several avenues are available for expediting the development and review processes for biologics used to
treat or prevent serious or life-threatening conditions and diseases. In its guidance, FDA generally
considers a condition or disease serious if it substantially affects day-to-day functioning and is
irreversible, persistent, or recurrent. A condition or disease may be found to be serious as a matter of
clinical judgment based on its effect on survival, day-to-day functioning, or the likelihood that it will
progress to a more serious condition if left untreated. As a matter of course, FDA considers any life-
threatening condition or disease to be serious. The drug must also be intended to treat the serious
condition or disease by having an effect on the disease itself or a serious aspect of the disease, such as a
symptom or other manifestation. Among the examples FDA provides in its guidance is a product intended
to prevent the serious condition. Given that COVID-19 is life-threatening, a vaccine intended to prevent
COVID-19 seems likely to qualify as a drug used to treat or prevent a serious or life-threatening condition
or disease—making it eligible for the following designations to accelerate the approval process.
Fast Track Product Designation
Section 506 of the FD&C Act allows FDA to designate certain biologics as fast track products, which
receive FDA assistance in expediting development and review. A biologic may be designated as a fast
track product if FDA determines that the biologic will treat or prevent a serious or life-threatening disease
or condition and fill an unmet medical need. An unmet medical need exists when available therapies do
not adequately address treating or diagnosing a condition or disease. FDA recognizes in its guidance that
an unmet medical need necessarily exists if there is no available therapy. Sponsors may provide FDA with
nonclinical or clinical data to demonstrate that the drug has the potential to fill that unmet medical need.
Given that there are no approved vaccines for COVID-19, any vaccine that showed potential to prevent
COVID-19 in laboratory or clinical trials would seem likely to qualify for fast track designation.

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At its discretion, the biologic’s sponsor requests fast track designation for its product. It may request fast
track designation when it submits an IND or any time thereafter. FDA has 60 days to determine if the
biologic qualifies for the designation. Once FDA designates a biologic as a fast track product, FDA must
facilitate its development and expedite review of the biologic. In practice, this process generally means
that the biologic’s sponsor has greater access to FDA through written and in-person communications
during the development and testing process to improve efficiency and ensure that appropriate data are
collected. FDA may also review the BLA for a fast track product on a rolling basis as sections are
complete (rather than waiting for a completed application) if initial clinical testing shows the biologic
may be effective.
Breakthrough Therapy Designation
Section 506 of the FD&C Act also allows FDA to designate certain biologics as breakthrough therapies,
which similarly heightens FDA involvement in the development and review process. Breakthrough
therapy designation is based on preliminary clinical evidence showing the biologic may be a substantial
improvement over available therapies for one or more clinically significant endpoints. Endpoints measure
the outcome of a clinical trial. Under FDA guidance, a clinically significant endpoint generally measures
an effect on irreversible morbidity or mortality or on symptoms representing serious consequences of the
disease or condition. Unlike fast track product designation, which can be based on laboratory data,
breakthrough therapy designation requires evidence from clinical trials. FDA exercises its judgment in
determining whether the data show a substantial improvement over existing therapies, taking into
consideration both the magnitude of the biologic’s effects on the endpoint and the importance of the effect
measured by that endpoint to treating the disease or condition. When there are no existing therapies, such
as with a COVID-19 vaccine, FDA compares the biologic to a placebo or well-documented historical
control. A COVID-19 vaccine may be eligible for breakthrough therapy designation if the sponsor can
demonstrate potential effectiveness in early clinical trials.
At its discretion, the sponsor requests breakthrough therapy designation and may do so with submission
of an IND or at any time thereafter. FDA must determine whether the biologic qualifies as a breakthrough
therapy within 60 days of receipt. As with fast track product designation, the FD&C Act directs FDA to
expedite the development and review of applications for breakthrough therapies. Per FDA guidance,
expedited development and review of breakthrough therapies entails (1) intensive assistance from FDA on
efficient development and clinical trial design; (2) organizational commitment from FDA, including
senior management and experienced staff; (3) rolling review of the BLA; and (4) other actions to expedite
review, such as priority review discussed below. Extensive FDA assistance during the development
process and the involvement of senior managers distinguishes breakthrough therapy designation from fast
track product designation.
Accelerated Approval
Section 506 of the FD&C Act also allows FDA to approve certain biologics based on surrogate or
intermediate endpoints, referred to as accelerated approval. In general, sponsors select endpoints that
directly measure the clinical outcome (i.e., the benefits expected from the biologic), such as whether the
patient feels better or lives longer. Surrogate and intermediate endpoints do not measure the clinical
benefit directly but instead measure an effect that is expected to predict a clinical benefit. For example, a
drug to treat strokes would have an intended clinical outcome of reducing the incidence or severity of
strokes. But rather than measuring the incidence of strokes directly, an investigator might measure the
drug’s effect on blood pressure as a surrogate endpoint due to the strong correlation between strokes and
blood pressure.
To qualify for accelerated approval, (1) the biologic must treat a serious or life-threatening condition or
disease and (2) FDA must determine that the biologic has an effect on a surrogate or intermediate

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endpoint that is reasonably likely to predict a clinical benefit. When deciding whether to approve a
biologic on this basis, FDA must consider how severe, rare, or prevalent the condition is and the
availability of alternative treatments. A vaccine for COVID-19 could qualify for accelerated approval if
investigators identified a surrogate or intermediate endpoint that could reasonably predict the vaccine
would be effective against the virus.
Priority Review
Once a BLA is submitted, FDA can designate the BLA for standard review or priority review. FDA aims
to act on priority review applications within 6 months, compared to 10 months or more for standard
review applications. FDA makes this determination for every application, though a sponsor can expressly
request priority review. FDA may designate a BLA for priority review if it represents a “significant
improvement” over existing treatments in terms of safety or effectiveness in treating, diagnosing, or
preventing the disease or condition. In the absence of any approved vaccine for COVID-19, FDA would
likely designate for priority review any BLA for such a vaccine.
Emergency Use Authorizations Before Approval
In certain emergency situations, Section 564 of the FD&C Act allows FDA to authorize the use of a drug
or biologic (e.g., a vaccine) before it is approved (i.e., an Emergency Use Authorization or EUA). FDA
may issue an EUA only if the Secretary of Health and Human Services has declared that circumstances
exist justifying emergency authorized use of the medical product. Of relevance to the COVID-19
pandemic, on February 4, 2020, the Secretary determined that there is a public health emergency that has
a significant potential to affect national security or the health and security of U.S. citizens living abroad,
and that involves a biological, chemical, radiological, or nuclear agent (BCRN agent)—namely, the virus
that causes COVID-19. Based on this determination, the Secretary has authorized the emergency use of
several diagnostic tests. On March 2, 2020, the Secretary determined that circumstances exist to allow for
the emergency use of certain respirators not approved by the agency, and FDA issued an EUA allowing
for the emergency use of such respirators.
After the Secretary determines a public health emergency exists (one of four bases for declaring an
emergency or threat), FDA may issue an EUA for a specific product if the Secretary concludes that:
 the BCRN agent can cause a serious or life-threatening disease or condition;
 it is reasonable to believe, based on the totality of the scientific evidence available, that:
 The product may be effective in diagnosing, treating, or preventing the disease or
condition caused by the BCRN agent; and
 The known and potential benefits of the product outweigh the known and potential
risks; and
 there is no adequate, approved, and available alternative to the product.
In evaluating a product for an EUA, FDA uses a lower evidentiary standard, determining whether the
product “may be effective” in diagnosing, treating, or preventing a disease rather than evaluating its
“effectiveness” in doing so. As discussed above, COVID-19 is a serious or life-threatening disease,
confirmed by the fact that FDA has already issued EUAs in connection with COVID-19 for diagnostic
tests and certain personal protective equipment. There is also no alternative to a COVID-19 vaccine at
this time. Any decision by FDA to issue an EUA for a COVID-19 vaccine would accordingly depend on
whether the totality of the evidence available to FDA shows that it is reasonable to believe (1) the vaccine
may be effective in preventing COVID-19 and (2) that those benefits outweigh any known or potential
risks from the vaccine. FDA would have to conduct this evaluation for each vaccine that is developed and
submitted for an EUA.

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The FD&C Act requires FDA to impose certain conditions on EUAs as necessary and appropriate to
protect the public health. The conditions vary depending on whether the product is unapproved or
approved but for a different use. In general, the conditions provide for monitoring, reporting, and
recordkeeping as well as ensuring that the health care professionals administering the product and the
individuals being treated with the product are informed about the benefits and risks of using the product.
FDA may also waive good manufacturing practices (GMP) and certain prescription requirements when
issuing an EUA and may impose conditions related to advertising the product.
Considerations for Congress
The current legal regime for approving new pharmaceutical products such as vaccines generally aims to
strike a balance between bringing products to market sooner and ensuring that products on the market are
safe and effective. For serious or life-threatening diseases and conditions or in emergency situations, the
law gives FDA a certain amount of discretion to shift that balance. FDA generally expedites the process
one of two ways: shifting its resources or shifting its standard in evaluating the risks and benefits.
In considering avenues to facilitate the development of a COVID-19 vaccine, Congress has similar
options. Congress could consider providing additional resources to FDA to exercise its existing
authorities. Congress is already employing this approach: The Coronavirus Preparedness and Response
Supplemental Appropriations Act, 2020, enacted on March 6, appropriated $61 million to FDA “to
prevent, prepare for, and respond to coronavirus, domestically or internationally, including the
development of necessary medical countermeasures and vaccines, advanced manufacturing for medical
products, the monitoring of medical product supply chains, and related administrative activities.”
Alternatively, Congress could direct FDA to strike a different balance when evaluating the risks versus the
benefits specifically in the context of potential COVID-19 vaccines. In assessing that balance, Congress
and FDA would face weighing the benefits from disseminating a vaccine to the public sooner (e.g.,
limiting the spread of the virus or reducing the economic consequences) against the risk that the vaccine
may have been authorized prematurely and prove ineffective or unsafe, potentially leading to worse
public health outcomes. Any alteration to this balance that requires FDA to exceed or contradict its
existing authority would require an act of Congress to amend the agency’s statutory authority.
Should FDA authorize or approve a COVID-19 vaccine, other considerations may come to bear.
For example, registered manufacturers may not be able to produce an adequate supply of the
vaccine. FDA is currently addressing hand sanitizer shortages by exercising its enforcement
discretion with respect to production by over-the-counter drug manufacturers and compounders.
Congress may consider other avenues for increasing supply of the vaccine. In addition, existence
of a vaccine would raise questions of mandatory vaccination to address the public health crisis,
which is addressed in a separate Sidebar.

Author Information

Erin H. Ward

Legislative Attorney

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