The FDA Regulatory Landscape for COVID-19 Treatments and Vaccines
As the United States and countries all over the world continue to grapple with the Covid-19 pandemic, the race is on for Covid-19 treatments and vaccines. There is currently no FDA-approved therapy or vaccine for Covid-19. Given the profound urgency, life sciences companies and other researchers are prioritizing research and development of potential therapies and vaccines. After a promising Covid-19 biologic treatment or vaccine emerges, FDA has several tools at its disposal to expedite its review and approval as a biologic. (Separately, a small-molecule drug for treatment of Covid-19 would be approved based on an NDA or efficacy supplement to an existing NDA.)
Basics of FDA Framework for Regulating Biological Treatments and Vaccines
In the United States, all biological products for the prevention, treatment, or cure of a disease or condition are regulated by FDA’s Center for Biologics Evaluation and Research (CBER). The definition of “biological products” includes all vaccines, and hence all vaccines are regulated as biologics by CBER.
Clinical research projects involving a new treatment or vaccine not approved by FDA must first be reviewed through the filing of an investigational new drug (IND) application. In the context of the Covid-19 emergency, FDA is encouraging sponsors of investigational Covid-19 treatments to submit information and questions through the Pre-IND Consultation Program. And in certain instances, the IND process has been accelerated, such that trials have gone forward based on pre‑IND discussions and highly expedited initial reviews.
The Landscape of Potential Pathways for Expedited Approval of a Covid-19 Biological Treatment or Vaccine
Multiple FDA programs exist to facilitate and expedite the development and review of therapies, including biologics, with the potential to address unmet medical needs in the treatment of serious or life-threatening conditions: fast track designation, breakthrough therapy designation, priority review designation, and accelerated approval. The core principle behind each of these programs is to make such therapies available as soon as it can be concluded that their benefits justify their risks. As explained below, fast track designation and priority review designation may be the most germane of these pathways for Covid-19 treatments and vaccines.
To qualify for any of these four expedited review programs, a therapy must treat a “serious condition”—a definition that Covid-19 meets. See 21 C.F.R. 312.300(b)(1). For purposes of these programs, diagnostic products that detect a serious condition, products such as vaccines that are intended to prevent a serious condition, and products that mitigate or treat the effects of such conditions all qualify.
Fast track designation is meant to expedite the review of drugs with the potential to meet unmet medical needs in the treatment of a serious or life-threatening disease or condition. Early in development, a sponsor may rely on non-clinical evidence to demonstrate such potential. Frequent FDA meetings as clinical testing proceeds provide opportunities for priority approval—even of portions of the marketing application while the development of the remainder is completed.
Breakthrough therapy designation provides for expedited approval of drugs that show the potential for improvement over existing therapies. Given that there is no existing treatment or vaccine for Covid-19, this pathway is likely not germane at this stage, where the race for the first Covid-19 treatments and vaccine is just underway.
Priority review designation gives priority to marketing applications for drugs that, if approved, would provide a significant improvement in safety or effectiveness in the treatment of a serious condition. Although this program is often used where clinical trials compare an investigational drug to a marketed product, it can also be used on the basis of other scientifically valid information where no adequate therapy currently exists. This designation puts a marketing application on a path for approval within six months of receipt, compared with ten months under standard review.
The accelerated approval pathway requires adequate and well-controlled clinical trials establishing that “the biological product has an effect on a surrogate endpoint that is reasonably likely . . . to predict clinical benefit or on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity.” 8 C.F.R. § 601.41. This pathway has primarily been used for treatments showing promise in treating diseases with long courses, such as cancers, for which an excessive time period would be required to measure ultimate clinical efficacy. Given Covid-19’s relatively short disease course from infection to morbidity or death, accelerated approval does not seem to be the pathway of choice for sponsors.
Still other expedited FDA approval programs to consider in addition to the four programs discussed above include the so-called “animal rule” and “Emergency Use Authorization.”
The “animal rule” permits the approval of vaccines or treatments using adequate and well-controlled animal studies when human efficacy studies are not ethical or field trials would not be feasible. The rule was passed in response to a terror attack in 2001 involving anthrax spores sent through the mail as a countermeasure to protect public safety. Although this rule is fitting where animal trials are highly probative of efficacy in humans, developing and validating a predictive animal model presents its own unique challenges. This is especially so for Covid-19, a disease for which the human course is still being determined. In the meantime, some researchers are proceeding directly to human clinical trials of investigational vaccines and treatments.
Emergency Use Authorization (EUA) permits the FDA commissioner to approve the emergency use of a vaccine or treatment for a particular purpose even though it has not been licensed. Manufacturers are immune from tort liability claims arising from the administration and use of such a product under the Public Readiness and Emergency Preparedness (PREP) Act of 2005. As relevant here, now that Covid-19 has been declared an emergency by the HHS Secretary, the FDA commissioner may issue an EUA for a Covid-19 vaccine or treatment if, after consulting with the directors of NIH and CDC, the commissioner concludes that:
- Covid-19 can cause a serious or life-threatening disease or condition;
- based on the totality of scientific evidence available, including data from adequate and well-controlled clinical trials, if available, it is reasonable to believe that the vaccine or treatment may be effective in preventing or treating Covid-19;
- the known and potential benefits of the vaccine or treatment outweigh its known and potential risks; and
- there is no adequate, approved, and available alternative product.
It is possible that an EUA may be used if a highly promising Covid-19 vaccine or treatment is developed during the ongoing pandemic. Indeed, FDA has already been granting EUAs for diagnostics and personal protective equipment to be used in treating Covid-19.
FDA has many tools at its disposal to expedite the development and approval of therapies meeting unmet medical needs in the treatment of serious diseases. Not all of these programs will be appropriate for expedited approval of a Covid-19 treatment or vaccine, however.
In contrast to some of the other expedited programs, “priority review” and “fast track” FDA designations do not require comparing the investigational drug to available therapies. This makes these designations promising for expedited approval of a treatment or vaccine for an emerging disease like Covid-19. That said, “priority review” simply accelerates FDA’s projected approval time from ten months to six. “Fast track” designation is a somewhat more flexible program, allowing for more frequent meetings and correspondence with FDA and rolling review of completed sections of the marketing application. If criteria are met, a sponsor may receive both priority review and fast track designations. And while FDA reviews applications for investigational therapies and vaccines using its expedited programs, Emergency Use Authorization is a potential interim measure.
 Under recently amended FDA regulations, “biological product” means “a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein, or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings.” 8 C.F.R. § 600.3(h); 85 Fed. Reg. 10,057, at 10,063.
 EUA was originally established by the Project BioShield Act of 2004 and was subsequently expanded by the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 and the Pandemic and All-Hazards Preparedness and Advancing Innovation Act of 2019.