Following up on our colleagues’ post earlier this month covering the Food and Drug Administration’s 2020 device law and policy activities, this post will explore prescription drug and biologic law and policy developments over the past year. We’ll also begin looking forward into 2021 and the agency’s transition to an incoming Biden Administration. One of the highest priorities for the Food and Drug Administration (FDA) during this “pandemic year 1” was authorizing the use of COVID-19 medical countermeasures. Another high priority was policing fraudulent COVID-19 drugs, preventative products, herbal cures, and even vaccines (not to mention fake test kits, personal protective equipment, and other things regulated as medical devices). As of December 18, 2020, FDA had sent more than 150 warning letters to peddlers of fraudulent COVID-19 products, many in conjunction with the Federal Trade Commission (FTC) – and we expect enforcement activity will be increasing next year as the pandemic continues into “year 2.”
Under a Democrat-led Biden Administration, we might expect to see even more frequent and aggressive enforcement of the law against these and other kinds of violations, particularly as emergency use authorizations (EUAs) granted during the pandemic reach their expiration dates. As Daniel Feith, Deputy Assistant Attorney General for the Consumer Protection Branch of the Department of Justice (DOJ), stated in remarks on December 15, 2020 at the FDLI Enforcement, Litigation, and Compliance Conference:
“Unfortunately, some individuals have sought to capitalize on the pandemic by peddling all manner of fake cures, vaccines, and PPE. And this is where the Consumer Protection Branch has focused its efforts. We have used—and will continue to use—every civil and criminal tool available to punish and deter those trying to cheat and harm the public during this time. … Early on, the Branch quickly established a multi-agency working group to identify, share, and de-conflict investigative leads. The engine of this working group was a set of data-review teams stood up within the Branch. To date, those teams have analyzed tens of thousands of consumer complaints received by the Department, FTC, and FDA, identifying the most troublesome schemes for action by the working group...
Over the last nine months, we have taken more actions against actors peddling fraudulent products purporting to prevent, treat, or cure COVID than any Department component, bringing 13 of the 15 total civil actions filed nationwide to date and advancing a number of significant criminal prosecutions. This work has included shutting down operations marketing ozone therapies, silver products, and even industrial bleach as cures for COVID, and one operation marketing a purported vaccine…And, through cooperation with FBI and industry partners, we have disrupted hundreds of other schemes by shutting down websites selling fake or unapproved treatments.
In these sorts of cases, our foremost concern is protecting the public from further harm by removing fraudulent and unlawful products from the market. Here, some of the fake cures—the bleach, for instance—threaten direct harm. Others risk giving consumers a false confidence that they have nothing to fear from COVID and can avoid taking prudent precautions. And overall, these unlawful products risk eroding public confidence in COVID therapies at a time when such confidence is more important than ever. Given these concerns, we have aggressively used civil injunctive authorities, under both the [Food, Drug, and Cosmetic Act] and the Anti-Fraud Injunction Act, to quickly shut down these operations, while pursuing parallel criminal investigations, often over a somewhat longer timeframe, to hold wrongdoers accountable.”
As of the date of this blog post, it’s unclear who President-elect Biden will nominate to serve either as Attorney General at the DOJ or as the Commissioner of Food and Drugs at the FDA and how those leadership changes may affect current programs and priorities. However, Biden’s choice to lead FDA’s parent agency, the Department of Health and Human Services (HHS), as HHS Secretary – California Attorney General Xavier Becerra – suggests the possibility of a more public health-forward and consumer protection-focused Administration than what we’ve seen over the course of President Trump’s four years in office.
COVID-19 Therapeutics and Vaccines
As we discussed in our first year-end post, FDA’s Center for Devices and Radiological Health (CDRH) continued to make efficient progress in the area of SARS-CoV-2 diagnostic tests and specimen collection kits. It has worked directly with manufacturers to develop robust validation methods to expedite technological innovations to market via EUAs under Section 564 of the Federal Food, Drug, and Cosmetic Act (most recently, on December 15, for the first non-prescription “fully at-home” test for viral antigens that can be used in children as young as age two, meaning the specimens do not have to be mailed to a clinical lab for analysis and diagnosis).
Similar critical emergency response activities by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) were prioritized and coordinated by FDA leadership, beginning with the creation of the Coronavirus Treatment Acceleration Program, or CTAP, in late March. The CTAP includes a periodically updated public dashboard on COVID-19 treatments authorized and in development. Although not generating as much widespread public interest as important vaccine-related news has in the past few weeks, it is noteworthy that FDA has granted a total of eight therapeutic product EUAs since the beginning of the COVID-19 pandemic.
Those eight emergency authorizations are in addition to the well-publicized authorization for hydroxychloroquine (now revoked) and the now-fully FDA-approved use of remdesivir in adults and children over age 12 hospitalized with COVID-19 (while remdesivir’s use in children under age 12 remains authorized under an EUA). In particular, several monoclonal antibody therapeutic products have been authorized for use under Section 564, as have treatments to help maintain care for patients in acute stages of the disease. A complete list of the FDA-authorized drug and biological products that are being deployed to respond to the ongoing public health emergency is available here. We expect that this work under the CTAP and related agency programs will continue to be a high priority for FDA next year, notwithstanding the emerging availability of COVID-19 vaccines to the American population.
After working hard to restore its credibility following the revocation of the hydroxychloroquine EUA in June, the agency moved diligently to authorize investigational vaccines for COVID-19. The first COVID-19 vaccine to be submitted to the agency for EUA was discussed at a day-long public meeting of the independent Vaccines and Related Biological Products Advisory Committee (VRBAC) on December 10, with an overwhelming majority of the panel voting to authorize the emergency use for individuals 16 years of age and older. (FDA is not required to follow advisory committee recommendations, but the agency often does.) The agency issued the Letter of Authorization for that vaccine on the evening of December 11 – only 21 days after the request from the product developers was submitted. FDA held a virtual press conference on the morning of December 12 to which it invited the general public and used as an opportunity for public education about the agency’s scientific and regulatory processes.
The speed with which the agency’s career scientists did their work and the broad support that they received from stakeholders that pushed back against the potential for political interference was quite extraordinary. We join the chorus of voices commending all the career scientists, lawyers, regulatory professionals, and others who worked non-stop under the leadership of CBER Director Dr. Peter Marks to achieve this incredible milestone, along with the vaccine developers and all the clinical trial subjects who volunteered to receive the investigational products and give the world the first glimmers of hope for an end to this terrible pandemic. This was truly a historic feat: the time between sequencing the SARS-CoV-2 virus genome to an emergency-authorized mRNA vaccine was a mere 11 months!
Simultaneously, Operation Warp Speed moved to distribute available vaccine inventory to the states for targeted distribution pursuant to their own vaccination plans, with many States delivering the first shots (of a two-shot regimen) to front-line health care workers and long-term care facilities beginning on Monday, December 14. Gustave Perna, the Army general who serves as chief operating officer for Operation Warp Speed, noted during a December 12 press conference that vaccine shipments were not pre-positioned in advance of the FDA’s issuance of the EUA to ensure that Warp Speed did not “get ahead” of FDA’s regulatory decision-making and cause potential confusion in the marketplace. Public reports of state, city, and hospital officials waking up early on Saturday December 12 in order to finalize operational plans and documents for their own vaccine roll-outs based on what the FDA authorized in the vaccine EUA with respect to safety warnings and instructions for use highlighted another layer of complexity to an already-difficult and not very well-coordinated national distribution and mass vaccination program.
Our health law colleagues previously described the minimum information that vaccine manufacturers are being asked to submit to the agency as part of their vaccine EUA requests. Additionally, in November, FDA published several consumer-directed educational resources about this topic to respond to continued reports of vaccine hesitancy and skepticism among the U.S. population. Those resources include a fact sheet on vaccine EUAs and a new “vaccine development 101” page. Separately, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) is driving the national immunization plan now that FDA has authorized the first COVID-19 vaccines. On December 3, ACIP released its interim recommendations for allocating initial supplies of those vaccines. On Saturday, December 12, following the issuance of the first vacine EUA, the committee met again and unanimously agreed with the FDA’s emergency authorization and the population covered by the EUA’s scope. States, however, are not required to follow ACIP’s recommendations, which could create disparities and differences across groups as the first-line populations are vaccinated, as well as potential implementation problems for large companies with a national presence and employees in multiple states.
A second vaccine EUA followed essentially the exact same timeline one week later, with the VRBAC members meeting publicly and voting to authorize the second mRNA vaccine candidate for use in individuals age 18 and older on Thursday, December 17. The FDA issued its Letter of Authorization on the evening of Friday, December 18, and initial shipments from the manufacturer to the U.S. government and the states began over the weekend so that deliveries and immunizations could begin on the following Monday. CDC’s ACIP held its emergency meeting to review and provide recommendations on the second FDA-authorized vaccine on Saturday, December 19. Unsurprisingly, the ACIP vote was unanimous in support of the second vaccine’s use and preliminary safety profile, mirroring FDA’s assessment in the EUA Letter of Authorization.
Both of the December 2020 EUA-authorized vaccines rely on mRNA innovations in biotechnology, and they represent the first mRNA vaccines authorized for mass distribution by any regulatory authority. Because mRNA has never been used in an FDA-authorized product before this year, mass-scale production systems for these highly sensitive vaccine formulations are gearing up for the first time right now. As a result, we’ve seen widespread media reports of manufacturing challenges associated with the operations of all of these mRNA vaccine makers, which at least for a few months are likely to be sought after to meet the front-line demands of the entire world. Both of them also require a two-dose regimen of vaccine administration for full protection, further complicating production, distribution, and patient-tracking efforts.
Critically, both of these two mRNA vaccine manufacturers – Pfizer/BioNTech for the first one, dubbed “BNT-162b2,” and Moderna for the second one, dubbed “mRNA-1273” – have indicated that they are working diligently on their clinical programs and will be seeking full approval for their respective COVID-19 vaccine products in 2021. (Pfizer/BioNTech more specifically estimates that its full marketing application will be submitted to FDA in April.) While both FDA advisory committee votes and discussions were overwhelming positive, that reflects the nature of the emergency and the urgent need for agents to slow the spread of this virus in our population rather than any indication that the products and their manufacturing facilities are ready for full regulatory approval.
In addition, many scientific questions remain about these investigational products. Basic and clinical research into their effects on the immune system and the virus will continue to be a focus for stakeholders in the vaccine enterprise for the foreseeable future. For example, it’s unclear whether vaccinated individuals can still shed the virus and potentially transmit it to others; whether the vaccines can protect against asymptomatic transmission in humans; how long protection from each vaccine might last; whether any long-term safety risks exist for some or all of the vaccine recipients; and whether special populations such as pregnant women and children should be included within the recommended uses or if they face any different safety risks than adults with no contraindications to the vaccine.
Currently, both of the FDA-authorized mRNA vaccines are labeled as being contraindicated only for “to individuals with a known history of a severe allergic reaction (e.g., anaphylaxis) to any component of” the respective COVID-19 vaccine being administered, although this may change as new safety information is collected as more people are inoculated. The emerging reports from health care workers of anaphylaxis in some inoculated patients are evidence that there remain a lot of scientific and technical issues to be resolved about this brand new mRNA technology and how to ensure both the safety and stability of these vaccines.
From our perspective, perhaps the most important thing FDA did when it came to the December 2020 EUA decisions for these first two COVID-19 vaccines was to be as transparent as possible and communicate directly with the American people. The publicly available materials for the first FDA-authorized vaccine include an internal review and decision memorandum, which is more documentation of the agency’s review and thinking on the Section 564 standards for authorization than we have seen for most of the issued EUAs during the current public health emergency, whether for therapeutic or medical device products. The posting of this internal memorandum underscores the ongoing importance of FDA restoring (and maintaining) its scientific credibility with this first vaccine authorization, and it also meets the agency’s re-emphasized commitment to scientific transparency as articulated in a November 17 public statement from FDA Commissioner Dr. Stephen Hahn. Still, vaccine hesitancy remains a public health challenge, partly because of the Trump Administration’s politicization of FDA during the pandemic and partly for other reasons including longstanding distrust of modern medicine among some subpopulations. Ensuring the successful implementation of a national vaccination program will be one of the first public health priorities of the Biden Administration when it assumes leadership of the federal government on January 20, 2021.
Part 3 of this post will summarize non-COVID related drug and biologic developments at the agency over the past year. Join us tomorrow for that!