It is, somewhat amazingly, the beginning of January again. During this time of year we typically publish a series of blog posts that recap the most interesting Food and Drug Administration (FDA) activities over the prior 12 months and consider what the agency is likely to focus on going forward. You can find our FDA year-in-review posts from 2020 and 2019 here. This year, however, we’re taking a different approach and will be providing more of a birds-eye view of our favorite federal agency as it stands as of the end of 2021. Because there is just too much going on at the administrative, enforcement, and legislative levels to get into the details of everything in one fell swoop.
First, what cannot be understated is the incredible commitment and sheer grit of FDA career staff and scientists who have worked almost non-stop throughout the ongoing public health emergency to review and authorize COVID-19 vaccines, diagnostic tests, and disease treatments. They have also toiled tirelessly to keep the American public safe by monitoring the various products that flooded the market in response to the pandemic, such as imported hand sanitizers (for which the agency has issued multiple alerts regarding methanol contamination and other problems), unauthorized COVID tests, and myriad fraudulent treatments for the disease; the latter bucket of work in particular is never-ending in light of how prevalent fraud becomes in the face of a public emergency such as the one we’ve all been living in as we near the end of “pandemic year 2.” We all are indebted to these public servants and should thank them by doing our part to control the spread of this insidious virus and by getting vaccinated and boosted if you have not done so already!
Of course, just as it did last year, FDA spent 2021 juggling these enormous COVID-related responsibilities while simultaneously attempting to make progress on a huge number of important regulatory priorities and programs either in need of reform or in the midst of active reform. Let’s recap a few of the agency’s notable actions over the past 12 months in the various product categories it oversees.
FDA’s Center for Drugs steadily rolled out announcements this year regarding its modernization of the OTC drug monograph program, as directed by Congress in 2020-enacted legislation (you can read our October 2021 post on this topic here). It also published a slew of new guidance over the summer concerning its ongoing implementation of the Drug Supply Chain Security Act, as we get closer to the end of the 10-year period for those complex amendments to the Federal Food, Drug, and Cosmetic Act (FD&C Act) to phase-in, and approved the first-ever interchangeable biosimilar biological product (an insulin) in July followed by the first interchangeable designation for a monoclonal antibody biosimilar in October.
In addition to reviewing 18,000 regular submissions and more than 2,200 emergency use authorization (EUA)/pre-EUA submissions from medical device developers in fiscal year 2021 (Oct. 1, 2020 to Sept. 30, 2021), per a recent FDA Voices blog post from CDRH leadership, FDA’s Center for Devices and Radiological Health (CDRH) released its first Action Plan for Artificial Intelligence/Machine Learning (AI/ML)-Based Software as a Medical Device in January and hosted a public workshop to hear from stakeholders on what transparency means for such software devices; published long-awaited guidance for industry on the highly contentious issue of medical device remanufacturing; and began making plans for the transition of COVID-19 device and diagnostic products from EUA status to “full” marketing authorization, as reflected both in its clearance of the first De Novo request for a SARS-CoV-2 nucleic acid test and its December 2021 release of the first guidance on how various product types will be treated when the public health emergency is officially terminated. CDRH also finalized a relatively large number of reclassification orders during 2021, half of which down-classified and the other half of which up-classified the device type in question. It also published the De Novo Classification Final Rule in October, with those now-codified procedural requirements going into effect in January 2022.
The Center for Biologics had its own incredibly busy year, given its lead role in the review and authorization of all the COVID-19 vaccines as well as the meteoric increase it has experienced in clinical trial, meeting, and marketing submissions for innovative cellular, gene therapy, and other regenerative medicine products; it also issued a 5-year strategic plan in March and continued its (somewhat ineffective) efforts to crack down on unauthorized stem cell products in the U.S. marketplace following the end of an enforcement discretion period on May 31, 2021.
FDA’s Center for Tobacco Products experienced a milestone year in clearing the backlog of premarket applications for electronic nicotine delivery (aka “vape” or e-cigarette) products that resulted from the agency’s 2016 Deeming Rule, which was promulgated under the authorities granted to FDA over a decade ago under the Family Smoking Prevention and Tobacco Control Act, in issuing its first-ever e-cigarette authorizations, and in finalizing additional key regulations for the industry.
The Center for Food Safety and Applied Nutrition was occupied with its Closer to Zero Action Plan, with cosmetic reform advocacy efforts, with its initiation of a research project on the use of “healthy” symbols on food packaging, and with broader efforts to grapple with the changing ways that people purchase and consume food in the 21st century.
On the enforcement side of the FDA’s diverse and wide-ranging missions, this past year brought us the first signs of federal enforcement of the Clinicaltrials.gov Final Rule, which was promulgated in 2017, many years after the requirements were created by Congress as part of FDA’s 2007 user fee reauthorization legislation. Pandemic-related emergency response products that were ostensibly being marketed under an enforcement policy also began to experience greater scrutiny from the agency. For example, warning letters were sent out to firms selling unauthorized thermal imaging devices. There were also several novel applications of FDA’s statutory authorities evident in its warning letters and other public statements during 2021, such as the first warning letters stemming from a facility’s failure to respond to a records request issued under Section 704 of the FD&C Act and what appears to be the first time that the agency has notified drug companies en masse about historical data integrity violations uncovered at a contract research organization that affected commercially available drug products.
We also noticed what appears to be an uptick in FDA’s actions against unlawfully marketed dietary supplements, which seems to be another area of perennial enforcement action for the agency (see related press releases here, here, and here), and a strengthening of the enforcement partnership between FDA and its consumer protection counterparts at the Federal Trade Commission and the Department of Justice’s Consumer Protection Branch. The latter observation was seemingly validated in recent public remarks by Deputy Assistant Attorney General Arun Rao, who commented at an enforcement conference in December 2021 that the Department’s “relationship with [the FDA’s Office of Chief Counsel and Office of Criminal Investigations] has never been better.” Ongoing problems with dietary supplements have also elevated calls for legislative reforms to be enacted in that area, given the differences that exist in today’s heavily e-retail marketplace as compared to how American consumers identified and purchased their vitamins and supplements back in 1994 when Congress created that product category within the FD&C Act.
Besides the potential for future dietary supplement legislative reforms, in vitro diagnostics and laboratory-developed tests (LDTs) look more likely to be in for massive programmatic changes in the next year or two, whether the current version of the bipartisan VALID Act or some other piece of reform legislation makes it through to the President’s desk. Regardless of what happens in 2022 on federal oversight of diagnostics and LDTs, it’s fair to assume that all parties would like for this issue to be resolved already, because the perpetual flip-flopping is neither sustainable nor in the best interests of patients or the overall health care system. In addition, the 2022 user fee reauthorizations for FDA’s prescription drug/biologic, medical device, biosimilar, and generic drug programs – which Congress must finalize before the end of September, although ideally sooner than that – are without a doubt going to usher in significant changes at the agency.
And with respect to broader, non-program specific reforms, this year FDA created a new Office of Digital Transformation reporting directly to the Office of the Commissioner and a strategic plan for “digital modernization,” which Acting Commissioner Janet Woodcock recently noted in an end-of-year statement as being expected to make “significant additional progress in 2022.” FDA also continued its work developing policies relating to the creation and use of real-world data and real-world evidence, as mandated by Congress in the now-five-year-old 21st Century Cures Act, releasing four draft guidances (see here, here, here, and here) and one final guidance (see here) in the period from September to December. At the tail end of the year, moreover, the agency issued a draft guidance on Digital Health Technologies for Remote Data Acquisition in Clinical Investigations as part of its “efforts to be responsive to [a] rapidly evolving technological ecosystem” and to share recommendations to facilitate the use of such so-called DHTs in clinical research to remotely record and analyze data directly from research participants. The new guidelines also build on the stakeholder engagement resource that is CDRH’s Digital Health Center of Excellence, which was launched last year, by including it as one possible option for regulatory consultations.
Finally, agency veteran Dr. Woodcock got the rare opportunity to serve as acting FDA Commissioner for an entire year, due to President Biden’s decision to nominate Dr. Robert Califf for confirmation for that role only recently. Dr. Califf’s confirmation hearing before the Senate Health, Education, Labor and Pensions (HELP) Committee took place before Christmas, and he is widely expected to receive the necessary votes, setting him up for a somewhat crazy 2022 if he takes the reins from Dr. Woodcock sometime in January. Here’s to hoping that Dr. Woodcock sticks around for a transition period or otherwise accepts Dr. Califf’s reported offer to remain on as part of his leadership team, because there is a lot for him to get up to speed on (hopefully the whirlwind tour above provides some context for that statement!).
©1994-2022 Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. All Rights Reserved.National Law Review, Volume XII, Number 5