- Speech by
Stacy Cline Amin
Leadership RoleChief Counsel - Office of the Chief Counsel
Remarks as prepared for delivery
Thank you, Amy, for your introduction and thank you to FDLI for inviting me to speak remotely. I’m really grateful for the opportunity to speak this year. As I sat down to think about my remarks, I have a lot I’d like to say.
It has been, quite simply, an unfathomable year. That’s true for everyone in the world, and especially people who have experienced loss and illness during this time. I want to start out by saying I am heartbroken for everyone who as experienced illness or loss. We are trying our hardest at FDA to help. We have never been so driven by our mission as we are right now. We know that our actions directly impact your health and well-being – we are working harder than ever before and holding ourselves to the highest standards.
The pandemic has broken down all barriers between work and home. Staff are working constantly and at all hours of the day, because all of our work is an emergency now. Any delay reviewing a guidance or an EUA could mean a delay getting someone a necessary test or treatment. There have been no ebbs and flows—it has been constant and relentless. We’ve been running a marathon at a sprint pace.
FDA is an agency that is used to being in the public eye, but not to the degree we have been during the pandemic. I’d like to give my own perspective on some of the areas of our COVID work that have received the most attention, and also commend our staff throughout the agency, who despite every controversy, have done nothing but tirelessly and faithfully execute their responsibilities to the best of their ability.
First, FDA and testing. It has become almost a maxim of the pandemic, that FDA slowed early testing capacity by requiring lab developed tests to get EUAs. I fundamentally disagree with this assessment. EUAs are not a burden. The EUA standard was created specifically to give the agency speed and flexibility during an emergency. CDRH reviewed tests rapidly, authorizing the first test within 24 hours after receiving the EUA request. They engaged extensively with industry even back in January and created templates to facilitate EUA submissions and FDA’s review.
While tests that undergo no review can get on the market faster, it can exacerbate a public health emergency to get a false result and continue spreading into the community. FDA’s premarket review ensures a baseline level of quality and accuracy. It was FDA’s experience in earlier public health emergencies that accuracy is especially critical when dealing with an infectious disease that can spread. Ultimately, we struck what we thought was the right balance between the competing objectives of speed and accuracy – by providing flexibility for diagnostic LDTs to be used while they prepare their EUA and during our review.
After our experience with these LDTs -- seeing a desire to get tests on the market before FDA review, and with the country still suffering from not having adequate testing capacity -- we exercised enforcement discretion for serology tests that had not undergone premarket review. And what happened is the market was flooded with poor performing tests, many of which we’re still struggling to address.
What is remarkable is that I have seen, sometimes in the same sentence, criticism of FDA for requiring LDTs to undergo premarket review, and for not requiring serology tests to undergo that same premarket review. This is the epitome of a no-win situation – every choice is wrong. I want to commend the staff both in OCC and CDRH and throughout the agency who continue to keep their heads up and review an ever-growing queue of EUA requests. I also want to commend those in industry who have developed some of the most innovative tests we’ve ever seen in history. It is an amazing time for in vitro diagnostics -- to see, in a matter of months, the country develop the range and capacity of tests available today.
Another area where it seems like we’ve been criticized from every direction, is over the emergency use authorizations for hydroxychloroquine and convalescent plasma. I just mentioned a moment ago that the EUA standard was created by Congress to give the agency a flexible authority to get products to market that could be helpful during an emergency. It’s not the same as the approval standard. It doesn’t require clinical trials. It doesn’t require proof of safety and efficacy to the same gold standard that would be required under 505 or 351.
So, what does it require? First, it requires a threshold determination by the Secretary that circumstances exist that warrant use of the emergency authority. Once that determination is made, on a case-by-case basis, the agency may authorize a product if, based on the totality of scientific evidence available, the agency determines 1) the product may be effective, 2) the known and potential benefits outweigh the known and potential risks; and 3) there is no adequate, approved, and available alternative.
Chloroquine and hydroxychloroquine, back in March, met this standard, and Convalescent Plasma clearly meets it today. Both of these decisions were made by our career Center Directors. OCC always defers to the Centers on the core scientific determination regarding the risk/benefit analysis, and I feel confident that anyone in the Chief Counsel’s office would stand by these decisions today that the statutory standard was met.
So, let’s rewind, back to the end of March. The country had just gone into quarantine, an unimaginable step at that time. Cases were going up astronomically, we were worried about running out of hospital beds, running out of PPE, running out of ventilators. And the world had NO treatments at that time. Nothing approved and nothing authorized and nothing even very far along in the pipeline. The future looked bleak.
FDA felt the tremendous weight of the situation – every day that we waited for more data on a treatment that could help people was a day that people could die because of our failure to act. And we had to balance that need to get people potential treatments against the potential that the treatment could be ineffective, or worse, harmful.
So, with respect to hydroxychloroquine, we had a drug that at that time in March, had a decades-long safety profile that the agency considered a low-risk drug. And there were no completed clinical trials, but there was some positive observational data. A number of national guidelines had been reported as incorporating recommendations regarding use of chloroquine or hydroxychloroquine in the setting of COVID-19, including guidelines used in countries with more experience with COVID-19 at that time, such as China and Korea.
So CDER decided to authorize hydroxychloroquine for hospitalized patients only—a category of patients whose condition was so severe they were fighting for their lives, and who could be guaranteed to be under the close supervision of a doctor—when clinical trials were not available, or participation was not feasible.
The EUA statute requires us to continue monitoring the appropriateness of the authorization. It can be issued quickly when circumstances warrant it, with whatever scope and conditions the agency believes appropriate, and it can and should be withdrawn if additional data undermines the basis for the authorization. That is how the EUA authority is supposed to work.
The agency’s EUA for convalescent plasma has also been unfortunately politicized and some have turned it into a cautionary tale for the agency as focus shifts to vaccines. I want to say clearly – the statutory standard for an EUA was met for convalescent plasma, and it is helping people today get access to this potentially life-saving therapy.
Regarding a vaccine, FDA believes the risk/benefit calculus under an EUA is much different when evaluating a prophylactic that would potentially be given to millions of healthy people, than it is when evaluating a therapy that would only be given to people who are already sick and fighting for their lives. For a vaccine, we are looking for an assurance of safety and a demonstration of efficacy that comes much closer to the BLA standard than what we have required for some therapeutics that are intended for very sick, hospitalized patients.
I’m not sure what could be surprising or alarming about that. FDA has not “raised the bar” for an EUA, as has been inaccurately reported. FDA issued a guidance in June that said an EUA might be appropriate where studies have demonstrated the safety and effectiveness of the vaccine, but before a complete BLA has been submitted or reviewed. As is typical during pre-review consultations, FDA scientists have extensively discussed the details of what we would consider to establish the safety and efficacy of a vaccine.
The manufacturers know what data we recommend submitting, and our scientists will not authorize a vaccine if safety and efficacy have not been demonstrated. There is not a single person at the Food and Drug Administration that would stand for anything less than that.
The leadership at FDA realizes that authorizing or licensing a vaccine for COVID is perhaps the most consequential action the agency will ever take. We will stand by our scientists no matter what.
The agency’s work on COVID-19 has given us an incredible amount to be proud of. We have 268 EUAs in effect for diagnostic and serology tests, 47 EUAs for other devices including personal protective equipment and an umbrella EUA for ventilators, covering dozens of ventilator models, tubing and other accessories, and 5 EUAs for therapeutics, including the recently expanded EUA for remdesivir.
Early in the pandemic, the Office of Chief Counsel worked with the Office of Policy and the Centers to develop a streamlined process to issue guidances in compliance with our Good Guidance Practices, which has helped us to issue 62 guidances. At our fastest we saw guidances conceived, drafted, and cleared all the way through the White House in as little as 24 hours. It’s a testament to the incredible team work across FDA that we’ve accomplished in months what would normally take years.
The same can be said of the agency’s compliance and enforcement work combatting unproven medical products marketed as tests or treatments for COVID-19. In just months, we’ve issued over 115 warning letters and sent hundreds of complaints to internet marketplaces and domain name registrars. In addition, working closely with the Department of Justice, we have obtained two temporary restraining orders under the FDCA, including one case that has already resulted in the issuance of a permanent injunction, and supported eight criminal prosecutions under the FDCA.
Those injunctions in particular represent some of the work I am proudest of during my entire tenure. Working together with the Consumer Protection Branch and DOJ leadership, we saw that COVID presented the opportunity to create a model for a more streamlined approach to compliance and enforcement. For products marketed to treat or prevent COVID, we have issued warning letters requesting response in only two days. We hope to obtain quick voluntary compliance and thereby mitigate the harm from unproven and potentially dangerous products marketed to a vulnerable public.
Where we have not achieved quick compliance, we have worked hand in hand with the Dept of Justice to bring TROs for the first time in decades. We have obtained two TROs, of which one has been converted to a permanent injunction and the other has been converted to a preliminary injunction. And we have other injunctions in the works.
This kind of work is extremely resource intensive. It’s not the kind of thing we can do on every case during normal times. But I’m incredibly proud of the teams in the agency that set this precedent for us anew and believe this will inspire a new era of compliance and enforcement for FDA.
When we see violative conduct that poses an immediate risk to public safety, and we cannot obtain voluntary compliance, we’ve now seen that we can enjoin that conduct on an emergency timeline to protect the public.
I never intended for this speech to only be about our COVID work. The agency has made important advancements on other priorities over the last year and I’d like to talk about that work as well. I understand that in the past some Chief Counsels have done “top 10” lists, so I thought it would be fun to quickly touch on my non-COVID top 10 list. Disclaimer: this is not a ranking, just a list of what I consider to be interesting legal developments.
- E-cigarettes – The e-cigarette battles of 2019 seem almost quaint now compared to COVID, but what a rollercoaster it was, nearly consuming the tenure of four different commissioners over the course of a year. OCC has played a critical role throughout – helping to craft the Jan 2020 policy that, knock on wood, has so far survived challenge in three different courts, and required the most complicated three-dimensional chess I have ever experienced. And I’m happy to say that, after two years of disturbing increases in youth e-cigarette use, we are encouraged that new data from the 2020 National Youth Tobacco Survey show 1.8 million fewer U.S. youth are currently using e-cigarettes compared to 2019. I also want to highlight the DC Circuit’s recent Nicopure decision, which we’re extremely happy with both on the First Amendment issues as well as the statutory issues.
- GE Salmon litigation – FDA’s approval of a genetically altered salmon has been mired in years of congressional delays and litigation. We got an important decision last December from the Northern District of California affirming FDA’s decades-old interpretation of the FDCA to encompass such intentional genomic alterations as animal drugs. The district court is still considering the environmental claims in that suit.
- Cigarette Health Warnings Final Rule – Cigarette smoking remains the leading cause of preventable disease and death in the United States and is responsible for a host of lesser-known but still serious health consequences. This rule is one of the most important steps the agency has taken to advance public health during my tenure. The tobacco industry has hired armies of lawyers from every top law firm in DC to try to keep this rule from going into effect. These lawsuits are on my top 10 cases to watch.
- DC Circuit’s Ipsen decision on final agency action – we’ve been sued four times over the last year by litigants challenging actions that FDA wouldn’t consider reviewable. While we’ve won all of those suits in courts that have issued decisions, this is certainly an area that will remain active, and was made even more lively by the Ipsen decision.
- Supreme Court’s DACA decision – as one of the government’s most frequent adopters of enforcement discretion policies, we are watching very closely how the Regents case gets interpreted by the lower courts. We already have one active lawsuit making a Regents challenge to the withdrawal of an FDA enforcement discretion policy.
- Appointments Clause – I wonder how many of you haven’t thought of this obscure provision of the Constitution since law school? Well, it’s on the vanguard among those who seek to shrink the administrative state. Senate-confirmed officials are clearly officers of the United States, and out of an abundance of caution, FDA has had our rules signed by Senate-confirmed officials for over a year. (As an addendum to the subject of constitutional doctrines making a comeback, the nondelegation clause has also been on the rise post-the Supreme Court’s decision in Gundy. I would expect this to be an area of interest in the future, especially if the Court shifts more conservative.)
- State Importation Plan Final Rule – we took a decades-old statutory provision and interpreted it in a completely novel way. This final rule is on my list because of the incredible lawyering it took to find a path forward that would protect the safety of the drug supply chain.
- Intended Use – we proposed an NPRM to clarify the regulatory language describing the types of evidence we consider relevant to determining a product’s intended uses, including that any relevant source of evidence may be considered. The proposed revisions also clarify an important point: that a firm’s knowledge that a health care provider has prescribed or used an approved or cleared medical product for an unapproved use, standing alone, is not sufficient to establish the product’s intended use.
- Food Safety – It’s been a busy year for food safety. We announced the New Era of Smarter Food Safety Blueprint to leverage technology and other tools to create a safer and more digital, traceable food system. We drafted and proposed the FSMA 204 traceability rule in just a year. And we’ve also been working hard on the Ag Water rule, which I consider to be one of the most significant contributions we could make to public health across our entire portfolio. Our ultimate goal is to bend the curve of foodborne illness in this country. While I’m not sure that this is really one of the top 10 legal developments this year, it belongs on this list because it’s among the work I am proudest of.
- Exclusivity/Biologics Transition Issues – we haven’t had as much generic drug litigation in my tenure as we have litigation over orphan and 505(b)(2) exclusivity. The “deemed to be a license” transition in March for certain biological products makes the last spot on my top 10 list, both as an important regulatory step, and also, as with any area of our jurisdiction where our interpretive decisions could impact exclusivity or competition, this will be one to watch.
When I accepted this job, I thought I’d be working in relative obscurity at an operating division of an agency located out in White Oak, Maryland. The reality of my tenure here could not be further from that. I remember –several lifetimes ago -- when the government shutdown felt like one of the worst storms the agency had ever weathered. I recall a mentor telling me at that time, “I’ll be remembered as the chief counsel who served during the longest shutdown in history.” Now the shutdown feels like a footnote. The agency’s leadership worked through two Christmases and New Years in a row—first on the shutdown and then on e-cigarettes—just to head into 2020 facing the worst global pandemic of our lifetimes.
I may never get the chance again to say this publicly, so I want to say it now – I am so honored I had this opportunity to lead this amazing group of lawyers at FDA, and to advance a mission that I support with every piece of my heart. I’m so grateful to Commissioner Gottlieb for having the trust and confidence in me to hire me into such an important role. He will forever be a mentor to me. We all learned so much from his leadership.
I’m grateful to Dr. Sharpless and Adm. Giroir for what really felt like friendship as much as partnership and stewardship of the agency during a tumultuous time.
And I’m grateful to Commissioner Hahn, who has shown a fortitude during crisis that I think few people will ever fully appreciate or understand. I may be one of the few who have seen even a piece of his moral strength up close, and I want to thank him for everything he has done to stand strong for this agency. I know he and the entire FDA leadership team will continue to stand by our scientists and public health experts – we will follow the law and the science and make the best decisions for the American public.