FDA Chief Counsel's Remarks to the 2019 FDLI Policy Conference May 2, 2019

Speech | In Person

• Speech by: Stacy Cline Amin

Washington, DC

(Remarks as prepared for delivery)

Thank you for that kind introduction, Jeff, and thank you to FDLI for inviting me to be here today.

I’m grateful to have the opportunity to talk about the important work the agency is doing. But before I do, I’d like to say a few words about what an honor it is to serve at the Food and Drug Administration.

I am reminded every day of what an awe-inspiring responsibility we shoulder at FDA. We regulate a fifth of the U.S. economy and our work impacts every single person in this country. Everyone in this country eats food FDA regulates, uses OTC or cosmetic products, many people have pets, and everyone at some point in their lives will need medical products. I’m not sure there’s any other agency of the U.S. government that has such an immediate and significant impact on people’s lives.

It is an incredible honor to work with the leadership of the agency and lead the brilliant and dedicated public servants in the Office of Chief Counsel. I’ve never before had the privilege of working with a group of people so talented and so dedicated to the singular purpose of improving and promoting public health.

For those of you in the audience who might be thinking about whether you’d like to work in the Office of Chief Counsel (or “OCC” as we call it), let me assure you that you will find no other work as rewarding or meaningful as the work you could do as one of FDA’s lawyers. And I believe that even for FDA, the OCC culture is special and makes it a very special place to work.

I’d also like to comment on what I’m sure everyone here is very curious about—the transition from Commissioner Gottlieb to Acting Commissioner Sharpless.

I’d like to be able to make a joke now about how my lawyers are finally getting some sleep because we don’t have as many press releases to review, but in fact the pace of the agency’s work has not let up at all under Commissioner Sharpless. There was an article in the Pink Sheet last week that noted this as well—saying “No Slow Down in FDA Communications Post-Gottlieb.”

Dr. Sharpless has dedicated his life to improving patient care, and that passion is a perfect match for the mission of FDA. He is a brilliant scientist and cancer researcher, and he has brought a scientist’s mindset to how he examines problems that is a great complement to all the lawyers at FDA. I also have to say that I have been amazed by his ability to absorb so many new issues so quickly—that really speaks to how brilliant he is.

We also have a new Principal Deputy Commissioner, Dr. Amy Abernethy, and Deputy Commissioner Frank Yiannis. I have enjoyed working with both of them—they are both committed to the agency’s mission and to using technology to address some of our current challenges to further advance public health. The government is often slow to adapt to changing technology, and that’s especially true in health care. One of the things I am most excited to be a part of is helping Commissioner Sharpless, Amy and Frank modernize our regulatory efforts.

The agency is fortunate to have such talented and accomplished leaders, and that includes our tireless Chief of Staff, Lauren Silvis.

So with those introductory comments, I’d like to dedicate the rest of my talk to giving an overview of the areas that I expect to dominate my time over the next year.

Enforcement

I’d like to start with enforcement, because FDA’s enforcement work is what brought me to the agency, and aside from maintaining the rule of law (which I’ll get to later in this speech), advancing our enforcement work has been my first priority at FDA.

The role of enforcement is particularly salient to the welfare of the public. We, the FDA and industry together, have a joint mission to ensure the safety of the food we eat and the products we use. The consequences of failure are severe.

Before I ever joined the executive branch, I worked on the Senate Health Committee, where I led investigations into the fungal meningitis outbreak caused by the New England Compounding Center and the superbug infections associated with reprocessed duodenoscopes. The impact on patients and their families caused by those outbreaks is haunting and is a constant reminder to me of the importance of the work we do at FDA—the stakes can literally be life or death.

That commitment to protecting the public health is what brought me to this job and it continues to be a passion.

Compounding

As you might expect from my work in the Senate, compounding is an enforcement area that has significant personal importance to me. Compounded drugs can pose unique risks. They’re not FDA approved and they don’t undergo premarket review for safety, effectiveness or quality.

Since enactment of the DQSA in 2013, FDA has conducted over 700 inspections, issued more than 200 warning letters advising compounders of significant violations of federal law, issued more than 100 letters referring inspectional findings to state regulatory agencies, overseen more than 200 recalls involving compounded drugs and worked with the Department of Justice on multiple civil and criminal enforcement actions.

In one recent case, the former CEO and owner of Pharmakon Pharmaceuticals, Inc., an Indiana-based 503B drug compounding facility, was convicted by a federal jury in the Southern District of Indiana of felony conspiracy and adulteration. This follows the earlier conviction of the former Compliance Director of Pharmakon, who was just sentenced to prison earlier this week. 

From 2013 to 2016, in addition to affirmatively misleading the FDA and interfering with FDA inspections, Pharmakon routinely shipped compounded drugs to customers without having received laboratory tests to verify that the drugs were the strength they were supposed to be, and Pharmakon failed to recall the drugs, notify the customer, or notify FDA of potency failures, or conduct any investigation to determine the cause of the failure. This conduct led to the distribution of approximately 70 lots of super- or sub-potent drugs nationally, including super potent morphine that was injected into three neonatal infants. One infant had to be revived through Narcan and sent by helicopter to receive ICU treatment.

In another recent case, the District Court for the Northern District of Texas entered a consent decree of permanent injunction against Guardian Pharmacy Services and Guardian’s owner. According to the complaint, defendants’ drugs were adulterated because they were prepared, packed, or held under insanitary conditions whereby they may have been contaminated or may have been rendered injurious to health. At least 43 patients who were administered eye injunctions compounded by Guardian developed symptoms including vision impairment.

Opioids

Tackling the opioid crisis continues to be a top priority for the President and the entire Administration. Commissioner Sharpless talked about many of our efforts to combat the opioid crisis, but I’d like to focus on our enforcement efforts.

One area of particular concern is the illegal sale of prescription opioids online, through rogue internet pharmacies, social media, and even the dark net. Patients who buy prescription medicines from illegal online pharmacies may be putting their health at risk because the products, while being passed off as authentic, may be counterfeit, contaminated, expired, or otherwise unsafe. In many cases, products illegally marketed online as opioids are counterfeit drugs that can contain potentially lethal doses of illicit compounds like fentanyl. Just two milligrams of fentanyl can be lethal—if I were to hold up a penny, the amount of lethal fentanyl would take up just a small dot.

Since 2017, FDA has sent warning letters to 23 networks operating more than 450 websites illegally marketing potentially dangerous, unapproved, and misbranded versions of opioids. In addition, more than 450 domain names were brought to the attention of search engines and the appropriate domain name registries and registrars. We have also pursued criminal cases against those who violate the law and contribute to the opioid crisis.

FDA has continued to build up staff and resources at the border to help prevent the entry of illegal products. Section 3022 of the SUPPORT Act (new section 801(u) of the FDCA) gives FDA new authorities to more efficiently stop illicit and potentially dangerous drugs from entering the U.S. through international mail facilities. For example, FDA will now be able to more easily detain, refuse, and destroy unlabeled and undeclared products containing certain active pharmaceutical ingredients that present significant public health concern.

We’re also doing more to secure the legitimate supply chain. This will mean doing more to hold distributors responsible for securing the drug supply chain under the Drug Supply Chain Security Act.

Stem Cells

There are many other enforcement priorities I would love to highlight in this speech, but I could keep you here all day, so I’ll just highlight one other area—stem cell therapies. 
The agency believes these products hold tremendous potential. Legitimate and well-intentioned investigators and firms are doing the essential groundwork to develop stem cell products.

But stem cell products can create unique and serious risks if they are more than minimally manipulated. Some actors are flouting the law and deceiving patients by illegally manufacturing or selling purported therapies, and falsely promoting their benefits. We’ve seen cases of companies making unsubstantiated claims that these treatments prevent, cure, or mitigate disease where the products have led to serious patient harm.

For all of our enforcement work, I must express my gratitude to the work done by our Office of Regulatory Affairs and Office of Criminal Investigations and our Center compliance offices—especially CDER’s compliance office for compounding and opioid work (led by Don Ashley, who shows an extraordinary passion for public safety), and CBER’s tireless work on illegal stem cell therapies.

I also want to recognize the tremendous work done by the Department of Justice.  Until recently, my good friend James Burnham led the Consumer Protection Branch and we have been fortunate for his exceptional leadership. I also want to thank the CPB Director Gus Eyler, who has been a wonderful partner to us and dedicated to our cases. We recognize how fortunate we have been to have both James and Gus at CPB, and thank the entire staff at CPB for their commitment to public health.

Tobacco

The agency’s tobacco work has been such a significant part of FDA’s work during my tenure, I’d be remiss if I didn’t discuss it next.

As many of you at this conference know well, some of the most important court cases in FDA’s recent history have been in the tobacco space, starting with the Supreme Court’s decision in Brown & Williamson in 2000 and including more recent cases interpreting the First Amendment in the context of FDA regulation of tobacco marketing.

For example, in 2012, the Sixth Circuit upheld the statutory provision that directs FDA to develop graphic health warnings for cigarettes, while the D.C. Circuit struck down FDA’s first attempt to do so. FDA has been actively engaged in the formidable task of developing a new proposal that appropriately accounts for the DC Circuit decision, while fulfilling our public health mandate to ensure the public is better informed of the health consequences of smoking.

FDA’s 2016 “deeming rule” has also been a source of active litigation for the agency. We’ve had more than a dozen lawsuits challenging various aspects of the deeming rule in federal courts across the country. Those cases continue to be a very active part of FDA’s litigation docket, with some aspects of the challenges on appeal in the DC Circuit following our successful defense of the rule in D.C. District Court. Other cases are still being briefed and argued in district court, while some have been stayed pending or consolidated with similar cases. With all that litigation, the core action the agency took to deem cigars and ENDS products as subject to FDA’s regulatory authority has consistently been upheld in district court.

In April, FDA issued a proposed rule to establish requirements for the content and format of reports intended to establish the substantial equivalence of a tobacco product. That NPRM is an important step forward in establishing the tobacco program’s foundational rules. The agency continues to work hard on a number of proposed rules, including for Pre-market Tobacco Product applications as well as Modified Risk Tobacco Products.

Perhaps the most significant development during my tenure has been FDA’s ongoing efforts to fight illegal sales of e-cigarettes to youth. Secretary Azar has called this “a public health crisis that threatens an entire generation.”

In March, with the strong support of Secretary Azar and President Trump, FDA proposed revisions to our current compliance policy as it applies to flavored ENDS products (other than tobacco-, mint-, and menthol-flavored). Under the proposed policy, we put all manufacturers and retailers on notice: you may be subject to FDA enforcement for selling certain flavored ENDS products without authorization, and propose to prioritize enforcement where the risk to minors is greatest.

Food Safety & Technology

Next I’d like to discuss food safety and technology. Deputy Commissioner Yiannis at FDA brings an unmatched knowledge of the industry and a passion for modernizing our food safety efforts, and he and Commissioner Sharpless have already demonstrated they will have a great partnership in achieving that progress.

Since arriving at FDA and learning about the breadth of our food and nutrition portfolio, it’s caused me to reflect a lot on how different our grocery stores and dinner tables are now vs. when I was a kid. Granted, I grew up in the Midwest and trends always seem travel to the heartland last, but the variety of foods accessible now is vastly different than what I remember from 30 years ago. We have a freezer (a small freezer, but still, an entire freezer!) devoted to the Gujarati spices my mother-in-law brings us we get from the Indian grocery store, and my toddler eats fruits I didn’t even know existed when I was well into my 20s.

When I got married, a friend of mine gave us a cookbook from the 1950s. It is like looking at a piece of history compared to how we cook now and how our palette has changed. There’s a section on making “curry,” described in the cookbook as exotic, that made us laugh after it grossed us out—the recipe calls for mixing what I can only describe as yellow powder with mayonnaise! I can promise you we have not made a single recipe from that cookbook, but we enjoy reading it as an artifact of life before globalization of the food supply chain.

The U.S. imports about 15 percent of its overall food supply from more than 200 countries or territories representing about 125,000 international food facilities and farms. Over the past 15 years alone, we’ve seen a trend of rising imported foods. Other countries now supply about 32 percent of the fresh vegetables, 55 percent of the fresh fruit and 94 percent of the seafood that Americans enjoy.

FDA has worked hard to ensure the safety imported human and animal drugs. We are excited about a new effort announced earlier this week, that FDA plans to conduct a new pilot that will leverage artificial intelligence and machine learning to explore new ways to enhance the agency’s review of imported foods at ports of entry to ensure they meet U.S. food safety standards.

FDA has also had great success leveraging technology to advance food safety, especially in the use of new analytical tools like the GenomeTrakr Network. When it comes to food traceability, many in the food system utilize a largely paper-based system of taking one step forward to identify where the food has gone and one step back to identify the source. The use of new and evolving digital technologies could potentially play a pivotal role in tracing the origin of a contaminated food to its source in minutes, or even seconds, instead of days or weeks, when contamination does occur.

To help accomplish this goal, earlier this week FDA announced that we’ll be working on a New Era of Smarter Food Safety to explore opportunities for new technologies to rapidly track and trace food through the supply chain.

We expect to see even more innovation in the agriculture, food production, and food distribution systems in the next 10 years than we’ve seen in the past 20, which will continue to provide an even greater variety of food options and delivery conveniences to American consumers.

As an example, biotechnologies are enabling the development of many promising, innovative food products, such as genome-edited animals and plants. At the same time, we are seeing increased interest in the development of new protein sources, such as cell-culture technology. Part of our public health mission is to advance these promising innovations—by clarifying our science-and-risk based approach for product developers and avoiding unnecessary barriers to future innovation—while also ensuring they’re safe and don’t have any unintended consequences.

It’s a very exciting time to be a foods lawyer at FDA. All these emerging technologies must be addressed through a statutory regime that was enacted before blockchain technology or meat grown from cultured cells ever existed. That of course means that we are addressing novel legal questions at the cutting edge of law. I look forward to helping the agency navigate through the FDCA as we move into a future that seems closer to Star Trek food replicators than that cookbook from the 1950s.

Artificial Intelligence - Devices

In the spirit of rapidly evolving technologies, we don’t just see the promise of Artificial Intelligence in the food safety context. Artificial intelligence and machine learning have the potential to fundamentally transform the delivery of health care. As technology and science advance, we can expect to see earlier disease detection, more accurate diagnosis, more targeted therapies and significant improvements in personalized medicine.

The ability of artificial intelligence and machine learning software to learn from real-world feedback and improve its performance is spurring innovation and leading to the development of novel medical devices. This is one of the technological advancements that holds the most promise for the future, but will also pose unique regulatory challenges.

Artificial intelligence algorithms are software that can learn from and act on data. These types of algorithms are already being used to aid in screening for diseases and to provide treatment recommendations. Last year, the FDA authorized an artificial intelligence based device for detecting diabetic retinopathy, an eye disease that can cause vision loss. The agency also authorized a second artificial intelligence based device for alerting providers of a potential stroke in patients.

FDA expects to see more medical devices incorporate advanced artificial intelligence algorithms to improve their performance and safety. In March, FDA released a discussion paper outlining a potential new regulatory framework specifically tailored to promote the development of safe and effective medical devices that use advanced artificial intelligence algorithms.

Our Device Center leadership has tackled the regulatory challenges faced by evolving technology at a breakneck pace. I am looking forward to working closely with Dr. Abernethy, as FDA’s new CIO, and all of the Device Center leadership on AI issues.

DCAP/BAP

I would next like to highlight an area that is one of the agency’s proudest—our work to make generic drug and biosimilar development more efficient and predictable. Our efforts have helped foster competition in the marketplace with the ultimate goal of improving access to high quality, affordable treatment options for Americans and improving patient care.

We’ve made significant progress over the past year advancing efforts that have helped to strengthen and streamline the generic drug review process – setting record numbers for generic drug approvals and tentative approvals from 2017-2018; providing scientific clarity and guidance to support the development of hard-to-develop complex generics; and calling out potential abuses of the system where companies were using tactics to delay market entry of generic competitors. And we’re also working to provide the generic industry with increased transparency to provide greater certainty around timing of first possible generic entry and potential competition from other generic entrants, and to make the scale up of manufacturing more efficient, to enable more informed decisions on how to prioritize their resources and come to market.

One of the ways we’ve been able to do that is through the dizzying pace in which we are putting out guidance to industry. Since February 2019 alone, we’ve issued more than 35 draft guidances and two final guidances, including over 22 product specific guidances.

In addition to some of the more technical and product-specific guidances, we have issued several guidances related to the application process, itself. And we’re taking important steps to modernize the Orange Book to provide transparency around circumstances where generic competition is lacking. Building on those efforts, in March, FDA issued the new draft guidance aptly titled, Competitive Generic Therapies, to help provide even greater clarity to industry about the CGT pathway.

Addressing the challenges related to developing generics, and promoting more generic competition to these medicines, is a key part of our Drug Competition Action Plan, and the agency’s efforts to help advance patient access to more affordable medicines.

As part of the Biosimilars Action Plan, or BAP, which was released in July of 2018, FDA has also been very busy providing guidance on the development of biosimilars. As part of the BAP, we have issued 3 draft guidances and 3 final guidances, as well as one proposed rule that are aimed at providing scientific and regulatory clarity for the biosimilar product development community and products currently regulated under NDAs that will be transitioned to BLAs on March 23, 2020.

Guidances

The guidance we have provided to product sponsors is an important topic for another reason, because the executive branch’s use of guidance documents has been under scrutiny in recent years. FDA’s mission is not only to protect and promote the public health, but like all agencies in the federal government, we have a responsibility to use our enforcement authorities in a way that’s consistent with the rule of law. That means our public health mission only extends as far as our statutes allow.

I think of the “rule of law” as the principle that people should be governed by law and not by the arbitrary decisions of government officials. The rule of law allows people and businesses to know in advance what rules will govern them; it is not only about fairness but also about giving American industry a foundation of predictability and consistency to allow them to continue to innovate.

This Administration is committed to the rule of law, and one of the areas we’ve seen that is in the approach to guidance documents.  The Justice Department’s 2018 “Brand Memo” prohibits DOJ litigators from using agency guidance documents as a basis for proving violations of applicable law. The memo prohibits the use of agency guidance in a way that would effectively convert them into regulations, thereby making an end run around notice and comment rulemaking.

The Solicitor General of the United States recently filed a brief with the Supreme Court arguing that limits should be put on the circumstances in which agency interpretations of ambiguous regulations, including those issued in guidance documents, should receive the heightened deference known by the courts as Auer, or sometimes Seminole Rock, deference. However, the Solicitor General did not advocate for agencies getting no deference at all, as some in the legal community had advocated.

I attended the oral argument in March, and it was a lively argument with heated questions from the justices for both sides. I think it’s fair to say that nobody outside of 1 First Street can predict how the case is going to come out, but it is the most significant case for federal agencies that the Court will decide this term, if not in the last decade.

I’m keenly aware of the scrutiny on agency guidance practices, and have made it part of my mission at FDA to ensure our guidances withstand that scrutiny.

But our guidance documents are important because they give industry notice of FDA’s regulatory policies, how FDA interprets its statutes and regulations, and where FDA intends to focus its finite enforcement resources. These guidance documents are not themselves binding—only the statute and the agency’s regulations can impose binding obligations. But non-binding guidance is an important component of the rule of law because it gives regulated parties notice of FDA’s policies and how FDA interprets its authorities.

We also have a unique history with guidance documents at FDA—our governing statute contemplates the use of agency guidance documents in section 701(h) of the Act, and in many cases Congress actually writes into our statute instructions to the agency to issue guidance to the public.

Because of this unique history, FDA’s process for issuing guidances is in many ways a model of good practices. Most FDA guidance documents are issued in draft form first to allow for a period of notice and comment before a guidance document is finalized. This is pursuant to section 701(h) and the Good Guidance Practices regulations FDA issued implementing that section, which require a notice and comment period and other procedural protections for many guidances. There is always room for improvement, but we believe our process promotes transparency and public participation in the process.

Conclusion

In conclusion, I want to thank you for indulging me in a long speech. I’m so proud of the work FDA does and consider it the honor of a lifetime that I can be a part of it. 

Together with the Department of Justice and OCC’s partners within the agency, I look forward to our continued, successful efforts in service of public health. And I hope that industry will help to share and promote that mission.