Remarks at the FDLI Enforcement, Litigation, and Compliance Conference December 12, 2018

Speech | In Person

• Speech by: Stacy Cline Amin

Remarks by Stacy Cline Amin
Chief Counsel, FDA
FDLI Enforcement, Litigation and Compliance Conference

Thank you for that kind introduction, Jennifer, 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 to ensure the safety of the medical products we use and the food we consume. 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, and to work alongside such a dynamic and passionate Commissioner.

You heard from Commissioner Gottlieb this morning so you’ve now seen first-hand the energy and vision he brings to the FDA. I can say from personal experience that he cares deeply about the agency and its critical public health mission. He is incredibly supportive of the enforcement work the agency does and recognizes that a robust enforcement agenda is essential to ensure the public continues to place trust and confidence in the products regulated by the agency.

I also want to say what an incredible honor it is to work with the leadership in the Centers and the Office of Regulatory Affairs and to 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. It’s a noble calling and so many people at FDA have dedicated their careers to it, including OCC’s Senior Principal Deputy, Liz Dickinson, who served as Chief Counsel as well in the last administration and I know you will have the treat of hearing from tomorrow. Every day I think of how fortunate I am to work with Liz and all of the people like her at FDA.

I am also reminded every day of what an awesome—and I mean that in the traditional way—what an awesome 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 the FDA regulates, 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.

The role of enforcement and compliance 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 medical 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 oversaw 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—the stakes can literally be life or death.

That commitment to the public health is what brought me to this job—the opportunity to work for a cause I believe in and to serve the public. And in my short time at FDA—I’ve only been on the job about three months—I’ve been impressed by the work I’ve seen and proud to be a part of it.

I’d like to focus the rest of my remarks by discussing a few areas in particular: tobacco, opioids, compounding, food safety, and duodenoscopes.

Tobacco

The FDA and the Centers for Disease Control recently published data from the 2018 National Youth Tobacco Survey showing astonishing increases in kids’ use of e-cigarette (or ENDS) products, reversing years of favorable trends in our nation’s fight to prevent youth addiction to tobacco products. From 2017 to 2018, there was a 78 percent increase in current e-cigarette use among high school students and a 48 percent increase among middle school students. The total number of middle and high school students currently using e-cigarettes rose to 3.6 million — that’s 1.5 million more students using these products than the previous year. Additionally, more than a quarter (27.7 percent) of high school current e-cigarette users are using the product regularly (on 20 or more days in the past month). More than two-thirds (67.8 percent) are using flavored e-cigarettes. Both these numbers have risen significantly since 2017.

When this data came out last month, the Commissioner pledged to use all available means to fight this epidemic that threatens to addict a generation of youth to nicotine.

But the agency has seen this trend developing over the course of 2018, and perhaps the most significant enforcement development in the last year has been FDA’s ongoing efforts to fight illegal sales to youth.

Throughout the year, FDA increased its efforts to reverse this trend.  For example:

• From June – September 2018, in the largest coordinated enforcement effort in the FDA's history, the agency issued more than 1,300 warning letters and civil money penalty complaints to retailers who illegally sold e-cigarette products to minors during a nationwide, undercover blitz of brick-and-mortar and online stores this summer.
• In May 2018, FDA issued 17 warning letters, many in partnership with the Federal Trade Commission, for e-liquids with false or misleading advertising or labeling because they imitated kid-friendly food products, such as juice boxes, candies, and cookies.
  • FDA issued a similar warning letter just last month to a manufacturer for nine e-liquids that resemble kid-friendly cereal, candy, and PB&J.
• From April - June 2018, as part of a crackdown focusing on illegal sales of e-cigarettes to minors, FDA issued over 60 Warning Letters or civil money penalties to retailers.
• In October 2018, FDA issued letters to 21 e-cigarette manufacturers requesting information to determine if the products meet the criteria for FDA’s compliance policy for premarket authorization.

In November, when the National Youth Tobacco Survey data came out, the Commissioner directed FDA’s Center for Tobacco Products to revisit its previously announced policy regarding the timing of compliance with the premarketing application requirements of the Federal Food, Drug, and Cosmetic Act (or, “the Act” as we call it at FDA). This will certainly be one of the most significant enforcement areas to watch in 2019.

As Secretary Azar said about youth e-cigarette use: “America’s youth are facing a public health crisis that threatens an entire generation: skyrocketing use of nicotine products, brought on by access to flavored products in particular….E-cigarettes present an important, potentially lifesaving opportunity to help currently addicted adult smokers quit combustible cigarettes. But in trying to build this off-ramp from a deadly addiction, we cannot let e-cigarettes become an on-ramp for kids to enter a lifetime of nicotine addiction and tobacco use.”

Opioids

Tackling the opioid crisis continues to be a top priority for the agency and the administration. As part of its strategy to address this epidemic, FDA has pursued multiple compliance and enforcement efforts.

One area of particular concern is the illegal sale of prescription opioids online and through social media. 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.

In October 2018, as part of Operation Pangea XI, FDA sent warning letters to seven different networks that were operating a total of 465 websites offering misbranded and unapproved drugs to U.S. consumers, including four networks operating approximately 300 websites offering to illegally distribute opioids online. In addition, more than 450 domain names were brought to the attention of search engines and the appropriate domain name registries and registrars. This year’s Operation Pangea also took place at three of the nine international mail facilities (IMFs) in the U.S., as well as at other facilities around the world. Of the 626 packages examined, 794 products were refused entry into the U.S.

We have also pursued criminal cases against those who violate the law and contribute to the opioid crisis. Just recently, DOJ and FDA announced the guilty plea of a corporate executive based on his role in a nationwide conspiracy to bribe practitioners to unnecessarily prescribe addictive, fentanyl-based medications. Targeting this type of conduct is critical to our efforts to combat the crisis.

Finally, FDA has continued to build up staff and resources at the border to help prevent the entry of illegal products. With the passage of the Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act, FDA has been given 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 certain unlabeled and undeclared products. FDA welcomes these new authorities. 

Compounding

As I mentioned earlier in my remarks, I led the Senate’s investigation into the New England Compounding Center fungal meningitis outbreak—so as you might expect, compounding is an enforcement area that has significant personal importance to me.

Since enactment of the DQSA, FDA has conducted nearly 500 inspections, issued more than 180 warning letters advising compounders of significant violations of federal law, issued more than 70 letters referring inspectional findings to state regulatory agencies, overseen more than 150 recalls involving compounded drugs and worked with the Department of Justice on multiple civil and criminal enforcement actions.

Compounded drugs can pose unique risks. They’re not FDA approved and they don’t undergo premarket review for safety, effectiveness or quality. Moreover, if an unregistered compounder distributes drugs to multiple states, it can be very difficult to gather information about whether there are adverse events associated with those drugs, connect them to the compounder, and undertake coordinated action to address a potentially serious public health problem.

One issue that’s been especially concerning to FDA is that we continue to identify insanitary conditions during many inspections of compounders. These conditions present a serious public health risk. Sometimes, these involve situations where the compounders have already been warned to correct violations of law. In such cases, it’s crucial that the FDA work in collaboration with the Department of Justice to act quickly to protect patients.

As an example of such enforcement activity, on April 19, 2018, United States District Judge Baker (E.D. Arkansas), entered a consent decree of permanent injunction against the Cantrell Drug Company, an outsourcing facility, and its Chief Executive Officer.  FDA inspections found that the defendants processed purportedly sterile injectable drugs in an environment that posed a significant risk of microbial contamination.  During inspections in 2018, 2017, and 2016, FDA investigators repeatedly observed that Cantrell failed to conduct adequate investigations of microbial contamination detected in aseptic processing areas where drugs intended to be sterile were processed, and then released those products for distribution notwithstanding the insanitary conditions and violations of current Good Manufacturing Practice requirements under which they were manufactured.  The company was shut down upon entry of the decree, and defendants were prohibited from manufacturing and distributing drugs until they hired an expert to ensure compliance with manufacturing requirements and received FDA’s approval to resume operations.  On September 21, 2018, pursuant to the decree, FDA provided Cantrell with written notification that it could resume operations.  The consent decree remains in effect and authorizes FDA to take action against the defendants for failing to comply with the decree’s terms or applicable laws.

In June 2018, the government entered into a consent decree of permanent injunction with the outsourcing facility Delta Pharmaceuticals and the company’s president and pharmacist-in-charge. FDA sought the consent decree with Delta for manufacturing and distributing purportedly sterile drug products that were adulterated under the Act because the drugs were made under insanitary conditions and in violation of current good manufacturing practice (CGMP) requirements. The consent decree prohibits Delta Pharma and other defendants from manufacturing, processing, packing, holding, or distributing Delta Pharma’s drugs until they comply with the Act and FDA regulations.

When we find compounders that continue to violate the law and put patients at risk, we’re going to hold them accountable. At the same time, we’re also pursuing new policy steps to help make it more feasible for compounders to meet the requirements of becoming an outsourcing facility while still meeting the Act’s core requirements for drug quality. We’re committed to ensuring that we balance the need to preserve access to appropriately compounded drugs with our commitment to help protect patients from drugs compounded under substandard conditions.

Monitoring compliance with the law and taking enforcement action when needed will remain a cornerstone of the FDA’s oversight role because of the ongoing and serious risks poorly compounded drugs can pose.

Food Safety

Food safety is an area that continues to be significant for FDA compliance and enforcement activity to help protect the public from the risks of dangerous food products.

The Food Safety Modernization Act gave FDA new enforcement tools such as facility registration suspension and mandatory recall authority.  FDA has used these tools sparingly, as voluntary recalls are often the quickest and most effective way to get a potentially contaminated product off the market. 

However, in 2018 FDA has had to use its suspension and mandatory recall authorities on multiple occasions. 

On October 19, 2018, the FDA suspended the food facility registration of Working Cow Homemade, Inc. of St. Petersburg, FL, because ice cream manufactured by Working Cow Homemade, Inc. had been linked to three cases of listeriosis.  Working Cow customers included ice cream parlors, independent living facilities and restaurants throughout the state of Florida.  The customer base was especially concerning because Listeria can cause serious and sometimes fatal infections in young children, frail or elderly people, and others with weakened immune systems.  FDA’s 2017 and 2018 inspections of Working Cow Homemade also identified insanitary conditions that could lead to contamination with Listeria in finished products. The firm ceased operations after receiving the registration suspension notice.

On April 2nd, FDA ordered a mandatory recall for the first time. It’s not the first time we’ve taken steps to invoke that authority, but in the previous two instances, receiving a “last chance” letter under section 423(a) of the Act was sufficient to initiate a voluntary recall.

In this case, the company, Triangle Pharmanaturals, refused to initiate a voluntarily recall of food products containing powdered kratom after samples tested positive for Salmonella.

So when the company in this case did not comply with our request for a voluntary recall, we moved quickly to remove these products from the marketplace. FDA determined that there was a reasonable probability that all food products containing powdered kratom manufactured, processed, packed, or held by the company were adulterated under section 402(a)(1) of the Act and that there was a reasonable probability that the use of or exposure to those products would cause serious adverse health consequences or death due to contamination with Salmonella.  This was the first time the agency has issued a mandatory recall order to protect Americans from contaminated food products.

Dixie Dew Products, Inc. – Food Facility Registration Suspension

On March 28, 2017, FDA issued a Suspension of Food Facility Registration Order (Suspension Order) to Dixie Dew Products, Inc. (Dixie Dew) of Erlanger, Kentucky, because FDA determined that foods manufactured, processed, packed, received, or held by Dixie Dew had a reasonable probability of causing serious adverse health consequences or death to humans.  FDA’s decision was primarily based on epidemiological information that their SoyNut Butter products were the likely source of a multistate outbreak of E. coli.  Additionally, during FDA’s most recent inspection of Dixie Dew in March 2017, the agency observed insanitary conditions that could lead to E. coli contamination in the company’s food products.  Shortly upon issuance of the food facility registration suspension, Dixie Dew’s owner informed the agency that the facility would be shutdown permanently.

Scopes

I mentioned duodenoscopes earlier in my speech, and for the past several years, these devices have been a significant focus of enforcement activity for the agency. These scopes are vital for minimally invasive, life-saving procedures to diagnose and treat problems in the pancreas and bile duct. However, because they contain many small working parts that come in contact with a patient’s bodily fluids, they must be thoroughly cleaned and disinfected between each use to prevent transmission of infections.

As part of its enforcement efforts, the FDA ordered all duodenoscope manufacturers—Olympus, Fujifilm, and Pentax—to conduct two postmarket surveillance studies to determine whether health care facilities were able to properly clean and disinfect the devices. On March 9, 2018, the FDA issued Warning Letters to all three device manufacturers for failure to provide sufficient data to meet these postmarketing surveillance requirements. After receiving the letters, the manufacturers collected additional data, and provided the FDA with interim study results.

On Monday, FDA issued a safety communication reporting on the interim study results, which show higher-than-expected contamination rates after reprocessing. Our safety communication included updated recommendations regarding steps that health care providers can take to enhance duodenoscope cleaning, reprocessing, and maintenance.

We rely on manufacturers to report adverse events caused by medical devices to the FDA in a timely manner – generally within 30 days of learning about the event. When they don’t, patients’ safety and sometimes their lives may be put at risk. And when this happens, the agency can and will take action.

For example, also on Monday, Olympus pled guilty to three counts of distributing misbranded devices in interstate commerce for failure to file required adverse event reports involving infections that occurred in Europe in 2012 and 2013 that were associated with a duodenoscope model. The company was fined $80,000,000 and ordered to forfeit $5,000,000.  As part of its plea agreement, Olympus is also required to undertake enhanced compliance measures, including specific measures to assure compliance with MDR reporting requirements.  FDA intends to vigorously enforce the law against device manufacturers that fail to comply with reporting requirements, especially, as in this case, where public health was put at significant risk.

Guidances

Before concluding, I would also like to discuss that 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.  I think of the “rule of law” as the principle that people should 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.

At FDA, I have a practice of always asking—what does the statute say? We spend our briefings parsing the text of Food Drug & Cosmetic Act to ensure agency policy is always consistent with the law. I’m fortunate to have a team of disciplined lawyers that return to the text of the statute to ground the agency and to guide our decisions.

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 instructs the agency to issue guidance to the public. Pursuant to section 701(h), 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 that promote transparency and public participation in the process.

These guidance documents are also 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 essential component of the rule of law because it gives regulated parties notice of FDA’s policies and how FDA interprets its authorities.

Conclusion

And of course, I can’t talk about the rule of law without also giving thanks to our partners at the Department of Justice for all they do help protect and serve the public as well. Tomorrow you’ll hear from James Burnham at the Department of Justice—he’s a smart and effective lawyer and leads a great staff in the Consumer Protection Branch. CPB and the US Attorney offices throughout the country have been excellent partners to the Food and Drug Administration and share our commitment to enforcing the food and drug laws. We also have DOJ to thank for many of the successful actions we’ve taken in the last year to protect the public health.

In conclusion, I want to thank you for indulging me in a long speech. I’m so proud of the work FDA has done and so proud to be a part of this amazing team at FDA—the agency’s Centers, the Office of Regulatory Affairs, the Commissioner’s Office, and of course, my own team in the Office of Chief Counsel. The entire agency is so focused and determined to promote and protect the public health and it is the honor of a lifetime that I can be a part of that. I appreciate that you let me share some of the most important work the agency has done in the last year. 

FDA continues to approve new medical products at a record pace, and we are very proud of that work as well. But the enforcement responsibilities of the agency go hand in hand with the side that promotes innovation and consumer choice. The public counts on FDA to continue to ensure that we are the world leaders in medical innovation and that we have a wide and diverse food options. But the public also trusts us to ensure that the food they consume and the medical products they use are safe—these are equal and complementary responsibilities of the agency.

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.