Remarks by FDA Commissioner Robert Califf at the Rx and Illicit Drug Summit April 1, 2024

Speech | In Person

• Speech by: Robert M. Califf, M.D., MACC

(Remarks as prepared for delivery)

Good afternoon. I want to thank Nancy Hale of Operation Unite and Congressman Hal Rogers for once again inviting me to be with you at this important gathering.  

This event has been an essential meeting place where concerned family members, health officials, caregivers, policy makers, and others come together to share experiences, find answers, and develop creative solutions for the continuing challenges posed by our nation’s tragic overdose epidemic.   

The engagement, experience, and activism of the people in this room have not only helped catalyze the nation’s response to this crisis, putting and keeping it on the front burner, but you have helped build partnerships, provide support and empowerment to families and policy makers alike, and advocated for important changes that have led to new and effective strategies to change the trajectory of this epidemic. 

Your impact on both federal and local policy is clear, further confirmed both by the presence of so many public officials at this meeting, as well as by each of our agency’s efforts – individually and in combination – to initiate and develop helpful policies and products in response to this crisis.  Since launching our Overdose Prevention Framework in August, 2022, we have taken some important steps to address this overdose crisis. Today, I want to focus on some of the most recent developments specific to the FDA that I believe are having a positive impact, including important gains in encouraging harm reduction and supporting the development and approval of overdose reversal agents.

But it’s also important for all of us to acknowledge that even as our collective and collaborative response has helped lead to some successes, the crisis persists and, unfortunately, continues to bring enormous pain to too many individuals and their families.  So today I also want to address some of these emerging sources of harm and the changing nature of this crisis, including the impact of new and illicit products and evolving means of distribution.  

As a physician and clinician I have been engaged with this issue for many years –at the FDA, before that as an intensive care cardiologist with a large outpatient practice, as a researcher involved in NIDA’s clinical trials effort, and in my work with individuals struggling with substance use disorders and overdoses.  In all of this work I’ve seen how even with successful strategies at our disposal, patients can still struggle due to complex societal factors that are continuing to evolve in ways that are not entirely predictable.    

Perhaps it is because of my background in medicine and research, but the challenges we face today remind me in some ways of our encounters with viruses.  Even after we have developed the means to eradicate them, through vaccines and other responses, the viruses find ways to adapt to the humans they target and thereby further endanger them.  

The analogy is not perfect, of course; opioids and stimulants are not viruses.  Indeed, the new threats from illicit drug use, including the increasing use of illicit stimulants and other substances, are troubling precisely because the new threats are not naturally occurring phenomena like viruses, but the result of human generated changes and often insidious actions designed specifically to take advantage of vulnerable people and put them at risk. 

It’s been said that it’s not the strongest or most intelligent species that survive, but instead those that are most adaptable to change.  Those who are promulgating these dangerous illicit drugs have changed their tactics, and we are determined that across government agencies we will adapt our strategies to stem the tide.  But we will succeed only if we continue to partner with patients, families, and the relevant industries for this complex problem. The original crisis had many sources, but certainly one of the main challenges we faced was the inappropriate prescribing and marketing of opioids, often with too little evidence to guide clinical practice.  

In no small part due to your efforts, we made significant progress in reducing this unnecessary exposure to prescription opioids.  Today, however, the threat is not only more potent, but more widespread, with not only illicit fentanyl and its analogs causing harm, but other substances, such as illicit stimulants and benzodiazepines that are being used in combination with opioids.  And, increasingly, we see even more dangerous combinations, the result of the addition of illicit and toxic products.  And because of the way these illicit products are being manufactured, often the person taking a dangerous combination of substances isn’t even aware of the risk. 

I want to spend some time today talking about this new threat, which includes the growing danger that comes from the distribution of these illicit substances online, through the mail, and by cartels, and some of the actions the FDA is taking in response. 

Before I turn to that, however, I want to discuss some important developments of the past year that have helped prevent the misuse of substances with abuse potential, specifically prescription opioids and stimulants.  

Last year, for example, we announced the final approval and implementation of required safety labeling updates for immediate-release and extended-release/long-acting opioid analgesics. We took this action to reduce the risk of overdoses for all opioid pain medicines and to urge health care professionals to take a more patient-centered approach when prescribing opioid analgesic products. This included recognizing that many acute pain conditions treated in the outpatient setting require no more than a few days of an opioid pain medicine. We further recommended that extended-release/long-acting opioid pain medicines be reserved for severe and persistent pain that requires an extended treatment period with a daily opioid pain medicine and for which alternative treatment options are inadequate.  

We also required a class-wide safety labeling change for certain stimulant medications used to treat ADHD and other disorders to more clearly inform patients, caregivers and health care professionals of risks associated with their prescription medications.  This was one of several actions we took to support the safe use of prescription stimulants and better understand diagnosis and treatment of ADHD in adults.

This is particularly important because misuse of prescription stimulants and use of illicit stimulants can give rise to stimulant use disorder, and we do not have an FDA-approved medication to treat stimulant use disorder. To address this challenge, we have issued draft guidance to support the development of novel therapies that are critically needed to address treatment gaps in this area. This guidance, when finalized, will help the overall development program and clinical trial design to develop drugs and biologics in support of treatment of moderate to severe cocaine, methamphetamine, and prescription stimulant use disorders.   in addition, we hope that the NIH’s important research efforts will help identify and develop treatment targets, which in turn will lead to the development of safe and effective medicines.

Another important area of focus is harm reduction through increased access to opioid overdose reversal agents. No overdose should be fatal. Yet in 2023, more than 112,000 Americans lost their lives to an overdose.  Last year when I spoke with you, the FDA had just approved the first over the counter branded naloxone nasal spray.   That was an important development.  But progress didn’t stop there.  

We have since approved a second branded OTC naloxone nasal spray, as well as the first generic OTC naloxone nasal spray.  We will continue to review both prescription and OTC naloxone products. And we also approved the first nalmefene hydrochloride nasal spray, developed with NIH funding and available by prescription to treat opioid overdoses. You’ll hear more about these developments later this week from one of my FDA colleagues, Dr. Marta Sokolowska. She will also highlight how we collaborate with our sister agencies at Health and Human Services to increase access to these lifesaving overdose reversal agents among individuals and communities who need them. Only by working together will we achieve the goal of preventing fatal overdoses.

As someone who has been focused throughout my career on the quality and quantity of data and evidence about which interventions truly work and which interventions are ineffective, I believe it is especially important that our policies and actions in response to the overdose crisis are guided by evidence.  This is particularly significant when it comes to the development of new substance use disorder treatment formulations and advances in the science on initiation and treatment with buprenorphine in the context of fentanyl. 

I’m pleased that we have been able to approve new medication formulations for treatment of substance use disorder, including an extended-release buprenorphine injection to treat moderate to severe opioid use disorder and the first generic application for naltrexone extended-release injectable suspension to treat alcohol and opioid use disorder. We also know that approval of medications for substance use disorder alone is not sufficient, so we have collaborated extensively with our sister agencies from HHS to increase access to these treatments -- another excellent example of how federal agencies are in coordination on these issues. You’ll have the chance to hear more about this effort from Assistant Secretary for Mental Health and Substance Use at SAMHSA, Dr. Miriam E. Delphin-Rittmon, later this week. 

We’ve also seen some other important developments related to detection and treatment of opioid overdose and opioid use disorder.  Last year, for instance, the FDA granted marketing authorization for a monitoring device intended to recognize and respond by a series of escalating notifications when an individual may be experiencing Opioid Induced Respiratory Depression (OIRD) due to opioid use or overdose. The device can be used in a hospital or in-home setting for individuals taking prescribed opioid medications, or those using opioids illicitly. 

And this past December, the FDA approved the first test that uses DNA in assessing whether certain individuals may have an elevated risk of developing opioid use disorder. The test is intended to be used as part of a clinical evaluation prior to first exposure to oral opioid pain medications in some patients, such as those scheduled to undergo a planned surgical procedure. 

The FDA also recently cleared two over-the-counter tests, one for the preliminary detection of fentanyl in urine and the other for the detection of norfentanyl in urine.  And our Center for Devices and Radiological Health continues to work with test developers to help facilitate development of additional detection tests.   We also issued a draft guidance to provide recommendations for clinical studies of devices intended to treat opioid use disorder and used to support marketing submissions.

As I hope these examples indicate, we are making headway. But even as we continue to see progress, it still feels tough to gain traction, in part because the landscape continues to shift around us.  This unfortunate reality means our response must shift as well. 

Let me offer an example of just how pernicious the challenge is today. Most of you have probably heard of xylazine.  And you may know that xylazine is an active ingredient in a non-opioid sedative approved by FDA for use … but in animals. It is not approved for use in humans. Indeed, it has not been shown to be safe for use in people and may cause serious and life-threatening side effects. 

So why discuss it here?  The answer is that xylazine increasingly is being added illicitly to fentanyl, leading to horrendous suffering by those who are taking these drugs without the knowledge that they contain adulterants. I would be remiss if I didn’t remind everyone that naloxone should always be administered for a suspected opioid-xylazine overdose.  To further the science on xylazine, we held a workshop on mitigating risks from human xylazine exposure and are funding research to examine xylazine pharmacology, abuse potential, and impact on wound formation when co-administered with fentanyl. The workshop will inform concrete strategies for drug development and clinical research that directly support the mitigation and reduction of risks associated with human exposure to xylazine.

The FDA’s Office of Regulatory Affairs (or ORA) has been partnering with DEA and other federal agencies, including Homeland Security Investigations and Customs and Border Protection, to exchange information related to the supply of xylazine and to develop intelligence on the sources of illegal fentanyl and fentanyl/xylazine tableting operations. This information will lead to interdiction and disruption of the illicit supply chain that is designating xylazine for human use.  

I mentioned the FDA’s action to restrict the unlawful entry of xylazine into the country as part of the response to a growing public health concern at this meeting last year. At that time, we issued an import alert that helps ensure that our import screening systems would automatically identify incoming shipments of products from violating firms, while allowing the legitimate use of xylazine in animals, where it is appropriate.  

But this was just the first layer of our efforts to stop these illicit activities, which also includes broad efforts to protect to the public by identifying and investigating the possible unlawful importation of xylazine into the U.S. through our ports of entry; and evaluating online marketplaces to identify the possible unlawful sale of xylazine on the Internet and assessing the potential for criminal investigation. 

And significantly, the FDA will continue to engage and collaborate with other government agencies to ensure information sharing, data driven strategies, and coordinated efforts to interdict illicit products offered for import. Much of this important work is done by FDA’s ORA, the branch of the FDA that performs inspections and conducts surveillance.  Our ORA investigators play a key role at International Mail Facilities, or IMFs, courier hubs, and Customs and Border Protection ports of entry to block dangerous and unauthorized products from entering U.S. commerce, working closely with the Customs and Border Protection and the U.S. Postal Service.  Particularly at IMFs, the substantial volume of parcels containing these illicit drug products obscures the influx of controlled substances, including opioids, into the United States. The FDA is proud to be part of the joint National Operational Strategy that will launch in this fiscal year.  We will provide surveillance and monitoring of unapproved drug supply chains.   

Finally, along the theme of collaboration, this crisis necessitates a global effort. In addition to working with our domestic partners, the FDA will continue to provide support in accessing information on production outside of the U.S., and intelligence on flows to the U.S. associated with FDA regulated entities. In collaboration with components across the FDA, we are engaging foreign governments and coordinating with foreign regulators as appropriate.  

Before I close, I want to mention an important area we are focused on, which can have serious implications for public health, including in the world of opioids and stimulants.  This involves the dissemination of misinformation about health, science, and medicine – and we’re working to counter misinformation, which undermines public trust in scientific research and facts.  

One way we’re doing this is through collaboration with the Reagan-Udall Foundation to explore the intersection of misinformation and consumer behavior, with a focus on prescription controlled substances that are available online. Findings from this project will be discussed at FDA’s fifth Online Controlled Substances Summit on July 25th and 26th, which, for the first time, will include a public workshop. I encourage you to sign up for this meeting, and I’m pleased to announce that registration is open effective today on both the FDA and RUF websites.  With this effort, our goal is to counter misinformation that is influencing folks to make risky choices, exacerbating the overdose crisis, and threatening the health of so many. Looking ahead, as we work toward restoring public trust in science and in our public institutions, the success of our endeavors will depend on effective collaborations with groups like yours.
 
We have a long way to go.  The FDA will continue to do what it can to fulfill its special responsibilities.  But we can’t solve this alone.  That’s why we will continue to work closely with our colleagues across federal, state, and local government to strengthen our enforcement efforts and build partnerships that lead to effective new strategies and solutions. 
We need everyone’s engagement in this continuing battle.   So, thank you for your commitment to this issue and for your time today.