By: Robert M. Califf, M.D., Commissioner of Food and Drugs
In 2021, a record number of Americans – more than 107,000 – died from drug overdoses. While the loss of human life alone is staggering, we know that the effects of the drug overdose crisis are even broader, including enormous individual and societal costs as people and families grapple with substance use disorder (SUD). Due to this unfortunate reality, in 2017 the opioid crisis was determined to be a public health emergency, which to this day is still in effect. Today’s drug overdose crisis is multifaceted and has evolved beyond prescription opioids. Illicit opioids, largely driven by fentanyl and its analogues, have become key contributors. Other controlled substances, including benzodiazepines and stimulants (particularly methamphetamine), also are being used in combination with opioids.
Recent data from the Substance Abuse and Mental Health Services Administration (SAMHSA) and the Centers for Disease Control and Prevention (CDC) highlight the magnitude and urgency of the issue and the need for attention to equity. By SAMHSA’s latest estimates, 18.4 million people suffer from illicit drug use disorders. In addition, the increase in drug overdose deaths, while accelerating in all demographics, is particularly growing among non-Hispanic Black and non-Hispanic American Indian or Alaska Native populations. Rural Americans are also increasingly affected by SUD. Furthermore, effective SUD treatment and holistic intervention centers are less likely to be available in racial and ethnic minority and rural communities.
My resolve to do something has only strengthened over the past several years. I have witnessed first-hand the impact of opioids in my professional life as a physician, through my government and academic roles, in my personal experience, and in my role providing community-based clinical care. Five years ago, I helped form a non-profit addiction treatment and recovery center in Dayton, Ohio. As the chair of that organization’s board, I learned a great deal about on-the-ground efforts to prevent misuse, reduce fatal overdoses, and provide evidence-based treatment and recovery support. I gained tremendous respect for the array of people who must work together across a community to battle this problem and achieve better long-term recovery outcomes.
As FDA Commissioner, with renewed opportunity and enhanced resolve, I intend to keep overdose prevention and reduction in SUD and its consequences a key priority throughout my tenure at the FDA. While the FDA’s previous strategies have largely focused on opioid use and overdoses, the evolving nature of the overdose crisis calls for both a new approach and honest reflection about what the FDA can do differently moving forward. For example, during my confirmation process, I committed to undertaking a review of our opioid decisions, including labeling. We have initiated this review with the intended goal of understanding what revisions are needed to support appropriate use of opioid analgesics. Our “lessons learned” will actively inform our future approach. I’m optimistic this review will provide us with recommendations to move forward in this multistep process, and we are working expeditiously to address this urgent situation.
FDA’s Overdose Prevention Framework
Today, we are introducing the FDA Overdose Prevention Framework – our vision to undertake impactful, creative actions to prevent drug overdoses and reduce deaths. While the four priorities within our framework are overarching, our activities are dynamic to allow us to recalibrate our approach as the overdose crisis continues to evolve. By design, our Framework flows from the U.S. Department of Health and Human Services (HHS) Overdose Prevention Strategy and supports the National Drug Control Strategy.
The four priorities within the FDA Overdose Prevention Framework are:
- Supporting primary prevention by eliminating unnecessary initial prescription drug exposure and inappropriate prolonged prescribing.
- Encouraging harm reduction through innovation and education.
- Advancing development of evidence-based treatments for substance use disorders.
- Protecting the public from unapproved, diverted, or counterfeit drugs presenting overdose risks.
Below is a snapshot of some of the FDA’s activities underneath the Framework, which are a mix of existing activities as well as our exploratory work to test out new strategies that meet the moment. These activities underscore that despite the FDA’s focus on this critical issue in the past, previous efforts have not been enough. We need to invest more resources and implement fresh ideas as the crisis evolves. These snapshots also bring into focus the interdependence of the FDA’s effort with government and non-government partners to implement strategies that will have impact. It is also evident that the primary basis for preventing overdoses and death is the use of strategies to prevent and reduce the magnitude of SUD, treat it effectively, and sustain long-term recovery.
Supporting Primary Prevention
Looking forward, we are exploring several strategies to support primary prevention. We are re-examining the role of opioid analgesic prescriber education, including the need for a mandatory unified, national-level education program to adequately inform opioid analgesic prescribers on managing pain. To support our considerations, we have held two Duke-Margolis workshops on Reconsidering Mandatory Opioid Prescriber Education and Identifying Key Competencies for Opioid Prescriber Education in the past year. Prescriber education is not new, and there has been a consistent reduction in the prescription of opioids in the U.S. But we are taking a fresh look at how to make prescriber education more effective and link it to behavioral change in optimizing appropriate prescribing and use of alternative interventions to treat pain. The growing evidence base from the National Institutes of Health’s (NIH) HEAL Initiative and the soon to be updated CDC Clinical Practice Guideline for Prescribing Opioids will further inform education efforts.
We are also exploring the need for potential new authorities for opioid approval standards, including whether drug developers seeking approval for the marketing of new opioid analgesics should be required to demonstrate that their products offer material safety advantages over existing approved opioid analgesics. We are considering additional disposal options, including a potential change that would require opioid analgesics dispensed in outpatient settings to be dispensed with prepaid mail-back envelopes and patient education on safe disposal of opioids. And we intend to publish a draft guidance for development of non-addictive treatments for chronic pain, following the February 2022 publication of a Draft Guidance: Development of Non-Opioid Analgesics for Acute Pain. These draft guidances should help stimulate academia and industry to improve the current inadequate pipeline of new interventions.
The FDA continues to view the development of evidence-based guidelines as a high-impact opportunity to support appropriate prescribing practices that will in turn prevent overdoses. In 2020, we awarded our first cooperative agreement to the University of Pittsburgh and the American Dental Association to develop guidelines for the treatment of acute dental pain, and we anticipate publication of adult dental pain guidelines soon. This year, we are supporting the development of two new clinical practice guidelines. One is on the safe tapering of benzodiazepines, which aims to help address inappropriate prolonged prescribing and was a key gap identified by patients and clinicians in our 2021 Duke-Margolis workshop on the safe use of benzodiazepines. The other is on the management of postoperative pain in obstetric patients; the FDA-commissioned National Academies of Sciences, Engineering, and Medicine (NASEM) 2020 report on Framing Opioid Prescribing Guidelines identified obstetric surgeries (e.g., cesarean delivery) as a priority area for evidence-based guideline development. Additionally, we continue to collaborate with our federal partners to support other guidelines as appropriate, such as the 2022 CDC Clinical Practice Guideline for Prescribing Opioids.
Throughout my career and during my first stint as Commissioner, I supported the development of FDA guidances and definitive evidence-based documents. These elements can help stimulate other critical constituencies to take actions within their control and I intend to use this approach aggressively as we work together on prevention.
Encouraging Harm Reduction
To help incorporate a systems approach into considerations about the public health impact of the opioid crisis, the FDA developed a national-level, data-driven, system dynamics model of the opioid crisis. This was partially a response to recommendations from a 2017 NASEM report I commissioned on Pain Management and the Opioid Epidemic. The team has recently published two peer-reviewed articles on the model, Modeling the evolution of the US opioid crisis for national policy development and Reducing opioid use disorder and overdose deaths in the United States: A dynamic modeling analysis. The latter paper described an initial analysis of 11 types of high-level hypothetical strategies, ranging from OUD prevention to harm reduction, and the effects projected by the model that those strategies could have on the opioid crisis. We are actively pursuing multiple strategies identified by the model with a focus on reducing the risk of opioid overdose involving fentanyl use. These include increasing the distribution of naloxone and recent support of two roundtables on community and clinical perspectives on fentanyl drug checking.
Looking forward, the FDA plans to build on our actions to help expand the availability and access to overdose reversal products, including naloxone. Through efforts like our Naloxone Access: Answering Questions public meeting, we have heard first-hand from harm reduction groups about the continued challenges in increasing access to naloxone. Despite state naloxone access laws, including standing orders, the prescription status for naloxone continues to pose a barrier to wider access. As such, an over-the-counter (OTC) naloxone switch remains an especially high priority. The FDA continues to encourage and advise industry in the development of OTC naloxone. We are also working with industry to bring novel and generic naloxone products to market. However, the FDA recognizes that the transition from prescription to OTC naloxone status may impact health insurance coverage, and has the potential to create other unintended barriers to access. This is an issue we are actively examining with our federal colleagues.
Advancing Evidence-Based Treatments for Substance Use Disorders
Through collaboration with other federal agencies, the FDA has contributed to efforts to broaden access to medications for opioid use disorder (MOUD). Simply put, MOUD is a proven intervention to improve outcomes for people with OUD, and recent CDC data indicate that it continues to be vastly underused, particularly in racial and ethnic minority and rural communities. We supported the development of the Practice Guidelines for the Administration of Buprenorphine for Treating Opioid Use Disorder that the HHS released in April 2021. These guidelines exempted eligible clinicians from certain federal certification requirements related to training, which were previously cited as a barrier to treating more people with buprenorphine.
We will continue to support development of new interventions and work with implementation partners as the evidence evolves. The potential for digital interventions and other devices to help with reducing SUD and its consequences is profound. Looking forward, we will continue partnering with NIH on facilitating medical device innovation for addressing opioid use. We also intend to publish a draft guidance on Clinical Considerations for Medical Device Premarket Submissions Targeting Opioid Use Disorder. Finally, we are looking to build on our October 2021 virtual public workshop on A Practical Research Agenda for Treatment Development for Stimulant Use Disorder, convened by the Reagan-Udall Foundation and held in collaboration with the National Institute on Drug Abuse, and the resulting white paper by exploring a draft guidance on development of stimulant use disorder treatments.
Protecting the Public from Unapproved, Diverted, or Counterfeit Drugs
The recent rapid growth of the sale of illicit, chemically synthesized fentanyl, fentanyl analogs, and methamphetamines has raised the need for new approaches. Cracking down on the market for diverted prescription and illegal drugs and securing the supply chain for approved medications, including opioids and other controlled substances, remains a top priority. We will further develop our surveillance, enforcement, and interdiction work targeting illegal, unapproved, counterfeit, and potentially dangerous products at international mail facilities, express courier hubs, and ports of entry across the U.S. We will build on our surveillance, compliance, and enforcement actions, including to address health fraud such as SUD treatment claims. This includes joint interdiction operations with other federal agencies such as Customs and Border Protection.
The FDA has also been aggressively working to address controlled substances illegally sold online, including through high-impact partnerships. For example, in 2020 we completed a pilot process with three major registries and the National Telecommunications and Information Administration to reduce the availability of unapproved opioids offered for sale online. As a result of the pilot, nearly 30 websites illegally offering opioids for sale became inaccessible to the public. The FDA has continued to work with registries to help prevent the illegal sale of opioids, in addition to other controlled substances over the internet. In April 2022, we also partnered with the Drug Enforcement Administration to issue first-of-their-kind joint warning letters to operators of two websites illegally selling Schedule II stimulants, including amphetamine drug products marketed as Adderall. We recognize the need to accelerate this type of joint effort across federal agencies to deal with this different method of illicit and highly dangerous sale of opioids and methamphetamine.
To conclude, overdose prevention is a complex problem, and no one action or one agency will solve the crisis. However, taken together, these actions by the FDA in partnership with patients, clinicians, harm reduction groups, the U.S. Congress, other governmental agencies, including federal, state, local, territorial and tribal levels—and many other stakeholders—can move us in the right direction. We welcome working with all partners to strengthen our response.
The FDA remains focused on responding to all facets of substance use, misuse, addiction, overdose, and death in the U.S. On my watch, we commit to doing all that we can to respond to this crisis, and reduce SUDs and overdoses—and ultimately achieve and sustain long-term recovery outcomes. And we commit to the American public that our work will remain grounded in science and transparency. We plan to give regular updates on our progress, beginning with an update next month on progress since the NASEM report on Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use.