For Immediate Release:
Statement From: Robert M. Califf, M.D., MACC, Commissioner of Food and Drugs – Food and Drug Administration
Addressing the drug overdose crisis and substance use disorder (SUD) is an issue of great concern for our nation and remains a top public health priority for the U.S. Food and Drug Administration. Upon returning to the FDA as Commissioner, I expressed my commitment to respond to all aspects of this ongoing crisis. As an agency focused on protecting public health, combatting this evolving emergency is an issue of particular urgency for us. Of note, a public health emergency, as a consequence of the opioid crisis, was declared by the U.S. Department of Health and Human Services in October 2017 and renewed on December 22, 2022.
In August 2022, I announced the FDA’s Overdose Prevention Framework – our expanded vision to undertake creative actions with an impact not only on preventing drug overdoses and reducing deaths from opioids and other substances, but also ameliorating the tremendous toll of addiction on American individuals and families. As part of that announcement, I shared that the agency would commission an independent external opioid-related activities review. That review was conducted by a team of subject matter experts affiliated with The Ohio State University who are familiar with the 2017 National Academies for Sciences, Engineering, and Medicine’s (NASEM) recommendations, a project initiated on my watch, and also related opioid prescribing issues. The review analyzed the FDA’s implementation of the NASEM recommendations along with key regulatory policies and decisions, including labeling.
Today, we are sharing that report, which provides lessons learned, recognizes the work already being done by the FDA, and makes the following three overarching recommendations outlined for the agency to take action:
- Continue efforts to comprehensively implement the recommendations in the 2017 NASEM Report, including evaluating scientifically-sound, inclusive study designs to inform a systems approach for regulatory decision-making that incorporates public health considerations.
- Consider seeking from Congress certain additional authorities regarding opioid analgesic approvals and review of the advertising and promotion for such products, as well as additional resources to implement such authorities to strengthen oversight of prescription opioid analgesics.
- Be as transparent as possible regarding decision-making for opioid analgesics, as increased transparency can encourage appropriate uses of prescription opioid analgesics, promote innovation in pain management and prevention of opioid use disorder, and enhance public trust.
We have reviewed these recommendations and while we are thoughtfully considering our actions to implement them, I am encouraged that the agency is already moving forward on multiple workstreams, while also adapting to the changing epidemiology of the ongoing public health emergency. New challenges confronting us include much more multidrug use and troubling distribution of powerful chemically-synthesized drugs.
While our response is centered on opioid regulation by the Center for Drug Evaluation and Research (CDER), all elements of the agency are involved as we work with digital applications of substance use disorder treatment, the inappropriate intermixing of prescription drugs—like certain veterinary medicines—in the illicit market, enforcement activities in the domain of the Office of Regulatory Affairs and the intersection of nicotine addiction with use of other addictive substances as the Center for Tobacco Products oversees tobacco products.
The activities outlined below are a sample of the broad and energetic effort across the agency to combat this emergency:
First, we’re taking steps to strengthen evidence generation within the agency and with multiple partner organizations in order to better inform our response to the opioid crisis. The FDA has invested significant resources to develop a data-driven, national-level simulation model of the opioids system, named SOURCE. We will continue to enhance systems modeling approaches, including SOURCE, to enable identification of evolving trends and gaps in our interventions.
Of particular interest is deepening our understanding of the long-term efficacy of opioid analgesics. To clarify the current state of this research and knowledge gap, we will hold an advisory committee meeting in April 2023. It will focus on clinical trial paradigms, including an enriched enrollment randomized withdrawal trial design to evaluate long term efficacy and the risk of opioid-induced hyperalgesia. This is part of a postmarketing requirement we issued to application holders of new drug applications for extended release and long-acting opioid analgesics. We appreciate the revised 2022 CDC Clinical Practice Guideline for Prescribing Opioids for Pain that once again pointed out the paucity of evidence on the potential benefits of long-term opioid use, raising questions for our consideration about the labeling of these drugs.
I had the opportunity to contribute to the planning in 2015-16 that eventually led to the NIH’s HEAL Initiative, which has multiple ongoing studies evaluating the clinical epidemiology, health services and interventions in clinical practice. As this extensive network conducts its work, we anticipate a steady stream of information that will inform our policies.
This information, along with other scientific evidence and insight, will aid our science-based evaluations of the benefit-risk assessment of opioid products, and help ensure that the benefit-risk assessment considers not only the outcomes of prescription opioids when used as prescribed but also the public health effects of inappropriate use.
Next, the report suggests the agency should consider seeking additional authorities through Congress. We know that having fit for purpose regulatory authority is key to addressing opioid use, misuse and abuse. As referenced in the agency’s Overdose Prevention Framework, we are 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.
For many years, the FDA has based decisions on whether to approve drugs, including opioids, on a framework for the assessment of the benefits and risks of a drug. That approach is the authority Congress mandated for us. When it comes to opioids, we also take into account public health factors such as the impact on family and others when reaching a decision on whether to approve a drug. Currently, the FDA lacks the statutory authority to require that drug developers seeking approval for the marketing of new opioid products demonstrate that their products offer material safety advantages (such as a reduction in abuse potential or a reduction in respiratory depression) over existing approved opioids. By enabling the FDA to refuse to approve new opioid analgesics that do not offer material safety advantages over already-approved opioids there is potential to, over time, improve the safety of opioid analgesics available to treat severe acute and chronic pain or drive research towards non-opioid alternatives to relieve pain. We stand ready to work with Congress on an improved regulatory tool for the agency.
As we examine the need for new authorities, we will continue to explore ways to use our current authorities, not only to regulate opioids more effectively, but also to improve the pipeline of non-addictive treatments for pain. While this has been a goal for many years now, the industry has been disappointingly unable to develop these much-needed alternatives.
Lastly, continuously working to earn and retain the public’s trust is not only important to our work, but also critical to our mission to protect public health. The report correctly highlights the importance of transparency in our decisions regarding opioid analgesics.
An area where we believe we can increase transparency is through further improvements of our advisory committee meetings. Our commitment to explore more effective use of our advisory committees to increase transparency regarding opioid analgesics will be a part of a broader internal effort to evaluate how to make the best use of all of our advisory committees and ensure agency decisions are informed by input from knowledgeable external advisors and the public and the decisions are shared publicly. Advisory committees play a crucial role in regulatory decision-making and publicly clarify the FDA’s expectations and the views of experts in the field while giving the public a chance for direct input. Although the airing of opinions at advisory committees, like democracy, can be messy, by improving transparency, better public understanding of the FDA’s decision-making process will lead to more confidence in it.
Within each of the overarching recommendations outlined are additional, more specific recommendations that we will continue to address and prioritize through our existing authorities and current activities within CDER and beyond.
I look forward to continuing to work across the agency to advance solutions that encourage appropriate prescribing, promote innovation in pain management, prioritize overdose prevention, reduce opioid and other substance use disorders, and champion effective treatment and support for those with SUD. We recognize that in the face of this ongoing emergency, we must continuously assess and improve our efforts and I appreciate the commitment of the FDA’s center directors and staff in this continuing effort while also dealing with other challenges that impact public health.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.