How Can FDA Address the Opioid Addiction Crisis?
FDLI’s Journal Symposium Panel Considers a Public Health Approach to Regulation
By Anthony Kakoyannis, Skadden, Arps, Slate, Meagher & Flom LLP
On October 20, 2017, the Food and Drug Law Journal hosted its 2017 Symposium, “FDA and Health Behavior Regulation.” Panels throughout the day focused on FDA’s regulatory action to influence consumer behavior as it relates to drugs, tobacco, and food. Draft Journal articles served as the basis for debate and discussion.
This edition of Update EXTRA briefly summarizes the “FDA and Opioid Use” panel, a discussion prompted by the working draft paper, “Implementing a Public Health Perspective in FDA Drug Regulation,” as presented by Patricia Zettler (Georgia State University).
Discussants Rick Ball (Duane Morris LLP and Member, FDLI Board of Directors) and John Gilbert (Hyman, Phelps & McNamara, P.C.) offered critiques of the public health approach outlined in the discussion draft as presented by Patricia Zettler, and Jodi Schipper (FDA-CDER and Member, FDLJ Editorial Advisory Board) moderated the panel. As participants in the academic Symposium, all panelists spoke as individual thought leaders contributing to idea generation, and were not speaking on behalf of their respective affiliations.
The draft of “Implementing a Public Health Perspective in FDA Drug Regulation” takes as its starting point the argument that FDA’s established methods for verifying the safety and efficacy failed to prevent the opioid crisis. The paper thus seeks to explore the ways in which FDA could use its existing statutory authority to mitigate the current crisis and guard against the next one. Specifically, to what extent can FDA consider, or regulate, the health care provider and patient behaviors that contribute to the overprescribing and misuse of opiates?
Despite the integral role these behaviors have played in precipitating the opioid crisis, FDA’s regulatory regime seems unable to address them. In Ms. Zettler’s view, this is because the agency’s approach to drug safety is based on “the drug as described in the FDA-approved labeling.” In other words, FDA’s traditional focus on appropriate drug use and prescribing is ill-equipped to prevent public health crises that arise from misuse. Therefore, it was proposed that the agency must broaden its perspective to consider how a drug affects the public at large, particularly when a drug shows it has the potential to have social externalities.
Ms. Zettler surveyed FDA’s authority in the approval and postapproval processes before moving on to a discussion of how that authority could be broadened. For example, FDA has long required New Drug Applications to examine a broad range of risks, including the potential for abuse. The agency also has incorporated a broader public health perspective in its treatment of vaccines by requiring drug-makers to predict effects on populations beyond those actually vaccinated.
As a matter of statutory interpretation, it was argued that FDA already has the authority to apply a broad public health perspective. Despite the express language of the Food Drug and Cosmetic Act limiting the agency to assess drugs “under the conditions prescribed, recommended, or suggested in the proposed labeling,” FDA’s public health mission lends to a broader reading of the statute. Furthermore, the FDA Amendments Act of 2007 directed the agency to create a system for monitoring post-market developments—showing an intention to expand FDA’s authority. Ms. Zettler also argued that the authority to take a wider public health approach is supported by the “absurdity doctrine,” congressional acquiescence to FDA’s growing authority over different phases of drug approval and use, and the deference courts afford to agency interpretations.
Finally, the presentation cautioned that no single FDA action alone can reinvigorate the regulatory regime that has failed to contain the opioid crisis. On the contrary, a coalition of state and federal agencies—particularly DEA—have a vital role to play as well. The interaction of these authorities was a topic frequently debated by the panel.
The panel’s discussion focused not on whether FDA (or another agency) should begin to consider and address the public health consequences of drugs it regulates, but how its authority would be applied in practice. Answering this question requires an understanding of what has caused the opioid crisis—a topic the panel debated throughout. The wide-ranging causes of the current epidemic also led to a discussion of the other authorities that play a role in regulating the pharmaceutical industry and public health generally.
Causes of the Crisis
Mr. Ball began the discussion by offering the critique that that the pharmaceutical industry’s role as partially responsible for the opioid crisis required greater acknowledgement. In particular, Mr. Ball argued that off-label marketing resulted in the massive proliferation of the drugs’ availability.
The argument that subsequently took shape is that the abundant supply of opioids is directly related to their widespread misuse. Mr. Gilbert contributed a DEA-focused perspective to this discussion—in particular, the agency’s use of quotas to control the supply of Schedule II drugs. He suggested that a new public health perspective at FDA might impact these quotas. Although quotas can theoretically reduce the diversion potential of controlled substances, DEA has struggled to come up with a reliable way of determining appropriate supply limits. Mr. Gilbert pointed out that DEA is set to lower opioid quotas in 2018, but it is unclear how the agency is determining the final number (outside of relying on manufacturer estimates). This has been a long-standing concern at DEA. In 2003, a GAO report found that DEA’s across-the-board supply cuts were well-intentioned but not necessarily well-grounded in the legitimate medical needs of pain patients.
Ultimately, this supply-side discussion circled back to the core of the focus of the day: patient and physician behavior. While understanding the recognition that pain was undertreated decades ago helped alleviate unnecessary suffering, the panel largely agreed that over-prescribing is one of the chief causes of the opioid crisis. Furthermore, Mr. Gilbert observed that the unique recreational value of opioids (for some users) influences the choices of a patient population that does not otherwise abuse drugs.
Practical Application of Broader FDA Authority
At the center of the panel discussion was what exactly a wider regulatory perspective would look like for FDA and other agencies. Most of the conversation focused on FDA, as that was the animating question for the Symposium. However, as the discussion progressed, it became clear that significant initiatives are probably needed from other authorities as well.
First, panelists grappled with FDA’s role in controlling the distribution and supply of opioid painkillers. Mr. Ball shared an anecdote illustrating how large prescriptions are doled out for temporary pain, but the excess supply is never disposed of. Ms. Zettler responded to this concern by speculating that FDA likely has the authority to administer a “take-back” program. This strategy would fit within the global framework Ms. Zettler advocates and which has already begun to unfold, with the recently passed 21st Century Cures Act expanding FDA’s mandate to not only patients, but patients’ family members.
With respect to physician practices, Ms. Zettler agreed with the other panelists that REMS is the “clearest way FDA can affect” prescribing behavior. Under a broader public health approach, FDA would use REMS to continually update the risk-benefit analysis undertaken as part of the approval process. The agency would take into account the effects a drug has on the public at large, make adjustments to its approval decision, and even consider revoking approval in some cases. Ms. Zettler agreed with Mr. Gilbert’s focus on the recreational potential of opioids and similar drugs. She posited that FDA needs to consider recreational users, in addition to the legitimate needs of patients in pain, when it makes and approval decisions and implements REMS.
Ms. Schipper, moderating the discussion, shifted the panelists away from REMS and other post-marketing processes to pre-approval. The panelists struggled with how to respond. Ms. Zettler could not speak to the specific data points that might be relevant, and she admitted that most of the major decisions FDA needs to make arise postapproval. Ms. Zettler and the other panelists suggested that FDA may need to start thinking about sacrificing efficacy to an extent in order to promote safety.
The Role of State Authorities
The panelists continually returned to the fact that FDA does not have a role in creating a “medical standard” by which prescribing can truly be regulated. Although Ms. Zettler argued that FDA is effectively controlling physician behavior through its post-marketing actions and labeling changes, the other panelists were unsure whether that can truly change behavior, even if applied in the broad manner Ms. Zettler advocates. As a result, the panel considered whether state governments and medical boards should feature more prominently in the conversation generally. For example, state authorities could require more training and physician education that embraces public health data and real-world patient behavior.
Ms. Zettler’s paper and the conversation it generated at the Symposium is in early stages, but the arguments considered illustrate the direction of academic and professional debate. As the opioid crisis continues to evolve in full public view, pressure is increasing for FDA and other agencies charged with protecting public health. The agencies appear to be recognizing this. For example, Mr. Ball observed that the Health and Human Services Office of the Inspector General is investigating whether FDA is properly enforcing REMS. It seems likely that those pressures will continue to mount until the public sees FDA as taking steps to enhance its regulatory regime, and perhaps broaden it in the manner Ms. Zettler and her co-authors advocate.
Feedback from panelists and audience questions will be incorporated into the final article, which will be featured in the Journal’s May 2018 issue along with the other draft articles discussed throughout the Symposium.
 Co-authored with Margaret Foster Riley (University of Virginia School of Law) and Aaron S. Kesselheim (Harvard Medical School).
 U.S. G.A.O., GAO-04-110, Report to Congressional Requester: Prescription Drugs: OxyContin Abuse and Diversion and Efforts to Address the Problem (2003).