The Food and Drug Administration (FDA) has a variety of challenges that it faces in the context of its slow shift to lifecycle regulation of pharmaceuticals, according to a new study.

Lifecycle regulation refers to the FDA’s regulation both prior to and following market approval. However, the FDA’s power in the postmarket arena is much less than in the premarket phase, wrote author Mathew Herder of Dalhousie University, Halifax, Nova Scotia, Canada.

Recently, Herder conducted a document-based legal and policy analysis — as well as interviews with 23 current and former FDA officials — to explore the implications of the FDA’s use of postmarketing requirements (PMRs).

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He identified 3 plausible explanations for why PMRs are challenging for the FDA to enforce. First, the FDA lacks resources. Because of that, PMRs are poorly defined at the time of market approval and the design of the trial is largely left in the hands of the trial sponsor.


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Second, the agency is limited in its legal powers. The FDA has legal authority to enforce PMRs, but doing so in practice is considered questionable.

“In principle, a sponsor’s failure to conduct a postmarket study in accordance with the agreed-upon timetable, whether attached under the accelerated approval, PREA [Pediatric Research Equity Act], or FDAAA [Food and Drug Administration Amendments Act] PMR authorities, can attract civil monetary penalties and/or misbranding charges provided the delays are not for ‘good cause’,” Herder wrote. “Failing to fulfill an accelerated approval PMR can also theoretically trigger proceedings to withdraw the approved indication.”

However, in practice, the FDA rarely threatens these actions, Herder found. Despite the the fact that the FDA has very little power to enforce the timely completion (and reporting) of postmarketing studies, the industry’s currently “surprising level of compliance” with PMRs in the absence of good enforcement tools, wrote Herder, “can be understood as a way of staving off more sweeping reform.” Herder added that this industry compliance may also “reflect the relational nature of firm-FDA interactions: companies likely abide by the terms of a PMR not because they fear FDA enforcement, but rather because the approved indication carrying the PMR is one of several indications in a sequence that they plan to submit to the agency.”

Third, postmarket drug regulation is entangled with the politics of patient engagement and real-world evidence. The idea of withdrawing a drug is not very palatable to anyone, a former FDA official told Herder. 

“The FDA’s stated commitment to lifecycle regulation implies a distribution of resources and decision-making authority across the premarket and postmarket phases as new evidence about a drug’s safety and effectiveness emerges,” Herder wrote. “Despite the rhetorical turn toward the postmarket phase of a drug’s lifecycle, this redistribution of resources and decision making does not appear to be occurring. The FDA’s resources remain concentrated on the premarket side of the equation.”

Reference

Herder M. Pharmaceutical drugs of uncertain value, lifecycle regulation at the US Food and Drug Administration, and institutional incumbency. Milbank Quarterly. 2019;97(3):820-857.