Recently, the United states Food and Drug Administration released a draft guidance for sponsors about the way the agency will determine whether an applicant has demonstrated good cause in failing to meet postmarketing requirements (PMRs) for human prescription drugs. Under Section 505(o) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) applicants with products subject to post marketing requirements are required to periodically update the FDA on the PMR status as well as provide a timetable for completion. Applicants that do not provide the updates violate the FD&C Act unless they have demonstrated good cause for PMR noncompliance, which the FDA is responsible for defining.
The guidance cites examples of PMR noncompliance such as a missed final protocol milestone, study/clinical trial completion milestone, or a missed final report submission milestone. The agency further noted that this list is not exhaustive and there may be other instances where noncompliance has occurred.
The FDA went on to say that good cause can be determined “when an applicant’s explanation for PMR noncompliance demonstrates that the noncompliance is reasonable under the circumstances,” including when a circumstance directly relates to a missed milestone, was out of the applicants control, and “could not have been reasonably anticipated and factored in at the time the original PMR timetable was finalized.” If any one of the aforementioned conditions is not met, generally speaking, the FDA will consider the noncompliance to not be reasonable under the circumstances and the applicant will be considered as failing to demonstrate good cause for the noncompliance. In determining whether PMR noncompliance is reasonable under the circumstances, the FDA may also consider any other available information that it deems pertinent.
The draft guidance also included information on the relevant procedures on how to communicate with the FDA when complying with PMR requirements. The FDA noted that it would like to know as soon as the sponsor anticipates missing a milestone. In situations where a sponsor anticipates a missed milestone, the FDA will make a determination on whether the applicant has provided sufficient justification prior to the anticipated missed milestone. The draft guidance also includes a list of general actions an applicant should take to correct PMR noncompliance, including promptly developing a corrective plan, proactively informing the agency of any actual or anticipated delays, and providing a reasonable revised timetable.
In cases where applicants do not comply with PMR requirements, enforcement actions may be instituted, including receiving a warning letter or untitled letter from the FDA, misbranding charges, or civil monetary penalties. When civil monetary penalties are involved, the FDA will determine the penalty – at least in part – based on whether the sponsor is taking actions to correct the PMR noncompliance.
Importantly, the draft guidance does not apply to non-prescription drugs that have been approved through a new drug application or to generic drugs approved under Section 505. The guidance also does not apply to PMRs that involve pediatric studies and accelerated approval trials under certain subsections of Section 505 as well as trials that are “required as a condition of approval based on evidence of effectiveness from studies in animals.” It is only intended for sponsors with prescription drugs that fall under Section 505(o)(3).
Finally, while the draft guidance primarily addresses noncompliance with the timetable for completion of PMR milestones, any violation of a requirement under section 505(o)(3)(E)(ii) of the FD&C Act is subject to enforcement action, in the absence of a demonstration of good cause.
As is the case with guidance documents, the draft guidance does not establish any legally enforceable responsibilities, save for any specific regulatory or statutory requirements, but only describes the FDA’s current thinking and should be viewed as recommendations. The FDA is accepting comments on the draft guidance through September 12, 2023.