Postmarketing requirements: FDA drafts guidance on determining non-compliance

The US Food and Drug Administration (FDA) has released a draft guidance for sponsors on how the agency determines an applicant has demonstrated good cause in failing to meet postmarketing requirements (PMRs) for human prescription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 (FD&C) Act, applicants with products subject to a PMR are required to update FDA on a drug’s PMR status, such as the current state of a clinical trial or study, and a timetable for the study’s completion. Applicants that fail to provide these updates violate this section of the FD&C Act “unless the applicant has demonstrated good cause for its PMR noncompliance,” which the agency is responsible for determining, FDA said.

The draft guidance is intended for sponsors with prescription drugs that fall under section 505 and does not apply to non-prescription drugs that have been approved through a new drug application or a generic drug 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 “required as a condition of approval based on evidence of effectiveness from studies in animals,” the agency said.

Examples of PMR non-compliance include a missed final protocol milestone, study/clinical trial completion milestone, or a missed final report submission milestone. However, there may be other instances where the agency determines non-compliance has occurred, they noted.

According to FDA, good cause can be determined “when an applicant’s explanation for PMR noncompliance demonstrates that the noncompliance is reasonable under the circumstances.” This includes when a circumstance directly relates to a missed milestone, was out of the applicant’s control, and “could not have been reasonably anticipated and factored in at the time the original PMR timetable was finalized,” they said.

The draft guidance also contains information on the relevant procedures for as well as how to communicate with FDA on complying with PMR requirements. In general, FDA said it wants to know as soon as the sponsor anticipates missing a milestone. In cases where a sponsor has anticipated a missed milestone, FDA said it will make a determination on whether the applicant has provided sufficient justification prior to the anticipated missed milestone. The agency provided a list of general actions an applicant should take to correct PMR non-compliance, which include promptly developing a corrective plan, proactively informing the agency of actual or anticipated delays, and providing a “reasonable revised timetable.”

“Because the required milestone may occur far in advance of the required periodic updates that are generally submitted in an annual report, FDA strongly encourages applicants to proactively inform FDA about the progress and status of their PMR(s),” the agency wrote. “If an applicant anticipates missing a milestone or has already missed the milestone and submission of an annual report is not imminent, FDA encourages the applicant to notify FDA as soon as possible of the delay and submit thorough explanations of the failure to meet the PMR milestones.”

For applicants who do not comply with PMR requirements, enforcement actions can include receiving a warning letter or untitled letter from the agency, misbranding charges, and civil monetary penalties. When deciding civil monetary penalties, FDA determines the penalty based on whether the sponsor is taking actions to correct the PMR non-compliance.

“Although this 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,” the agency wrote in its Federal Register notice.

Draft guidance

Postmarketing requirements: FDA drafts guidance on determining non-compliance

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