by Aarthi Iyer

How to Maximize the Impact of Postmarketing Surveillance

Since issuing the Postmarketing Studies and Clinical Trials – Implementation of Section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act (FDAAA), the U.S. Food and Drug Administration (FDA) has acted against companies for failure to conduct required postmarketing studies in a timely manner, citing sponsors with warning letters for violations of required postmarketing activities.

The FDA’s Watchful Eye on Patient Safety

While regulatory parameters vary throughout the product cycle, regulatory agencies, including the FDA, are increasingly focused on examining medical product safety and efficacy during the postmarketing phase.

Postmarketing research is conducted after medical products have received regulatory approval. They provide pharmacovigilance data on real-world populations, uncover trends in adverse events, and lead to the enhancement of the overall safety profile of a product.

The FDAAA provides the FDA with the authority to enforce postmarketing study requirements at the time of product approval or after approval if it becomes aware of new safety information.1

FDA may request any of the following postmarketing activities in enforcing FDAAA:

  • Postmarketing studies or clinical trials to demonstrate clinical benefit for medical products approved under the accelerated approval requirements in 21 CFR 314.510 and 21 CFR 601.41
  • Deferred pediatric studies (21 CFR 314.55(b) and 601.27(b)), where studies are required under the Pediatric Research Equity Act (PREA)
  • Studies or clinical trials to demonstrate safety and efficacy in humans that must be conducted at the time of use of products approved under the Animal Efficacy Rule (21 CFR 314.610(b)(1) and 601.91(b)(1))
  • Studies to assess a known serious risk related to the use of the drug
  • Studies to assess signals of serious risk related to the use of the drug
  • Identification of an unexpected serious risk when available data indicate the potential for a serious risk

Enforcement Actions

Once FDA notifies a medical product sponsor of the need for postmarketing research, the sponsor is required to provide a timetable (including study milestones) and status reports on progress toward completion of the study or clinical trial.  In the event of non-compliance with this timetable, FDA can take enforcement action against the sponsor (unless it demonstrates good cause).

This may include:

  • Issuance of a Warning Letter,
  • Deeming that a product is misbranded, and
  • Assessment of civil monetary penalties of up to $250,000 per violation, with the possibility of additional monetary penalties if the violation continues uncorrected

With a steady increase in FDA’s commitment to enforce FDAAA provisions, it will be important for sponsors to implement strategies for comprehensive postmarketing activities that will allow for regular reporting of safety and analysis results.

Preparing for Postmarketing Studies

Postmarketing studies often have a large volume of patients and can be extensive longitudinal trials covering multiple geographic regions where the research objective is to gather substantial quantities of data echoing clinical trends throughout the marketplace. Additionally, this research typically takes place outside the clinical setting, occurring in community-based practices or in arenas independent of traditional medical facilities (e.g. online platforms and telephone interactive voice response).

Given the scope, size, and expanse of these research activities, sponsors should consider the following when developing postmarketing studies or clinical trials:

  • Maximize efficiency and enhance consistency of research reviews by working with a central institutional review board (IRB). Central IRBs have a systematic understanding of the postmarketing arena and conform to regulatory provisions, including protocol design, study safety and confidentiality limitations, as well as reporting requirements as mandated by FDAAA. Also consider hiring a regulatory consultant to further clarify regulatory complexities and ensure compliance.
  • For subjects recruited outside of traditional practice settings, identify appropriate technology pathways for utilization of remote informed consent processes (e.g. eConsent, telephone) to maintain subject enrollment and participation.
  • Develop a flexible and synchronized approach for data collection that combines multiple avenues of data aggregation at the sponsor, site, and patient levels.
  • Collaborate with clinical research organizations and reviewing entities that can start activities promptly and absorb a considerable number of research sites in an efficient manner.

While compliance with required postmarketing activities may seem resource-intensive, the FDA is dedicated to continuously monitoring the effects of medical products to ensure patient safety. Attentive planning, collaboration with, and guidance from experts in the research and regulatory arenas as well as timely action throughout the stages of medical product development will allow sponsors to identify and efficiently execute adherence to postmarketing surveillance requirements.



[1] 21 U.S.C. § 355(o)

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