Health Law Daily Wrap Up, DRUGS AND BIOLOGICS—OIG REPORTS: Data management problems still plague FDA’s postmarket efforts, (Jul 22, 2016)
The FDA continues to have problems with its data management system and work processes, which in turn hinders its ability to effectively monitor postmarketing reports (PMR). According to an HHS Office of Inspector General (OIG) report, the FDA used its authority pursuant to the Food and Drug Administration Amendments Act (FDAAA) to issue half of all the PMRs from fiscal year (FY) 2008 through FY 2014. Gaps in the agency’s data management system, however, limited its ability to effectively track various components supporting PMR status and tracking (OIG Report, OEI-01-14-00390, July 22, 2016).
The FDAAA expanded the FDA’s authority to require postmarketing studies and to take enforcement action when sponsors are out of compliance. Prior to passage of the FDAAA, the OIG found that FDA could not readily identify whether or how timely postmarketing studies were nearing completion, and that the FDA lacked an effective monitoring system for postmarketing studies.
Following up on the intervening years since the passage of the FDAAA, the OIG reviewed data from the FDA’s Document Archiving, Reporting, and Regulatory Tracking System (DARRTS) for all prescription drug PMRs, as well as Annual Status Reports (ASR) and ASR review documents, initiated between FY 2008 through 2014. In this 7-year period, FDA issued 1,256 PMRs for 468 applications.
PMRs. Postmarketing studies and clinical trials measure an approved drug’s clinical safety, clinical efficacy, clinical pharmacology, or nonclinical toxicology. The FDA may use this information to request an update to a drug’s label, approve a drug for new uses, require additional risk management interventions, or, in rare cases, seek to have the manufacturer withdraw a drug from the market. Likewise, FDA may determine that the PMR results indicate that no further action is needed.
PMRs were issued for both supplemental applications and new drug applications (NDA) and the majority of PMRs were related to the NDAs. The FDA also issued PMRs more frequently for NDAs reviewed through expedited programs than non-expedited NDAs. Of the 115 expedited NDAs, 73, or 63 percent, had PMRs compared to 51 percent of non-expedited NDAs with PMRs. Sponsors were found to be completing most PMRs according to schedule; half of all PMRs fulfilled in FY 2014 required sponsors to make labeling changes or take other actions to ensure the safety of their drugs.
Of those PMRs that the FDA categorized as delayed in FY 2014, 32 were delayed for one year, 34 for two years, and 24 for three to five years. According to the FDA, sponsors may have good reasons for these delays. For example, a PMR may fall behind schedule because the sponsor and the FDA have not reached an agreement on the study design or because patient enrollment in a clinical trial is taking longer than planned. The FDA determines whether there is a good cause for delay, and if so, the FDA does not consider the sponsor to be out of compliance.
ASR tracking and status. Although the FDA monitors PMRs, shortcomings in DARRTS, the FDA’s data management system, limit PMR tracking abilities. DARRTS is used to track PMRs and the corresponding ASRs, and to identify sponsors that are out of compliance with the terms of a PMR, such as the timetable for completion. DARRTS does not automatically generate reports of late ASRs or PMRs with upcoming ASR due dates. As a result, the FDA at times independently generates this information. This leaves a gap, as the FDA cannot readily identify late or upcoming ASRs. In addition, the lack of a standard format for ASRs makes it difficult for FDA to track PMRs and ASRs and to extract data from ASRs. For example, the OIG noted that some ASRs are many pages long and include detailed information, while others are just a few sentences.
Next steps. The OIG recommended that the FDA provide a standardized form for ASRs, ensure that the forms are complete, and require sponsors to submit them electronically. Standardized forms and electronic submission would provide FDA staff with baseline information in ASRs and potentially eliminate the need for manual data entry. In addition, DARRTS capacity should be improved to support PMR oversight. This could involve automated reports that would allow the FDA to identify pending ASR due dates, PMS status updates, or missing and late ASRs. Finally, the OIG was concerned that some PMRs have been delayed for years and recommended that the FDA determine why and take appropriate action. The FDA concurred with all of the OIG recommendations.
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