FDA warning letter study

An article in the October 2012 issue of Applied Clinical Trials describes a warning letter study that was undertaken by Rajendra Talele of Lambda Therapeutic Research and Dr. Suresh K. Bowalekar of Pharmanet Clinical Services. Although both authors are located in Mumbai, India, their article is informed by a global perspective on clinical research.

To conduct their study, the authors identified a total of 466 clinical trial warning letters that were issued by the US Food and Drug Administration (FDA) between 1996 and 2010. Both drug and medical device trials were covered. The letters were broken down into 2422 distinct violations, which the authors categorized by stakeholder group (clinical investigator, sponsor, sponsor/investigator, contract research organization and institutional review board) and by CFR section (21 CFR Parts 50, 54, 56, 312, 812 and 814). Interestingly, only one of the letters in the sample was directed to a contract research organization.

Clinical investigators received a larger share of warning letters than any other stakeholder group, accounting for almost 60% of the total. Sponsor-investigators accounted for another ~7%. The most commonly noted violations by investigators were problems with protocol compliance, record keeping and record retention.

Institutional review boards (IRBs) received almost 21% of the warning letters that were included in this analysis. Overall, about 23% of the violations were for IRB operations and records – failure to have and follow adequate written procedures for IRB operations, and failure to maintain adequate records of IRB membership and review activities. Another 8% were related to informed consent.

None of this information will be new to those who routinely review FDA warning letters. The authors recommend focused training in the following areas:

  • Overall investigator responsibilities, as defined by regulations and guidelines
  • Obtaining and documenting subject consent
  • Comprehensive and correct understanding of [the] protocol
  • Investigational record keeping and record retention
  • IRB functions and operations, as per regulations and guidelines
  • IRB records and maintenance of records

They believe that increased attention to these gaps will lead to increased quality as well as increased public confidence in clinical research.

Share This Post