FDA IRB Warning Letters Dominated by Seven Deficiencies

FDA Logo

Warning Letters issued by the U.S. Food and Drug Administration (FDA) after Bioresearch Monitoring (BIMO) inspections identified seven common deficiencies related to institutional review board (IRB) activities, according to a report from the agency.

The agency did not rank the deficiencies in any order. Those cited:

  • Inadequate initial and/or continuing review of studies
  • Inadequate written procedures
  • Inadequate meeting minutes and membership rosters
  • Quorum issues
  • Prompt reporting of noncompliance in, and suspension/termination of, studies
  • Code of Federal Regulations Title 21, Part 50, Subpart D issues (Additional Safeguards for Children in Clinical Investigations)
  • Lack of or incorrect Significant Risk/Nonsignificant Risk determination in medical device studies

Earlier this month, the agency issued a guidance designed, in part, to help IRBs avoid these problems.

In fiscal year 2016, there was a total of 1,055 BIMO inspections, including 775 inspections of clinical investigators, according to a report by IMARC Research, Inc. Those are the most recent numbers available from the agency.

Overall, about 65% of sponsor/monitor/contract research organization inspections were labeled “No Action Indicated” (NAI), meaning no objectionable conditions or practices were found during the inspection (or the objectionable conditions found do not justify further regulatory action), according to the FDA BIMO report. About one-quarter were labeled “Voluntary Action Indicated” (VAI), meaning objectionable conditions or practices were found, but the agency is not prepared to take or recommend any administrative or regulatory action. Fewer than 10% were “Official Action Indicated” (OAI). In those instances, regulatory and administrative actions will be recommended.

Meantime, the agency has “long considered” use of alternate members as an appropriate way for an IRB to function, says Doreen Kezer, MSN, FDA’s Senior Health Policy Analyst, Office of Good Clinical Practice, Office of the Commissioner.

“The use of formally appointed alternate IRB members is acceptable to the FDA, if the IRB’s written procedures describe the appointment and function of alternate members,” Kezer says. “The IRB roster should identify the primary member(s) for whom each alternate member may substitute.”

In addition, IRB minutes should document when an alternate member replaces a primary member, FDA says.

However, ad hoc substitutes are not acceptable to the agency, Kezer explains. That noted, a member who is unable to be physically present at the meeting may participate via phone or video conference if he or she has received a copy of the documents to be reviewed at the meeting. If allowed by IRB procedures, ad hoc substitutes may attend as consultants and to gather information for the absent member, but they cannot be counted as part of the quorum.

Related Readings

FDA BIMO Report

FDA Guidance Emphasizes IRB Meeting Expectations

Author: Michael Causey