Cause for Concern
What are the factors that cause the U.S. Food and Drug Administration (FDA) to inspect a clinical trial site, especially when the visit is unannounced? A blog by Michael Causey of the Association of Clinical Research Professionals sheds some light on this subject, which is dreaded by clinical trial sponsors, clinical investigators and institutional review boards, who struggle to understand the rationale behind the dreaded visits.
As Causey writes, “The prospect of an unannounced FDA inspection can loom over a clinical trial site. While the vast majority of inspections are prescheduled, FDA is more likely to arrive without warning if the inspection was assigned as a result of information that raises concern about the site, such as about the adequacy of its subject protection measures, or issues with data integrity, and/or a history of problems with the inspected party, FDA officials say.”
The FDA describes inspections of entities involved in clinical trials as bioresearch monitoring (BIMO) inspections. This nomenclature distinguishes them from the manufacturing inspections that are more commonly conducted by FDA inspectors. FDA usually pre-announces BIMO inspections. Most likely, an FDA investigator will contact the clinical trial site and suggest a date for the inspection, as opposed to offering to schedule it. Normally, the contact takes place about five days before the date the FDA investigator wants to start the inspection. The phone call comes at the time that the FDA is ready to move. From that time, FDA will work with the inspected party — up to a point.
According to Doreen M. Kezer, MSN, a senior health policy analyst with the Office of Good Clinical Practice in the Office of the Commissioner for FDA, the agency will make adjustments of inspection dates if there are extenuating circumstances. However, if the trial site continues to attempt to postpone an inspection, the FDA will consider it a refusal of inspection, which would be “a serious violation,” Kezer said. If the site refuses the inspection, the FDA can obtain a warrant to inspect it.
FDA uses Compliance Program Guidance Manuals (CPGM) to direct its field personnel on the conduct of inspectional and investigational activities. Five of these manuals — CPGM for Clinical Investigators; CPGM for Sponsors, Contract Research Organizations and Monitors; CPGM for Good Laboratory Practice (Non-Clinical Laboratories); CPGM for In-Vivo Bioequivalence Compliance Programs 7348.001; and CPGM for Institutional Review Boards — form the basis of FDA’s Bioresearch Monitoring Program. Each program is designed to “ensure the protection of research subjects and the integrity of data submitted to the agency in support of a marketing application,” according to the FDA.
The Association of Clinical Research Professionals (ACRP) attempts to set standards for clinical research competence and workforce development, according to its website. The Washington, DC-based non-profit organization has more than 13,000 members. It supports clinical research professionals and organizations with the “membership, training and certification programs necessary for clinical trial quality and efficiency improvements,” the website explains.