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GAO Evaluated Limitations of the FDA’s GCP Audits
(Thursday, March 28, 2024) A survey by the General Accountability Office (GAO) reported many interesting facts about the state of clinical trial audits by the FDA inspectors. The purpose of the GAO survey was to identify deficiencies in the FDA audits for compliance with Good Clinical Practices (GCP), but in the process, it reports several surprising facts about the FDA’s audit practices and its inspectors. FDA has only about 100 inspectors trained to conduct all GCP inspections who together conduct a total of a few hundred inspections each year, showing the extreme limitations of the FDA audit program. GCP compliance is critical for ensuring the accuracy and integrity of the clinical trial data used in support of market approval applications. FDA audits are an important tool for enforcement of the regulations. It is well-established that lax enforcement leads to deficient compliance and hence the laws mandate that the FDA inspectors conduct audits of the clinics and hospitals participating in clinical trials. But it is easier said than done. FDA is grossly understaffed to meet its GCP enforcement mandate. The GAO reports many reasons why stakeholders should be worried. Over the last decade, the FDA has maintained about 100 inspectors in its Bioresearch Monitoring (BIMO) program, the department that is responsible for GCP inspections. That is across the Agency. Based on the scale of the clinical trial enterprise, this is a very small workforce, in the first place, that already conducts a very small number of inspections, which should be obvious even when looked at a very high level. According to the clinicaltrials.gov registry, about 10,000 Phase 2 and 3 clinical trials were completed in the last decade, of which about half (~5700) were conducted in the US. It is safe to assume that all these trials involved multiple clinical sites. Even assuming a very modest number of 10 sites per trial, that brings us to more than 100,000 sites worldwide or about 60,000 clinical sites in the US that participated in clinical trials whose results were likely used in market approval applications. The total number of inspections conducted by the FDA inspectors before the pandemic was about 800 per year which dropped to about 400 per year in 2020 onwards, due to the pandemic, according to the FDA. The total number of audits conducted by FDA inspectors in the last decade comes to about 6000 worldwide, which roughly translates to about 6% of the sites. There are several obvious caveats in the above assumptions such as an inspection may have involved more than one trial, the same site may be involved in multiple trials and hence if they were found to be good for one trial, they were assumed by extrapolation to be compliant in all other trials, and the number of remote inspections that may not have been counted by the GAO. Still, about 800 inspections by 100 inspectors in a year, means about 8 inspections on average per inspector, which seems very little. At the most, an inspection on average should take about a week so an inspector should be able to conduct between 2-4 inspections in a month or about 20-40 inspections in a year. Something doesn’t add up. There must be an explanation for this. Set that aside, the FDA told the GAO that it is finding it hard to recruit and train enough inspectors even with higher salaries and other perks, due to the high amount of travel. The attrition rate for FDA inspectors is very high. For the industry, this confirms the established norm that most clinical sites have never been audited by the FDA, and that does not seem inclined to change. The most common audit finding by the FDA inspectors was not following the protocol, which indicates the lack of enforcement of quality by the sponsors, which in turn reflects complacency on the part of the industry due to the lack of enforcement by the FDA. The GAO report paints a very bleak picture of the state of the FDA's ability to enforce clinical trial regulations. This should worry all stakeholders. 
AUTHOR
Dr. Mukesh Kumar Founder & CEO, FDAMap Email: [email protected] Linkedin: Mukesh Kumar, PhD, RAC Instagram: mukeshkumarrac Twitter: @FDA_MAP Youtube: MukeshKumarFDAMap |
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