Although relatively rare, clinical investigator inspections by the U.S. Food and Drug Administration (FDA) can have a significant business impact. Audits are conducted more frequently than regulatory inspections, which are estimated to take place at fewer than 3% of sites, but adequate responses in either case are essential to successful outcomes. Clinical research professionals who deal with complex study issues need to understand requirements, including key areas of Good Clinical Practice and how best to address any observations. This may include identifying root causes and creating corrective and preventive action (CAPA) plans in order to address FDA citations from documents such as Form 483s and Warning Letters.
“Post-COVID, the numbers of FDA inspections are returning to pre-pandemic levels,” says Glenda Guest, RQAP-GCP, TIACR, CCRA, ACRP-MDP, FACRP, Independent Consultant, Assured of Quality Consulting & Training. “Clinical research professionals should be aware that there are many useful tools on the FDA website, including Bioresearch Monitoring Program Compliance Program guides and the 2024 Inspections Operations Manual. By reviewing these resources, sites can be better prepared to answer questions, offering an opportunity give investigators a positive impression of the organization’s level of preparedness.”
In addition to agency inspections, sites may be audited by their sponsors or contract research organizations. The process for resolving any findings is similar. “Major findings may result in repeat inspections, including follow-ups to check that improvements have been made,” states Janet Holwell, TIACR, CCRC, CCRA, FACRP, Clinical Research Consultant/Trainer. “Such findings move the site to the top of the list for future attention. This is another reason that it’s critical to find the root cause and put effective CAPAs in place.”
Holwell explains that common clinical investigator inspectional observations include:
- Failure to comply with Form FDA 1572 requirements or to follow the investigational plan
- Inadequate and/or inaccurate case history records, or inadequate study records
- Inadequate subject protection, for example, informed consent issues
- Inadequate accountability and/or control of the investigational product
- Safety reporting, such as failure to report and/or record adverse events
Possible reasons for non-compliance at the site level may include lack of time, insufficient training, staff turnover, or pressure from the sponsor or principal investigator to enroll, according to Holwell. “Challenges to a successful response may include the need to find the root cause, identify solutions, globalize the preventive action, and check the correctness of the response (for example, by questioning response owners, verifying statements, and auditing).”
Managing the Consequences of Audits and FDA Inspections
Join Glenda and Janet at ACRP 2025 [April 24-27; New Orleans, La.], where they will cover important Good Clinical Practice topics to prepare for audits and regulatory inspections and for addressing any resulting observations. View complete schedule.
“Appropriate behavior and communications with FDA Investigators will help ensure a smooth process,” concludes Guest. “Specifically, clinical research professionals should not overpromise, confess, be argumentative, be overly strident, or challenge the regulations. Responses to FDA should include a timeframe for correction that is as short as possible; a detailed corrective action plan rather than piecemeal corrections; specific solutions that are not open to more than one interpretation; and corrections that do not have an adverse effect on other systems.”
Edited by Jill Dawson
