Advice on Preparing for Regulatory Inspections
Regulatory inspections are not something clinical research personnel enjoy; however, they often have to deal with them. Inspection readiness is an emerging concept that is rapidly gaining importance in clinical trials, and Marci Macpherson, executive director, quality assurance and compliance at Ionis Pharmaceuticals, will discuss her perspectives on inspection readiness and offer a few tips on preparing for inspections.
Moe Alsumidaie: What is clinical trial inspection readiness?
Marci Macpherson: Inspection readiness is a state of being in which sponsors and organizations are prepared for an audit at any time. This includes having procedures to enforce adherence to applicable regulatory guidelines and promoting a culture focused on quality—a solid commitment to proactive quality and risk management from every department involved in clinical trials at all times. Quality is not solely a QA responsibility; activities conducted by other teams are essential in this space, too, ensuring compliance with your procedures and having adequate policies and practices, such as real-time storyboarding, which helps with audit preparation efforts several years down the line.Inspection readiness is distinct from inspection preparation, which typically is owned by QA at sponsor companies and is a discrete activity focused on an upcoming planned inspection.
MA: How do you anticipate what regulatory authorities will look for during inspections?
MM: Following FDA warning letters and other published inspection metrics from health authorities, such as EMA and MHRA, are a good source, as surveilling them helps you keep tabs on what the agencies focus on. And then there's much outreach that the health authorities are doing; for example, FDA holds many webinars and other outreach efforts. I attended the first FDA MHRA joint conference in Washington, DC in 2018, and the next one in the UK in 2020, both of which focused on data integrity. The third was held earlier this year in London and also included Health Canada.Many of these sessions are downloadable, and they sometimes publish papers following those sessions. Another good place to start is the revised BIMO compliance program, especially if you're anticipating a potential FDA inspection. This document will tell you exactly what topic FDA inspectors will review.While many of the areas remained the same, there are new sections and expanded areas of focus included in the 2021 sponsor/CRO revision, including oversight documentation for outsourced services, remote monitoring, data safety monitoring board/data monitoring committee, just to name a few.
MA: What sorts of findings are regulators focusing on right now?
MM: Sponsor oversight and risk management are lighter in the literature, but emerging topics as health authorities look at sponsors' approaches particularly if issues have been noted.For example, in phase one trials, they’ll focus on dose escalation, and you'll see findings about those decisions. We continue to see findings with trial management; EMA and FDA are looking at the sponsors’ failure to monitor their trials and failure to select qualified monitors. Another area is the investigational product supply chain; are sponsors keeping up with their record-keeping requirements to show that chain of custody? Next is safety-related adverse event reporting. Are you meeting your 7–15 day reporting timelines? Data integrity and protocol compliance are also long-standing topics. Finally, the trial master file (TMF) is an area of focus (particularly for EMA/MHRA) and something you may want to storyboard if you had a transition in personnel or technology systems.
MA: Why is it essential to engage QA before and during an inspection?
MM: I can't stress enough how important it is toidentify subject matter experts as early as possible and engage them. Cross-functional involvement is critical, and QA is your partner and, hopefully, your best friend. The value is helping teams anticipate questions when issues arise. What questions will regulators ask, and how do we practice that? We've done these inspections before and can help. What went well, what didn't, and what needs to be followed up on.
MA: How can QA help personnel prepare for an inspection?
MM: Your QA department can sit down with the subject matter experts and conduct Q&A sessions, which are very useful. Knowing what to expect makes personnel more comfortable during an inspection and removes fear. Additionally, I recommend conducting a formal mock inspection, when feasible, to help with preparation, particularly for inspection-naïve teams.
