This monthly feature presents questions clinical trial professionals have asked and the answers several experts have provided. This month, the questions come from attendees at a recent WCG FDAnews webinar on data integrity who wanted to know how the FDA is handling site and sponsor inspections during the COVID-19 pandemic. Answering the questions are four former FDA inspection and compliance officials: David Chesney, principal of DL Chesney Consulting; David Elder, executive vice president of regulatory compliance at Greenleaf Health; Cynthia Schnedar, executive vice president of regulatory compliance at Greenleaf Health; and Sarah Barkow, lead, GxP external engagement at Bristol Myers Squibb.

Question: How is the FDA handling the inspection of clinical sites that are closed due to COVID-19 and how would it handle preapproval inspections of sponsors?

Chesney: There are two different scenarios there. A clinical trial site is typically a caregiving environment, and patient safety and nondisruption of patient care is a big priority. And I’m sure the FDA doesn’t want to do anything to disrupt the proper delivery of patient care. So, site inspections are a bit more difficult than sponsor inspections in a situation like this.

On the other hand, a lot can be done remotely to inspect either a site or a sponsor. Offices and sites may be closed, but people are continuing to work remotely. I’ve done two or three remote sponsor mock inspections. So, it certainly can be done.

For example, a client of mine was contacted recently by the FDA about scheduling an inspection. The agency investigator showed up on day one, issued the formal notice of inspection — which is a requirement for FDA investigators — and met briefly with two senior officials. The visit lasted about an hour and a half. The rest of the inspection was conducted remotely. So, it’s kind of a hybrid approach.

Elder: The ability to do this well and efficiently is contingent on the site or sponsor having document systems and document production capability that would facilitate the review. To the extent some of these sites are still deep into paper, with many hundreds of pages of paper that aren’t in an electronic system, it would really impede the ability to share that information to enable an efficient off-site review.

The example of an FDA investigator showing up on-site, having a brief discussion, collecting materials and doing the rest off-site is exactly the kind of hybrid approach the agency can use to make decisions just as it would with a traditional inspection.

Question: Could a Form 483 — Notice of Observational Inspection — still be issued at the end of an inspection that relies solely on document review?

Elder: I think it’s fair to say it could be but it’s doubtful from my view because if the FDA doesn’t present a notice of inspection and just requests records, then they shouldn’t be issuing a 483 because those are issued at the conclusion of inspections.

The decision the agency would make as a result of a remote document review, as told to me by senior FDA officials, is not the same as the decision it would make from an actual inspection. The agency could make a decision that says we will waive an inspection. They could make a decision that says we’ll prioritize the site for an inspection. If it’s coupled with recent inspection information from other health authorities, the FDA could say they have enough information to inform that decision. They just won’t call it an inspection.

I think we’re trying to convey what can very much be a fast-evolving policy. The policy may very well be different one month, six months or a year from now. And the FDA may get more comfortable considering these remote inspectional activities to be near-equivalent to an inspection, but more importantly to the industry, to inform the decisions that an inspection would inform.

Question: Could remote document reviews lead to misinterpretation by the FDA?

Schnedar: I think there’s always the possibility that remote review could lead to misinterpretations. And that’s where I think you have to step up the communication. Don’t just dump the documents and let agency investigators read them. Be kind of proactive in communication. If you want to avoid misinterpretations of information you’ve provided, you would follow up.

Barkow: I think there’s probably the same potential for misinterpretation as in an on-site inspection. If you don’t have context, if you don’t have people there who can explain, you’re going to get misinterpretation. You’re going to get issues popping up.

I’ve seen a significant number of cases where the person who was showing the FDA investigator the audit trail didn’t actually know what audit trail they were supposed to be looking at or how to access the system. I mean, misinterpretation doesn’t suddenly come in when it’s remote. So, if you can provide context, I would recommend providing it upfront: “Here is the data. Here is what it means. Here is how we use it.”