Voluntary Remote Records Reviews Will Not Replace Formal On-Site Inspections
The FDA is conducting clinical trial oversight through informal remote review of site, sponsor and CRO records while the COVID-19 pandemic is limiting the agency’s ability to conduct traditional on-site inspections. But the agency stresses that these reviews are not taking the place of formal inspections and possible enforcement actions.
In March, because of COVID, the FDA stopped doing on-site inspections. In July, the agency said it had resumed mission-critical on-site investigations although they have been few and far between. To make sure trial oversight was still being addressed, the FDA has been doing voluntary and informal remote records reviews. Experts say they are similar to on-site inspections, but the FDA says they do not replace a legally binding inspection.
“It is important to note these are voluntary assessments and are not inspections conducted under FDA’s authority,” an agency spokesperson said. To date, the agency says it has conducted 33 remote records review since April, nine for trials in the U.S. and 24 abroad.
Based on discussions with “very senior FDA officials,” the voluntary remote records reviews are helping the FDA keep on top of what trials are doing for the agency’s internal assessment purposes, says David Chesney, who served the FDA for 23 years as investigator, supervisory investigator, director of investigations and ultimately director of the San Francisco district office.
The remote records reviews are one way for the FDA to continue its oversight function in the absence of on-site inspections. However, “if they conduct an assessment remotely and they tell the site — in this case, clinical trial sites — that this a voluntary, consensual participation that they’re entering into, then it’s not technically an inspection,” he told CenterWatch Weekly.
And Chesney acknowledges the remote records review process is no substitute for a formal inspection. “They don’t call them ‘remote inspections’ on purpose because [the FDA has] very clear and longstanding defined authority to conduct inspections, and that’s not what they’re doing,” said Chesney, general manager for DL Chesney Consulting. “Frankly, they don’t want anybody litigating this and then end up with an adverse precedent on the books. So, they’re taking great pains not to use the word ‘inspection.’”
Chesney said the scope of documentation and questions the FDA could pose during a remote regulatory assessment are the same as outlined in the agency’s inspection instructions: informed consent forms, source records, case report forms, electronic records, monitoring plans and reports, and any other study-related records.
“You’ll see most of it could be done remotely just as easily as on-site,” Chesney said. “Logistically, it may be a little more complicated because you have to figure out the best way to transmit documents.”
Despite the clear differences between an on-site inspection and an informal records review, Chesney said the agency is gathering much of the same information. “From a practical standpoint, is it really all that different? No, they’re doing pretty much the same things,” Chesney explains. Findings that would normally be presented on a Form 483 after an inspection are instead conveyed orally during a discussion with the site at the conclusion of the assessment.
But another key difference between an inspection and a remote records review: sites are not automatically given a copy of the final report; they can request one through FOIA. Although FOIA requests can take several weeks to process, getting the final report would be a way for sites and sponsors to document what has happened.
In a traditional inspection, which begins with FDA investigators presenting an official Form 482 — Notice of Inspection, any deviations or violations found would be listed on a Form 483 — Inspectional Observations, and the agency would determine whether enforcement action — such as warning letters, trial suspensions, seizures or even criminal charges — is necessary.
But under the FDA’s remote regulatory assessment model, the agency is reaching out to sites for their voluntarily participation in a records review without issuing the Form 482 that gives it the statutory authority to inspect and enforce, according to Chesney.
Chesney warns that a formal inspection could be a consequence of a remote records review if serious issues are uncovered. The FDA concurs. According to an FDA spokesperson, “Follow-up inspections will be conducted as deemed necessary based upon the information obtained during these assessments. In some case, no follow-up inspection will be necessary. Also, a remote regulatory assessment may be ended early if significant concerns are raised during the assessment and an inspection scheduled as conditions at the establishment allow.”
“Based on my own experience in the agency,” Chesney said, “I would imagine that if something came up during one of these remote regulatory assessments that was quite serious and [the FDA] felt it was necessary to pursue it more strongly, they could certainly go and conduct an on-site inspection and gather evidence in that realm in order to have that evidence be usable in some litigation, theoretically.”
Chesney says the remote records reviews are meant to be an oversight tool but not to replace the inspection and enforcement responsibilities the FDA has. “They’re like all the rest of us, trying to cope with current circumstances and get their job done as efficiently as they can.”
It’s too early to tell if the FDA would continue to utilize remote regulatory assessments post-COVID. For its part, the agency says, “The FDA continues to assess a full return to our routine inspection capabilities and is evaluating the use of remote assessments when on-site inspections cannot be conducted.”
Chesney believes the continued use of remote records reviews “could, for example, extend the FDA’s reach and it could end up saving the agency a good deal of money. If they wanted to include a mix of in-person and some remote assessments for a given study, they could probably get more clinical trial sites in less time and for less resource expenditure and [have them run] much more efficiently.”