This monthly feature presents questions from clinical trial professionals with answers from FDA and industry experts. This month, we look into the FDA’s new inspection tool, remote interactive evaluation, with insight from several former FDA inspection officials on its impact on clinical trial sites and investigators. These comments were made at the FDAnews 16th Annual FDA Inspections Summit.

Question: To help streamline inspections and catch up with a backlog due to pandemic restrictions, the FDA is replacing some traditional onsite inspections with a virtual activity it calls a remote interactive evaluation (RIE). How do these differ from inspections we’ve had in the past and are we required to accept an RIE request from the agency?

Answer: While the FDA can use RIEs to support its decisionmaking, the agency is adamant that these evaluations are not inspections. For instance, no Form 483 is issued. However, an RIE does include a written list of observations, an opportunity for the subject organization to respond to those observations and a final “remote interactive evaluation report,” according to Kalah Auchincloss, executive vice president at Greenleaf Health and a former deputy chief of staff for two FDA commissioners.

The RIE is a voluntary activity, unlike an inspection, which cannot be declined without penalty. However, while no direct penalty will occur if a company declines to participate in an RIE, Auchincloss cautions, that does not mean it is consequence-free. It is in any company’s best interest to accept an RIE, she says. Refusal to participate in this type of evaluation could “impede [FDA’s] ability to make a timely regulatory decision,” according to an April 2021 guidance on the use of RIEs during the COVID-19 emergency.

“The RIE is just one of the FDA’s tools; the agency hasn’t waived any of its other tools,” says Cynthia Schnedar, principal, regulatory compliance at Greenleaf Health and a former director of the Office of Compliance in the agency’s Center for Drug Evaluation and Research. “It can still have an onsite inspection, request a recall or conduct any of its normal enforcement activities when it discovers a critical issue,” she says, “regardless of how that problem is discovered.”

If an RIE discloses a critical issue, it is certain that the FDA will take some additional action. This could include scheduling an in-person inspection or use of another compliance enforcement method, such as a warning letter.

“To a certain extent, saying ‘this is not an inspection’ brings confusion to industry,” Dan Barreto, president and owner of PharmQ Global Consulting and a former FDA investigator, says. Barreto says he would consider some RIE activities to be inspection activities as they allow the FDA to evaluate regulatory compliance.

Question: Do observations noted during an RIE carry the same weight and consequences as those cited on a traditional Form 483 (Inspectional Observations)?

Answer: While RIEs do not include the same type of closeout meeting as seen in a traditional inspection, they do conclude with a list of observations. The process for dealing with those observations is somewhat different from an inspection, says Auchincloss. For instance, the agency does not classify its observations as “official action indicated,” “voluntary action indicated” or “no action indicated” as is done in a traditional inspection’s final establishment inspection report (EIR). But that doesn’t mean that the process couldn’t evolve in that direction.

“I would not be surprised if we move toward a world where the RIE outcome can be similar to an onsite inspection,” she says.

But not all industry experts agree with the FDA’s assessment of the RIE’s place in the overall enforcement scheme. For instance, the lack of an EIR or 483 is really a semantic game, according to David Chesney, principal and general manager of DL Chesney Consulting and an FDA veteran with more than 25 years of experience working in the agency’s inspectorate.

“While there is no document titled EIR for an RIE, there is a report. It will not be provided routinely to the company or public,” Chesney says. “You won’t get it as a courtesy but will have to request it” through the agency’s Freedom of Information Act program.

But it is still in your best interest to cooperate with any RIE request and to respond to any findings from an RIE just as you would if you received a 483. And even though RIEs are voluntary to an extent, records requests continue to be voluntary for clinical trial organizations, Chesney adds. This is an important distinction as drug and device manufacturers may not refuse a records request.

“We have seen warning letters and other regulatory actions as a result of [manufacturers refusing] records requests,” Auchincloss emphasizes.

Question: Could RIEs eventually replace onsite FDA inspections?

Answer: “In theory, there’s no reason the RIE couldn’t develop into a fully virtual inspection,” Chesney says. “The FDA has been reluctant to do that until now due to the limitations. You can’t get as good a look, no matter how good the technology, as you can in person. But it’s a matter of agency discretion and there is no reason they couldn’t apply that discretion.”

RIEs and the FDA’s other remote approaches to oversight aren’t actually new, says Schnedar. The agency has always had the authority to use them but had been reluctant to use them until the pandemic made it necessary.

The FDA hopes its new remote tools will make its inspections more efficient, alleviating some, replacing others and generally shortening all, she says. “The pandemic has forced FDA into finally embracing these remote tools,” she says. “I think the FDA wanted to, but it’s accelerated that timeline rapidly.”

Read the FDA guidance on remote interactive evaluations at https://bit.ly/3KzZHXP.