Onsite Inspections Back to Normal, But Some Things Remain Changed
After nearly two years of postponed or remote site inspections due to the pandemic, the FDA appears to have returned to normal on its good clinical practice (GCP) inspections and routine surveillance.
“If they’re not [back to a normal schedule], they’re close to it,” Dave Borasky, vice president of IRB compliance for WCG, said during the WCG FDAnews FDA Inspections vSummit. “IRBs were one of those things that I think they, I wouldn’t say totally backburnered, but if it wasn’t for-cause, that wasn’t the first thing they were jumping out of the gate to look at in terms of surveillance audits. The fact that they’re doing those again now, I would say is getting quite back to normal.”
But even though Bioresearch Monitoring Program (BIMO) inspectors are back on the road, teams that respond to FDA inspections may not be able to travel as freely as they could prior to the pandemic to be there, in-person, for an agency visit.
“The tide has changed, and general expectations for who needs to get up out of their seat and go travel somewhere have really changed,” said Denise Lacey, founder and principal of Ready Room, an inspection management platform. “And I think that even the government has to catch up with that at some point.”
Tellingly, the FDA is now routinely asking about ClinicalTrials.gov compliance, another sign, beyond issuing its first enforcement letters this year, that it’s taking the timely reporting of trial information seriously. While the FDA investigators didn’t actually check to see if the data was up to date on the website, at least during the visit, they did inquire if people were aware of the updating and reporting requirements.
Lacey said she believes the rise in vendors being hired by sponsors to support sites during the pandemic, such as remote clinics, telehealth vendors and contract study coordinators, should be carefully considered, as their increased use could potentially come up during inspections.
“I think… that’s going to be kind of a flashpoint for future inspections, looking at those relationships, who is transferring obligations to whom, who’s on the [1572 — Statement of Investigator], who is supervising these vendors — is it the site’s responsibility, is it the sponsor’s? Are there any inherent conflicts of interest in having the sponsor hire somebody that is then being supervised by the site and is really supporting the site?” she said.
“I think it could get interesting when you’re looking at site inspections, sponsor inspections and then those vendor inspections, what kind of documentation is getting requested in each one and who is providing it. I expect that we’ll see [further] guidance from FDA on that. I expect as people are encountering these situations more and more during inspections that FDA will eventually come out with some guidance on best practices for approaching these relationships and for documenting these situations.”
For Patty Mendoza, manager of regulatory affairs, compliance and clinical trial management at Houston Methodist Research Institute, the pandemic has not dramatically altered her inspection experiences. Having gone through 18 inspections since the 1990s, Mendoza’s latest experience just a few months ago was largely the same, she said, although the first thing the agency asked about was the site’s SOP for COVID-19 and people and participants coming into the site.
The agency looked at everything on the site’s BIMO review checklist as normal, but she noted that they asked for specifics about the site’s principal investigator (PI), making it clear that they expected him to be available for the inspection and able to talk in-depth about the study. Mendoza, who nearly always preps for inspections, didn’t have that opportunity this visit due to the timing, and the difference was definitely noticeable: the PI wasn’t as clear as he could have been if there had been time for preparation. Mendoza swears by making a “cheat sheet” to ensure sites and investigators are ready when the agency comes knocking.
“Sometimes studies are reviewed so [much] later that the research team, the PI have moved on, so I make, basically, a high summary for the PI. I recommend and always stay with the same plan: go through a high-level summary of the study once it was approved all the way through the amendments, any SAEs, high-level issues that came up, deviations. Focus on the monitoring visits, follow reports, look for trends and be able to speak to that. It’s hard to go back and do that, but one of the things the FDA [investigator] said — she pulled one of the studies at random that had no opportunity for a check — was that she’s used to people coming in and preparing for reviews.”
Mendoza urges research staff to act, on every trial, like they’re going to be reviewed and to have a proactive quality assurance (QA) program in place. Mendoza’s own system includes decision-making skills she’s learned, such as Six Thinking Hats and Lean Six Sigma.
“You work with teams on improving areas that they want, and you do it in real-time. From [the point of] IRB approval, you have checks all the way through, you do mock runs, you review the source, you review processes and how they’re following up on issues,” she said. “That proactive QA has made such a difference in our inspection readiness. I can tell you that it’s night and day, and it has a better staying power compared to traditional compliance.”
Suellen Bigaj, vice president/principal consultant for Pharma Compliance Partners, also found that the FDA’s inspection process and site selection methods aren’t changing as a result of the pandemic — but the logistics (how they’re conducted) are.
“Moving forward, are those things going to continue to stay in existence? I think … the things that have worked well and the things that we know and that came about as of COVID, they’re going to stay, but there’s also gaps that we’ve learned. There’s things we can accept and things we do still need to be conscious of from the old ways. I don’t see it moving forward in any other way at this point in time,” she said.
The biggest issues Bigaj has seen right now have been related to trial master file and investigator site file maintenance. These files should both be ready for an FDA inspection at all times, and not ensuring that they’re ready for agency eyes can lead the issue to “trickle down” to sites that are already busy with other activities. The problem is one that should be viewed with concern, Bigaj said.
Mendoza, who belongs to a U.S.-based IND task force with other academic centers, recently participated in a session with the group about their recent audits. Seven sites at that meeting underwent inspections, and all had the same things selected for their investigator-initiated trials.
The agency was straight up: they wanted to know what the sponsors’ responsibilities were, how those were determined, how the PI either covered those responsibilities or made sure they were covered and how the monitoring process worked, she said.
Still, because so many people are working remote all or part of the time, it has become a challenge for sites to make sure that all staff are onsite when the FDA comes knocking.
Lacey predicts — though she noted she’s seen no signals from the FDA on this yet — that future GCP inspections may incorporate some of the remote approaches brought on during the pandemic, though it’s a “wait and see” situation right now.