The FDA conducted about 34 percent fewer clinical investigator (CI) inspections in fiscal 2020 compared to the prior year, dropping from 516 to 338.

The agency halted all inspections in March 2020, but when it started inspections again in the second half of the fiscal year, it conducted 125: 91 onsite, 17 face-to-face inspections carried out at a location other than the trial site and 17 conducted remotely through record reviews and regulatory assessments. Most CI inspections conducted — 213 — occurred in the first half of the fiscal year.

The FDA is still trying to get back to the prepandemic level of inspections, and there are some signs that a rebound is under way. The number of Form 483s issued to clinical investigators dropped to zero in April and May 2020 and began to pick up in the final months of 2020 — the start of fiscal 2021 — rising to an average of eight per month.

The FDA issued a guidance last week formalizing some of the alternative methods the agency will continue to use during the duration of the pandemic to replace onsite inspections, including remote document review and video conferencing.

According to the guidance on what the agency is now calling remote interactive evaluations (RIE), the FDA will use a risk-based approach to selecting institutions and investigators for RIEs. And while participation in the evaluations is voluntary, the guidance cautions that declining participation could “impede [the agency’s] ability to make a timely regulatory decision,” such as granting an investigational new drug application (IND) or reviewing a new drug application.

Although RIEs will follow the same procedures as official onsite inspections, with FDA discussing observations with the inspected party and presenting a written report, there will be no 483s issued or enforcement action taken based on the RIE alone. Instead, the agency will use its findings to support further regulatory actions, prioritize an institution for future formal inspection or justify a follow-up inspection.

The FDA’s fiscal 2020 Bioresearch Monitoring Program (BIMO) report on inspection metrics also covered other types of clinical inspections involving sponsors, CROs and sponsor-investigators. Those inspections declined to 59 inspections in fiscal 2020 — down from 78 in fiscal 2019, a 24.4 percent drop year-to-year.

Broken down by type, the agency inspected 36 sponsors, 14 CROs and nine sponsor-investigators in fiscal 2020, compared to 43 sponsors, 16 CROs and 19 sponsor-investigators in fiscal 2019.

There were 27 inspections of IRBs in fiscal 2020, the FDA said, down from 54 in fiscal 2019. Of 18 postinspection letters the agency sent to IRBs in fiscal 2020, six involved issues with records while five were for written procedures, two involved quorums and one was for suspension or termination of a study.

But even as clinical trial inspections increase, they probably won’t be first on the agency’s priority list, according to WCG Chief Compliance Officer David Forster, taking a backseat to good manufacturing practice (GMP) inspections needed to keep the drug supply safe. “My expectation is that FDA will slowly return to a regular auditing schedule as we move to a postpandemic setting,” Forster says. “I assume that in that process, they will focus on GMP audits that are required for drug production.”

Despite a drop-off in inspections, the FDA has continued to issue warning letters for serious violations during the pandemic and has issued at least five such letters to CIs during the first three months of 2021 compared to three in all of 2020.

Data posted by the FDA’s Center for Drug Evaluation and Research show three warning letters and two untitled letters have been issued to CIs so far this year. One warning letter shows a site received a 483 after an onsite inspection in June 2020 revealed the site did not follow dosing requirements of the trial’s protocol for an unspecified number of participants. In a second warning letter, an onsite inspection between August and September 2020 found a site enrolled and randomized three participants who should have been excluded, among other protocol violations. A third warning letter was sent to a sponsor for failing to submit an IND application.

The two untitled letters to CIs were in response to “objectionable conditions” found during BIMO onsite inspections conducted in November 2020. Specifically, one site had failed to prepare and maintain adequate and accurate case histories — at least 23 of 53 trial participants had not completed an eDiary entry at a specific point in the protocol — while another site was flagged for not conducting follow-up safety calls with 47 of 103 trial participants. Both sites were also cited for additional protocol violations.

The agency also classified four inspections as official action indicated (OAI) in fiscal 2020. While there were no OAIs in fiscal 2019, there were five OAIs in fiscal 2018. The report also showed that of the four OAIs in fiscal 2020, 75 percent of them involved a protocol issue, while 25 percent were for submission of false information, 25 percent were for IRB communication and 25 percent involved some other issue. The numbers don’t add up to 100 percent because in some instances, CIs had multiple deficiencies, the FDA said.

Read the BIMO report here: https://bit.ly/3e2Uc52.