Decrease in FDA Pandemic-Era Inspections Could Risk Public Health

From March to October 2020, during the height of the COVID-19 pandemic, the FDA conducted just 52 domestic on-site pharmaceutical inspections and all but halted foreign inspections ― moves that have worried some regulatory experts.

The numbers mark a staggering decline since the FDA usually conducts an average of 1,600 drug inspections annually, according to data from a Government Accountability Office (GAO) report. And for that same period ― from March to October ― in 2019 and 2018, the FDA conducted 400 domestic inspections on average and 600 foreign inspections.

But the FDA stopped almost all foreign inspections and scaled back domestic inspections in March 2020, only conducting three foreign inspections from that month until October. Two were “for-cause” inspections, one regarding a Canadian hand sanitizer producer and another regarding an active pharmaceutical ingredient manufacturer in Germany, while the last one was a pre-approval inspection for an Indian firm’s chloroquine phosphate tablets, says the GAO.

“The total number of FDA inspections of foreign and domestic establishments was 56 percent lower in fiscal year 2020 than during each of the previous two fiscal years,” the report states.

Unsurprisingly, the number of Form 483s the FDA issued to drug companies also plummeted. In fiscal year 2020, defined as from Oct. 1, 2019, to Sept. 30, 2020, pharmaceutical companies received a total of 349 Form 483s, according to agency figures. By comparison, drugmakers received a total of 770 Form 483s in fiscal year 2019 and 716 for fiscal year 2018.

In late July 2020, the FDA announced it would be implementing a new risk assessment process for agency investigators, creating a COVID-19 advisory rating system to determine in which geographic regions inspections could be safely conducted.

In a statement, the FDA said it would be “conducting only ‘mission-critical’ inspections, or, where possible to do so safely, resuming prioritized domestic inspections, which generally include pre-approval and surveillance inspections. … For the foreseeable future, prioritized domestic inspections would be pre-announced to FDA-regulated businesses.”

However, the agency has been criticized in the past for pre-announced inspections because they give companies time to prepare and the inspections don’t necessarily reflect the normal conditions of a facility. Pre-announcing inspections, which the FDA had historically done for foreign inspections, but not domestic ones, was considered a risk to public health.

In fact, the GAO report warned, “In June 2020, we testified before Congress about possible risks to pre-announcing inspections, including that they can give establishments the opportunity to fix problems before inspection staff arrive.”

And Michael Carome, the director of advocacy organization Public Citizen’s health research group, agrees with this assessment. The FDA claims it is examining “record reviews or relying upon reports of inspections done by their counterparts,” Carome said, noting that many global regulators aren’t conducting live inspections either.

“That is not sufficient,” Carome added. “You lose a lot when you don’t do an on-site inspection,” which creates “an opportunity for the company being inspected to not share all the records you may be seeking, to destroy records … to change records, and that’s happened [before].”

“Often, there are conditions you just won’t detect unless you’re on site and seeing how the facility is being run,” Carome suggested, offering examples like how filthy the plant might be or that two drugs are located too close together during manufacturing. “You won’t find that in the paper records,” he said.

As a compromise, Eric Good, director of compliance for industry consulting firm ProPharma Group, advocates for the use of virtual audits to allow the FDA to conduct more inspections while not risking its personnel during the pandemic. “I’m concerned, I’m very concerned, about what the FDA is not able to do … [I] would challenge the FDA to step up and improve their on-site [inspections], and if not on-site, virtual auditing.”

An FDA spokesperson did confirm to FDAnews that virtual inspections are, in fact, happening but did not offer any specifics on the program.

Click to read the GAO report from late January: www.fdanews.com/01-28-21-GAO.pdf. — Jason Scott