番茄社区

The FDA hasn't recovered from its pause in foreign drug manufacturer inspections during the COVID-19 pandemic, with inspections in 2022 remaining "well below" pre-pandemic surveillance levels, a study found.

Researchers tracking a decade of FDA inspections observed an expected decline in inspections in 2020, but 2 years later foreign inspections remained 79% lower than 2019, and domestic inspections remained 35% lower, without any "corresponding reduction in drug manufacturing or imports," David Ridley, PhD, of Duke University in Durham, North Carolina, and co-authors wrote in .

While the study does not include 2023 data, Ridley noted that fiscal year 2023 inspection rates changed little since 2022, based on publicly available information.

"No one would be surprised that there was a big fall in inspections in 2020 -- much of the world shut down -- but we are surprised to see that those inspections had not bounced back in 2022," Ridley told 番茄社区.

Prior to 2020, the average inspection in foreign countries was between 5 and 8 inspector-days; post-pandemic, that average increased to between 7 and 15 inspector-days, the authors noted. They defined inspector-days as "the total number of days required to complete an inspection by all assigned investigators." For instance, a 2-day inspection with two inspectors would count as 4 inspector-days.

Domestically, the average number of inspector-days also grew between 2012 to 2019 and 2020 to 2022. Among the inspections that did happen, the share of inspections which led to an "official action indicated" (OAI) -- which is the "most severe classification" indicating an unsatisfactory level of compliance -- increased.

Foreign Versus Domestic Inspections

In 2019, roughly 14% of domestic and 9% of foreign inspections resulted in an OAI finding. In 2021, rates for both doubled, though the authors observed "a partial reversal in this trend" in 2022, the study noted.

Prior to the pandemic, foreign inspections were increasing and domestic inspections were falling, the researchers noted. In 2012, there were 648 foreign and 1,392 domestic inspections, but in 2019, foreign inspections grew to 954 and domestic inspections dropped to 738.

However, after the FDA issued revised guidance in 2020, overall inspections declined significantly and by 2022, inspections, especially those conducted overseas, failed to recover, the authors noted. The agency did not inspect any drug manufacturing facilities in China or India from April 2020 to March 2021, they stressed.

The decline in foreign inspections is perhaps the most concerning data in the analysis, Ridley observed. Although the FDA appears to have the overall inspector resources, it isn't clear they are "optimally allocating" them; they "don't seem to be sending them abroad, even in 2022 and 2023," he said.

"[M]any of these foreign establishments haven't been visited by the FDA in years, and I think the longer the lag between inspections, the more the potential for manufacturers to get sloppy or ... to compromise on quality," he added.

Study Details

Ridley and co-authors leveraged data on inspections conducted by the FDA's Office of Regulatory Affairs from 2012 to 2022 obtained through a Freedom of Information Act request.

To measure the intensity of inspections, the researchers used the average number of inspector-days per inspection by region per month. They also examined the share of inspections resulting in an "official action indication" finding, which occurs when "there is an unsatisfactory level of compliance with current good manufacturing practices."

The study underscores the need to explore alternative methods for ensuring drug safety, the authors said. They called for the FDA to prioritize foreign inspections, hire more inspectors who can travel, and leverage technology to supplement remote inspections. They also urged the agency to continue to use "mutual recognition agreements" with other countries to make use of their inspection reports and to "share the drug quality assurance burden."

A key takeaway is that FDA inspections of foreign drugmakers are both "rare and announced," Ridley said. In addition, the agency rarely tests drugs itself. But some purchasers, including Kaiser Permanente and the Department of Defense, have begun paying labs to test drugs for them, Ridley noted. "So, there is a role for your retail pharmacy chain, or ... others... to test a few of the drugs and then to choose which manufacturers they trust based on the outcomes of the test," he said.

In an emailed response to 番茄社区, an FDA spokesperson stated that "the American public should rest assured that the drugs they rely on are high-quality, safe, and effective. Protecting patients is the highest priority of the FDA and the agency remains committed to using all available tools to oversee the safety, effectiveness, and quality of FDA-regulated drug products."

"Drugs intended for the U.S. market manufactured outside the U.S. must meet the same standards as drugs made in the U.S.," the spokesperson said. "We remain committed to using all available tools to oversee the safety and quality of FDA-regulated products and help ensure that Americans have access to essential and innovative therapies. Additionally, we continue to adjust our processes and guidance as necessary to maintain the appropriate level of review to ensure the safety of FDA-regulated products."

A study limitation was that the researchers did not observe the actual resources available for inspection activities and relied on aggregated data about budget and staffing to design proxy measures. The doubling of official actions may be due to the lag between inspections, but also could be because the FDA focused on the most potentially problematic establishments, Ridley noted.

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