FDA’s lack of onsite inspections may have compromised drug quality, study says

The US Food and Drug Administration’s (FDA) decision to pause its onsite inspections during the COVID-19 pandemic may have had negative consequences for drug quality, according to a new analysis in Health Affairs.

The study, which was led by Emily Cuddy, assistant professor of economics at Duke University in Durham, NC, examined the total number of drug quality inspections conducted per month by the FDA Office of Regulatory Affairs (ORA) from 2012 through 2022. It examined inspections in five regions—China, Europe, India, Latin America and other foreign nations -- and analyzed inspections outcomes, such as whether firms were classified as Official Action Indicated (OAI), meaning that quality improvements were needed.

“Deferring inspections for operational establishments may have consequences. Increases in time elapsed since the last inspection are associated with decreases in regulatory adherence. As these inspections play a crucial role in upholding manufacturing standards, the delay could have exposed US consumers to lower-quality products,” Cuddy and colleagues wrote.

The researchers found a 79% decrease in foreign inspections and a 35% decline in domestic inspections in 2022 compared with 2019. Yet during this time, the share of inspections resulting in an OAI dramatically increased, from 14% of domestic inspections and 9% of foreign inspections in 2019, to a doubling of both numbers in 2021.

A change in the criteria that FDA used in selecting sites for onsite inspections may explain the increased incidence of OAI findings during the COVID-19 pandemic, according to the researchers. “Establishments inspected during the pandemic were nearly twice as likely to have had a history of objectionable conditions or practices than those that were not inspected,” they wrote.

Yet FDA’s decision to pre-announce inspections during the pandemic and give “bad actor” firms a chance to “hide quality issues” does not explain the increase in the OAI rate, Cuddy and colleagues wrote.

The researchers also noted that while travel restrictions are no longer a concern, most foreign inspections still remain on hold. “It is hard to rationalize continuing to postpone foreign inspections, given the data available to us. As the world moves beyond the pandemic, it is crucial for the FDA to address the backlog of inspections and to consider new approaches for the future,” they wrote.

The researchers recommend that FDA hire more inspectors, noting that additional staff can allow more inspections, reduce the time between inspections, and enable staff to rotate across different establishments. These measures are “essential to counteract complacency arising from repeat visits by the same inspector” the wrote.

They also recommend that FDA prioritize foreign inspections in an effort to “close the foreign-domestic inspection disparity that COVID-19 reopened.”

Other recommendations include increasing international cooperation through the use of mutual recognition agreements that recognize inspection reports made by overseas regulators, increasing the use of third parties to assess drug quality, and increasing patients’ awareness of drug quality issues.

“Few know that foreign drug production sites are rarely inspected by the FDA and receive advance warning before an inspection,” Cuddy and colleagues wrote. “If patients were made aware of average quality differences across manufacturers of generic drugs, then they could make quality-informed purchase decisions.”

Health Affairs

FDA’s lack of onsite inspections may have compromised drug quality, study says

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