FDA’s drug quality report notes ‘significant’ uptick in inspections since pandemic

In its latest State of Pharmaceutical Quality report, the US Food and Drug Administration’s (FDA) Office of Pharmaceutical Quality (OPQ) reported significant increases in both foreign and domestic inspections since the COVID-19 pandemic, along with a substantial rise in warning letters following these inspections.

The report is the seventh annual State of Pharmaceutical Quality report from OPQ, detailing key data that characterize drug and manufacturing site quality. This includes data from inspections, product quality defects, import alerts, and recalls.

FDA’s site catalogue lists 4,619 manufacturing sites globally, an 11% increase over the past five years. According to the report, 41% of the sites are located in the US and the remainder are outside the US. Five countries—China, Spain, Germany, India, and South Korea—saw site increases of over 15%.

The number of drug quality assurance inspections conducted by the FDA for both foreign and domestic manufacturers—encompassing surveillance and for-cause inspections—has significantly increased since the COVID-19 Public Health Emergency (PHE). Specifically, there were 522 inspections in FY2022, 766 inspections in FY2023, and 972 inspections in FY2024.

The report states that “in FY2024, more than 62% of drug quality assurance inspections were at foreign sites —an all-time high. This progress in foreign inspections was particularly evident in India and China, where 34% and 28% of sites in the Site Catalog, respectively, were inspected. By comparison, 24% of the U.S. sites in the Site Catalog were inspected in FY2024.”

The increase in foreign inspections has been accompanied by a growing number of inspections conducted under Mutual Recognition Agreements (MRAs): 44 in FY2022, 190 in FY2023, and 198 in FY2024, the highest number achieved to date.

In FY 2024, FDA issued 105 warning letters to human drug manufacturing sites, marking the highest number of quality-related warning letters for human drugs issued in the past five years.

The report noted that the FY2024 increase “was driven largely by inspection-based warning letters, which increased by 21% from FY2023, and resulted from the increased number of FY2024 inspections. During the past three years, the proportion of warning letters issued to foreign sites increased, in part because FDA performed more drug quality assurance inspections at foreign sites.”

The report highlighted that, in contrast to the overall increase in warning letters driven by inspections, the rise in warning letters issued to sites in China concerning FY2024 was mainly attributed to quality deficiencies identified in §704(a)(4) records requests. Specifically, eight out of the thirteen warning letters were related to these deficiencies.

Nine manufacturers of OTC monograph products in South Korea received warning letters in FY 2024. Notably, six of these nine letters cited the companies for failing to test drug product components for harmful substances such as diethylene glycol (DEG), ethylene glycol (EG), or methanol.

Europe had the highest rate of No Action Indicated (NAI) or Voluntary Action Indicated (VAI) following inspections, with a rate of 98%. In contrast, India had the lowest rate of NAI and VAI at 87%. China reported a rate of 93% for NAI and VAI findings. Additionally, 92% of sites in the US were categorized as either VAI or an Action Other Than Inspection (AOI).

China had the highest percentage of import alerts, accounting for 39%, while both India and Europe each represented 13%. The report notes that the number of import alerts associated with China is disproportionately high, considering that sites in China represent only 175 of the total foreign sites listed in the catalogue.

The report said that more than 60% of quality-related import alert additions in FY2024 were based on record requests.

For manufacturers of OTC monograph drug products, the most common reason to be placed on import alert was quality-related deficiencies identified in their responses to §704(a)(4) records requests. For non-sterile API manufacturers, the most likely reason was failure to respond to these records requests.

The number of recall events in FY 2024 increased to 165 sites generated recall events, 15% more recall events than in FY2023. While the number of recall events increased, the number of recalled products per event in FY2024 “was the lowest in five years, resulting in only 421 recalled products.”

Microbial contamination of products was the major reason for recalls at 31%, followed by sterility assurance issues at 28% and foreign material/particulates contamination at 20%.

Report

FDA’s drug quality report notes ‘significant’ uptick in inspections since pandemic

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