A 7-Year Analysis of the U.S. FDA Good Clinical Practice Inspection Outcomes for Marketing Applications

对美国FDA良好临床规范检查结果(针对上市申请)的7年分析

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Abstract

BACKGROUND: The U.S. Food and Drug Administration (FDA) conducts Good Clinical Practice (GCP) inspections to support regulatory decisions on marketing applications. Inspection outcomes including issuance of Form FDA 483 and a comparison of recommended and final inspection classifications have never been reported. METHODS: GCP inspections conducted from calendar year 2017 to 2023 were analyzed by characteristics and outcomes. The recommended and final inspection classifications were compared to determine no change, upgrades, or downgrades. The inspection deficiency areas for upgrades and downgrades were summarized. RESULTS: The FDA completed 2836 review-based routine GCP inspections in support of Center for Drug Evaluation and Research (CDER) marketing applications between 2017 and 2023. Overall, final no action indicated (NAI), voluntary action indicated (VAI), and official action indicated (OAI) classifications were determined for 81.2%, 18.5%, and 0.3% of all inspections (The majority of final OAI classifications are driven by for-cause GCP inspections rather than review-based GCP inspections). The percent of establishments issued a Form FDA 483 decreased from 2017 (23.5%) to 2023 (10.4%). Roughly 97% of recommended NAI and 96% of recommended VAI classifications received the same final classification, but there was an increase of VAI to NAI downgrades during years 2020 to 2022. Common deficiency areas related to both upgrades and downgrades were adherence to trial protocol and adequacy of records. CONCLUSIONS: Nearly all (99.7%) inspections were classified as either NAI or VAI during the study period, and their recommended and final classifications remained highly congruent. The Coronavirus Disease 19 (COVID-19) pandemic likely impacted the number of VAI to NAI downgrades.

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