{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T07:36:15Z","timestamp":1792136175849,"version":"4.4.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T00:00:00Z","timestamp":1752883200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T00:00:00Z","timestamp":1752883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ther Innov Regul Sci"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s43441-025-00835-6","type":"journal-article","created":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T20:15:55Z","timestamp":1752956155000},"page":"1421-1431","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A 7-Year Analysis of the U.S. FDA Good Clinical Practice Inspection Outcomes for Marketing Applications"],"prefix":"10.1007","volume":"59","author":[{"given":"Courtney","family":"McGuire","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenn W.","family":"Sellers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"Muldowney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,19]]},"reference":[{"key":"835_CR1","unstructured":"FDA, Bioresearch Monitoring Program Information. 4 August 2022. Accessed on February 21. 2025. https:\/\/www.fda.gov\/inspections-compliance-enforcement-and-criminal-investigations\/fda-bioresearch-monitoring-information\/bioresearch-monitoring-program-information"},{"key":"835_CR2","unstructured":"FDA, Compliance Program Guidance Manual (CPGM), 7348.810, Sponsors and Contract Research Organizations. Accessed on February 21, 2025. https:\/\/www.fda.gov\/media\/75916\/download"},{"key":"835_CR3","unstructured":"FDA, Compliance Program Guidance Manual (CPGM), 7348.811, Clinical Investigators and Sponsor-Investigators. Accessed on February 21, 2025. https:\/\/www.fda.gov\/media\/75927\/download"},{"key":"835_CR4","unstructured":"FDA, E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1.). Guidance for Industry. March 2018. Accessed on February 21, 2025. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/e6r2-good-clinical-practice-integrated-addendum-ich-e6r1"},{"key":"835_CR5","unstructured":"Investigations Operations FDA. Manual 2025. https:\/\/www.fda.gov\/media\/166525\/download?attachment"},{"key":"835_CR6","unstructured":"FDA, Processes and Practices Applicable to Bioresearch Monitoring Inspections. Draft Guidance for Industry. June 2024. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/processes-and-practices-applicable-bioresearch-monitoring-inspections"},{"key":"835_CR7","unstructured":"FDA, Program Alignment and ORA. 29 April 2019. Accessed on February 21, 2025. via https:\/\/web.archive.org\/web\/20190913125913\/ https:\/\/www.fda.gov\/about-fda\/office-regulatory-affairs\/program-alignment-and-ora"},{"key":"835_CR8","unstructured":"FDA Launches New ORA Structure to Align Inspections with Expertise. Regulatory Focus. 15 May 2017. Accessed on February 21, 2025. https:\/\/www.raps.org\/news-and-articles\/news-articles\/2017\/5\/fda-launches-new-ora-structure-to-align-inspection"},{"key":"835_CR9","unstructured":"FDA, ORA Program Division Boundary Maps and Fact Sheets. 15 May 2017. Accessed on February 21, 2025. https:\/\/web.archive.org\/web\/20190531164404\/ https:\/\/www.fda.gov\/about-fda\/office-regulatory-affairs\/ora-program-division-boundary-maps-and-fact-sheets"},{"key":"835_CR10","unstructured":"FDA, Conducting Remote Regulatory Assessments- Questions and Answers. Draft Guidance for Industry. February 2024. Accessed on February 21, 2025. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/conducting-remote-regulatory-assessments-questions-and-answers"},{"issue":"2","key":"835_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.47912\/jscdm.216","volume":"2","author":"K Ayalew","year":"2022","unstructured":"Ayalew K, Sellers J, Kronstein PD, et al. The United States Food and Drug Administration's Innovative Alternative Tools to Evaluate Good Clinical Practice During the COVID-19 Public Health Emergency. J Soc Clin Data Manage. 2022;2(2):1\u20137. https:\/\/doi.org\/10.47912\/jscdm.216","journal-title":"J Soc Clin Data Manage"},{"key":"835_CR12","unstructured":"Azar AM, Secretary of Health and Human Services. Determination that a Public Health Emergency Exists- COVID-19. 31 January 2020. Accessed on February 21, 2025. https:\/\/aspr.hhs.gov\/legal\/PHE\/Pages\/2019-nCoV.aspx"},{"key":"835_CR13","unstructured":"FDA, FDA\u2019s Actions in Response to 2019 Novel Coronavirus at Home and Abroad. 14 February 2020. Accessed on February 21, 2025. https:\/\/web.archive.org\/web\/20200215220747\/ https:\/\/www.fda.gov\/news-events\/press-announcements\/fdas-actions-response-2019-novel-coronavirus-home-and-abroad"},{"key":"835_CR14","unstructured":"FDA News Release, Coronavirus (COVID-19) Update: FDA Continues User-Fee Related Reviews Through COVID-19. 16 April 2020. Accessed on February 21. 2025. https:\/\/web.archive.org\/web\/20200416223752\/https:\/\/www.fda.gov\/news-events\/press-announcements\/coronavirus-covid-19-update-fda-continues-user-fee-related-reviews-through-covid-19"},{"key":"835_CR15","unstructured":"FDA News Release, Coronavirus (COVID-19) Update: FDA Continues to Accelerate Development of Novel Therapies for COVID-19. 31 March 2020. Accessed on February 21. 2025. https:\/\/web.archive.org\/web\/20200401035222\/https:\/\/www.fda.gov\/news-events\/press-announcements\/coronavirus-covid-19-update-fda-continues-accelerate-development-novel-therapies-covid-19"},{"key":"835_CR16","unstructured":"Trump DJ, President of the United States. Proclamation on Declaring a National Emergency Concerning the Novel Coronavirus Disease (COVID-19) Outbreak. 13 March 2020. Accessed on June 25, 2025. https:\/\/trumpwhitehouse.archives.gov\/presidential-actions\/proclamation-declaring-national-emergency-concerning-novel-coronavirus-disease-covid-19-outbreak\/"},{"key":"835_CR17","unstructured":"FDA, Manufacturing, Supply Chain, and Drug and Biological Product Inspections During COVID-19 Public Health. Emergency- Questions Answers. Guidance for Industry. August 2020. Updated May 17, 2021. Accessed on February 28, 2025. https:\/\/web.archive.org\/web\/20210618143845\/ https:\/\/www.fda.gov\/media\/141312\/download"},{"key":"835_CR18","unstructured":"FDA, Coronavirus (COVID-19) Update: FDA prepares for resumption of domestic inspections with new risk assessment system. 10 July 2020. Accessed on June 25, 2025. https:\/\/web.archive.org\/web\/20250521024851\/ https:\/\/www.fda.gov\/news-events\/press-announcements\/coronavirus-covid-19-update-fda-prepares-resumption-domestic-inspections-new-risk-assessment-system"},{"key":"835_CR19","unstructured":"FDA, An update to the resiliency roadmap for FDA inspectional oversight. November 2021. https:\/\/www.fda.gov\/media\/154293\/download?utm_medium=email&utm_source=govdelivery"},{"key":"835_CR20","unstructured":"FDA, Resiliency Roadmap for FDA Inspectional Oversight. May 2021. https:\/\/www.fda.gov\/media\/148197\/download"},{"key":"835_CR21","unstructured":"FDA, A risk-based approach to monitoring of clinical investigations questions and answers. Guidance for industry. April 2023. https:\/\/www.fda.gov\/media\/121479\/download"},{"key":"835_CR22","unstructured":"FDA, E8(R1) General Considerations for Clinical Studies. Guidance for Industry. April 2022. https:\/\/www.fda.gov\/media\/157560\/download"},{"key":"835_CR23","unstructured":"FDA, M11 Technical Specification.: Clinical Electronic Structured Harmonised Protocol (CeSHarP). Draft Guidance. December 2022. https:\/\/www.fda.gov\/media\/164116\/download"},{"key":"835_CR24","unstructured":"FDA, Bioresearch Monitoring Technical Conformance Guide. Tech Specifications Doc, Version 3.1. September 2024. https:\/\/www.fda.gov\/media\/85061\/download"},{"key":"835_CR25","unstructured":"FDA. Standardized format for electronic submission of NDA and BLA content for the planning of bioresearch monitoring (BIMO) inspections for CDER submissions guidance for industry. December 2024. https:\/\/www.fda.gov\/media\/85056\/download"},{"key":"835_CR26","unstructured":"CITI Program. List of TransCelerate Mutually Recognized GCP Training CITI Program GCP Courses, Version 2. Accessed on June 24, 2025. https:\/\/support.citiprogram.org\/s\/article\/List-of-TransCelerate-Mutually-Recognized-GCP-Training?_ga=2.100413533.2117509409.1750782357-915267733.1750782357"},{"key":"835_CR27","unstructured":"FDA, FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic. Guidance for Industry, Investigators, and Institutional Review Boards. March 2020. Updated April 2, 2020. Accessed on February 28, 2025. https:\/\/www.hhs.gov\/ohrp\/sites\/default\/files\/fda-covid-guidance-2apr2020.pdf"},{"key":"835_CR28","doi-asserted-by":"publisher","unstructured":"Sellers JW, Mihaescu CM, Ayalew K, et al. Descriptive Analysis of Good Clinical Practice Inspection Findings from U.S. Food and Drug Administration and European Medicines Agency. Ther Innov Regul Sci. 2022;56(5):753\u201364. https:\/\/doi.org\/10.1007\/s43441-022-00417-w","DOI":"10.1007\/s43441-022-00417-w"}],"container-title":["Therapeutic Innovation &amp; Regulatory Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-025-00835-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43441-025-00835-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-025-00835-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T10:13:48Z","timestamp":1781604828000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43441-025-00835-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,19]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["835"],"URL":"https:\/\/doi.org\/10.1007\/s43441-025-00835-6","relation":{},"ISSN":["2168-4790","2168-4804"],"issn-type":[{"value":"2168-4790","type":"print"},{"value":"2168-4804","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,19]]},"assertion":[{"value":"16 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}