TY - JOUR
T1 - Trends in FDA Data Integrity Enforcement Before and After the COVID-19 Pandemic
T2 - An Analysis of 1766 Warning Letters (2016–2023)
AU - Park, Yoseok
AU - Kwon, Kyenghee
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to The Drug Information Association, Inc 2025.
PY - 2026/1
Y1 - 2026/1
N2 - Background: Data integrity (DI) has become a cornerstone of regulatory oversight in pharmaceutical manufacturing. The COVID-19 pandemic coincided with increased digitalization and wider use of remote inspection approaches, drawing renewed attention to data governance. In response, global regulatory agencies emphasized structured DI compliance through harmonized guidelines. However, empirical studies quantifying longitudinal enforcement patterns remain limited. Methods: This study conducted a full-enumeration analysis of 1766 FDA Warning Letters issued between 2016 and 2023. DI-related violations were reclassified into nine categories based on the ALCOA and ALCOA + frameworks using a predefined rubric derived from EMA, PIC/S, and WHO guidance. Violations were segmented into pre-pandemic (2016–2019) and post-pandemic (2020–2023) periods. Descriptive statistics and exploratory t-tests and chi-square analyses were used to identify directional trends. Results: Although statistical tests did not yield significant differences between the two periods, violations related to “Endurance,” “Availability,” and “completeness” showed year-over-year increases after 2020. The average number of DI violations per company increased in 2023. Because fewer firms were cited that year, this pattern may reflect more targeted inspections or an atypical case mix. However, causality cannot be inferred. Conclusion: The observed patterns are consistent with a regulatory emphasis on risk-based DI oversight, particularly under remote or hybrid inspection models. For manufacturers—especially in PIC/S member countries where hybrid documentation persists—these findings underscore the practical importance of strengthening electronic quality systems. By offering a standardized ALCOA/ALCOA + -based rubric aligned with international guidance, this study provides a replicable framework for future DI inspection analysis and policy discussion.
AB - Background: Data integrity (DI) has become a cornerstone of regulatory oversight in pharmaceutical manufacturing. The COVID-19 pandemic coincided with increased digitalization and wider use of remote inspection approaches, drawing renewed attention to data governance. In response, global regulatory agencies emphasized structured DI compliance through harmonized guidelines. However, empirical studies quantifying longitudinal enforcement patterns remain limited. Methods: This study conducted a full-enumeration analysis of 1766 FDA Warning Letters issued between 2016 and 2023. DI-related violations were reclassified into nine categories based on the ALCOA and ALCOA + frameworks using a predefined rubric derived from EMA, PIC/S, and WHO guidance. Violations were segmented into pre-pandemic (2016–2019) and post-pandemic (2020–2023) periods. Descriptive statistics and exploratory t-tests and chi-square analyses were used to identify directional trends. Results: Although statistical tests did not yield significant differences between the two periods, violations related to “Endurance,” “Availability,” and “completeness” showed year-over-year increases after 2020. The average number of DI violations per company increased in 2023. Because fewer firms were cited that year, this pattern may reflect more targeted inspections or an atypical case mix. However, causality cannot be inferred. Conclusion: The observed patterns are consistent with a regulatory emphasis on risk-based DI oversight, particularly under remote or hybrid inspection models. For manufacturers—especially in PIC/S member countries where hybrid documentation persists—these findings underscore the practical importance of strengthening electronic quality systems. By offering a standardized ALCOA/ALCOA + -based rubric aligned with international guidance, this study provides a replicable framework for future DI inspection analysis and policy discussion.
KW - ALCOA/ALCOA +
KW - Data integrity
KW - GMP compliance
KW - Regulatory harmonization
KW - Remote inspection
UR - https://www.scopus.com/pages/publications/105018310187
U2 - 10.1007/s43441-025-00870-3
DO - 10.1007/s43441-025-00870-3
M3 - Article
C2 - 41071512
AN - SCOPUS:105018310187
SN - 2168-4790
VL - 60
SP - 190
EP - 198
JO - Therapeutic Innovation and Regulatory Science
JF - Therapeutic Innovation and Regulatory Science
IS - 1
ER -
