Clinton A Rogers1, Jennifer D Ahearn2, Michael G Bartlett3. 1. Department of Pharmaceutical and Biomedical Sciences, University of Georgia, 250 West Green Street, Athens, GA, 30602, USA. 2. Pharmaceutical and Medical Devices, Engineering Systems, Inc, Norcross, GA, USA. 3. Department of Pharmaceutical and Biomedical Sciences, University of Georgia, 250 West Green Street, Athens, GA, 30602, USA. mgbart@uga.edu.
Abstract
BACKGROUND: Warning Letters issued by the Food and Drug Administration's Bioresearch Monitoring (BIMO) Program provide insight into data integrity issues and other research misconduct in the premarket side of the pharmaceutical industry. The objectives of this study were to understand the common compliance issues for clinical investigators, institutional review boards, sponsors of clinical studies, good laboratory practice laboratories, and bioequivalence studies and to see how compliance has changed over time. METHODS: Warning letters and closeout letters issued by the BIMO program between US fiscal years 2007-2018 were analyzed by categorizing regulatory violations into violation themes. Inspections during the same time period were analyzed based on the assigned inspection classification. RESULTS: A combined total of 300 warning letters were analyzed as a part of this study. The most common violations found in all warning letter categories included failing to follow and maintain procedures and poor documentation practices. Inspection results show that overall the percentage of Official Action Indicated results has decreased over time, while the percentage of No Action Indicated results has increased. CONCLUSION: Although the number of warning letters has decreased over the past decade and inspection results have been improving, there are still significant data integrity and other regulatory compliance issues found in the premarket side of the pharmaceutical industry. It is unclear if the reduction of warning letters is due to improved compliance in the industry or other factors unrelated to compliance.
BACKGROUND: Warning Letters issued by the Food and Drug Administration's Bioresearch Monitoring (BIMO) Program provide insight into data integrity issues and other research misconduct in the premarket side of the pharmaceutical industry. The objectives of this study were to understand the common compliance issues for clinical investigators, institutional review boards, sponsors of clinical studies, good laboratory practice laboratories, and bioequivalence studies and to see how compliance has changed over time. METHODS: Warning letters and closeout letters issued by the BIMO program between US fiscal years 2007-2018 were analyzed by categorizing regulatory violations into violation themes. Inspections during the same time period were analyzed based on the assigned inspection classification. RESULTS: A combined total of 300 warning letters were analyzed as a part of this study. The most common violations found in all warning letter categories included failing to follow and maintain procedures and poor documentation practices. Inspection results show that overall the percentage of Official Action Indicated results has decreased over time, while the percentage of No Action Indicated results has increased. CONCLUSION: Although the number of warning letters has decreased over the past decade and inspection results have been improving, there are still significant data integrity and other regulatory compliance issues found in the premarket side of the pharmaceutical industry. It is unclear if the reduction of warning letters is due to improved compliance in the industry or other factors unrelated to compliance.
Entities:
Keywords:
Clinical trials; Compliance; Regulatory action; US Food and Drug Administration; Violations