Background: The US Food and Drug Administration (FDA) ensures clinical trials meet regulatory/ethical standards through inspections. If FDA Investigators observe potential violations of regulatory requirements during an inspection, a firm will receive a Form FDA 483, Inspectional Observations. Violations cited have resulted in the death of human research subjects, prosecution of research personnel, and denial of approval for new medical products. Objectives included the standardization of Violation Themes cited for analysis by inspection firm type, geographic location, and Violation Theme citation to provide insight into regulatory violations.
Methods: Cross-sectional analysis of citations published in public databases between October 1, 2005, and September 30, 2015, by the FDA for inspections under the Bioresearch Monitoring program. For each inspection citation, the main measure was the Code of Federal Regulation cited coded into a standardized Violation Theme for citation analysis.
Results: Under the Bioresearch Monitoring program, 3281 inspections received a Form FDA 483 in 2007-2015. FDA inspections have increased over this period but the rate of Form FDA 483 issuance has decreased. On average, Sponsor-Investigators received 4.41 citations per inspection compared to clinical researchers alone receiving 2.21. One-third of violations were related to adherence to investigational procedures followed by informed consent and study records issues.
Conclusions: In the last decade, the number of violations observed under the Bioresearch Monitoring program has decreased; however, significant improvements can still be made regarding adherence to study procedures, the consenting of human research subjects, and creation of adequate and accurate study documentation.
Keywords: Bioresearch Monitoring; Code of Federal Regulations; Form FDA 483; deviation; inspection.