FDA and EMA mostly align on GCP inspection deficiencies, study finds

Regulatory NewsRegulatory News | 31 May 2022 |  By 

A study conducted by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) found that the agencies are identifying the same types of deficiencies in joint good clinical practice (GCP) inspections with respect to protocol compliance, documentation deviations, and human subject protections.
The paper follows a mutual transatlantic cooperation on GCPs between the regulators that went into effect on 1 September 2009. Under the program, regulators agreed to collaborate on GCP inspections and share information on inspection planning and outcomes.
This study compared decisions on 49 GCP inspections conducted by the two agencies related to clinical investigations submitted in marketing authorization packages between  2009 and 2015, and outlined the similarities and differences in findings for common inspection deficiencies.
“GCP inspection findings from 49 common clinical investigator and sponsor/contract research organization inspections were comparable,” Jenn Sellers of FDA’s Division of Clinical Compliance Evaluation in the Office of Scientific Investigations, Camelia Mihaescu of EMA’s inspections office, and colleagues wrote. The paper was published online on 24 May by the Drug Information Association Journal’s Therapeutic Innovation & Regulatory Science.
The survey compared GCP inspection findings to support 31 marketing applications having the same trial data. It evaluated inspection data from 26 clinical investigator site inspections and 23 sponsor/contract research organization inspections.
The study dataset included 170 FDA findings and 320 EMA findings for clinical investigator inspections and 165 FDA findings and 300 EMA findings for sponsor/clinical research organization (CRO) inspections.
For the clinical investigator inspections, the study looked at deficiencies in four areas: protocol compliance, documentation, human subject protections and conditions for the study drug such as adhering to instructions for supplying, storing and retrieving the drug.
For the sponsor/contract research inspections, it looked at deficiencies related to trial management, documentation, protocol compliance and conditions for the study drug.
Overall, the two regulators identified similar problems with respect to the clinical investigator inspections and the CRO inspections.
For example, for the clinical investigator inspections, regulators identified protocol compliance problems at 22 of the 25 clinical investigator sites, reaching an 88% concordance rate. They also found documentation deficiencies at 17 of the 25 clinical investigator sites, aligning on this finding 68% of the time. Human subject protection violations were observed at 11 of the 19 sites, for a concordance rate of 58%. Regulators also found deficiencies with the study drug at 10 of the 23 sites, agreeing on the issue 43% of the time.
Regarding the CRO inspections, both agencies identified deficiencies related to trial management at 17 of the 19 sites with a concordance rate of 89%, and found problems related to documentation and identified violations at 16 of the 23 sites with a concordance rate of 70%. In addition, regulators reported problems with protocol compliance at 11 of the 17 sites. Six of the 11 sites had deviations related to the study drug cited by both regulators.
In conclusion, the study said that “GCP inspection findings from 49 common clinical investigator and sponsor/contract research organizations inspections were comparable. The analysis provides support for our existing practice of sharing information between the two agencies for GCP inspection planning purposes, as well as for the exchange of inspection reports.”
There was some divergence with respect to the inspectional findings. For example, for clinical investigator inspections, FDA’s most frequent inspection findings were in the area of protocol compliance (23%) and documentation (28%); while for EMA, the most common findings were in the areas of documentation (45%) and trial management (40%).
The research used FDA and EMA internal databases, FDA’s establishment inspection reports and clinical inspection summaries, and EMA’s individuals’ inspection reports and integrated inspection reports.


© 2023 Regulatory Affairs Professionals Society.

Discover more of what matters to you