VP Global Quality Assurance
March 2, 2021
In the first blog in this series, we discussed why it is so important to be FDA GCP inspection ready and to remove as many obstacles as possible to a program’s success. With so much at stake, program managers should – at a minimum – act on the following three tips as they prepare their clinical development program for a marketing application.
Tip 1: Develop a Detailed FDA GCP Inspection Readiness Plan Well in Advance
Creating a detailed FDA GCP Inspection Readiness Plan well in advance of an inspection enables identification of any gaps in readiness while there is still time to take corrective actions and develop a strategy for addressing any issues identified. The FDA GCP Inspection Readiness Plan should identify all components of inspection preparation and provide associated timelines. Components include a Trial Master File audit, an assessment of Bioresearch Monitoring Compliance, and a schedule for meetings to review and address gaps in inspection readiness and to obtain or develop missing documentation. The plan should address inspection readiness for sites, CROs and key vendors in addition to the sponsor. It is important to understand the nature and scope of any issues and their potential effect on critical data. The FDA Inspection Readiness Plan should identify the best approach to mitigating such risks and minimizing their impact on trial outcomes, data quality and the inspection itself.
Tip 2: Arrange an Independent Audit of the Trial Master File
An independent audit of the Trial Master File is a prudent step even when there is high confidence in the project team, the execution of the clinical study and resulting data quality. While an internal audit of the Trial Master File is valuable, an internal auditor may exhibit unconscious bias in favor of the program and may make assumptions that limit the scope of the audit to areas considered most likely to be problematic. By contrast, an independent auditor with experience auditing clinical studies for a variety of sponsors is likely to consider and investigate a wider range of potential issues. A TMF audit should include attention to issues at the protocol level, country level and investigator site level. Ideally, an independent interim audit would have taken place at 50% enrollment. An independent final audit should take place within 30 days of the last site Close-Out Visit. The program manager should ask an independent auditor to deliver a report with a table of observations and findings within 10 business days of the last day of the audit.
Tip 3: Arrange for Creation and Annotation of a Bioresearch Monitoring (BIMO) Compliance Checklist
Rigorous preparation for an FDA GCP inspection should include attention to the following manuals:
Utilizing these two documents as a basis for creating and annotating a BIMO Compliance Checklist specific to your program ensures thorough and rigorous preparation for an FDA GCP inspection as FDA inspectors themselves are guided by these manuals. The annotated BIMO Compliance Checklist should be used by all functional leads to assess and assemble information required to satisfy all questions that are likely to arise during an inspection. An annotated BIMO Compliance Checklist should include compilation of all major findings from TMF audits and findings from any prior investigator site and vendor audits as well as compilation of CAPAs (Corrective and Preventive Actions) and monitoring, vendor and sponsor issues identified during clinical study conduct. Such a checklist should be made available within 14 days of the final TMF audit. The checklist is an ideal tool for generating questions for an FDA mock inspection. Furthermore, the BIMO Compliance Checklist should be a living, working document up to the time of a mock inspection. The sponsor should distribute the annotated BIMO Compliance Checklist to all key clinical study team members prior to a mock inspection as a basis for development and rehearsal of appropriate, accurate responses to anticipated requests.
In the upcoming part three of this series, we will discuss three final tips for developing and implementing a rigorous program to ensure FDA GCP inspection readiness.