Tony Bumarch
VP Global Quality Assurance

February 17, 2021

As clinical development programs near completion, even the best of program managers may become anxious about previously unknown issues arising at a most inopportune time – an impending FDA GCP inspection. Such inspections may result in a handful of benign findings or, in the absence of a strong Quality Assurance program, the FDA GCP inspection may lead to critical and systemic findings that can result in a show-stopping failed submission. The most common issues identified by FDA inspection audits with respect to sponsors and CROs are inadequate monitoring, failure to ensure investigator compliance, inadequate accountability for the Investigational Product and failure to obtain FDA or Institutional Review Board approval before clinical study initiation. For study sites, common issues include failure to follow the investigational plan or regulations, protocol deviations and deficiencies in record keeping, informed consent, Adverse Event reporting and accountability for the Investigational Product (IP).

Clinical development programs are such complex and extensive undertakings that it is unrealistic to expect perfect execution and compliance in all aspects. Clinical development programs may involve hundreds of investigational sites and thousands of clinical trial subjects, not to mention the program managers, project managers, site monitors, principal investigators, study coordinators and a variety of vendors. End points may involve complex assessments dependent on factors such as consistency across sites in subjective interpretations, instrument calibration or sample handling. Personnel turnover in key roles at a site or CRO is another potential source of inconsistency. Even the most experienced, expert and conscientious members of a study team remain human, and therefore, subject to error. It is easy to see why the period leading up to an FDA GCP inspection can be stressful for program managers.

A Program Manager’s Worst Nightmare

A program manager’s worst nightmare is to see the Investigational Product demonstrate efficacy and safety and yet have the program fail – or at least experience a major delay or substantial unbudgeted expenses – because of an FDA GCP inspection resulting in findings of GCP noncompliance. However, there are proactive steps that program managers can take to reduce stress before an FDA inspection audit and identify and address potential issues. Indeed, a rigorous plan to ensure inspection readiness represents cost-effective insurance against program failure for a reason other than shortcomings in the efficacy or safety of the IP itself.

Two follow-on posts will describe six essential tips for optimizing the outcome of an FDA GCP inspection. Part 2 of this article focuses on three tips that merit consideration as a precaution even when the program manager has full confidence in the project team and its ability to mitigate key risks: development of an Inspection Readiness Plan, completion of an independent TMF audit, and annotation of a Bioresearch Monitoring (BIMO) Compliance Checklist.

Part 3 of this article will present three additional tips that take on increasing importance when the program manager has lingering concerns about any aspect of trial execution or inspection readiness: providing study team training for the inspection, conducting an independent mock FDA inspection, and arranging for someone with prior experience to help manage the inspection. Acting on these tips will enable the program manager to identify potential gaps in inspection readiness, address and manage any gaps, effectively host an FDA GCP inspection, and increase the likelihood of a successful outcome.