The crucial role of Trial Master File (TMF) audits in clinical trials

Trial Master File (TMF) audits are essential in demonstrating clinical trial oversight and confirming the integrity, compliance, and success of a clinical trial.

TMF audits help to ensure that a trial is conducted and documented in compliance with regulatory requirements, such as those set by the FDA (U.S. Food and Drug Administration), EMA (European Medicines Agency), and other health authorities.

This also includes compliance with the International Council for Harmonization’s (ICH) Good Clinical Practices (GCP), which are the ethical and scientific quality principles and standards for conducting clinical trials.

Regular audits of the TMF also prepare a site for regulatory inspections by identifying and correcting gaps or errors in documentation before being inspected by regulatory authorities, thus reducing the risk of findings/observations during an inspection and demonstrating proper Sponsor/CRO oversight.

The essential documents within the TMF are examined to ensure they are current, complete, and filed correctly as per the Drug Information Association’s (DIA) TMF Reference Model and the sponsor’s specific TMF Index.

The TMF Index outlines all the essential documents that need to be collected and maintained during a clinical trial at a specific study milestone. It also serves as a tool for quality control by providing a checklist against which the completeness, accuracy, and timeliness of the TMF are verified.

In terms of completeness, the TMF Index specifies whether a document is a core or recommended document that should be present. For accuracy, the TMF Index provides the naming convention that the filed documents must follow.

To verify timeliness, the TMF Study Milestones/Events are checked to ensure all documents up to the specific milestone/event have been filed in the TMF.

It is not possible to review all documents comprised within the TMF during a specific audit. As a result, auditors will define a specific number of documents (sampling) to be reviewed at each TMF level (trial, country, and site).

Continued oversight by the Sponsor and communication of expectations, actions, and deadlines with cross-functional study teams, CROs, and vendors will be key in remediating any issues identified during the TMF audit.

Veronique Brisson is G&L’s Assistant Vice President of Quality Assurance and Regulatory Affairs.