Clinical Trials Toolkit Routemap

Trial Master File

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Trial Planning Phase

The Trial Master File station follows the Funding Secured station and precedes the Trial Registration station. This process occurs in parallel with Funding Secured, Confirm Sponsor, Feasibility & Investigator Selection, and Contracts & Agreements. The Trial Master File is a legal requirement that is relevant to all trials. This station is part of the 'trial planning phase' group of stations.

Trial Master File (TMF)

A Trial Master File (TMF) must be established at the start of a clinical trial. It must contain all essential records demonstrating that the trial was conducted in compliance with regulatory requirements and Good Clinical Practice (GCP). These records should be stored securely while remaining accessible to authorised individuals. A well-maintained TMF supports efficient trial management and enables reconstruction of the trial’s conduct during audits or inspections.

The GCP Inspectors Working Group has issued a Guideline on the content, management and archiving of the clinical trial master file (paper and/or electronic (2018 .PDF) (.PDF), which provides additional guidance. For multi-centre trials, the TMF is typically held at the coordinating site, such as the Chief Investigator’s office or Coordinating Centre.

Each participating trial location should maintain an Investigator Site File (ISF) containing locally relevant documents. Sponsors usually provide guidance on the structure and content of the TMF/ISF, based on their internal policies or procedures.

The TMF (and the ISF) should be well-designed with appropriate functionality, clear naming conventions and a logical folder structure. It must be actively maintained throughout the lifecycle of a trial. Responsibility for maintaining these files should be clearly documented, typically on the study Delegation Log. When essential records are stored across multiple locations or systems, the sponsor must have clear oversight of where each record is held.

ICH GCP (R3) Appendix C outlines the key records typically found in the TMF, and an MHRA blog on inspecting the TMF offers further advice. The MHRA also supports a risk-based approach to documentation; for instance, it permits the ISF and TMF to be combined in certain trials, such as those sponsored by an academic institution or hospital that also employs the investigator.

Electronic TMFs

When electronic TMFs are developed, the MHRA requires evidence that the system complies with GCP and is appropriately validated to demonstrate that it is fit for its intended use. An MHRA blog on computer system validation provides further information.

Retention of the TMF

The amended Clinical Trials Regulations require the retention period for the archive of the TMF to be at least 25 years. Sponsor must also appoint a named individual within the organisation responsible for archiving essential records from the TMF. Access to these records must be restricted to this appointed individual, auditors and inspectors.

Non-CTIMPs

For non-CTIMP, it is good practice to retain any records that support the full reconstruction of study conduct. GCP guidelines provide a framework. The sponsors and host organisations may provide further guidance on TMF/ISF content through their policies and procedures.