Storage and filing of essential documents (Trial Master File) in connection with clinical trials

The essential documents concerning a clinical trial must be available for inspection.

In order to be able to demonstrate compliance with the protocol, the sponsor and the investigator must, in accordance with Regulation (EU) No 536/2014, keep a Trial Master File (TMF) of the clinical trial. This must contain relevant documentation to allow effective supervision (monitoring by the sponsor and inspection by EU/EEA Member States). The clinical TMF file should be archived appropriately to allow for supervision also after the clinical trial has ended. Archiving must be performed in accordance with Regulation (EU) No 536/2014 and GDPR.

The clinical TMF must be established from the start of the trial and be permanently updated.

The clinical TMF will often constitute the starting point of the Danish Medicines Agency's control. The TMF is divided into the investigator and the sponsor. The investigator is responsible for the investigator's part of the TMF, also called the investigator site file (ISF), and the sponsor is responsible for the sponsor's part of the TMF. A clinical TMF must contain all documents which individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced. Based on the TMF, the Danish Medicines Agency must be able to control if the sponsor, investigator and other parties involved have ensured that the trial was completed in accordance with the authorised protocol and meets the good clinical practice (GCP) requirements.

The clinical TMF kept by the investigator and that kept by the sponsor may have different contents if this is justified by the different nature of the responsibilities of the investigator and the sponsor.

Based on deviations observed during several inspections, the Danish Medicines Agency emphasises that emails concerning important decisions made during the trial are also considered part of the TMF.

It should be noted that when using a clinical TMF, such file must comply with the requirements and expectations described in the guideline prepared by the GCP Inspectors and available on the EU Commission's website: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-content-management-and-archiving-clinical-trial-master-file-paper-andor-electronic_en.pdf, and the GCP Inspectors' guideline on computerised systems and electronic data in clinical trials available on the GCP Inspectors Working Group's part of the website of the European Medicines Agency (EMA).

Storage period

Unless archiving for a longer period is required under other EU law, the sponsor and the investigator must archive the content of the clinical TMF for at least 25 years after the end of the clinical trial.  However, the medical files of trial subjects are to be archived in accordance with national law.

Reference is made to article 58 of the Regulation for further information.

Storage conditions

The media used to archive the content of the clinical TMF must be such that the content remains complete and legible throughout the storage period.

Change log:

August 16, 2025 - no substantive changes, just clarifications aligned to Regulation (EU) 536/2014