In April 2017, the European Medicines Agency (EMA) issued a draft guideline (Draft Guideline“) concerning the Trial Master Files (“TMF”) for public consultation. The Draft Guideline updates the previous guideline on TMF that was issued in 2013 in the form of a reflection paper. The Draft Guideline incorporates further guidance concerning international guideline for good clinical practice (“ICH-GCP”) E6. Its purpose is to assist sponsors and investigators in their compliance with the requirements concerning the TMF as specified in Regulation (EU) 536/2014 on clinical trials on medicinal products (“Regulation”).

The current requirements for TMF are provided in the Regulation, which is anticipated to take full effect in October 2018. The ICH-GCP E6 also provides the requirements that should be fulfilled concerning TMFs. According to the TMF related requirements, the sponsor and investigator are obliged to keep a TMF containing essential documentation to permit effective supervision.

Article 57 of the Regulation provides:

“The sponsor and the investigator shall keep a clinical trial master file. The clinical trial master file shall at all times contain the essential documents relating to that clinical trial which allow verification of the conduct of a clinical trial and the quality of the data generated, taking into account all characteristics of the clinical trial, including in particular whether the clinical trial is a low-intervention clinical trial.”

The Draft Guideline provides a non-exhaustive list of examples of documents that are considered essential, but are not listed in the ICH GCP E6. Essential documents can be considered:

  • documents that are generated from following quality system procedures, i.e. any forms, checklists and reports;
  • qualified person certification of the investigational medicinal product;
  • assay method validation report for analysis of the investigational medicinal product or metabolite(s) in clinical samples;
  • traceability records of advanced therapy investigational medicinal product; and
  • documentation to demonstrate validation of trial-specific builds of computer systems (eg, electronic case report form, and interactive response technologies).

Furthermore, the Draft Guidance describes in detail the requirements for TMF and intended to assist organisations to acquire a TMF that promotes clinical trial management, Good Clinical Practice compliance and inspections.

As an example, the Draft Guideline provides clarifications regarding Article 57 of the Regulation. It states that the expression “at all times” provided in this Article presents the obligation of the sponsor and the investigator to keep their TMF updated.

Furthermore, it is provided that the sponsor should follow quality assurance provisions of the TMF to ensure that the TMF is easily accessible and immediately available.

The Draft Guidance provides guidance on “archiving of the TMF, clarifying retention times, in particular expectations in case of digitization and consecutive destruction of paper documentation.” In accordance with Article 58 of the Regulation, the sponsor and investigator:

“shall archive the content of the clinical trial TMF for at least 25 years after the end of the clinical trial. However, the medical files of subjects shall be archived in accordance with national law”.

It provides that the requirements related to TMFs shall be fulfilled independently of the form of the TMF concerned, i.e. paper or electronic form.

The Draft Guideline will be open for public consultation until the 11th of July 2017.