For nearly 30 years, the ICH GCP guideline has set the international standard of ethics and quality for conducting clinical trials. The latest version, ICH GCP E6 (R3), was adopted on 06 Jan 25, an update 9 years in the making. It contains an entire appendix dedicated to the Trial Master File. Let’s explore some of the principles within:
The title of the appendix sets the tone with the word “documents” being replaced with the word “records”. This reflects the shift from a paper-based mindset to a data-based mindset, where documents would become the digital output narrative of data and not data being collected from documentation to recreate the trial story.
Accessibility of records is another focus of the guideline update. As the essential records allow for the evaluation of the conduct of a clinical trial, it is imperative that they are easily located in their official system of record. Sponsors must have an appropriate level of access to be able to oversee records kept in vendor systems and to be able to have visibility into ongoing issue trends. Just because one has outsourced the management of the TMF to a CRO does not absolve the sponsor from the ultimate responsibility of ensuring complete records are being kept, are being submitted to the TMF contemporaneously and are of acceptable quality. (Reference §C.1.3 and §C.2.2)
A sponsor might have multiple systems across multiple organizations that contain their essential records. Though it is always best to reduce fragmentation, the reality is that sometimes it isn’t possible to streamline and unify essential record repositories. The location of the source systems for all records should be defined in the TMF index. This will serve as a map for regulators to be able to easily locate records kept in multiple systems. (Reference §C.2.4 and §C.2.6)
The Trial Master File (TMF) is the unified collection of essential records for a clinical trial and should be accurate, locatable and easily accessible to regulators. Following the advice above will ensure you’re compliant with the international standard.