A Trial Master File (TMF) is set up at the beginning of the trial. It is a collection of all essential documents pertaining to the trial, which in turn will allow for effective monitoring and supervision (audit). In order to demonstrate compliance with the applicable regulations, Good Clinical Practice (GCP) guidelines and the protocol – a well organised TMF is essential.

According to the GCP guidelines, it is the responsibility of the sponsor to ensure that the TMF includes all relevant essential documents, and is stored in a secure location, with restricted access. Generally, the TMF is maintained at the sponsor’s office, co-ordinating site or by the Contract Research Organisation (CRO), if contracted. In addition to the TMF, copies of all relevant documents must be kept at each participating site, in an Investigator Site File (ISF). The ISF will also include all site-specific essential documents. For example, site preparedness log or site visit logs, etc.

A member of the research or trial team, should be delegated with the task of updating, maintaining and reviewing the TMF and ISF, periodically throughout the course of the clinical trial as per the defined SOPs. Ideally, the documents included in the TMF are:

• Trial documents (protocol, investigator’s brochure, participant information documents, SOPs, instructions, manuals, guidelines, etc.)
• Documents related to the Investigational Product (certificates of analysis, shipment records, storage records, etc.)
• Training documentation for trial team
• Details of the laboratories, if applicable.
• Contracts, agreements, budgets, etc.
• Monitoring visit reports (for each site visit – onsite or central)
• Documents related to the safety reporting
• Ethics Committees’ documents (composition of the EC, approvals, notifications, reports, etc.)
• Site specific documents (list of site staff and their curriculum vitae, investigator’s undertaking, site preparedness documents, training of site staff, etc.)
• Audit related documents, if available (if an audit was conducted).
• Significant communications
• Others

The GCP guidelines provide a comprehensive guidance regarding the documents to be included in a Trial Master File categorised according to the lifecycle of the trial. This information can also be accessed here.

It shall be the responsibility of sponsor to make arrangements for safe and secure custody of all study related documents and material for a period of three years after the completion of the study or submission of the data to the regulatory authority (ies) whichever is later.

References

• Good Clinical Practices for Clinical Research in India, Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, 2001, available online (last accessed on 26.02.2019).
• ICH Harmonised Guideline, Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2), current step 4 version, dated 9^th November 2016, available online (last accessed on 26.02.2019).