A Trial Master File (TMF) is a comprehensive collection of documentation that provides a complete record of a clinical trial and proves that a clinical trial has been conducted following Good Clinical Practice (GCP) guidelines and all regulatory requirements and also demonstrates that the integrity of trial data has been maintained. The TMF contains all essential documents related to the trial, such as study protocols, informed consent forms, investigator brochures, monitoring reports and others.
Regulatory agencies, such as the FDA or EMA, may inspect the TMF as part of their oversight of clinical trials to ensure compliance with applicable regulations and guidelines. The agency may also review the TMF to assess the quality of the trial’s data and the validity of the trial’s results.
The regulatory agency may conduct the TMF inspection on-site or remotely. The inspection may include a review of the TMF documentation, as well as interviews with study staff and site visits to verify the trial’s conduct.
Some of the most common findings during FDA inspections are:
- Inadequate monitoring of the trial by the sponsors/ CROs
- Non-compliance by investigators such as failure to follow investigational plan and/or regulations, high number of protocol deviations etc.
- Inadequate accountability for the investigational product by both investigators and sponsors/ CROs
- Inadequate subject protection (failure to report AEs)
If the FDA finds repeated or deliberate violations or potential violations during the TMF inspection, they may initiate the investigator disqualification process by issuing a Notice of Initiation of Disqualification Proceedings and Opportunity to Explain (NIDPOE), issue a FDA form 483, or initiate other regulatory action, depending on the severity of the issue.
To prepare for a TMF regulatory inspection, clinical trial sponsors, CROs and investigators should maintain an organized and complete TMF that includes all essential documents and records. They should also establish standard operating procedures (SOPs) for TMF management or create a TMF plan and ensure that all study staff are trained in TMF documentation and management.
Here is a checklist of items to consider for a TMF inspection:
- Essential documents: Ensure that all essential documents such as the protocol, informed consent forms, case report forms, adverse event reports, Investigator’s Brochure, and others are present in the TMF.
- TMF plan: Verify that the TMF plan has been followed and that all documents have been filed in the appropriate sections
- Document quality: Review the quality of the documents to ensure that they are legible, complete, accurate, contemporaneous and dated.
- Filing and indexing: Verify that documents are filed in the appropriate section and that they are indexed appropriately for easy retrieval.
- Version control: Ensure that document versions are clearly identified and that previous versions have been removed from the TMF.
- Organization: Verify that the TMF is organized and that the documents are easy to locate.
- Timeliness: Ensure that the documents are filed in a timely manner and that they reflect the most recent version of the document.
- Signatures: Verify that all documents requiring signatures have been signed by the appropriate individuals, and that the signatures are legible and dated.
- Inspection readiness: Ensure that the TMF is inspection-ready and that all relevant documents are identifiable, available and easily accessible.
Cloudbyz eTMF solution is a digitalized repository for all clinical trial documents, including files, images, and information. It allows users to capture, manage, share, and store all clinical trial-related content and documents in one central location. This solution provides real-time visibility and access to CROs, sponsors, and other stakeholders of the study trial. With Cloudbyz eTMF, all clinical trial documents are easily accessible and managed efficiently.
To know more about Cloudbyz eTMF solution contact us at info@cloudbyz.com
