The trial master file is the sponsor's evidence that the trial was run properly and the data can be trusted. A good one is built before the first site is activated and kept current as you go. This guide covers structure, ownership, filing rules, quality checks and the close-out, for paper, hybrid and electronic files.
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Plan: owner, index, naming, access
Before site activation
Populate: start-up documents
Protocol, approvals, contracts
Maintain: file contemporaneously
Weekly check
Quality check: completeness and timeliness
Monthly review
Close out and archive
Reconcile, certify, retain
The TMF in brief
The file
ICH GCP describes essential documents: records that individually and collectively permit evaluation of how a trial was conducted and of the quality of the data produced. The sponsor keeps the sponsor set, the TMF. The investigator keeps the site set, the investigator site file (ISF). The two overlap deliberately: a protocol signature page, the approvals, the delegation of authority and the safety correspondence exist on both sides, so that each can be checked against the other. In the EU, the Clinical Trials Regulation requires sponsors and investigators to keep a trial master file with the essential documents (check Article 57 in the current text).
ICH E6(R3), finalised in January 2025, shifts the vocabulary from essential documents to essential records and expects an approach proportionate to risk and technology-neutral about format. For the practical build, that means two things: decide what matters for your trial (what is critical to participant safety and data reliability), and do not over-engineer folders for records that add nothing. See our ICH E6(R3) guide.
Small teams often ask how the TMF differs from the data system. The EDC holds participant data and its audit trail. The TMF holds the evidence around it: approvals, contracts, plans, training, monitoring and safety correspondence, validation evidence. Our EDC versus eTMF explainer draws the line, and for the site-side file see the investigator site file index.
Structure
Larger programs follow a full reference model. A lean team can start with groups like these and add detail only where the trial needs it. Folder names are examples, not a prescribed list.
| Section | Typical contents | Owner |
|---|---|---|
| Trial management | Protocol and amendments with signature pages, investigator brochure or product information, trial plans (monitoring, data management, safety), meeting minutes, key correspondence. | Sponsor / project lead |
| Regulatory and ethics | Ethics or IRB submissions and approvals, regulatory authority submissions and approvals, consent form versions with approvals, insurance, registry entries. | Regulatory lead |
| Sites and investigators | Site selection and qualification, contracts and budgets, CVs, licences, Form FDA 1572 where applicable, delegation logs, training records, financial disclosure. | Site manager |
| Product and supply | Product release documents, labelling, shipment and receipt, accountability and destruction, randomisation and blinding records under restricted access. | Pharmacy / unblinded role |
| Data management and statistics | Data management plan, CRF design and versions, validation and UAT, user lists and access reviews, statistical analysis plan, database lock and unblinding records. | Data manager / statistician |
| Safety | Safety reporting plan, expedited reports and acknowledgements, annual safety reports, DSMB charter and recommendations. | Safety lead |
| Monitoring and quality | Monitoring visit reports and follow-up letters, deviation logs, audit certificates, CAPA records. | Monitor / QA |
| Close-out | Site close-out letters, reconciliation, final report, archive index and retention plan. | Project lead |
Example grouping adapted to a small trial. For a formal model, use the EMA TMF guideline and the current DIA TMF Reference Model.
The setup
Allow a few days at start-up. It saves weeks at close-out.
A role with the time and authority to chase documents. Record responsibilities in a TMF plan or SOP.
Weigh volume, sites, remote access and budget. Electronic gives audit trail, controlled access and search. Paper needs locked storage and a filing log. Hybrid needs a clear rule for which copy is the original.
Start from the EMA guideline or the DIA TMF Reference Model, then remove what is not relevant and add trial-specific items. Record the decision and the version of the index.
Document title, version, date, country and site code. One naming rule across the file makes search and checks possible. Keep draft and superseded versions marked.
Who can file, read and delete. Keep randomisation lists and unblinding records restricted. See blinded and unblinded roles.
Set a target for filing after a document is final, for example within a defined number of days, and a process for certified copies when paper originals are scanned and replaced.
File the protocol, approvals, contracts, delegation, training and plans before the first participant is enrolled. Include evidence the data system was validated, see the URS template.
Review completeness, timeliness and correct placement on a set rhythm, track findings and close them out. Reconcile the TMF with the site files at monitoring visits.
Much of the evidence in a TMF starts as an export: a blank eCRF PDF, the audit trail, signed consent PDFs, user lists. Try the exports in the free sandbox and see what you would file.
What Capture contributes
Capture is an EDC, eCRF, ePRO, eConsent and randomization platform. It is not an eTMF and does not manage your regulatory binder. It produces several records that belong in one.
Data management plan v1.1
Blank eCRF PDF, final form versions
From platform export
User acceptance test records
User list and access review, quarterly
Audit trail export at database lock
Randomisation and unblinding record (restricted)
Quality control
Run these at least monthly during enrolment and before every inspection or audit.
Every expected document type per the index is present, or marked not applicable with a reason.
Documents are filed within the target time, and late filings are logged with causes.
Documents sit in the right section and have the right metadata and version.
Signatures and dates are present where required; electronic signatures are traceable.
Compare delegation logs, approvals and training with each ISF at monitoring visits.
User list reviewed, leavers removed, restricted areas verified.
In an eTMF, the audit trail of filing and changes is available and retained.
Pick five random documents and time how long retrieval takes. This is the inspection test.
Close-out and inspection
At the end of the trial, reconcile the TMF against the site files, resolve open findings, file the final report and close-out letters, and record the archive location and retention end date. The EMA guideline expects the TMF, including the audit trail for an electronic TMF, to be archived so supervision remains possible after the trial ends. Retention periods differ by region; our data archiving and retention guide compares them.
Inspectors typically ask for the TMF early and then follow documents into the system and the site. A file that is organised, current and consistent makes the rest of the inspection easier, see the FDA inspection checklist and audit-ready clinical trial data. If you are a sponsor-investigator, the TMF is your file; how to become a sponsor-investigator lists the other duties that come with it.
This page is general guidance. Your sponsor SOPs, the protocol and the applicable regulation decide what exactly goes in your file and how long it must be kept.
The TMF is the sponsor's collection of essential documents or records that allow the conduct of the trial and the quality of its data to be evaluated. It is kept alongside the investigator site files at each site.
Before the first site is activated. Decide the owner, the index, naming and access at start-up, then file documents as they are finalised.
The sponsor keeps the TMF; the investigator keeps the site file. They overlap on documents such as approvals and delegation, so each can be checked against the other. See the investigator site file index template.
Not necessarily. The EMA guideline applies the same core requirements to paper, hybrid and electronic TMFs. An eTMF adds controlled access, search and an audit trail, which becomes more valuable with many sites or documents.
No. Capture is an EDC, eCRF, ePRO, eConsent and randomization platform. It produces records you file in a TMF, such as the blank eCRF PDF, audit trail and signed consent PDFs. See the EDC versus eTMF explainer.
Many teams start from the EMA guideline on TMF content, management and archiving, or the DIA TMF Reference Model, and adapt it to the trial. Check the current version of any model before adopting it.
It depends on region and contract. The EU Clinical Trials Regulation requires at least 25 years after the end of the trial; US rules use different triggers. See the data archiving guide and confirm with your regulatory adviser.
Keep exploring
EDC vs eTMF explainer
Where each system fits.
Investigator site file index template
The site-side file.
Delegation log template
Who does what.
Clinical trial data archiving and retention
How long to keep records.
Audit-ready clinical trial data
Inspection readiness.
FDA inspection checklist
What inspectors ask for.
ICH E6(R3) guide
Essential records.
How to become a sponsor-investigator
Your duties when you are the sponsor.
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