The Trial Master File (TMF) is a collection of essential documents that provides a comprehensive record of activities and documentation related to a clinical trial. It serves as the repository of all the essential documents and information necessary for the conduct, management, and oversight of a clinical trial. With the advancement of technology, electronic Trial Master File (eTMF) systems have been developed to manage and maintain the TMF electronically. Here's an overview of the TMF and eTMF in clinical research: Trial Master File (TMF): Purpose: The TMF is created to ensure compliance with Good Clinical Practice (GCP) guidelines and regulatory requirements. It contains the documentation that supports the quality, integrity, and validity of the clinical trial data. Contents: The TMF includes a wide range of documents, such as: Protocol and protocol amendments Investigator Brochure (IB) Informed Consent Forms (ICFs) Case Report Forms (CRFs) Study-related correspondence Institutional Review Board (IRB) or Ethics Committee (EC) approvals Investigator and site personnel training records Monitoring reports and visit documentation Data management and statistical analysis plans Safety and adverse event reports Clinical study reports Financial disclosures and contracts Organization: The TMF should be well-organized and easily accessible. It is typically divided into sections or folders based on the nature of the documents, such as regulatory documents, study-related documents, or data management documents. The organization of the TMF should follow standardized guidelines to facilitate efficient inspection and auditing. Electronic Trial Master File (eTMF): Introduction: An eTMF is an electronic system designed to manage and maintain the TMF electronically. It replaces traditional paper-based TMFs, offering several advantages, including improved accessibility, version control, searchability, and collaboration among trial stakeholders. Features and Benefits: eTMF systems provide features such as document upload and indexing, electronic signatures, version control, audit trails, and role-based access controls. Benefits of using eTMF include streamlined document management, increased efficiency, real-time visibility of TMF status, and enhanced compliance with regulatory requirements. Compliance and Validation: eTMF systems need to comply with regulatory requirements, including electronic records and signatures regulations. Validation of the eTMF system is necessary to ensure its accuracy, reliability, and security. This involves testing and documentation to demonstrate that the system operates as intended and meets regulatory expectations. Integration: eTMF systems can integrate with other clinical trial management systems, electronic data capture (EDC) systems, and document management systems to facilitate seamless data and document exchange, reducing manual data entry and improving data quality.

1. Welcome
Trial Master File (TMF/eTMF)
Shraddha Khobragade
Master of Pharmacy
CSROL_INT_ONL_WKD_188/2022
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2. Index
• What are TMF and eTMF?
• Structure and Contents of TMF
• Security & control of TMF
• Quality of TMF
• Scanning & transfer to other media
• Archiving of TMF
• Retention of TMF
• References
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3. Trial Master File (TMF/eTMF)
According to ICH-GCP E6 (R2) Chapter 8. Essential documents for the conduct of Clinical trials-
A Trial Master File (TMF) is a collection of documentation that makes it possible to evaluate the conduct
of the clinical trial, the credibility of the trial data, and the compliance of the trial with the GCP.
In general, it is the collection of essential documents that is used by sponsors, CROs, and
investigators/institutions for the management of the trial and by monitors, auditors, and inspectors to
review and verify whether the sponsor and the investigators/institutions have conducted the trial in line
with the applicable regulatory requirements and the principles and standards of GCP.
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4. Cont.…..
 The TMF was historically been composed of paper documents, images and media captured
centrally in physical file cabinets.
 The current version of ICH GCP E6 (R2) guidelines states that submitting the essential documents
in an electronic or digital format is mandatory.
 The submission of clinical trial documents using electronic systems is referred to as an Electronic
Trial Master File (eTMF).
 It is simply an electronic way of managing your trial documents.
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5. Structure and Content of TMF
Sponsor and Investigator Trial Master File
Contract Research Organizations (CRO)
Third parties-contracted by Investigator/Institution
Trial Master File structure
Trial Master File contents
(Essential documents, Superseded documents, Correspondence, Contemporariness of the trial
master file)
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6. Sponsor and Investigator Trial Master File
 TMF- prepared at the beginning of the trial.
 Single document- For Sponsors and Investigators.
 TMF maintained by the Sponsor organization is called
Sponsor TMF.
 TMF held by Investigator/Institute is called
Investigator Site File (ISF).
 Investigator/ Institution- generates essential documents
 Should have randomized codes
 Must be protected with passwords
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INVESTIGA
TOR
Spo
nsor
TMF
ISF
Institutes/ CROs/ Sites
SPONSOR

7. Contract Research Organizations (CROs)
 Sponsors choose to outsource the work to CROs.
 An agreement or contract is signed by the parties
 Agreement must include the following-
• Party holding parts of TMF
• Structure and Indexing of TMF
• Arranged access for each party
• Lists of procedures and training requirements needed
• Type of document maintained by each document
• Availability to competent authorities
• Retention times, etc.
 In case of multiple CROs, the sponsor must indicate their
creation, management, remote access, and retention
documents.
 Management and exchange of eTMF must be validated before
sending.
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SPONSOR
C
R
O
Role & Responsibilities of CROs
Evaluate feasibility
Provide adequate & well-managed staff
Conduct trial activities
Manage processes
Alert sponsors regarding problems and their solutions
Ensure the study is cost-effective

8. Third parties
 The investigator/institution may choose to delegate
duties and functions related to the conduct of the trial
to a third party (e.g. site management organization
or external archive).
 The third party may generate/hold essential
documents relating to the contracted duties.
 Considering the principles of CROs.
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Contract
Third Parties
INVESTIGATOR

9. Trial Master File Structure
 Sponsor & Investigator must identify & maintain a record of locations of essential documents required for
preparing TMF.
 A primary TMF system helps to retain essential documents entirely digital or on paper or both.
 A central system may exist containing: a central e-mail repository, SOP-management system, central
training records, delegation logs, software validation records, and records concerning more than one trial-
like document.
 Other systems- Minimal and primarily aimed at placing documents in TMFs.
 Appropriate Indexing of contents is a must to trace the TMF data.
 A standardized TMF (Paper/Electronic) document must be approved by Sponsor/CRO and Investigator/
Institute.
 TMF must follow chronological order.
 Special attention is given to defining dates used for filing.
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10. Trial Master File Content
Essential documents
• Assist SI to manage
& conduct trials
with regulatory
standards
• Contents differ in
Sponsor TMF &
Investigator TMF
• No definitive
checklist for TMF
• Avoid unnecessary
duplication of
documents
Superseded documents
• To reconstruct the final trial
document and retain the TMF
• Sponsor-produced documents
(e.g. trial protocol, IB and
eCRF)
• Available in Investigator TMF
• Can reconstruct without a
sponsor need.
• Include the date of receipt,
review, approval and
implementation by an
investigator.
Correspondence
• Relevant
correspondence
with EC, DSMC &
RA- to reconstruct
trial activities &
decisions
• Electronically
correspondence of
emails between SI-
readily available &
retainable
Contemporariness of
the trial master file
• Defined timelines
for the submission
& filing of
documents in TMF
• Important in case
of multiple
parties/ CROs are
involved in the
study
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11. Security & Control of Trial Master File
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Access to TMF
(Based on role &
permission given by
Sponsor/Investigator)
Storage Areas
(TMF must be legible, complete, retained & easily available to Competent Authority)
Sponsor/ CRO eTMF
- eTMF must be linked to other systems
- Provide robust communication of CT data & meta-data
- Stored in Excel files/ SAS database as a PDF
Investigator eTMF
- May be in electronic/ paper/ hybrid format
-Available before, during & after CT
- Includes source documents of subjects
- Sole responsibility of the investigator to update, control and access data
- Remote access to the sponsor/CRO (only in direct identifiers)

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Quality checks and review processes
•Documents are filed in the correct locations.
•Documents added to the TMF promptly.
Documents are correctly indexed.
•Documents are only accessible to those with the correct permissions and roles.
•Audit trail review
•The Sponsor needs to ensure that the TMF is available and accessible to regulatory
authorities for inspection.
Q
U
A
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Y
T
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13. Scanning & Transfer to other media
 The copies of the eTMF that replaces the original documents should be
certified copies of the original.
 Quality checks of certified copies need to be carried out before the
destruction of the original documents, including:
o The similarity of the information contained between the original and
certified copy.
o Accuracy of the file name.
o Quality of the images.
o Completed and detailed eTMF audit trail.
o Approval of certification processes.
 Printing, copying, or transferring documents depends on the nature of the
data in question.
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Scanner

14. Archiving of TMF
 Archiving makes TMF easily available & accessible.
 Archived data should be maintained to access the original TMF before converting to the new
format.
 Transfer to another media form may be needed in case the storage starts to deteriorate.
 Before transferring any documents, validation is a must to ensure that the migrated data
has the same information as the original data.
 In the case of external archiving, a formal agreement between the Sponsor,
Investigator/Institution, and the external archiver.
 In the case of multiple sites, the exact location of the TMF needs to be known at all times.
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15. Retention of TMF
 The TMF Retention Depends on:
o Digitization of the patient’s medical records after validation- so that the data can
be easily accessible in the future.
o The retention of documents & medical files should be agreed on between the
Sponsor & Investigator/Institution.
o The Sponsor needs to inform the Investigator/Institution when the trial documents
no longer need to be held.
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16. Thank You!
www.clinosol.com
(India | Canada)
9121151622/623/624
info@clinosol.com
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