Trial Master File (TMF/eTMF)

Trial Master File (TMF/eTMF)

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  Welcome Trial Master File(TMF/eTMF) Shraddha Khobragade Master of Pharmacy CSROL_INT_ONL_WKD_188/2022 5/18/2023 www.clinosol.com | follow us on social media @clinosolresearch 1
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  Index • What areTMF 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 5/18/2023 www.clinosol.com | follow us on social media @clinosolresearch 2
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  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. 5/18/2023 www.clinosol.com | follow us on social media @clinosolresearch 3
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  Cont.…..  The TMFwas 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. 5/18/2023 www.clinosol.com | follow us on social media @clinosolresearch 4
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  Structure and Contentof 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by Investigator/Institution Trial Master File structure Trial Master File contents (Essential documents, Superseded documents, Correspondence, Contemporariness of the trial master file) 5/18/2023 www.clinosol.com | follow us on social media @clinosolresearch 5
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  Sponsor and InvestigatorTrial 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 5/18/2023 www.clinosol.com | follow us on social media @clinosolresearch 6 INVESTIGA TOR Spo nsor TMF ISF Institutes/ CROs/ Sites SPONSOR
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  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. 5/18/2023 www.clinosol.com | follow us on social media @clinosolresearch 7 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
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  Third parties  Theinvestigator/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. 5/18/2023 www.clinosol.com | follow us on social media @clinosolresearch 8 Contract Third Parties INVESTIGATOR
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  Trial Master FileStructure  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. 5/18/2023 www.clinosol.com | follow us on social media @clinosolresearch 9
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  Trial Master FileContent 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 5/18/2023 www.clinosol.com | follow us on social media @clinosolresearch 10
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  Security & Controlof Trial Master File 5/18/2023 www.clinosol.com | follow us on social media @clinosolresearch 11 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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  5/18/2023 www.clinosol.com | followus on social media @clinosolresearch 12 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 L Y T I T M F
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  Scanning & Transferto 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. 5/18/2023 www.clinosol.com | follow us on social media @clinosolresearch 13 Scanner
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  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. 5/18/2023 www.clinosol.com | follow us on social media @clinosolresearch 14
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  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. 5/18/2023 www.clinosol.com | follow us on social media @clinosolresearch 15
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  Thank You! www.clinosol.com (India |Canada) 9121151622/623/624 [email protected] 5/18/2023 www.clinosol.com | follow us on social media @clinosolresearch 16