filing, and maintaining essential documents during the conduct of a clinical trial, as per ICH E6 §8 requirements. These documents collectively enable the evaluation of trial conduct and ensure compliance with GCP, regulatory expectations, and subject protection.

Scope

This SOP applies to sponsors, CROs, investigators, site staff, and QA responsible for maintaining essential documents in the TMF and ISF during the trial. It covers monitoring reports, approvals, informed consent forms, IP accountability logs, correspondence, safety reporting, and other trial-related documentation.

Responsibilities

• Sponsor: Ensures TMF is complete and contemporaneous.
• CRO: Maintains documents delegated by sponsor under oversight.
• Investigator: Maintains ISF and subject-level essential documents.
• CRA: Collects and files monitoring reports, logs, and site-level records.
• QA: Audits TMF and ISF to ensure inspection readiness.
• TMF Administrator: Classifies, indexes, and files documents with quality checks.

Accountability

The Head of Clinical Operations is accountable for overall TMF maintenance during the trial. Investigators are accountable for ISF completeness. QA is accountable for verifying inspection readiness.

Procedure

1. Protocol and Amendments
1.1 File final approved protocol and all subsequent amendments.
1.2 Ensure all amendments are approved by EC/IRB and regulatory authorities.

2. Informed Consent Documentation
2.1 File signed informed consent forms (ICFs) for each subject.
2.2 Ensure contemporaneous version control and language approvals.
2.3 Maintain ICF Filing Log (Annexure-1).

3. Investigator and Site Documentation
3.1 File updated CVs and training certificates of PI and site staff.
3.2 File updated Delegation of Authority Logs.
3.3 File Investigator communication with sponsor/CRO.

4. Monitoring Documentation
4.1 File monitoring visit reports, follow-up letters, and responses.
4.2 Ensure reconciliation between reports and trial activities.
4.3 Maintain Monitoring Report Log (Annexure-2).

5. Investigational Product Documentation
5.1 File IP accountability logs, receipts, dispensing records, and destruction logs.
5.2 File temperature logs and excursion reports.
5.3 Maintain IP Accountability Log (Annexure-3).

6. Safety Documentation
6.1 File SAE reports, SUSAR submissions, and follow-up documentation.
6.2 File DSUR/PSUR submissions and safety committee communications.
6.3 Maintain Safety Reporting Log (Annexure-4).

7. Subject-Level Documentation
7.1 File subject ID logs, screening and enrolment logs.
7.2 File eligibility verification checklists.
7.3 Maintain Subject Tracking Log (Annexure-5).

8. Correspondence and Communication
8.1 File essential correspondence with regulators, ECs/IRBs, CROs, and vendors.
8.2 File minutes of meetings and teleconferences.
8.3 Maintain Correspondence Log (Annexure-6).

9. Training and Qualification
9.1 File training records for staff joining during the trial.
9.2 Maintain GCP training certificates.
9.3 Maintain Training Record Log (Annexure-7).

10. Quality Control
10.1 Perform monthly QC checks on TMF/ISF.
10.2 Document findings in TMF QC Log (Annexure-8).
10.3 Correct discrepancies within 10 working days.

Abbreviations

• SOP: Standard Operating Procedure
• TMF/ISF: Trial Master File / Investigator Site File
• PI: Principal Investigator
• CRA: Clinical Research Associate
• QA: Quality Assurance
• EC/IRB: Ethics Committee / Institutional Review Board
• SAE: Serious Adverse Event
• SUSAR: Suspected Unexpected Serious Adverse Reaction
• DSUR/PSUR: Development Safety Update Report / Periodic Safety Update Report

Documents

1. ICF Filing Log (Annexure-1)
2. Monitoring Report Log (Annexure-2)
3. IP Accountability Log (Annexure-3)
4. Safety Reporting Log (Annexure-4)
5. Subject Tracking Log (Annexure-5)
6. Correspondence Log (Annexure-6)
7. Training Record Log (Annexure-7)
8. TMF QC Log (Annexure-8)

References

• ICH E6(R2/R3) – Essential Documents During Trial
• FDA – TMF Maintenance Guidance
• EMA – TMF and ISF Inspection Guidance
• CDSCO – Essential Documents Filing
• WHO – GCP Essential Documents

Version: 1.0

Approval Section

Prepared By	Ravi Kumar, TMF Administrator
Checked By	Sunita Reddy, QA Officer
Approved By	Dr. Anil Sharma, Head Clinical Quality

Annexures

Annexure-1: ICF Filing Log

Subject ID	Consent Version	Date Signed	Filed By
SUBJ-101	v1.0	10/09/2025	Coordinator

Annexure-2: Monitoring Report Log

Date	Site	CRA	Report Filed	Status
12/09/2025	Site 001	Meena Sharma	Yes	Filed

Annexure-3: IP Accountability Log

Date	IP Batch	Dispensed	Returned	Balance
13/09/2025	B001	10	2	8

Annexure-4: Safety Reporting Log

Date	Event	Type	Submitted To	Status
14/09/2025	SAE – hospitalization	SAE	Regulatory, Sponsor	Submitted

Annexure-5: Subject Tracking Log

Subject ID	Screening Date	Enrollment Date	Status
SUBJ-201	15/09/2025	16/09/2025	Ongoing

Annexure-6: Correspondence Log

Date	From/To	Subject	Filed By
12/09/2025	Sponsor to PI	Protocol Amendment 1	CRA

Annexure-7: Training Record Log

Name	Training	Date	Certificate Filed
Arjun Patel	GCP Training	10/09/2025	Yes

Annexure-8: TMF QC Log

Date	Section	Reviewed By	Findings	Action Taken
17/09/2025	Safety	QA Officer	Late SAE report	Corrected

Revision History

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
26/08/2025	00	Initial version	New SOP creation	Head Clinical Quality

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