consistency, accuracy, and compliance. Hybrid records (paper + electronic) must be harmonized to maintain data integrity, subject safety, and regulatory inspection readiness.

Scope

This SOP applies to sponsors, investigators, CROs, QA, archivists, and data management personnel handling Trial Master File (TMF), Investigator Site File (ISF), source documents, and essential clinical trial data maintained in both paper and electronic formats. It covers reconciliation, duplicate management, version control, and archiving.

Responsibilities

• Sponsor: Defines reconciliation requirements and ensures oversight of CRO/vendor compliance.
• Investigators: Maintain ISF reconciliation between paper and electronic copies.
• Archivist: Ensures both paper and eArchives are synchronized.
• QA: Conducts audits to confirm consistency of hybrid records.
• Data Management: Manages electronic record updates and versioning.

Accountability

The Sponsor is accountable for ensuring reconciliation processes are defined and implemented. Investigators are accountable for site-level hybrid records, while QA is accountable for compliance verification.

Procedure

1. Identification of Hybrid Records
1.1 Identify documents existing in both paper and electronic formats.
1.2 Maintain Hybrid Record Register (Annexure-1).

2. Reconciliation of TMF and ISF
2.1 Compare paper and electronic TMF/ISF contents quarterly.
2.2 Ensure versions are aligned and discrepancies documented.
2.3 Record reconciliation in TMF/ISF Reconciliation Log (Annexure-2).

3. Duplicate Verification
3.1 Confirm duplicate records contain identical content and signatures.
3.2 Where discrepancies exist, mark as “Superseded” and retain original.

4. Version Control
4.1 Each document must have version numbers and effective dates.
4.2 Ensure electronic version reflects paper version updates and vice versa.

5. Archiving of Hybrid Records
5.1 Archive paper and electronic records under the same index structure.
5.2 Maintain Archive Reconciliation Log (Annexure-3).

6. Regulatory Compliance
6.1 Ensure reconciliation practices comply with FDA, EMA, CDSCO, WHO, GDPR, and HIPAA requirements.
6.2 Maintain inspection readiness at all times.

7. Deviation Management
7.1 Record all reconciliation failures in Deviation Log (Annexure-4).
7.2 Investigate and implement CAPA.

Abbreviations

• SOP: Standard Operating Procedure
• TMF: Trial Master File
• ISF: Investigator Site File
• QA: Quality Assurance
• CRO: Contract Research Organization
• CAPA: Corrective and Preventive Action
• GDPR: General Data Protection Regulation
• HIPAA: Health Insurance Portability and Accountability Act

Documents

1. Hybrid Record Register (Annexure-1)
2. TMF/ISF Reconciliation Log (Annexure-2)
3. Archive Reconciliation Log (Annexure-3)
4. Deviation Log (Annexure-4)

References

• ICH E6(R2/R3) – Essential Documents in Clinical Trials
• FDA – Guidance on Clinical Trial Records
• EMA – Paper and Electronic Record Requirements
• CDSCO – Record Keeping Regulations
• WHO – Data Integrity and Record Management

Version: 1.0

Approval Section

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

Annexures

Annexure-1: Hybrid Record Register

Date	Document Title	Format	Location	Responsible
01/09/2025	Informed Consent Form	Paper + eFile	Site & eTMF	Site Coordinator

Annexure-2: TMF/ISF Reconciliation Log

Date	File	Paper Status	Electronic Status	Reconciled By
05/09/2025	Monitoring Visit Report	Complete	Complete	QA Officer

Annexure-3: Archive Reconciliation Log

Date	Record Type	Paper Status	Electronic Status	Verified By
10/09/2025	TMF Documents	Archived	Archived	Archivist

Annexure-4: Deviation Log

Date	Document	Deviation	Action Taken	Status
12/09/2025	Lab Data	Mismatch in paper vs electronic	Corrected and reconciled	Closed

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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