Standard Operating Procedure for Maintaining Investigator Site File (ISF) in BA/BE Studies

Department	BA-BE Studies
SOP No.	SOP/BA-BE/026/2025
Supersedes	SOP/BA-BE/026/2022
Page No.	Page 1 of 13
Issue Date	17/04/2025
Effective Date	20/04/2025
Review Date	17/04/2026

1. Purpose

To define the standard procedure for establishing, organizing, maintaining, and archiving the Investigator Site File (ISF) for BA/BE clinical studies, ensuring regulatory and GCP compliance throughout the study lifecycle.

2. Scope

This SOP applies to all study sites participating in Bioavailability/Bioequivalence (BA/BE) studies sponsored or managed by the organization, including clinical investigators, site staff, and clinical monitors.

3. Responsibilities

• Investigator: Maintains the ISF and ensures availability for inspections.
• Clinical Research Associate (CRA): Verifies completeness and accuracy during site monitoring visits.
• Clinical Project Manager: Ensures ISF is created before site initiation and archived post-study.
• Quality Assurance: Conducts periodic audits of the ISF.

4. Accountability

The Principal Investigator is accountable for the integrity, accessibility, and regulatory compliance of the ISF maintained at the study site.

5. Procedure

5.1 ISF Structure and Sections

1. Organize the ISF using a standardized Table of Contents (ToC) including:
   • Regulatory Documents
   • Ethics Committee Approvals
   • Study Protocol and Amendments
   • Informed Consent Forms
   • Site Staff CVs and Training Logs
   • Study Drug Accountability
   • Monitoring Logs and Communications
2. Maintain both hard copy and electronic format (eISF) if applicable.

5.2 ISF Setup and Initiation

1. Setup ISF before Site Initiation Visit (SIV).
2. Provide investigator with:
   • Binder/Folder with labeled dividers
   • Printed copies of ToC and filing guidelines
3. Document creation in Annexure-1: ISF Setup Record.

5.3 Document Filing and Maintenance

1. Ensure documents are filed chronologically and updated promptly.
2. Each document must be signed, dated, and version-controlled.
3. Cross-reference document filing in Annexure-2: ISF Document Checklist.

5.4 Monitoring and Verification

1. During each monitoring visit, CRA should verify:
   • Presence of updated protocol and ICF versions
   • Timely submission of safety reports and deviations
   • Proper documentation of drug accountability
2. Complete Annexure-3: ISF Monitoring Visit Log.

5.5 ISF Closure and Archival

1. At study completion:
   • Reconcile ISF content against checklist
   • Seal physical ISF in a secure archive box
   • Label with study code, site code, and archive date
2. Retain ISF for minimum of 5 years post-study or as per sponsor requirement.

6. Abbreviations

• ISF: Investigator Site File
• CRA: Clinical Research Associate
• PI: Principal Investigator
• EC: Ethics Committee
• SIV: Site Initiation Visit

7. Documents

1. ISF Setup Record – Annexure-1
2. ISF Document Checklist – Annexure-2
3. ISF Monitoring Visit Log – Annexure-3

8. References

• ICH E6(R2) – Good Clinical Practice
• Schedule Y – Drugs and Cosmetics Rules
• WHO Guidance on Clinical Trial Documentation

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: ISF Setup Record

Study Code	Site Code	Date of Setup	Initiated By
BE-036	Site-101	15/04/2025	Sunita Reddy

Annexure-2: ISF Document Checklist

Document	Version	Date Filed	Initials
Study Protocol	V2.0	16/04/2025	RK
ICF (Hindi)	V1.1	17/04/2025	RK

Annexure-3: ISF Monitoring Visit Log

Date	CRA Name	Visit Type	Key Observations	Signature
18/04/2025	Rajesh Kumar	Interim	All sections complete

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
15/01/2022	1.0	Initial SOP	New Study Management Requirement	QA Head
17/04/2025	2.0	Added eISF details and expanded annexures	Regulatory Enhancement	QA Head