Standard Operating Procedure for Audit Readiness of CLD Documentation in Biosimilars

Department	Biosimilars
SOP No.	SOP/BS/054/2025
Supersedes	SOP/BS/054/2022
Page No.	Page 1 of 11
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To outline a systematic process for maintaining the audit readiness of documentation generated during Cell Line Development (CLD) in biosimilar manufacturing, ensuring compliance with regulatory requirements and internal QA standards.

2. Scope

This SOP applies to all scientific records, batch protocols, development reports, logbooks, raw data files, and electronic databases associated with the biosimilar CLD process, including MCB/WCB generation, clone screening, transfection, and stability studies.

3. Responsibilities

• CLD Staff: Ensure timely, accurate, and legible completion of all documentation with traceable signatures and dates.
• QA Department: Conducts routine documentation audits, verifies record integrity, and manages corrective actions.
• Documentation Coordinator: Maintains master list of CLD documents and audit trails.

4. Accountability

The Head of QA is accountable for ensuring that all CLD documentation is consistently audit-ready and stored according to GMP documentation practices.

5. Procedure

5.1 Document Classification and Master List

1. All CLD documents must be categorized as:
   • Raw data
   • Controlled forms/logs
   • Development reports
   • Regulatory submissions (where applicable)
2. Create and maintain a CLD Document Master Register (Annexure-1) with version history and storage location.

5.2 Routine Documentation Review

1. CLD personnel must review and close each logbook entry within 24 hours of activity completion.
2. QA performs monthly sample audits of:
   • Lab notebooks
   • Clone evaluation records
   • Cell bank transfer forms
3. Document findings in the Audit Checklist Sheet (Annexure-2).

5.3 Corrective and Preventive Action (CAPA)

1. In case of non-conformance (e.g., missing signature, incomplete data), initiate a CAPA as per QA directive.
2. Track CAPA in the CLD CAPA Log (Annexure-3).

5.4 Electronic Record Management

1. Scan and archive all signed records in PDF format within 3 working days of completion.
2. Digital files must be stored in a validated Document Management System (DMS) with role-based access control.

5.5 Audit Preparation and Mock Audits

1. QA shall conduct mock audits quarterly using pre-approved checklists based on US FDA, EMA, and WHO expectations.
2. Document audit findings, assign responsibility, and ensure CAPA closure within 15 calendar days.

5.6 Archival of CLD Records

1. All finalized records to be submitted to QA Archives for long-term storage.
2. QA to label folders with SOP number, title, date range, and index number.
3. Archival retention shall be a minimum of 10 years or as per product lifecycle requirements.

6. Abbreviations

• CLD: Cell Line Development
• QA: Quality Assurance
• CAPA: Corrective and Preventive Action
• DMS: Document Management System

7. Documents

1. CLD Document Master Register (Annexure-1)
2. Audit Checklist Sheet (Annexure-2)
3. CLD CAPA Log (Annexure-3)

8. References

• ICH Q9 – Quality Risk Management
• WHO TRS 999 – GMP for Biotechnological Products
• 21 CFR Part 211 – Subpart J: Records and Reports

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: CLD Document Master Register

Document ID	Title	Version	Location	Archived On
CLD-ELISA-007	Clone Screening – ELISA	1.0	QA Archive-R1	02/05/2025

Annexure-2: Audit Checklist Sheet

Date	Auditor	Documents Reviewed	Observations	Status
01/05/2025	Sunita Reddy	Logbooks, CAPA Logs	Minor data gaps	CAPA Open

Annexure-3: CLD CAPA Log

CAPA ID	Description	Initiated By	Due Date	Status
CLD-CAPA-021	Missing analyst signature on transfection log	Ajay Verma	10/05/2025	In Progress

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Incorporated CAPA tracking and quarterly mock audits	Audit Readiness