Standard Operating Procedure for Review and Approval of CLD Protocols in Biosimilars

Department	Biosimilars
SOP No.	SOP/BS/058/2025
Supersedes	SOP/BS/058/2022
Page No.	Page 1 of 10
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To establish a standardized procedure for the review, approval, and archival of Cell Line Development (CLD) protocols used during biosimilar product development, ensuring scientific validity, documentation control, and regulatory alignment.

2. Scope

This SOP applies to all protocols drafted for activities within CLD including clone screening, gene transfection, productivity evaluation, and creation of MCB/WCB under the biosimilar manufacturing framework.

3. Responsibilities

• CLD Scientist: Prepares draft protocols based on project goals and prior studies.
• Technical Reviewer: Reviews protocols for scientific accuracy, methodology, and feasibility.
• QA Reviewer: Reviews protocols for GMP alignment and regulatory compliance.

4. Accountability

The Head of Biosimilars is accountable for final approval and ensuring that only validated protocols are implemented during CLD operations.

5. Procedure

5.1 Protocol Preparation

1. CLD scientists prepare a draft protocol in the approved template format (Annexure-1).
2. Each protocol must contain:
   • Objective and scope
   • Materials and methods
   • Acceptance criteria
   • Data collection strategy
3. Assign a unique protocol ID using format: CLD/PRT/YYYY/XXX (e.g., CLD/PRT/2025/014).

5.2 Technical Review

1. Protocol is routed to an independent subject matter expert for technical review.
2. The reviewer checks:
   • Scientific rationale
   • Feasibility in lab scale and production
   • Reference alignment
3. Comments and suggestions are logged in the Protocol Review Form (Annexure-2).

5.3 QA Review and GMP Compliance

1. Post-technical clearance, QA reviews the document for:
   • Consistency with SOPs
   • Regulatory alignment (ICH, WHO, etc.)
   • Document control and format compliance
2. QA signs off or returns for revision via Review Summary Log (Annexure-3).

5.4 Final Approval and Release

1. Upon successful reviews, Head of Biosimilars authorizes the protocol for implementation.
2. Stamped “Approved for Execution” and logged in the Protocol Register (Annexure-4).
3. Only the approved version shall be distributed to execution teams.

5.5 Protocol Revision

1. Revisions must be initiated with change justification and version control.
2. Follow same review and approval workflow.

5.6 Archival

1. All original and superseded protocols must be archived by QA for a minimum of 10 years.
2. Electronic versions must be password-protected and version-tracked.

6. Abbreviations

• CLD: Cell Line Development
• QA: Quality Assurance
• SOP: Standard Operating Procedure

7. Documents

1. Protocol Template – Annexure-1
2. Protocol Review Form – Annexure-2
3. Review Summary Log – Annexure-3
4. Protocol Register – Annexure-4

8. References

• ICH Q8 – Pharmaceutical Development
• WHO Technical Report Series No. 999
• EU GMP – Part I and Part II Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Protocol Template

Section	Description
Objective	To evaluate expression levels in CHO clones
Method	ELISA-based quantification of supernatant
Acceptance Criteria	≥20 mg/L titer

Annexure-2: Protocol Review Form

Reviewer	Review Date	Comments	Status
Sunita Reddy	01/05/2025	Clarify incubation time	Revised

Annexure-3: Review Summary Log

Protocol ID	Version	QA Reviewer	Status	Date
CLD/PRT/2025/014	1.0	Ajay Verma	Approved	02/05/2025

Annexure-4: Protocol Register

Protocol ID	Title	Version	Status	Archived
CLD/PRT/2025/014	Clone Evaluation – ELISA	1.0	Active	No

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Included QA compliance steps and protocol register	Process Enhancement