Standard Operating Procedure for Periodic Review of Expression Cell Lines in Biosimilars

Department	Biosimilars
SOP No.	SOP/BS/051/2025
Supersedes	SOP/BS/051/2022
Page No.	Page 1 of 9
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To define a standardized approach for the periodic review of expression cell lines used in biosimilar product development and manufacturing to ensure genetic stability, expression consistency, and ongoing regulatory compliance.

2. Scope

This SOP applies to all expression cell lines stored in master or working cell banks and used for biosimilar product development and production, including CHO, HEK293, or other mammalian lines.

3. Responsibilities

• CLD Team: Performs and documents cell line evaluations as per defined frequency.
• QA Department: Reviews data, ensures compliance with the review schedule, and manages audit readiness.
• Head of CLD: Approves continuation or discontinuation of a cell line based on review outcomes.

4. Accountability

The Head of Biosimilars Department is accountable for implementing this SOP and ensuring that cell line review data are complete, accurate, and compliant with regulatory expectations.

5. Procedure

5.1 Review Frequency

1. Conduct a full review of each expression cell line at least once every 6 months.
2. Additional reviews shall be triggered in case of:
   • Process changes
   • Unexpected batch failures
   • Change in product quality attributes

5.2 Parameters for Review

1. Evaluate the following:
   • Expression level (e.g., mg/L output)
   • Genetic stability (via qPCR/Southern blot)
   • Cell growth rate and viability
   • Product quality (e.g., glycosylation, charge variants)
   • Number of passages post-MCB/WCB

5.3 Data Collection

1. Use the Expression Cell Line Review Form (Annexure-1) to capture and trend data.
2. Ensure all entries are completed legibly and verified by the reviewer.

5.4 Evaluation and Decision

1. Compare performance parameters against reference data from initial characterization.
2. Determine if the cell line:
   • Is suitable for continued use
   • Requires additional investigation
   • Should be retired
3. Document decisions in Cell Line Evaluation Summary Sheet (Annexure-2).

5.5 Record Review and Archival

1. Submit completed forms and summaries to QA for review and archival.
2. Store records in the CLD-controlled Expression Cell Line History File.

6. Abbreviations

• CLD: Cell Line Development
• MCB: Master Cell Bank
• WCB: Working Cell Bank
• qPCR: Quantitative Polymerase Chain Reaction

7. Documents

1. Expression Cell Line Review Form (Annexure-1)
2. Cell Line Evaluation Summary Sheet (Annexure-2)

8. References

• ICH Q5D – Derivation and Characterization of Cell Substrates
• WHO Technical Report Series No. 978 – Annex 3
• US FDA Guidance on Characterization of Cell Lines Used to Produce Biologicals

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Expression Cell Line Review Form

Date	Clone ID	Expression (mg/L)	Passage No.	Cell Viability	Assessed By
01/05/2025	CLD-CHO-017	6.8	24	96%	Ajay Verma

Annexure-2: Cell Line Evaluation Summary Sheet

Clone ID	Reviewed By	Result	Decision	Remarks
CLD-CHO-017	Sunita Reddy	Stable	Continue	Performance consistent

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Clarified evaluation parameters and review intervals	Process optimization