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
- Conduct a full review of each expression cell line at least once every 6 months.
- Additional reviews shall be triggered in case of:
- Process changes
- Unexpected batch failures
- Change in product quality attributes
5.2 Parameters for Review
- 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
- Use the Expression Cell Line Review Form (Annexure-1) to capture and trend data.
- Ensure all entries are completed legibly and verified by the reviewer.
5.4 Evaluation and Decision
- Compare performance parameters against reference data from initial characterization.
- Determine if the cell line:
- Is suitable for continued use
- Requires additional investigation
- Should be retired
- Document decisions in Cell Line Evaluation Summary Sheet (Annexure-2).
5.5 Record Review and Archival
- Submit completed forms and summaries to QA for review and archival.
- 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
- Expression Cell Line Review Form (Annexure-1)
- 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 |