Standard Operating Procedure for Phase-Gate Review of Cell Line Progression in Biosimilar Development
| Department | Biosimilars |
|---|---|
| SOP No. | SOP/BS/060/2025 |
| Supersedes | SOP/BS/060/2022 |
| Page No. | Page 1 of 11 |
| Issue Date | 04/05/2025 |
| Effective Date | 06/05/2025 |
| Review Date | 04/05/2026 |
1. Purpose
To establish a structured framework for the phase-gate review process for biosimilar cell lines, enabling objective evaluation at each developmental stage and decision-making based on predefined scientific and quality criteria.
2. Scope
This SOP applies to all biosimilar CLD activities involving candidate selection, transfection, clone screening, MCB/WCB generation, and transfer to upstream production within the R&D and manufacturing interface.
3. Responsibilities
- Project Lead: Coordinates the preparation of review documentation and convenes review board.
- CLD Scientist: Provides data summaries and supporting documentation at each gate.
- Review Board: Composed of QA, Regulatory, CLD Head, and Manufacturing to assess and authorize progression.
4. Accountability
The Head of Biosimilars is accountable for ensuring each phase-gate is completed and documented prior to initiating the next development milestone.
5. Procedure
5.1 Phase-Gate Model Definition
- The following gates shall be implemented:
- Gate 1: Post-vector design and sequence verification
- Gate 2: After transfection and initial expression screening
- Gate 3: After stable clone generation and productivity evaluation
- Gate 4: Pre-MCB creation and clone stability assessment
- Gate 5: Prior to technology transfer for upstream processing
5.2 Preparation for Phase-Gate Review
- CLD team prepares a Phase-Gate Dossier (Annexure-1) containing:
- Experimental data (qP, titer, stability)
- Risk assessments
- Compliance to critical criteria
- Deviations and CAPAs if applicable
5.3 Conduct of Phase-Gate Review
- Review Board to convene meeting with minutes captured in Review Meeting Record (Annexure-2).
- Each member evaluates and scores the readiness based on:
- Scientific merit
- GMP readiness
- Risk status
- Decision documented as: Approved / Conditional Approval / Reject.
5.4 Documentation and Approvals
- Final decision documented in Gate Decision Log (Annexure-3).
- Project Lead circulates signed approval for execution of next phase.
- Any rework requirements must be closed before progression.
5.5 Archive and Traceability
- All gate documents to be archived in QA-controlled records with cross-references to batch IDs and clone IDs.
- Gate Decision Matrix to be reviewed during internal audits and regulatory inspections.
6. Abbreviations
- CLD: Cell Line Development
- MCB: Master Cell Bank
- CAPA: Corrective and Preventive Action
- QA: Quality Assurance
7. Documents
- Phase-Gate Dossier – Annexure-1
- Review Meeting Record – Annexure-2
- Gate Decision Log – Annexure-3
8. References
- ICH Q10 – Pharmaceutical Quality System
- WHO TRS 1004 – Biotechnological Products
- Internal Project Governance Charter
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Phase-Gate Dossier Summary
| Clone ID | Phase | Criteria Met | Deviation Reported | Remarks |
|---|---|---|---|---|
| CHO-105 | Gate 3 | Yes | No | Ready for MCB |
Annexure-2: Review Meeting Record
| Date | Gate No. | Reviewers Present | Discussion Points | Outcome |
|---|---|---|---|---|
| 03/05/2025 | Gate 3 | QA, CLD, Regulatory | Expression stable, titer acceptable | Approved |
Annexure-3: Gate Decision Log
| Clone ID | Gate No. | Decision | Date | Authorized By |
|---|---|---|---|---|
| CHO-105 | Gate 3 | Approved | 03/05/2025 | Review Board |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 04/05/2025 | 2.0 | Updated gate criteria and documentation process | Periodic Review |