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

1. 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

1. 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

1. Review Board to convene meeting with minutes captured in Review Meeting Record (Annexure-2).
2. Each member evaluates and scores the readiness based on:
   • Scientific merit
   • GMP readiness
   • Risk status
3. Decision documented as: Approved / Conditional Approval / Reject.

5.4 Documentation and Approvals

1. Final decision documented in Gate Decision Log (Annexure-3).
2. Project Lead circulates signed approval for execution of next phase.
3. Any rework requirements must be closed before progression.

5.5 Archive and Traceability

1. All gate documents to be archived in QA-controlled records with cross-references to batch IDs and clone IDs.
2. 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

1. Phase-Gate Dossier – Annexure-1
2. Review Meeting Record – Annexure-2
3. 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