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Standard Operating Procedure for Media Compatibility Assessment in Biosimilar Upstream Manufacturing
| Department | Biosimilars |
|---|---|
| SOP No. | SOP/BS/111/2025 |
| Supersedes | SOP/BS/111/2022 |
| Page No. | Page 1 of 11 |
| Issue Date | 04/05/2025 |
| Effective Date | 06/05/2025 |
| Review Date | 04/05/2026 |
1. Purpose
To define the procedure for evaluating the compatibility of cell culture media with biosimilar-producing cell lines during upstream development to ensure optimal growth, productivity, and scalability.
2. Scope
This SOP applies to R&D, process development, and manufacturing science teams evaluating basal and feed media formulations for compatibility with CHO, HEK293, and other host cell lines used in biosimilar manufacturing.
3. Responsibilities
- MSAT/Process Development: Design and execute media compatibility studies.
- Manufacturing: Provide pilot scale vessels and assist in preparation.
- QA: Review protocol, results, and approve final media selection.
4. Accountability
The Head of Process Development is accountable for ensuring appropriate selection of media based on data-driven compatibility assessments.
5. Procedure
5.1 Media Selection
- Shortlist commercial or in-house media for evaluation based on:
- Cell line history
- Growth profile requirements
- Availability and cost
- Prepare test matrix of at least 3–5 different media options (Annexure-1).
5.2 Experimental Setup
- Thaw MCB vial and seed shake flasks with 3 × 10⁵ cells/mL in each selected media.
- Maintain at 37°C, 5% CO₂, 120 rpm in orbital shaker incubator.
- Monitor daily:
- Viable Cell Density (VCD)
- Viability (%)
- Glucose/Lactate/Ammonia
- pH and osmolality
5.3 Compatibility Criteria
- Acceptable performance includes:
- ≥ 90% viability over 5 days
- Growth doubling time ≤ 30 hours
- Metabolite profiles within physiological range
- Document results in Annexure-2: Compatibility Evaluation Table.
5.4 Data Analysis and Media Selection
- Analyze statistical performance across replicates.
- Select top 2 media for small-scale bioreactor validation (optional).
- Prepare summary report for QA and sponsor review.
6. Abbreviations
- VCD: Viable Cell Density
- MSAT: Manufacturing Science and Technology
- QA: Quality Assurance
- MCB: Master Cell Bank
7. Documents
- Media Evaluation Matrix – Annexure-1
- Compatibility Evaluation Table – Annexure-2
8. References
- ICH Q8 – Pharmaceutical Development
- WHO TRS 1004 – Guidelines on Process Development
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Media Evaluation Matrix
| Media Name | Supplier | Formulation | Lot No. | Date Prepared |
|---|---|---|---|---|
| CD OptiCHO | Gibco | Powder | CH12345 | 01/05/2025 |
| ActiPro | Merck | Liquid | AP65432 | 01/05/2025 |
Annexure-2: Compatibility Evaluation Table
| Media | Day 0 VCD | Day 3 VCD | Day 5 Viability (%) | Doubling Time (hrs) | Status |
|---|---|---|---|---|---|
| CD OptiCHO | 0.3 | 2.6 | 92 | 28 | Compatible |
| ActiPro | 0.3 | 2.3 | 85 | 35 | Not Compatible |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 04/05/2025 | 2.0 | Included optional scale-up and revised acceptance criteria | Process standardization |