Standard Operating Procedure for Addition of Antifoam Agents in Bioreactor Operations for Biosimilars
| Department | Biosimilars |
|---|---|
| SOP No. | SOP/BS/072/2025 |
| Supersedes | SOP/BS/072/2022 |
| 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 procedure for the selection, preparation, and controlled addition of antifoam agents to bioreactors during biosimilar upstream processing in order to prevent or mitigate foam generation without impacting product quality.
2. Scope
This SOP applies to all production bioreactors used in mammalian cell culture processes for biosimilar manufacturing within the upstream processing department.
3. Responsibilities
- Process Operators: Monitor foam level, add antifoam as per guidelines, and document actions.
- Process Development Scientists: Approve antifoam selection and permissible concentration.
- QA Personnel: Review logs and ensure antifoam addition complies with validated ranges.
4. Accountability
The Upstream Process Manager is accountable for authorizing and ensuring correct and compliant addition of antifoam agents.
5. Procedure
5.1 Selection of Antifoam Agent
- Select antifoam agents that are pharmaceutically approved, non-toxic, and non-reactive. Common agents include polydimethylsiloxane-based products (e.g., Antifoam C).
- Ensure compatibility with cell lines and downstream purification processes.
5.2 Preparation of Antifoam
- Obtain approved stock solution as per master batch record or SOP/BS/005/2025.
- Transfer the required quantity into a sterile single-use syringe or bottle under laminar airflow.
- Label with batch number, quantity, and preparation date (Annexure-1).
5.3 Foam Monitoring
- Monitor foam visually through the bioreactor sight glass or using a foam sensor.
- Log foam height and trends every 2 hours or more frequently if needed (Annexure-2).
5.4 Addition of Antifoam
- Perform addition via:
- Sterile addition port
- Peristaltic pump (for large-volume or continuous addition)
- Manual syringe injection under aseptic conditions
- Dosage guideline: typically 0.01–0.05% v/v based on bioreactor volume.
- Record actual volume added, time, and foam response in Annexure-3.
5.5 Post-Addition Monitoring
- Continue monitoring foam for 1 hour post addition.
- Ensure foam has stabilized; if not, escalate to supervisor.
6. Abbreviations
- SOP: Standard Operating Procedure
- QA: Quality Assurance
- v/v: Volume/Volume
7. Documents
- Antifoam Preparation Label – Annexure-1
- Foam Monitoring Log – Annexure-2
- Antifoam Addition Log – Annexure-3
8. References
- WHO TRS 999 – Biotechnological Products Manufacturing
- ICH Q8 – Pharmaceutical Development
- SOP/BS/005/2025 – Media and Supplement Preparation
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Antifoam Preparation Label
| Label No. | Antifoam Type | Quantity Prepared | Prepared By | Date |
|---|---|---|---|---|
| AF-001 | Antifoam C | 100 mL | Sunita Reddy | 04/05/2025 |
Annexure-2: Foam Monitoring Log
| Date | Time | Foam Height (cm) | Observation | Operator |
|---|---|---|---|---|
| 04/05/2025 | 11:00 | 4.5 | Moderate | Rajesh Kumar |
Annexure-3: Antifoam Addition Log
| Date | Time | Volume Added (mL) | Foam Status | Remarks |
|---|---|---|---|---|
| 04/05/2025 | 11:10 | 2 | Reduced | Stabilized |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 04/05/2025 | 2.0 | Expanded dosage guidelines and post-addition monitoring | Process Improvement |