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

1. Select antifoam agents that are pharmaceutically approved, non-toxic, and non-reactive. Common agents include polydimethylsiloxane-based products (e.g., Antifoam C).
2. Ensure compatibility with cell lines and downstream purification processes.

5.2 Preparation of Antifoam

1. Obtain approved stock solution as per master batch record or SOP/BS/005/2025.
2. Transfer the required quantity into a sterile single-use syringe or bottle under laminar airflow.
3. Label with batch number, quantity, and preparation date (Annexure-1).

5.3 Foam Monitoring

1. Monitor foam visually through the bioreactor sight glass or using a foam sensor.
2. Log foam height and trends every 2 hours or more frequently if needed (Annexure-2).

5.4 Addition of Antifoam

1. Perform addition via:
   • Sterile addition port
   • Peristaltic pump (for large-volume or continuous addition)
   • Manual syringe injection under aseptic conditions
2. Dosage guideline: typically 0.01–0.05% v/v based on bioreactor volume.
3. Record actual volume added, time, and foam response in Annexure-3.

5.5 Post-Addition Monitoring

1. Continue monitoring foam for 1 hour post addition.
2. Ensure foam has stabilized; if not, escalate to supervisor.

6. Abbreviations

• SOP: Standard Operating Procedure
• QA: Quality Assurance
• v/v: Volume/Volume

7. Documents

1. Antifoam Preparation Label – Annexure-1
2. Foam Monitoring Log – Annexure-2
3. 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