Standard Operating Procedure for Buffer Preparation for Harvest Operations in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/136/2025
Supersedes	SOP/BS/136/2022
Page No.	Page 1 of 10
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To define the procedure for the preparation, filtration, labeling, storage, and documentation of buffers used during harvest operations in biosimilar downstream processing to ensure product quality and GMP compliance.

2. Scope

This SOP applies to all personnel involved in buffer preparation for harvest clarification and primary purification processes, including centrifugation, depth filtration, and conditioning steps in the biosimilar manufacturing facility.

3. Responsibilities

• Production: Prepare buffers as per batch requirements and SOP instructions.
• QC: Perform pH and conductivity verification of prepared buffers.
• QA: Review and approve buffer preparation records and confirm compliance.

4. Accountability

The Head of Manufacturing is accountable for ensuring buffer preparation is carried out as per validated procedures and documentation is complete before buffer release for use.

5. Procedure

5.1 Preparation and Planning

1. Review the Buffer Preparation Instruction Sheet (Annexure-1) specific to each batch.
2. Ensure availability of all raw materials (chemicals, WFI, etc.) and verified equipment (balances, mixers).
3. Check expiry date and status label of raw materials before use.

5.2 Buffer Compounding

1. Transfer WFI to the compounding vessel under controlled environment.
2. Add chemicals slowly under mixing:
   • Use precision balances with proper tare.
   • Document each weight in Annexure-2: Buffer Compounding Log.
3. Adjust pH using pre-approved acid/base solutions.
4. Ensure complete dissolution before sampling.

5.3 In-Process Testing

1. QC to perform:
   • pH check
   • Conductivity check
   • Appearance observation
2. Record test results in Annexure-3: Buffer Testing Record.

5.4 Filtration and Storage

1. Filter buffer through 0.22 µm sterilizing grade filters into cleaned and labeled containers.
2. Label each container with:
   • Buffer Name
   • Batch No.
   • Date of Preparation
   • Expiry Date (as per validation)
3. Store buffer under defined temperature and conditions.

5.5 Traceability and Documentation

1. Attach preparation, testing, and release documents to the batch record.
2. QA shall verify traceability of all buffer lots used in a batch during review.

6. Abbreviations

• WFI: Water for Injection
• QC: Quality Control
• QA: Quality Assurance
• GMP: Good Manufacturing Practice

7. Documents

1. Buffer Preparation Instruction Sheet – Annexure-1
2. Buffer Compounding Log – Annexure-2
3. Buffer Testing Record – Annexure-3

8. References

• EU GMP Chapter 5 – Production
• WHO TRS 986 – GMP for Biotech Products
• USP <1045> – Buffer Solutions

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Buffer Preparation Instruction Sheet

Buffer Name	Components	Target pH	Volume
Harvest Buffer A	NaCl, Tris	7.4	50 L

Annexure-2: Buffer Compounding Log

Date	Buffer Name	Material	Weighed Qty	Operator
04/05/2025	Harvest Buffer A	NaCl	58.4 g	Ajay Verma

Annexure-3: Buffer Testing Record

Buffer Name	pH	Conductivity	Appearance	QC Analyst
Harvest Buffer A	7.42	15.5 mS/cm	Clear	Sunita Reddy

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Added testing verification and label format	Process optimization