Standard Operating Procedure for Use of Single-Use Systems in DSP in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/183/2025
Supersedes	SOP/BS/183/2022
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 selection, inspection, assembly, use, and disposal of single-use systems (SUS) in downstream processing (DSP) operations of biosimilar products in accordance with GMP standards.

2. Scope

This SOP applies to all SUS components such as bags, tubing sets, filters, connectors, and pre-sterilized manifolds used during chromatography, filtration, pooling, buffer storage, and final bulk handling operations in DSP.

3. Responsibilities

• Production: Assemble and verify integrity of SUS components, ensure traceability, and record usage data.
• Engineering: Support leak and pressure integrity tests of SUS and connect to skid or pump systems.
• QA: Review and approve SUS lot documentation, ensure correct disposition post-use.

4. Accountability

The Downstream Process Manager is accountable for ensuring validated and GMP-compliant use of single-use assemblies in manufacturing operations.

5. Procedure

5.1 Selection and Receipt of SUS

1. Select SUS components from approved vendors with validated biocompatibility and extractables/leachables profiles.
2. On receipt, inspect packaging for damage, verify lot number, sterility status, and CoC/CoA documentation.
3. Store at designated controlled temperature if applicable (e.g., 15–25°C).

5.2 Assembly and Pre-Use Checks

1. Assemble SUS in classified area as per validated layout drawing (Annexure-1).
2. Visually inspect seals, ports, and connectors for defects.
3. Perform leak test using pressurized air or nitrogen as per supplier specification.
4. Document assembly lot details in Annexure-2.

5.3 Integration with Process Equipment

1. Connect SUS to chromatography skid, filtration pump, or pooling tank using validated aseptic connectors.
2. Ensure flow direction matches process layout and labeling.

5.4 Usage and Monitoring

1. Monitor pressure, temperature, and flow rate during processing as applicable to operation (e.g., bulk hold or sterile filtration).
2. Do not reuse SUS; discard after single campaign or lot as per supplier guidelines.

5.5 Post-Use Handling

1. Disconnect SUS and place in designated biohazard bins after draining residual product.
2. Record disposal details and batch linkage in Annexure-3.
3. Send for incineration or validated destruction process as per SOP.

6. Abbreviations

• SUS: Single-Use System
• CoC: Certificate of Conformance
• CoA: Certificate of Analysis
• DSP: Downstream Processing

7. Documents

1. SUS Assembly Diagram – Annexure-1
2. SUS Usage and Lot Traceability Log – Annexure-2
3. SUS Disposal Log – Annexure-3

8. References

• ICH Q9 – Quality Risk Management
• PDA Technical Report 66 – Single-Use Systems
• WHO TRS 1004 – GMP Guidelines for Biologics

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: SUS Assembly Diagram

Component	Part No.	Flow Direction	Remarks
Bag – 50L	SUS-BAG50L	Inlet	Product Pool
Tubing Set	SUS-TUB202	Outlet	To Sterile Filter

Annexure-2: SUS Usage and Lot Traceability Log

Date	Batch No.	SUS Lot No.	Used In Operation	Operator
04/05/2025	BS-DSP-081	SUS-2398	Post-Protein A Filtration	Sunita Reddy

Annexure-3: SUS Disposal Log

Date	SUS Lot No.	Disposed By	Disposed To	Remarks
04/05/2025	SUS-2398	Ajay Verma	Biohazard Bin #4	Completely drained

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Added disposal traceability log and pressure leak test verification	Audit recommendation