Standard Operating Procedure for Product Contact Surface Management in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/194/2025
Supersedes	SOP/BS/194/2022
Page No.	Page 1 of 9
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To establish a GMP-compliant procedure for the management, cleaning, inspection, and maintenance of product contact surfaces used in biosimilar manufacturing to ensure product integrity and safety.

2. Scope

This SOP applies to all vessels, tubing, fittings, and components that come into direct contact with biosimilar drug substance or intermediates during production, purification, or storage operations.

3. Responsibilities

• Production: Execute cleaning and inspection of contact surfaces per batch requirement.
• Engineering: Maintain integrity and surface finish of contact equipment.
• QA: Review cleaning logs and surface inspection records; ensure compliance with cleaning validation.

4. Accountability

The Head of Manufacturing and Head of Engineering are jointly accountable for the control and validation of all product contact surfaces in compliance with GMP standards.

5. Procedure

5.1 Identification of Product Contact Surfaces

1. List all parts of equipment and accessories that contact product or buffer solutions including:
   • Stainless steel vessels (grade 316L)
   • Tubing (silicone, TPE)
   • Filter housings, gaskets, sampling valves
2. Update product contact component register (Annexure-1).

5.2 Cleaning and Sanitization

1. Use validated cleaning procedures for each equipment type post-use.
2. For stainless steel: perform CIP with alkaline/acid detergents followed by WFI rinses.
3. For single-use systems: ensure visual cleanliness and proper disposal post-use.

5.3 Visual and Surface Integrity Checks

1. Perform visual inspection under white light for:
   • Scratches, pitting, discoloration
   • Signs of corrosion or damage
2. Perform boroscope examination for internal surfaces annually or post-cleaning validation failure.
3. Record findings in Annexure-2.

5.4 Surface Roughness and Passivation

1. Confirm surface finish of stainless steel parts is Ra ≤ 0.5 µm.
2. Perform passivation (e.g., with nitric or citric acid) every 12 months or post-maintenance.
3. Document passivation activity and results in Annexure-3.

5.5 Labeling and Status Management

1. Label all equipment and parts post-cleaning as “CLEANED – PRODUCT CONTACT” with:
   • Date of cleaning
   • Time and initials
   • Next due date for cleaning/inspection

5.6 Deviation and Requalification

1. Report damage or non-conformance to QA and Engineering immediately.
2. Requalify surface integrity post-repair, maintenance, or replacement before reuse.

6. Abbreviations

• CIP: Clean-in-Place
• Ra: Surface Roughness Average
• QA: Quality Assurance
• WFI: Water for Injection

7. Documents

1. Product Contact Component Register – Annexure-1
2. Surface Inspection Checklist – Annexure-2
3. Passivation Record – Annexure-3

8. References

• ASME BPE Standards for Bioprocessing Equipment
• FDA Guidance on Equipment Cleaning and Maintenance
• WHO TRS 999 – GMP Guidelines for Biotherapeutics

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Product Contact Component Register

Equipment ID	Component	Material	Last Cleaned	Status
BX-401	Dip Tube	SS316L	04/05/2025	Cleaned

Annexure-2: Surface Inspection Checklist

Equipment ID	Inspected Area	Observation	Inspector	Date
BX-401	Inner Wall	No defects	Ajay Verma	04/05/2025

Annexure-3: Passivation Record

Date	Equipment ID	Agent Used	Contact Time (min)	Result	Performed By
01/03/2025	BX-401	20% Nitric Acid	30	Pass	Sunita Reddy

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Expanded to include single-use system references and surface passivation tracking	Process harmonization