Standard Operating Procedure for Hold Vessel Cleaning and Sterilization in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/193/2025
Supersedes	SOP/BS/193/2022
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 cleaning and sterilizing stainless steel or single-use hold vessels used for biosimilar drug substance storage, ensuring microbial and chemical cleanliness prior to use.

2. Scope

This SOP applies to all portable and fixed hold vessels used in downstream processing and purified bulk storage areas within biosimilar manufacturing operations.

3. Responsibilities

• Manufacturing Operator: Execute cleaning and sterilization procedures as per batch and equipment log.
• Maintenance: Ensure integrity and calibration of steam sterilization or CIP/SIP systems.
• QA: Review cleaning records and validate cleanliness status before batch use.

4. Accountability

The Head of Manufacturing and Head of QA are accountable for compliance with cleaning validation, sanitation schedules, and preventive maintenance of hold vessels.

5. Procedure

5.1 Pre-Cleaning Inspection

1. Visually inspect vessel interiors for any residual product, stains, or foreign material.
2. Ensure all vessel accessories (e.g., gaskets, valves, spray balls) are intact and in validated configuration.

5.2 Cleaning Process

1. Rinse hold vessel with purified water (PW) to remove loose debris.
2. Apply validated cleaning agent (e.g., alkaline detergent) using either manual scrubbing or automated CIP system.
3. Rinse thoroughly with PW followed by WFI (Water for Injection) until rinse water is clear and pH neutral.
4. Collect final rinse sample for TOC (Total Organic Carbon) and conductivity testing (Annexure-1).

5.3 Visual and Analytical Verification

1. Post-cleaning, visually inspect vessel interior under adequate lighting for cleanliness.
2. Record inspection result in Annexure-2 and attach cleaning checklist to equipment logbook.

5.4 Sterilization Process

1. Connect vessel to validated SIP (Steam-In-Place) system or use autoclave (for small vessels).
2. Achieve sterilization temperature (121°C) for defined hold time (e.g., 30 minutes).
3. Monitor and document sterilization parameters (Annexure-3).

5.5 Storage and Status Labeling

1. Once sterilized, apply “CLEANED & STERILE” label with date, time, and initials.
2. Store vessel in designated clean area under covered condition to avoid contamination.

5.6 Hold Time Validation

1. Do not use vessel beyond validated hold time post-sterilization (e.g., 72 hours).
2. If hold time is exceeded, repeat the cleaning and sterilization cycle.

5.7 Deviation Handling

1. In case of failed TOC, microbial load, or visible residue, document deviation and re-clean the vessel.
2. Investigate root cause and log in Annexure-4.

6. Abbreviations

• CIP: Clean-in-Place
• SIP: Steam-in-Place
• WFI: Water for Injection
• TOC: Total Organic Carbon

7. Documents

1. Final Rinse Sample Test Report – Annexure-1
2. Visual Inspection Checklist – Annexure-2
3. Sterilization Cycle Report – Annexure-3
4. Cleaning Deviation Form – Annexure-4

8. References

• ICH Q7 – Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
• WHO GMP Annex 4 – HVAC and Cleanroom Classification
• FDA Guidance on Cleaning Validation

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Final Rinse Sample Test Report

Date	Equipment ID	TOC (ppb)	Conductivity (µS/cm)	Tested By
04/05/2025	HV-012	38	1.1	Neha Rao

Annexure-2: Visual Inspection Checklist

Date	Equipment ID	Interior Clean?	Residue Present?	Inspector
04/05/2025	HV-012	Yes	No	Ajay Verma

Annexure-3: Sterilization Cycle Report

Date	Equipment ID	Temp (°C)	Hold Time (min)	Operator
04/05/2025	HV-012	121.5	30	Sunita Reddy

Annexure-4: Cleaning Deviation Form

Date	Deviation Description	Root Cause	Corrective Action	QA Reviewer
03/05/2025	TOC > limit	Inadequate rinse	Repeat rinse with WFI	Dr. Neha Rao

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Added hold time validation and deviation reporting annexures	GMP Enhancement