Standard Operating Procedure for Pressure Vessel Safety Checks in Bioreactor Operations for Biosimilars

Department	Biosimilars
SOP No.	SOP/BS/093/2025
Supersedes	SOP/BS/093/2022
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 standard procedure for conducting safety checks, inspection, and preventive maintenance of pressure vessels used in biosimilar bioreactor operations. This SOP ensures all pressure-bearing equipment complies with safety and regulatory standards to avoid risk to personnel and product.

2. Scope

This SOP applies to all pressure vessels including bioreactors, media preparation tanks, buffer hold vessels, and CIP/SIP skids used in biosimilar manufacturing facilities.

3. Responsibilities

• Engineering Team: Conduct routine inspection, pressure tests, and calibration of gauges and valves.
• Production Department: Report anomalies and confirm safety checks before every batch run.
• QA Department: Review maintenance logs and verify safety certification status.

4. Accountability

The Engineering Head is accountable for ensuring all pressure vessels are operated and maintained in accordance with safety regulations and certified at defined intervals.

5. Procedure

5.1 Visual Inspection

1. Inspect vessel surfaces, manways, and weld joints for corrosion, pitting, or cracks before use.
2. Check for leaks around gaskets, agitator seals, and pressure connections.

5.2 Pressure Relief Device Check

1. Ensure that safety relief valves are calibrated and tagged with last inspection date.
2. Verify valve capacity and set pressure is in compliance with design specifications.

5.3 Pressure Gauge Verification

1. Check that the pressure gauge is:
   • Properly zeroed before pressurization
   • Calibrated within the last 6 months
   • Legible and within accuracy limits

5.4 Hydrostatic Pressure Testing

1. Conduct hydrostatic testing annually or per local regulation using deionized water.
2. Test pressure shall be 1.5 times the maximum allowable working pressure (MAWP).
3. Hold pressure for 30 minutes with no visible leakage or pressure drop.
4. Document test in Annexure-1.

5.5 Leak Testing Using Soap Solution

1. Apply soap solution around flanges, welds, and nozzles during pressurization.
2. Check for bubble formation indicating leaks and rectify before use.

5.6 Vessel Certification and Tagging

1. Affix inspection tag on vessel with:
   • Inspection Date
   • Next Due Date
   • Engineer Initials
2. Do not operate vessels without valid safety tag.

5.7 Emergency Protocol

1. If over-pressurization or audible leaks are detected:
   • Shut down vessel operation immediately
   • Vent vessel slowly to atmospheric pressure
   • Inform engineering and QA for investigation

6. Abbreviations

• MAWP: Maximum Allowable Working Pressure
• CIP: Clean-In-Place
• SIP: Sterilize-In-Place
• QA: Quality Assurance

7. Documents

1. Pressure Vessel Safety Checklist – Annexure-1
2. Calibration Certificate Log – Annexure-2

8. References

• Indian Boiler Regulations (IBR)
• WHO TRS 986 Annex 3 – Biopharmaceutical Production Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Pressure Vessel Safety Checklist

Date	Vessel ID	MAWP (bar)	Hydro Test Pressure	Result	Next Due Date	Engineer
04/05/2025	BR-300L	4.0	6.0	Pass	04/05/2026	Rajesh Kumar

Annexure-2: Calibration Certificate Log

Instrument	Tag No.	Calibration Date	Due Date	Performed By
Pressure Gauge	PG-BR-12	03/04/2025	03/10/2025	Sunita Reddy

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Added hydrostatic testing frequency and soap solution test steps	Safety Enhancement