Standard Operating Procedure for Emergency Shutdown of Bioreactor in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/118/2025
Supersedes	SOP/BS/118/2022
Page No.	Page 1 of 11
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To provide a standardized procedure for safely shutting down a bioreactor in case of an emergency during upstream biosimilar manufacturing, including power failure, equipment malfunction, contamination, or personnel safety threats.

2. Scope

This SOP applies to all bioreactors used in biosimilar upstream processing, including seed and production-scale vessels operating under batch, fed-batch, or perfusion modes.

3. Responsibilities

• Operator: Initiate emergency shutdown procedure and notify responsible authorities.
• Engineering: Assess and resolve root cause, support safe handling of equipment.
• QA: Review incident documentation and ensure compliance with deviation handling SOP.

4. Accountability

The Head of Manufacturing is accountable for ensuring that emergency shutdown procedures are executed correctly and deviations are documented.

5. Procedure

5.1 Triggers for Emergency Shutdown

1. Sudden power failure or UPS malfunction.
2. Sensor failure or critical alarm for DO, pH, temperature, or agitation.
3. Risk of contamination due to gasket/tubing breach.
4. Spillage, fire, or personal safety hazard in vicinity.

5.2 Immediate Response

1. Press the Emergency Stop (E-Stop) on the bioreactor control panel.
2. Disconnect power if electrical hazard is suspected.
3. Close all manual inlet/outlet valves to isolate the vessel.
4. Stop feed pump and aeration to prevent overpressure or foaming.

5.3 Notification and Escalation

1. Inform the shift supervisor and QA immediately.
2. Log the alarm code, time, and system message from SCADA or HMI.
3. Escalate to Maintenance and EHS for joint inspection if personnel or facility risk is present.

5.4 Containment and Assessment

1. Inspect vessel status and secure lid/port areas.
2. Take sample (if safe) for microbial/chemical testing.
3. Document status in Annexure-1: Emergency Shutdown Checklist.

5.5 Recovery or Disposition

1. If safe and authorized, restart after Engineering clearance using SOP for restart (referenced separately).
2. If batch is compromised, coordinate with QA for batch rejection and cleanout using standard decontamination procedure.

5.6 Documentation

1. Fill Annexure-2: Emergency Shutdown Log.
2. Initiate deviation report and investigation within 24 hours.

6. Abbreviations

• SCADA: Supervisory Control and Data Acquisition
• QA: Quality Assurance
• UPS: Uninterruptible Power Supply
• EHS: Environment, Health, and Safety

7. Documents

1. Emergency Shutdown Checklist – Annexure-1
2. Emergency Shutdown Log – Annexure-2

8. References

• WHO TRS 999 Annex 2 – GMP for Biologicals
• ICH Q9 – Quality Risk Management
• Internal SOP for Restart of Bioreactors (Ref: SOP/BS/090/2025)

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Emergency Shutdown Checklist

Checkpoint	Status (Y/N)	Remarks
Emergency Stop Pressed	Y	Manual shutdown confirmed
Valves Closed	Y	All ports isolated
Feed Pumps Off	Y	Confirmed by HMI

Annexure-2: Emergency Shutdown Log

Date	Time	Reason	Operator	Immediate Action	Escalated To
04/05/2025	04:30	Power failure	Ajay Verma	Isolated vessel	Maintenance & QA

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Added shutdown checklist and clarified restart authority	Audit recommendation