Procedure for Microbial Excursions Handling in Biosimilar Upstream Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/112/2025
Supersedes	SOP/BS/112/2022
Page No.	Page 1 of 12
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To establish a systematic approach for the detection, investigation, response, and documentation of microbial excursions in upstream biosimilar processes, ensuring GMP compliance and prevention of recurrence.

2. Scope

This SOP applies to all biosimilar upstream manufacturing areas including seed train, bioreactor systems, sampling operations, and associated equipment where microbial contamination may be detected or suspected.

3. Responsibilities

• Operators: Report any microbial excursions immediately and isolate affected systems.
• QA/QC: Investigate, document, and assess impact on product quality.
• Manufacturing: Support root cause analysis, implement immediate containment actions.

4. Accountability

The Head of Quality Assurance is accountable for oversight and resolution of all microbial excursion events and for implementing preventive actions.

5. Procedure

5.1 Identification of Microbial Excursion

1. Microbial excursions include:
   • Bioreactor contamination
   • Positive sterility test results
   • High bioburden in process samples
   • Environmental monitoring out-of-specifications
2. Immediately notify QA and isolate the affected system.

5.2 Initial Containment

1. Stop ongoing operations in affected equipment/area.
2. Close sampling ports, cap connections, and switch off feed supply if required.
3. Quarantine the affected batch and place “Under Investigation” status.

5.3 Investigation Process

1. Raise a deviation and initiate root cause analysis (Annexure-1: Excursion Report Form).
2. Perform microbial identification using gram stain and culture-based methods.
3. Evaluate:
   • Media lot records
   • Operator aseptic logs
   • Cleanroom EM records
   • Equipment sanitization status
4. Collect swab samples from suspected contamination points.

5.4 Impact Assessment

1. Determine if product quality is impacted using:
   • Batch history
   • In-process control data
   • Sterility test records
2. Assess if batch rejection, reprocessing, or requalification is necessary.

5.5 Corrective and Preventive Actions (CAPA)

1. Define corrective measures:
   • Sanitization protocol revision
   • Operator retraining
   • Change in gowning material or technique
2. Implement and track CAPAs in Annexure-2.

5.6 Documentation

1. Update batch record, deviation record, and QA logs with final disposition.
2. Submit full investigation and CAPA closure report for QA approval.

6. Abbreviations

• EM: Environmental Monitoring
• CAPA: Corrective and Preventive Action
• QA: Quality Assurance
• OOS: Out of Specification

7. Documents

1. Microbial Excursion Report Form – Annexure-1
2. CAPA Implementation Log – Annexure-2

8. References

• FDA Guidance for Industry – Sterile Drug Products Produced by Aseptic Processing
• WHO TRS 986 Annex 2 – GMP for Biological Products

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Microbial Excursion Report Form

Date	Area	Excursion Type	Detected By	Immediate Action	Microbe Identified
04/05/2025	Seed Bioreactor 03	EM Alert	Ajay Verma	Area Isolated	Bacillus subtilis

Annexure-2: CAPA Implementation Log

CAPA ID	Description	Owner	Due Date	Status	Closure Date
CAPA-221	Operator Aseptic Retraining	QA	10/05/2025	Completed	09/05/2025

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Expanded root cause checklist and added dedicated annexures	Compliance enhancement