Standard Operating Procedure for Deviation Management During Upstream Runs in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/102/2025
Supersedes	SOP/BS/102/2022
Page No.	Page 1 of 13
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To define the procedure for identifying, documenting, evaluating, investigating, and resolving deviations that occur during upstream manufacturing runs of biosimilars. This ensures consistent quality, regulatory compliance, and traceability.

2. Scope

This SOP applies to all upstream production activities including seed train, media preparation, inoculation, bioreactor operation, and sampling processes at the biosimilars manufacturing facility.

3. Responsibilities

• Operator: Identify and immediately report any deviation from standard procedures or set parameters.
• Supervisor: Ensure deviation is logged, impact assessed, and initiate preliminary investigation.
• QA: Classify deviation, lead root cause analysis, and verify closure with CAPA implementation.

4. Accountability

The Head of Quality is accountable for ensuring all upstream deviations are tracked, closed, and reported as per regulatory expectations.

5. Procedure

5.1 Deviation Identification

1. Deviation may include but is not limited to:
   • Out-of-specification parameter (e.g., pH, DO)
   • Operator error
   • Equipment failure
   • Utility interruption
   • Environmental excursions
2. Operators must immediately inform the supervisor and record initial details in Annexure-1.

5.2 Initial Documentation

1. Log deviation in Upstream Deviation Log (Annexure-1).
2. Record:
   • Date, time, and stage of process
   • Brief description of deviation
   • Immediate containment actions

5.3 Impact Assessment

1. Production and QA jointly assess:
   • Impact on product quality
   • Batch disposition status
   • Need for batch rejection, reprocessing, or further analysis

5.4 Root Cause Investigation

1. Initiate within 24 hours of deviation report.
2. Use tools like:
   • 5 Whys Analysis
   • Ishikawa (Fishbone) Diagram
3. Document investigation in Annexure-2.

5.5 CAPA Implementation

1. Define Corrective and Preventive Actions including:
   • Training/retraining of personnel
   • Equipment calibration or repair
   • Procedure revision
2. Track CAPA to closure and record completion in Annexure-3.

5.6 Deviation Closure

1. QA reviews CAPA effectiveness and approves deviation closure.
2. All records must be retained for a minimum of 5 years.

6. Abbreviations

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

7. Documents

1. Upstream Deviation Log – Annexure-1
2. Root Cause Analysis Form – Annexure-2
3. CAPA Implementation Record – Annexure-3

8. References

• ICH Q9 – Quality Risk Management
• WHO TRS 981 – Good Manufacturing Practices for Biologicals

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Upstream Deviation Log

Date	Time	Deviation Type	Detected By	Initial Action	Logged By
04/05/2025	14:10	Low DO	Sunita Reddy	Increased airflow	Rajesh Kumar

Annexure-2: Root Cause Analysis Form

Deviation ID	Investigation Date	Analysis Tool	Root Cause	Investigated By
UPD-035	05/05/2025	5 Whys	Airflow sensor drift	Ajay Verma

Annexure-3: CAPA Implementation Record

CAPA ID	Action	Responsible	Completion Date	Verified By
CAPA-089	Sensor recalibrated, operator trained	Engineering	06/05/2025	QA Officer

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Expanded deviation types and added CAPA log annexure	Process improvement