Standard Operating Procedure for Reporting Critical Deviations to QA in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/142/2025
Supersedes	SOP/BS/142/2022
Page No.	Page 1 of 9
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To define the procedure for promptly identifying, recording, assessing, and reporting critical deviations to the Quality Assurance (QA) department in biosimilar manufacturing operations, ensuring compliance with GMP and minimizing product quality risks.

2. Scope

This SOP applies to all departments involved in GMP operations including production, QC, warehouse, and engineering within the biosimilar manufacturing facility where critical deviations may impact product safety, efficacy, or regulatory compliance.

3. Responsibilities

• Departmental Heads: Ensure all deviations are escalated and reported as per defined timelines.
• QA: Investigate and evaluate the criticality of deviations, approve the investigation reports, and determine disposition.
• All Employees: Immediately inform supervisors and initiate deviation documentation upon observation.

4. Accountability

The QA Head is accountable for ensuring that all critical deviations are thoroughly investigated, documented, and reported to regulatory bodies as needed.

5. Procedure

5.1 Identification of Critical Deviations

1. Any unexpected event or non-compliance that may affect product quality, data integrity, or regulatory status must be flagged as a potential critical deviation.
2. Examples include:
   • Use of expired materials
   • Unplanned equipment failure during manufacturing
   • Missed or incorrect process parameters (e.g., temperature, pH)
   • Data falsification or manipulation
   • Environmental excursions in cleanroom conditions

5.2 Immediate Actions

1. Pause the affected operation, isolate impacted material (if applicable), and label as “On Hold.”
2. Notify the Department Head and QA within 30 minutes of detection.
3. Complete Annexure-1: Deviation Reporting Form with preliminary details.

5.3 QA Assessment and Investigation

1. QA shall:
   • Determine criticality and classify deviation as Critical, Major, or Minor.
   • Initiate root cause analysis using tools like 5 Whys or Fishbone diagram.
   • Define and assign Corrective and Preventive Actions (CAPA).
2. Complete Annexure-2: Deviation Investigation Report.

5.4 Review and Closure

1. QA shall review effectiveness of CAPA before closing deviation.
2. Deviation must be closed within 30 calendar days unless extension is approved.
3. Final disposition must be recorded in Annexure-3: Deviation Closure Record.

5.5 Regulatory Reporting

1. Report deviations affecting marketed product, critical quality attributes, or patient safety to applicable regulatory bodies (e.g., CDSCO, EMA, USFDA).
2. Maintain a log of reported deviations in Annexure-4: Regulatory Notification Log.

6. Abbreviations

• QA: Quality Assurance
• CAPA: Corrective and Preventive Action
• GMP: Good Manufacturing Practice
• CDSCO: Central Drugs Standard Control Organization

7. Documents

1. Deviation Reporting Form – Annexure-1
2. Deviation Investigation Report – Annexure-2
3. Deviation Closure Record – Annexure-3
4. Regulatory Notification Log – Annexure-4

8. References

• ICH Q10 – Pharmaceutical Quality System
• WHO TRS 986 – GMP for Biological Products
• FDA Guidance on Quality Systems Approach to Pharmaceutical CGMP Regulations

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Deviation Reporting Form

Date	Reported By	Department	Deviation Description	Immediate Action
04/05/2025	Ajay Verma	Production	Temperature spike in bioreactor	Process stopped

Annexure-2: Deviation Investigation Report

Deviation ID	Root Cause	CAPA	Investigator	Date
DEV/BS/042	Controller fault	Recalibration and SOP update	Sunita Reddy	05/05/2025

Annexure-3: Deviation Closure Record

Deviation ID	CAPA Verified	Closed On	QA Reviewer
DEV/BS/042	Yes	06/05/2025	QA Head

Annexure-4: Regulatory Notification Log

Deviation ID	Agency	Date Notified	Reference No.	Status
DEV/BS/042	CDSCO	06/05/2025	CD-INT/2025/042	Closed

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Added regulatory reporting annexure	Compliance Enhancement