Standard Operating Procedure for Deviation Handling During Clone Development in Biosimilars

Department	Biosimilars
SOP No.	SOP/BS/050/2025
Supersedes	SOP/BS/050/2022
Page No.	Page 1 of 11
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To outline a systematic process for identifying, documenting, investigating, and resolving deviations encountered during clone development activities in biosimilar manufacturing, ensuring compliance with GMP and data integrity standards.

2. Scope

This SOP applies to all clone development procedures including transfection, clone screening, culture maintenance, and documentation activities carried out in the biosimilars division.

3. Responsibilities

• Research Associate: Identifies and reports deviations promptly using the Deviation Form.
• Functional Head: Reviews, investigates, and recommends corrective/preventive actions (CAPA).
• QA Representative: Verifies documentation, tracks resolution, and ensures closure.

4. Accountability

The Head of Biosimilars Department is accountable for ensuring timely investigation and closure of all deviations as per SOP guidelines and regulatory expectations.

5. Procedure

5.1 Definition of Deviation

1. A deviation is any unplanned event or non-conformance to approved procedures, specifications, or instructions that occurs during clone development.
2. Examples include:
   • Incorrect culture conditions
   • Missed time points for assays
   • Use of expired media/reagents
   • Documentation discrepancies

5.2 Immediate Action and Reporting

1. Stop the activity (if applicable) to prevent escalation.
2. Notify the supervisor or designee immediately.
3. Fill out the Deviation Reporting Form (Annexure-1) with:
   • Date and time of event
   • Description of deviation
   • Initial impact assessment

5.3 Investigation and Impact Assessment

1. Functional Head and QA jointly investigate the root cause using tools such as 5-Why Analysis or Fishbone Diagram.
2. Assess impact on:
   • Product quality
   • Data integrity
   • Compliance and reproducibility
3. Document findings in the Investigation Report (Annexure-2).

5.4 Corrective and Preventive Action (CAPA)

1. Identify actions to prevent recurrence of the deviation.
2. Assign responsible person and implementation timeline.
3. QA to monitor closure and effectiveness of CAPA.
4. Record in CAPA Implementation Log (Annexure-3).

5.5 Classification of Deviations

1. Minor: No impact on data, product, or compliance (e.g., typo in logbook).
2. Major: May affect process but controlled before impacting output.
3. Critical: Direct impact on product quality, safety, or regulatory compliance.

5.6 Documentation and Record Keeping

1. Maintain deviation records for a minimum of 10 years.
2. All forms must be signed and verified by QA.
3. Deviation register to be updated sequentially with unique numbers.

6. Abbreviations

• CAPA: Corrective and Preventive Action
• QA: Quality Assurance
• GMP: Good Manufacturing Practice

7. Documents

1. Deviation Reporting Form (Annexure-1)
2. Deviation Investigation Report (Annexure-2)
3. CAPA Implementation Log (Annexure-3)

8. References

• ICH Q10 – Pharmaceutical Quality System
• WHO TRS 1010 – GMP for Biologics
• 21 CFR Part 211 – Subpart J: Records and Reports

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	Time	Description	Reported By	Initial Impact
03/05/2025	14:30	Missed timepoint for ELISA	Ajay Verma	Low

Annexure-2: Deviation Investigation Report

Deviation ID	Root Cause	Investigated By	Date	Conclusion
DEV/CLD/025	Improper scheduling	Sunita Reddy	04/05/2025	Process Rescheduled

Annexure-3: CAPA Implementation Log

CAPA ID	Corrective Action	Responsible Person	Due Date	Status
CAPA/050	Update scheduling SOP	Vinay Pawar	10/05/2025	In Progress

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Expanded deviation classification and CAPA tracking log	GMP enhancement