ensures that all modifications are scientifically justified, appropriately reviewed, documented, and implemented in accordance with GMP and ICH Q10 guidelines.

2. Scope

This SOP applies to all validated or in-development analytical methods used for the analysis of raw materials, intermediates, APIs, and finished pharmaceutical products. It includes changes arising from method optimization, equipment upgrades, regulatory updates, or transfer feedback.

3. Responsibilities

• Method Owner / Analytical Scientist: Initiates change request, provides justification and supporting data.
• Reviewer (Team Lead or Peer): Assesses scientific impact and verifies data accuracy.
• QA: Ensures documentation compliance and tracks change through closure.
• Regulatory Affairs: Assesses need for post-approval change notification (if applicable).
• Head – AMD: Provides final decision on implementation and directs any revalidation activities.

4. Accountability

The Head of AMD is accountable for the effective management and regulatory compliance of all method changes initiated or approved within the department.

5. Procedure

5.1 Change Identification

1. Change may be triggered due to:
   • Unexpected results during routine use
   • Feedback from QC or CROs
   • Regulatory query or update
   • Transfer failure or deviation
   • Improved equipment or reagents
2. Initiator shall complete Annexure-1: Method Change Request Form.

5.2 Categorization of Change

1. Categorize the change as:
   • Minor: Typographical errors, formatting, updated logos
   • Moderate: Adjustment in flow rate, mobile phase composition
   • Major: Change in column, detection wavelength, method principle, or calculation formula
2. Record category in Annexure-2: Change Control Categorization Sheet.

5.3 Impact and Risk Assessment

1. Use structured tools like:
   • FMEA (Failure Modes and Effects Analysis)
   • Risk ranking matrix
2. Evaluate impact on:
   • Product quality
   • Method performance
   • Regulatory compliance
3. Document in Annexure-3: Risk and Impact Assessment Log.

5.4 Evaluation and Approval

1. Submit change documentation to QA and Head – AMD for review and approval.
2. If change impacts regulatory filings, Regulatory Affairs shall be consulted.
3. Approval outcome to be documented in Annexure-4: Method Change Approval Sheet.

5.5 Implementation

1. Update affected documents:
   • Analytical method SOP
   • Validation protocol/report
   • Technical transfer documents
2. Train impacted users and record in training matrix.
3. Execute re-validation if required as per ICH Q2(R2) and document.

5.6 Closure and Archival

1. QA to ensure all documents, approvals, and impacted systems are updated.
2. Complete Annexure-5: Method Change Closure Record and archive with all supporting data.

6. Abbreviations

• AMD: Analytical Method Development
• QA: Quality Assurance
• RA: Regulatory Affairs
• ICH: International Council for Harmonisation
• FMEA: Failure Modes and Effects Analysis

7. Documents

1. Method Change Request Form – Annexure-1
2. Change Control Categorization Sheet – Annexure-2
3. Risk and Impact Assessment Log – Annexure-3
4. Method Change Approval Sheet – Annexure-4
5. Method Change Closure Record – Annexure-5

8. References

• ICH Q10 – Pharmaceutical Quality System
• ICH Q14 – Analytical Procedure Development
• ICH Q2(R2) – Validation of Analytical Procedures
• WHO Technical Report Series 996 – Annex 3

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Method Change Request Form

Method Code	Initiated By	Date	Description of Change
AMD/LC/045	Ajay Mehra	05/05/2025	Change mobile phase from buffer pH 3.0 to pH 4.0

Annexure-2: Change Control Categorization Sheet

Change Type	Category	Justification
Mobile Phase Composition	Moderate	Improved resolution of degradants

Annexure-3: Risk and Impact Assessment Log

Parameter	Risk Rating	Impact	Mitigation
Retention Time Shift	Medium	Deviation from standard RT	Re-define RT window in SST

Annexure-4: Method Change Approval Sheet

Reviewer	Remarks	Approved By	Date
QA	No regulatory impact	Dr. Vinay Pawar	15/05/2025

Annexure-5: Method Change Closure Record

Change ID	Status	Closure Date	Filed By
CHG/AMD/2025/012	Closed	17/05/2025	Sunita Reddy

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Enhanced change categorization and impact assessment formats	ICH Q10 alignment