Developer: Proposes changes and provides scientific rationale.

QA Officer: Reviews impact assessment and ensures regulatory compliance.

Bioanalytical Reviewer: Evaluates justification and method performance post-change.

Bioanalytical Head: Approves final implementation and updates documentation.

4. Accountability

The Head of Bioanalytical Laboratory is accountable for ensuring that all method changes are justified, documented, verified, and approved prior to implementation.

5. Procedure

5.1 Types of Changes Requiring Control

1. Instrument configuration changes (e.g., detector, pump, column switch).
2. Reagent grade or source changes.
3. Change in sample extraction technique (e.g., LLE to SPE).
4. Modifications in mobile phase composition or flow rate.
5. Software upgrades affecting integration or calculation parameters.
6. Any parameter that impacts method performance.

5.2 Initiating Change Request

1. The analyst submits a Change Control Request (Annexure-1) detailing:
   • Current method parameters
   • Proposed changes
   • Scientific rationale
   • Supporting validation or development data
2. Assign a unique Change Control Number (e.g., BCC-025/2025).

5.3 Risk and Impact Assessment

1. The bioanalytical reviewer assesses:
   • Impact on accuracy, precision, linearity, selectivity, recovery, matrix effect
   • Potential impact on reported data and subject safety
2. Document findings in Annexure-2: Risk Impact Assessment Form.

5.4 Approval and Implementation

1. QA reviews compliance with ICH M10 and GLP guidelines.
2. The Head of Bioanalytical Lab approves or rejects the request based on risk profile and data justification.
3. Upon approval:
   • Document updated method parameters
   • Conduct partial or full revalidation as required
   • Archive supporting documents with the Change Control File

5.5 Communication and Training

1. Inform all impacted personnel via Change Notification Memo (Annexure-3).
2. Conduct targeted training before implementation.
3. Record training in the Training Logbook with employee acknowledgment.

5.6 Post-Implementation Review

1. Conduct a performance check on initial three analytical runs using updated method.
2. QA to verify that system suitability and QC acceptance are met consistently.
3. Close the change control by completing Annexure-4: Change Closure Report.

6. Abbreviations

• SOP: Standard Operating Procedure
• BA/BE: Bioavailability/Bioequivalence
• GLP: Good Laboratory Practices
• QA: Quality Assurance
• ICH: International Council for Harmonisation

7. Documents

1. Change Control Request – Annexure-1
2. Risk Impact Assessment Form – Annexure-2
3. Change Notification Memo – Annexure-3
4. Change Closure Report – Annexure-4

8. References

• ICH M10: Bioanalytical Method Validation
• OECD Principles of GLP
• US FDA Guidance for Bioanalytical Method Development

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Change Control Request

Change ID	Date	Requested By	Proposed Change	Rationale
BCC-025/2025	17/04/2025	Rajesh Kumar	Change mobile phase pH from 3.0 to 3.5	Improved peak shape

Annexure-2: Risk Impact Assessment Form

Parameter	Impacted (Y/N)	Risk Level	Remarks
Accuracy	N	Low	Within limits
Linearity	Y	Moderate	Requires revalidation

Annexure-3: Change Notification Memo

Date	Change ID	Communicated To	Mode	Remarks
18/04/2025	BCC-025/2025	Analytical Team	Email & Briefing	Training completed

Annexure-4: Change Closure Report

Change ID	Implementation Date	Outcome	Closed By	Closure Date
BCC-025/2025	20/04/2025	All validation criteria met	Sunita Reddy	24/04/2025

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial release	New Method SOP	QA Head
17/04/2025	2.0	Included risk assessment and training compliance	ICH M10 Compliance	QA Head