appropriate corrective and preventive actions (CAPA), and document the findings in a manner that ensures regulatory compliance, data integrity, and traceability.

2. Scope

This procedure is applicable to all method transfer failures encountered during the validation, qualification, or application of analytical procedures transferred from a Sending Unit (SU) to a Receiving Unit (RU). It applies to in-house and contract analytical labs involved in method development and transfer for APIs, excipients, and drug products.

3. Responsibilities

• RU Analyst: Reports any method transfer deviation immediately and documents preliminary findings.
• SU Scientist: Supports troubleshooting and provides historical method validation data.
• AMD Investigation Coordinator: Leads the investigation, performs root cause analysis, and prepares the investigation report.
• QA Reviewer: Reviews and approves the investigation report and ensures CAPA effectiveness.

4. Accountability

The Head of Analytical Method Development is accountable for the execution, review, and closure of all method transfer failure investigations in accordance with this SOP and applicable regulatory requirements.

5. Procedure

5.1 Detection and Documentation

1. RU analyst notifies the SU and AMD Investigation Coordinator about the transfer failure.
2. Initiate a Deviation Record (Annexure-1) with details such as batch ID, method number, equipment ID, test type, and description of failure.
3. Secure and label affected samples, reagents, and test solutions to preserve integrity for re-evaluation.

5.2 Preliminary Review

1. Review method transfer protocol and compare results between SU and RU for each parameter (accuracy, precision, linearity, etc.).
2. Check whether acceptance criteria were pre-defined and followed appropriately.
3. Evaluate training records and qualification status of the RU analyst.

5.3 Root Cause Analysis (RCA)

1. Form an investigation team including representatives from AMD, QA, and both SU and RU labs.
2. Perform RCA using tools like Fishbone Diagram, 5 Whys, or Fault Tree Analysis.
3. Identify whether failure originated from:
   • Method misunderstanding or misapplication
   • Instrument malfunction or uncalibrated device
   • Environmental variation or sample integrity issues
   • Incorrect reagent preparation or expired materials

5.4 Corrective and Preventive Actions (CAPA)

1. Document CAPA plan in Annexure-2 with target dates and responsible persons.
2. Examples of CAPA include:
   • Method clarification or re-training of analyst
   • Instrument servicing and recalibration
   • Repeat transfer under controlled supervision
   • Amendment of protocol with updated acceptance limits
3. QA to monitor effectiveness of implemented CAPAs within 30 days of closure.

5.5 Investigation Report Preparation

1. Investigation Coordinator compiles data, analysis, and outcomes in the Method Transfer Failure Investigation Report (Annexure-3).
2. Attach supporting documents: chromatograms, raw data sheets, audit trails, calibration records, deviation form, and CAPA plan.
3. Submit report to QA for final review and approval.

5.6 Closure

1. Close investigation only after QA verifies that CAPA has been implemented and no reoccurrence has been observed.
2. Archive the investigation report and annexures in the central AMD documentation system.

6. Abbreviations

• SOP: Standard Operating Procedure
• RCA: Root Cause Analysis
• CAPA: Corrective and Preventive Action
• RU: Receiving Unit
• SU: Sending Unit

7. Documents

1. Deviation Record – Annexure-1
2. CAPA Plan Template – Annexure-2
3. Method Transfer Failure Investigation Report – Annexure-3

8. References

• ICH Q2(R1): Validation of Analytical Procedures
• ICH Q9: Quality Risk Management
• 21 CFR Part 211 – Current Good Manufacturing Practice
• WHO TRS No. 996, Annex 7: Transfer of Analytical Methods

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Ravi Deshmukh	Meenal Kulkarni	Dr. Harshita Goyal
Designation	Method Transfer Analyst	QA Reviewer	Head – AMD
Department	Analytical Method Development	Quality Assurance	Analytical Method Development

11. Annexures

Annexure-1: Deviation Record

Deviation ID	Test/Method	Description	Date	Reported By
DEV-305-01	HPLC Assay	Precision failed at RU	27/05/2025	Anita R.

Annexure-2: CAPA Plan Template

CAPA ID	Corrective Action	Preventive Action	Responsible Person	Due Date
CAPA-305-01	Repeat test with fresh mobile phase	Analyst re-training on dilution steps	Rajesh Patel	10/06/2025

Annexure-3: Method Transfer Failure Investigation Report

Method: Related Substances by HPLC
Failure Point: RSD of replicate injections beyond 2.0%
Root Cause: Improper integration method
Corrective Action: Re-evaluate integration parameters
Preventive Action: SOP update and analyst requalification

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/06/2025	2.0	Expanded CAPA section, new annexure formats	Annual Review	Dr. Harshita Goyal
15/05/2022	1.0	Initial Release	New SOP	QA Head