SOP Guide for Pharma

Analytical Method Development: Troubleshooting Methods Developed in AMD – V 2.0

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Analytical Method Development: Troubleshooting Methods Developed in AMD – V 2.0

SOP for Troubleshooting Analytical Methods Developed in the AMD Department


Department Analytical Method Development
SOP No. SOP/AMD/026/2025
Supersedes SOP/AMD/026/2022
Page No. Page 1 of 15
Issue Date 19/05/2025
Effective Date 20/05/2025
Review Date 19/05/2026

1. Purpose

This SOP provides a systematic procedure for troubleshooting analytical methods that have been developed within the Analytical Method Development (AMD) department. The goal is to identify root causes of method-related failures or inconsistencies and implement corrective actions while maintaining data integrity and regulatory compliance.

2. Scope

This SOP applies to all analytical methods developed in the AMD department for drug substances, intermediates, and drug products that encounter issues during method development, validation, technology transfer, or routine application.

3. Responsibilities

See also  Analytical Method Development: Archiving Method Development Reports - V 2.0

4. Accountability

The Head of AMD is accountable for ensuring that analytical method issues are resolved scientifically and documented thoroughly, maintaining compliance with ICH, WHO, and GMP guidelines.

5. Procedure

5.1 Identification of Method Issue

  1. Issues may be reported by analysts, validation teams, or QC during:
    • Development trials
    • System suitability failures
    • Reproducibility concerns
    • Unexpected peak behavior (ghost peaks, co-elution)
  2. Record the issue in Annexure-1: Method Issue Reporting Form.

5.2 Preliminary Review

  1. Review relevant documents:
    • Method development report
    • Chromatograms/spectra
    • Raw data logs
  2. Interview analyst and review instrument calibration, column history, mobile phase prep, and standard solution handling.

5.3 Root Cause Analysis (RCA)

  1. Apply structured tools such as:
    • Ishikawa (Fishbone) Diagram
    • 5 Whys
    • Cause-Effect Matrix
  2. Categorize probable root causes into:
    • Method design-related
    • Instrument-related
    • Sample/standard preparation errors
    • Environmental factors
  3. Document findings in Annexure-2: RCA Worksheet.
See also  Analytical Method Development: Use of Design of Experiments (DoE) in Method Development - V 2.0

5.4 Corrective Actions

  1. Depending on root cause, perform actions such as:
    • Re-prepare mobile phase/standard
    • Replace column or filter
    • Adjust flow rate, injection volume, or gradient program
    • Use different buffer/salt/solvent
  2. Perform method modifications only after QA and HOD review and approval.
  3. Document outcomes in Annexure-3: Corrective Action Log.

5.5 Verification of Resolution

  1. Repeat system suitability runs and recovery tests using adjusted method.
  2. Ensure RSD, retention time, and resolution are within expected ranges.
  3. Attach evidence to Annexure-4: Troubleshooting Resolution Summary.

5.6 Change Control and Documentation

  1. If method parameters are revised:
    • Initiate change control
    • Update method version and method report
    • Perform partial or full revalidation if applicable
  2. Submit all annexures and investigation report to QA for closure and archiving.

6. Abbreviations

7. Documents

  1. Method Issue Reporting Form – Annexure-1
  2. RCA Worksheet – Annexure-2
  3. Corrective Action Log – Annexure-3
  4. Troubleshooting Resolution Summary – Annexure-4
See also  Analytical Method Development: Preparation of Method Development Protocol - V 2.0

8. References

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 Issue Reporting Form

Date Reported By Method ID Issue Description
14/05/2025 Ajay Mehra HPLC/AMD/078 Baseline drift observed post 6 minutes

Annexure-2: RCA Worksheet

Cause Category Details RCA Tool Used Root Cause Identified
Mobile Phase Old buffer used 5 Whys Buffer degradation

Annexure-3: Corrective Action Log

Corrective Step Performed By Date Remarks
Prepared fresh buffer with new lot Sunita Reddy 15/05/2025 Baseline stabilized

Annexure-4: Troubleshooting Resolution Summary

Parameter Before After Status
%RSD 4.8% 1.6% Resolved
Baseline Drift Yes No Resolved

Revision History:

Revision Date Revision No. Details Reason Approved By
04/05/2025 2.0 Added annexures and structured RCA process GMP audit recommendation
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