validated appropriately, and aligned with regulatory expectations.

2. Scope

This SOP applies to all non-pharmacopoeial (in-house or custom) test methods used for active pharmaceutical ingredients (APIs), excipients, intermediates, and finished products, including chemical, physical, or instrumental procedures.

3. Responsibilities

• Analytical Scientist: Develops and justifies the need for a non-pharmacopoeial method; documents all method parameters and supporting data.
• Team Lead: Reviews technical feasibility, robustness, and scientific rationale.
• QA: Ensures documentation compliance and validation readiness.
• Regulatory Affairs: Verifies global filing acceptability and compendial deviation handling.
• Head – AMD: Approves method and coordinates validation pathway.

4. Accountability

The Head of AMD is accountable for ensuring that all non-pharmacopoeial methods follow scientific and regulatory justification and that their development, use, and validation are appropriately documented and traceable.

5. Procedure

5.1 Identification and Justification

1. Determine the necessity for a non-pharmacopoeial method when:
   • No suitable compendial method exists
   • Compendial method does not meet specificity/selectivity
   • Innovative formulation/excipient requires alternate detection
2. Document rationale using Annexure-1: Non-Pharmacopoeial Method Justification Form.

5.2 Method Development

1. Use standard method development protocols as per SOP/AMD/013/2025.
2. Define:
   • Detection technique
   • Critical method parameters (e.g., pH, temperature, wavelength, flow)
   • Acceptance criteria based on scientific rationale
3. Document complete development results in Annexure-2: Development Summary Sheet.

5.3 Risk Assessment and Feasibility

1. Conduct method risk assessment (e.g., fishbone diagram or FMEA).
2. Evaluate robustness through controlled variations.
3. Record in Annexure-3: Risk Assessment Log.

5.4 Validation Readiness and Approval

1. Submit data to Team Lead and QA for review using Annexure-4: Validation Readiness Checklist.
2. Upon successful review, proceed to validation protocol drafting per ICH Q2(R2)/Q14 guidelines.
3. Obtain method approval using Annexure-5: Method Approval Record.

5.5 Change Control and Regulatory Communication

1. For changes to compendial procedures:
   • Initiate change control with supporting data
   • Inform Regulatory Affairs for variation submission or justification
2. Cross-reference pharmacopoeial monographs and justification in regulatory filings or dossiers.

5.6 Control and Archival

1. Store original method development records and annexures in the AMD central archive.
2. Record method details in the Non-Pharmacopoeial Method Master List.

6. Abbreviations

• AMD: Analytical Method Development
• QA: Quality Assurance
• ICH: International Council for Harmonisation
• FMEA: Failure Mode and Effects Analysis
• API: Active Pharmaceutical Ingredient

7. Documents

1. Non-Pharmacopoeial Method Justification Form – Annexure-1
2. Development Summary Sheet – Annexure-2
3. Risk Assessment Log – Annexure-3
4. Validation Readiness Checklist – Annexure-4
5. Method Approval Record – Annexure-5

8. References

• ICH Q14 – Analytical Procedure Development
• ICH Q2(R2) – Validation of Analytical Procedures
• WHO TRS 996 – Good Practices for Pharmaceutical Quality Control Laboratories
• USP General Chapter <1225> – Validation of Compendial Procedures

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Non-Pharmacopoeial Method Justification Form

Product	Test	Reason for Custom Method	Approved By
Levocetirizine	Assay	Ph. Eur. method not stability-indicating	Sunita Reddy

Annexure-2: Development Summary Sheet

Trial Date	Conditions	Outcome	Conclusion
05/05/2025	C18, 250 mm, pH 4.5 buffer	Good resolution	Selected for validation

Annexure-3: Risk Assessment Log

Parameter	Risk	Impact	Control Strategy
Column batch change	Medium	Peak shift	Monitor RT window ±2%

Annexure-4: Validation Readiness Checklist

Requirement	Status	Remarks
Robustness data	Yes	Submitted in development report
LOD/LOQ	Yes	Estimated via calibration curve

Annexure-5: Method Approval Record

Method Code	Approved By	Date	Remarks
NP/AMD/LC/058	Dr. Vinay Pawar	15/05/2025	Ready for validation

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Annexures expanded; ICH Q14 integration	Regulatory alignment