SOP for Handling Non-Pharmacopoeial Test Methods in Analytical Method Development
| Department | Analytical Method Development |
|---|---|
| SOP No. | SOP/AMD/028/2025 |
| Supersedes | SOP/AMD/028/2022 |
| Page No. | Page 1 of 14 |
| Issue Date | 19/05/2025 |
| Effective Date | 20/05/2025 |
| Review Date | 19/05/2026 |
1. Purpose
This SOP outlines the procedure for development, evaluation, justification, and approval of non-pharmacopoeial test methods within the Analytical Method Development (AMD) department. It ensures that such methods are scientifically sound, 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
- 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
- Document rationale using Annexure-1: Non-Pharmacopoeial Method Justification Form.
5.2 Method Development
- Use standard method development protocols as per SOP/AMD/013/2025.
- Define:
- Detection technique
- Critical method parameters (e.g., pH, temperature, wavelength, flow)
- Acceptance criteria based on scientific rationale
- Document complete development results in Annexure-2: Development Summary Sheet.
5.3 Risk Assessment and Feasibility
- Conduct method risk assessment (e.g., fishbone diagram or FMEA).
- Evaluate robustness through controlled variations.
- Record in Annexure-3: Risk Assessment Log.
5.4 Validation Readiness and Approval
- Submit data to Team Lead and QA for review using Annexure-4: Validation Readiness Checklist.
- Upon successful review, proceed to validation protocol drafting per ICH Q2(R2)/Q14 guidelines.
- Obtain method approval using Annexure-5: Method Approval Record.
5.5 Change Control and Regulatory Communication
- For changes to compendial procedures:
- Initiate change control with supporting data
- Inform Regulatory Affairs for variation submission or justification
- Cross-reference pharmacopoeial monographs and justification in regulatory filings or dossiers.
5.6 Control and Archival
- Store original method development records and annexures in the AMD central archive.
- 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
- Non-Pharmacopoeial Method Justification Form – Annexure-1
- Development Summary Sheet – Annexure-2
- Risk Assessment Log – Annexure-3
- Validation Readiness Checklist – Annexure-4
- 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 |