Q2(R1), GMP, and regulatory expectations.

2. Scope

This SOP applies to the Analytical Method Development (AMD) team responsible for establishing test procedures including identification, assay, related substances, residual solvents, and physicochemical tests for APIs used in research, development, and commercial batches.

3. Responsibilities

• AMD Scientist: Designs and performs method development experiments based on literature review and API properties.
• Team Leader: Reviews developmental data and approves optimized test parameters.
• QA Department: Verifies adherence to protocol and documentation standards.
• Head – AMD: Provides final authorization for the developed test procedure.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring that all API test procedures are scientifically sound, documented properly, and validated according to applicable regulatory guidelines.

5. Procedure

5.1 Understanding the API Profile

1. Collect the following data for the API:
   • Chemical structure, molecular weight
   • pKa, solubility, and logP
   • UV absorption, stability profile
   • Impurity profile and known degradants
2. Record API attributes in Annexure-1: API Profile Sheet.

5.2 Literature and Regulatory Review

1. Review literature, pharmacopoeias (USP, IP, BP), and previously validated methods.
2. Summarize existing analytical techniques, conditions, and parameters for similar molecules.
3. Document findings in Annexure-2: Reference Summary Log.

5.3 Experimental Design for Method Development

1. Design method development experiments based on:
   • Chromatographic technique (e.g., HPLC, GC)
   • Sample and standard preparation procedures
   • Selection of mobile phase, column, and detection wavelength
2. Ensure evaluation of peak purity, resolution, retention time, tailing factor, and plate count.

5.4 Optimization of Test Parameters

1. Optimize based on system suitability and robustness:
   • Buffer pH, ionic strength, gradient programs
   • Injection volume and flow rate
   • Detection wavelength
2. Document optimized parameters in Annexure-3: Method Optimization Log.

5.5 Drafting of Test Procedure

1. Prepare draft test procedure covering:
   • Purpose
   • Scope
   • Principle of method
   • Equipment and chemicals required
   • System suitability criteria
   • Stepwise procedure for standard and sample preparation
   • Calculation formula
2. Use Annexure-4: Draft Test Format for initial documentation.

5.6 Internal Review and Approval

1. Submit the draft to the AMD Team Lead for review.
2. Incorporate corrections and finalize the document.
3. Obtain QA review and Head – AMD approval before use.

5.7 Method Transfer and Validation Readiness

1. Once approved, initiate method transfer to Quality Control (QC) for verification or validation.
2. Ensure validation protocols are aligned with ICH Q2 requirements (specificity, precision, linearity, range, accuracy, robustness, LOD, LOQ).

5.8 Documentation and Archival

1. Store final version of the test procedure in the AMD document control system.
2. Ensure backups are maintained and version history is traceable.
3. File supporting development data with traceable links to project ID and molecule name.

6. Abbreviations

• API: Active Pharmaceutical Ingredient
• AMD: Analytical Method Development
• LOD: Limit of Detection
• LOQ: Limit of Quantitation
• HPLC: High-Performance Liquid Chromatography
• QA: Quality Assurance
• QC: Quality Control

7. Documents

1. API Profile Sheet – Annexure-1
2. Reference Summary Log – Annexure-2
3. Method Optimization Log – Annexure-3
4. Draft Test Format – Annexure-4

8. References

• ICH Q2(R1) – Validation of Analytical Procedures
• Pharmacopoeial Standards (USP, IP, BP)
• WHO GMP Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: API Profile Sheet

API Name	Molecular Weight	Solubility	pKa	LogP
Metformin HCl	165.63	Water soluble	12.4	-1.43

Annexure-2: Reference Summary Log

Source	Title	Year	Reviewed By
USP 43	Metformin Monograph	2022	Sunita Reddy
PubMed	HPLC Method for Metformin Impurity Profiling	2021	Rajesh Kumar

Annexure-3: Method Optimization Log

Date	Parameter Adjusted	Final Value	Observed Effect	Performed By
11/04/2025	Flow Rate	1.0 mL/min	Improved resolution	Ajay Mehra

Annexure-4: Draft Test Format

Section	Description
System Suitability	RSD of standard injections ≤ 2%, resolution between peaks ≥ 2.0
Sample Preparation	Dissolve 100 mg in 100 mL diluent, filter, inject 10 µL
Calculation	% Assay = (Sample area / Standard area) × Std weight / Sample weight × 100

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Expanded method documentation and optimization log format	Audit observation