to ensure drug safety, efficacy, and regulatory compliance over shelf-life.

2. Scope

This SOP applies to all stability indicating assay method development and validation activities performed in the Analytical Method Development (AMD) department for both API and finished dosage forms intended for regulatory submission and ongoing stability studies.

3. Responsibilities

• Analyst: Performs forced degradation studies, develops the chromatographic method, and documents procedures and results.
• Method Development Scientist: Designs method development strategy and oversees system optimization.
• QA Personnel: Reviews documentation, ensures GDP compliance, and approves method reports.
• Validation Team: Validates the developed method as per ICH guidelines.

4. Accountability

The Head of Analytical Method Development is accountable for the scientific integrity, compliance, and regulatory suitability of all stability indicating methods developed under this SOP.

5. Procedure

5.1 Pre-requisite Evaluation

1. Review API structure, known degradation pathways, and prior analytical data if available.
2. Define method objective: assay, related substances, impurity profiling, etc.
3. Procure qualified reference standards and required reagents with COA.

5.2 Forced Degradation Studies

1. Subject API and/or formulation to stress conditions as per ICH Q1A (R2):
• Thermal (60°C or higher)
• Photolytic (UV 254/366 nm)
• Acid/base hydrolysis (0.1N HCl/NaOH)
• Oxidative degradation (3-6% H₂O₂)
• Humidity (75% RH)
2. Collect time-point samples and store under controlled conditions.
3. Analyze to determine degradant profile and extent of degradation.

5.3 Chromatographic Method Development

1. Select appropriate technique: HPLC/UPLC with UV/PDA/ELSD detectors.
2. Evaluate various stationary phases (e.g., C8, C18, Phenyl) and mobile phase systems (buffered aqueous + organic solvents).
3. Optimize method for resolution (Rs > 2) between API and all degradants.
4. Ensure peak purity using PDA and system suitability compliance.
5. Perform specificity test to confirm separation from placebo and excipients.

5.4 Method Optimization

1. Optimize key parameters: flow rate, injection volume, pH, gradient profile, and detection wavelength.
2. Demonstrate method reproducibility and robustness under variable conditions.

5.5 Documentation

1. Prepare detailed method development summary including:
   • Objective
   • Forced degradation results
   • Chromatographic conditions
   • Optimization rationale
2. Attach representative chromatograms, peak purity reports, and degradation profiles.

5.6 Validation

1. Submit the method for validation as per ICH Q2(R1): specificity, accuracy, precision, linearity, range, robustness, LOD, LOQ.
2. Maintain validation protocol and summary report in validated templates (see Annexures).

6. Abbreviations

• API: Active Pharmaceutical Ingredient
• PDA: Photodiode Array
• LOD: Limit of Detection
• LOQ: Limit of Quantitation
• HPLC: High-Performance Liquid Chromatography

7. Documents

1. Method Development Worksheet – Annexure-1
2. Forced Degradation Summary Template – Annexure-2
3. Chromatographic Condition Log Sheet – Annexure-3
4. Validation Protocol Template – Annexure-4

8. References

• ICH Q1A(R2) – Stability Testing of New Drug Substances
• ICH Q2(R1) – Validation of Analytical Procedures
• WHO TRS 1010 Annex 4 – Development of Stability Indicating Methods
• FDA Guidance for Industry – Analytical Procedures and Methods Validation

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Vikas Mehra	Priya Nair	Dr. Harshita Goyal
Designation	Method Development Scientist	QA Reviewer	Head – AMD
Department	Analytical Method Development	Quality Assurance	Analytical Method Development

11. Annexures

Annexure-1: Method Development Worksheet

Includes input sections for objective, trial parameters, results, observations, chromatographic systems, peak evaluation, and resolution factors.

Annexure-2: Forced Degradation Summary Template

Condition	Time	% Degradation	Degradants Identified
0.1N HCl, 60°C	4 hours	12%	D1, D2
3% H2O2	2 hours	9%	D3

Annexure-3: Chromatographic Condition Log Sheet

Records buffer composition, pH, solvent ratio, column type, flow rate, detection wavelength, and run time for each successful trial.

Annexure-4: Validation Protocol Template

Structured format including validation parameters, criteria, sample preparation strategy, number of replicates, acceptance criteria, and summary template.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/06/2025	2.0	Updated protocol alignment with latest ICH guidance	Annual Review	Dr. Harshita Goyal
10/08/2022	1.0	Initial issue	New SOP	QA Head