of analytical methods. The studies help in identifying potential degradation pathways and degradation products.

2. Scope

This SOP applies to all APIs and drug products under development or stability evaluation in the Analytical Method Development (AMD) department. It includes acidic, basic, oxidative, thermal, and photolytic degradation conditions.

3. Responsibilities

• Analytical Scientist: Designs degradation study protocols and monitors study progress.
• Lab Analyst: Executes degradation experiments, samples, and analyzes data.
• QA Officer: Reviews degradation profiles and ensures proper documentation.
• Head – AMD: Approves final degradation reports and ensures regulatory compliance.

4. Accountability

The Head of AMD is accountable for ensuring the forced degradation studies are conducted in accordance with ICH guidelines and support the stability-indicating nature of the analytical method.

5. Procedure

5.1 Preparation of Degradation Study Plan

1. Draft a degradation protocol that includes:
   • List of degradation conditions to be evaluated
   • Concentration of stress agents
   • Sampling time points
   • Analytical method and detection wavelength
2. Review and approve the plan prior to initiation.

5.2 Stress Conditions and Treatment

1. Acid Hydrolysis: Use 0.1N HCl; expose sample for 1–3 hours at 60°C.
2. Base Hydrolysis: Use 0.1N NaOH; treat for 1–3 hours at 60°C.
3. Oxidation: Use 3% H₂O₂; incubate at room temperature for 1–6 hours.
4. Thermal Stress: Expose solid or solution at 80°C for 24–48 hours in a hot air oven.
5. Photolytic Degradation: Expose to UV and visible light (1.2 million lux hours and 200 Wh/m² UV).

5.3 Sample Neutralization and Dilution

1. Neutralize acid/base hydrolyzed samples using appropriate neutralizer (NaOH for acid, HCl for base) prior to analysis.
2. Filter samples using 0.45 µm PVDF filter if required.
3. Dilute samples to required concentration with mobile phase or diluent.

5.4 Analysis and Data Interpretation

1. Analyze each sample using validated HPLC/UPLC/UV method.
2. Record retention time, area, purity, and any new degradation peaks.
3. Compare chromatograms of stressed vs. unstressed samples.
4. Determine percentage degradation; should ideally be between 5%–20% for method suitability.
5. Summarize in Annexure-1: Forced Degradation Summary Report.

5.5 Documentation and Reporting

1. Prepare degradation study report with:
   • Study design and conditions
   • Chromatograms and data tables
   • Conclusion on method specificity and peak purity
2. Review by QA and approval by Head – AMD.

6. Abbreviations

• API: Active Pharmaceutical Ingredient
• HPLC: High-Performance Liquid Chromatography
• UV: Ultraviolet
• SOP: Standard Operating Procedure
• ICH: International Council for Harmonisation

7. Documents

1. Forced Degradation Summary Report – Annexure-1

8. References

• ICH Q1A(R2) – Stability Testing of New Drug Substances and Products
• ICH Q2(R2) – Validation of Analytical Procedures
• 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
Designation
Department

11. Annexures

Annexure-1: Forced Degradation Summary Report

Stress Condition	Reagent/Temp/Time	% Degradation	New Peaks Observed	Remarks
Acid Hydrolysis	0.1N HCl, 60°C, 2 hrs	12.6%	Yes	Complies
Base Hydrolysis	0.1N NaOH, 60°C, 2 hrs	9.8%	No	Complies
Oxidation	3% H₂O₂, RT, 4 hrs	15.2%	Yes	Complies
Thermal	80°C, 48 hrs	6.7%	No	Complies
Photolytic	UV + Visible, 1.2 MLH	8.5%	Yes	Complies

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Updated stress time windows and annexure structure	Annual SOP review and harmonization