Q2(R2).

2. Scope

This SOP applies to all drug substances and products undergoing analytical method development in the AMD department. It includes procedures for testing under stress conditions such as acid/base hydrolysis, oxidation, thermal, photolytic, and humidity exposure.

3. Responsibilities

• Analytical Scientist: Designs and executes forced degradation studies and analyzes results.
• Stability Analyst: Handles stressed samples and performs chromatographic evaluations.
• QA Officer: Reviews documentation and compliance with protocol and ICH requirements.
• Head – AMD: Approves the method’s classification as stability-indicating.

4. Accountability

The Head of AMD is accountable for ensuring that methods used in stability testing meet regulatory standards for indicating degradation and do not compromise product quality assurance.

5. Procedure

5.1 Forced Degradation Study Design

1. Develop and approve a forced degradation protocol covering the following stress conditions:
   • Acid and base hydrolysis (e.g., 0.1N HCl/NaOH at 60°C)
   • Oxidative stress (e.g., 3% H₂O₂)
   • Thermal stress (e.g., 80°C dry heat)
   • Photolytic exposure (as per ICH Q1B)
   • Humidity (e.g., 90% RH at 25–40°C)
2. Ensure targeted degradation is between 5% and 20% of the API.

5.2 Sample Analysis

1. Analyze both stressed and unstressed samples using the proposed method.
2. Use PDA or mass spectrometry to assess peak purity.
3. Ensure degradants are well-resolved from the main API peak (Rs ≥ 2.0).

5.3 Specificity Assessment

1. Inject blank, placebo, and degradation samples.
2. Confirm no interference at API or impurity peaks.
3. Document chromatographic overlays in Annexure-1: Specificity Report.

5.4 Peak Purity Evaluation

1. Use PDA detection or spectral scanning to determine purity angle and purity threshold.
2. Ensure purity angle is less than purity threshold for API peak in all stressed conditions.

5.5 Conclusion and Documentation

1. Prepare a report summarizing:
   • Degradation profiles and chromatograms
   • Resolution factors
   • Peak purity analysis
   • Specificity conclusion
2. Include summary in Annexure-2: Stability-Indicating Conclusion Report.
3. Obtain QA and departmental approval.

6. Abbreviations

• PDA: Photodiode Array Detector
• API: Active Pharmaceutical Ingredient
• Rs: Resolution
• SOP: Standard Operating Procedure
• AMD: Analytical Method Development

7. Documents

1. Specificity Report – Annexure-1
2. Stability-Indicating Conclusion Report – Annexure-2

8. References

• ICH Q1A(R2) – Stability Testing of New Drug Substances and Products
• ICH Q2(R2) – Validation of Analytical Procedures
• ICH Q1B – Photostability Testing of New Drug Substances and Products

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Specificity Report

Sample Type	Retention Time (API)	Interference Observed	Conclusion
Blank	—	No	Specific
Placebo	—	No	Specific
Stressed Sample	5.8	No	Specific

Annexure-2: Stability-Indicating Conclusion Report

Condition	% Degradation	Resolution	Peak Purity Status	Conclusion
Oxidation	12.4	2.5	Pass	Stability-Indicating
Thermal	8.9	2.2	Pass	Stability-Indicating

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Updated acceptance criteria for peak purity and added resolution factor threshold	Audit preparedness and regulatory compliance