degradants, as per ICH Q1A and Q2(R1).

2. Scope

This SOP applies to all drug substances (APIs) and drug products undergoing analytical method development in the Analytical Method Development (AMD) department for establishing stability-indicating methods.

3. Responsibilities

• Analytical Scientist: Designs and executes forced degradation studies, documents data, and interprets results.
• Team Lead: Reviews degradation profiles and approves stress conditions and duration.
• QA: Verifies compliance of degradation protocols with ICH and internal documentation procedures.
• Head – AMD: Approves final degradation report for submission and reference.

4. Accountability

The Head of AMD is accountable for ensuring forced degradation studies are conducted in a scientifically sound and regulatory-compliant manner and that conclusions are properly justified and documented.

5. Procedure

5.1 Planning and Setup

1. Conduct a literature review and consult pharmacopoeial or internal sources to understand known degradation pathways.
2. Select appropriate stress conditions:
   • Acidic and basic hydrolysis
   • Oxidation
   • Thermal degradation
   • Photolytic degradation
   • Humidity stress (as applicable)
3. Record plan in Annexure-1: Forced Degradation Study Plan.

5.2 Sample Preparation

1. Prepare:
   • API solution
   • Placebo (for formulations)
   • Product solution (where applicable)
2. Use appropriate diluent as per target method and known solubility.
3. Label all samples with stress condition, batch ID, analyst initials, and date.

5.3 Stress Conditions

1. Acid Hydrolysis: Treat sample with 0.1N HCl at 60°C for 2 hours.
2. Base Hydrolysis: Treat with 0.1N NaOH at 60°C for 2 hours.
3. Oxidation: Use 3% hydrogen peroxide at 25°C for 1 hour.
4. Thermal: Expose dry powder to 80°C for 48 hours.
5. Photolytic: Expose to UV light (200 watt hours/m²) for 1.2 million lux hours.
6. Document all stress conditions in Annexure-2: Stress Condition Log.

5.4 Neutralization and Sample Analysis

1. Neutralize acidic or basic samples before injection:
   • Acid stress: Neutralize with equimolar NaOH
   • Base stress: Neutralize with equimolar HCl
2. Filter all samples through 0.45 µm membrane filters.
3. Inject on validated/optimized analytical method (typically HPLC or UPLC).

5.5 Data Interpretation

1. Compare degraded samples to:
   • Blank
   • Placebo
   • Undegraded sample
2. Determine:
   • Extent of degradation (target 5–20%)
   • Peak purity using PDA or mass spec where available
   • Presence of co-eluting degradation products
3. Record observations in Annexure-3: Degradation Profile Summary.

5.6 Reporting and Documentation

1. Compile data including chromatograms, overlays, and tables.
2. Prepare a final report using Annexure-4: Forced Degradation Report Format.
3. Submit report to QA and Head – AMD for final approval.
4. Archive electronically and in physical records with controlled access.

6. Abbreviations

• API: Active Pharmaceutical Ingredient
• HPLC: High-Performance Liquid Chromatography
• PDA: Photodiode Array Detector
• QA: Quality Assurance
• UV: Ultraviolet
• SOP: Standard Operating Procedure

7. Documents

1. Forced Degradation Study Plan – Annexure-1
2. Stress Condition Log – Annexure-2
3. Degradation Profile Summary – Annexure-3
4. Forced Degradation Report Format – Annexure-4

8. References

• ICH Q1A(R2) – Stability Testing of New Drug Substances and Products
• ICH Q2(R1) – Validation of Analytical Procedures
• USP General Chapter <1225> – Validation of Compendial 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 Study Plan

API	Formulation	Study ID	Initiated By	Date
Amlodipine	Tablet	FDS/2025/03	Ajay Mehra	10/04/2025

Annexure-2: Stress Condition Log

Condition	Details	Duration	Temperature	Remarks
Acid	0.1N HCl	2 hr	60°C	Partial degradation observed
Oxidation	3% H2O2	1 hr	RT	Significant degradation

Annexure-3: Degradation Profile Summary

Condition	Degradation (%)	New Peak RT	Peak Purity	Conclusion
Acid	12.5	7.3 min	Pure	Acceptable
Oxidation	28.6	6.9 min	Impure	Requires resolution improvement

Annexure-4: Forced Degradation Report Format

Section	Content Summary
Objective	To evaluate method specificity under stressed conditions
Conditions Applied	Acid, Base, Oxidation, Heat, Light
Results Summary	All major degradants resolved; peak purity established
Conclusion	Method qualifies as stability-indicating

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Expanded stress conditions and updated annexure templates	Regulatory alignment