under elevated temperature conditions and support the development of stability-indicating methods in compliance with ICH Q1A(R2).

2. Scope

This SOP is applicable to all solid, semi-solid, and liquid pharmaceutical substances and finished dosage forms tested within the Analytical Method Development (AMD) department to determine thermal sensitivity during method development and forced degradation assessment.

3. Responsibilities

• Analytical Scientist: Prepares the thermal degradation protocol and oversees the design of the method.
• Lab Analyst: Executes degradation under defined thermal conditions and performs data recording and analysis.
• QA Officer: Reviews compliance, chromatograms, and documentation for integrity and completeness.
• Head – AMD: Approves degradation reports and final method for regulatory use.

4. Accountability

The Head of AMD is accountable for ensuring thermal degradation studies are performed as per ICH and internal regulatory protocols and are scientifically robust and reproducible.

5. Procedure

5.1 Study Protocol Development

1. Prepare a protocol detailing:
   • API/formulation name and batch number
   • Sample form (powder, solution, suspension, etc.)
   • Temperature(s), exposure time, and sample quantity
   • Analytical method(s) and sample processing details
2. Route protocol through QA review and AMD head approval.

5.2 Thermal Stress Conditions

1. Expose sample in:
   • Hot air oven: 60°C, 80°C, or 105°C for 24–72 hours
   • Water bath: 60°C for solution-based formulations
2. Protect control sample by storing in ambient conditions.
3. Use open or loosely closed containers to avoid internal pressure buildup.

5.3 Sampling and Processing

1. After defined time intervals (e.g., 24h, 48h, 72h), withdraw aliquots of samples.
2. Dissolve or dilute as per validated test method (typically using mobile phase).
3. Filter through 0.45 µm PVDF membrane prior to analysis.

5.4 Analytical Evaluation

1. Analyze test and control samples by validated HPLC or UPLC method.
2. Compare:
   • Assay result (%)
   • Presence of degradation peaks
   • Peak purity using PDA detector
3. Log results in Annexure-1: Thermal Degradation Data Sheet.

5.5 Data Interpretation and Acceptance

1. Degradation between 5% to 20% is considered suitable to demonstrate method capability.
2. No co-elution with the main API peak is acceptable.
3. Document specific degradants and retention times if observed.

6. Abbreviations

• API: Active Pharmaceutical Ingredient
• HPLC: High-Performance Liquid Chromatography
• PDA: Photodiode Array
• SOP: Standard Operating Procedure
• AMD: Analytical Method Development

7. Documents

1. Thermal Degradation Data Sheet – Annexure-1

8. References

• ICH Q1A(R2) – Stability Testing of New Drug Substances and Products
• ICH Q2(R2) – Validation of Analytical Procedures
• FDA Guidance – 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: Thermal Degradation Data Sheet

Sample ID	Temp (°C)	Time (hrs)	Assay (%)	% Degradation	New Peaks	Conclusion
API-TD-011	80	48	88.3	11.7	Yes	Thermally Labile

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Included use of water bath for liquid formulations and clarified container requirements	Scope enhancement