Standard Operating Procedure for Stability Testing of API Batches
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/130/2025 |
| Supersedes | SOP/API/130/2022 |
| Page No. | Page 1 of 9 |
| Issue Date | 13/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 13/04/2026 |
1. Purpose
To define the procedure for conducting stability testing of Active Pharmaceutical Ingredient (API) batches to assess product integrity over time and establish or confirm shelf-life in accordance with ICH Q1 guidelines.
2. Scope
This SOP applies to all Quality Control and Quality Assurance personnel involved in the planning, execution, evaluation, and documentation of stability studies for development, validation, and commercial batches of APIs.
3. Responsibilities
- QC Analyst: Perform stability sample testing as per defined intervals and STP.
- QA Officer: Monitor storage conditions and maintain stability chambers.
- Stability Coordinator: Maintain inventory, pull schedules, and data compilation.
- QC Reviewer: Verify results and compile interim and final stability reports.
4. Accountability
The Head – Quality is accountable for the scientific justification, regulatory compliance, and execution of the stability program for API batches.
5. Procedure
5.1 Study Design
- Refer to ICH Q1A(R2) and ICH Q1E for designing stability protocols.
- Include:
- Study type (accelerated, long-term, intermediate)
- Storage conditions (25°C/60% RH, 30°C/65% RH, 40°C/75% RH)
- Testing intervals (e.g., 0, 3, 6, 9, 12, 18, 24 months)
- Specifications to be monitored (appearance, assay, impurities, moisture content, etc.)
5.2 Sample Storage
- Stability samples must be:
- Representative of production batches
- Packed in containers that simulate market packaging
- Labeled with unique stability ID, batch number, storage condition, and interval schedule
- Place samples in qualified stability chambers monitored continuously using calibrated temperature and humidity sensors.
5.3 Testing Procedure
- At each interval, withdraw samples per schedule and perform testing as per STP.
- Ensure all tests are conducted within ±5 days of the scheduled interval date.
- Use validated analytical methods and retain all chromatograms and raw data for review.
- Document observations such as color change, precipitation, or odor.
5.4 Data Compilation and Evaluation
- Compare results against acceptance criteria and note any trends.
- Prepare interim reports after each interval and a comprehensive report at the end of the study.
- Include graphical trends for key parameters (e.g., assay, impurity).
5.5 Out-of-Trend or OOS Results
- If any OOT or OOS result is observed:
- Notify QA immediately
- Initiate deviation/investigation
- Conduct root cause analysis
- Evaluate impact on shelf-life and future batches
5.6 Record Keeping and Archival
- All stability data, test records, and reports must be retained for at least 5 years post expiry of the batch.
- Ensure electronic and physical copies are secured and backed up.
6. Abbreviations
- API: Active Pharmaceutical Ingredient
- STP: Standard Test Procedure
- OOS: Out of Specification
- OOT: Out of Trend
- ICH: International Council for Harmonisation
- RH: Relative Humidity
7. Documents
- Stability Protocol
- Stability Sample Inventory Log (Annexure-1)
- Stability Pull and Testing Log (Annexure-2)
- Stability Reports
8. References
- ICH Q1A(R2) – Stability Testing of New Drug Substances and Products
- ICH Q1E – Evaluation of Stability Data
- 21 CFR Part 211 – US FDA cGMP
- WHO Technical Report Series 1010
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Stability Sample Inventory Log
| Date | Stability ID | Batch No. | Condition | Container Qty | Initial Weight |
|---|---|---|---|---|---|
| 13/04/2025 | STB-API-001 | API-20250413 | 25°C/60% RH | 10 | 500 g |
Annexure-2: Stability Pull and Testing Log
| Date | Stability ID | Interval | Tests Performed | Analyst | Reviewed By |
|---|---|---|---|---|---|
| 13/07/2025 | STB-API-001 | 3 Months | Assay, Impurity | Sunita Reddy | Rajesh Kumar |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial Release | Regulatory Requirement | QA Head |
| 13/04/2025 | 2.0 | Inclusion of pull log and OOT section | Audit Observation | QA Head |