Procedure for Identifying Degradation Pathways in Stability Studies

1) Purpose

The purpose of this SOP is to provide a standardized procedure for identifying degradation pathways of drug products through stability studies. Understanding these pathways helps in determining the causes of degradation and developing strategies to enhance product stability.

2) Scope

This SOP applies to all drug products that require stability studies to identify their degradation pathways. It is relevant for personnel in quality control, research and development, and regulatory affairs departments.

3) Responsibilities

The responsibilities for determining degradation pathways in stability studies are as follows:

• Quality Control Team: To perform stability tests and document results to identify degradation products.
• R&D Team: To analyze the degradation data and determine possible degradation pathways.
• Regulatory Affairs Team: To ensure compliance with regulatory guidelines during degradation analysis.
• Stability Study Coordinator: To manage testing schedules, sample management, and data analysis.

4) Procedure

The detailed stepwise procedure for identifying

degradation pathways in stability studies is outlined below:

1. Preparation of Stability Study Protocol:
1. 4.1 Define the purpose, scope, and objective of the stability study for identifying degradation pathways.
2. 4.2 Identify the drug product and critical quality attributes (CQAs) to be monitored.
3. 4.3 Determine the stress conditions to be tested (e.g., temperature, humidity, light, oxidation).
4. 4.4 Establish the time points for testing under each condition.
5. 4.5 Develop a protocol outlining procedures, equipment, and materials required for testing.
2. Sample Preparation and Storage:
1. 4.6 Select representative samples of the drug product for testing.
2. 4.7 Prepare and store samples under specified stress conditions in stability chambers or other controlled environments.
3. Testing and Monitoring:
1. 4.8 Retrieve samples at specified time points and perform the required tests (e.g., assay, degradation products, dissolution).
2. 4.9 Record all test results in a stability testing log sheet.
3. 4.10 Evaluate the results against predefined acceptance criteria.
4. Data Analysis and Interpretation:
1. 4.11 Analyze the degradation data to identify possible degradation products.
2. 4.12 Use advanced analytical techniques (e.g., HPLC, mass spectrometry) to determine degradation pathways.
3. 4.13 Document the identified degradation pathways and their impact on product stability.
5. Documentation and Reporting:
1. 4.14 Compile a comprehensive report detailing the degradation pathways, methods used, and conclusions drawn.
2. 4.15 Ensure the report is reviewed and approved by relevant stakeholders.
3. 4.16 Submit the report to regulatory bodies or internal stakeholders as required.
6. Review and Update:
1. 4.17 Regularly review the degradation pathway analysis protocol and update it based on new data or regulatory changes.
2. 4.18 Archive the approved protocol and report in a controlled document management system.

5) Abbreviations, if any

• CQA: Critical Quality Attribute
• HPLC: High-Performance Liquid Chromatography

6) Documents, if any

• Degradation Pathway Analysis Report
• Stability Testing Log Sheets
• Analytical Method Validation Reports

7) Reference, if any

• ICH Q1A(R2): Stability Testing of New Drug Substances and Products

8) SOP Version

Version 1.0