Guidelines for Creating Stability-Indicating Methods as per ICH Q2(R1)

1) Purpose

The purpose of this Standard Operating Procedure (SOP) is to outline the process for developing and validating a stability-indicating method for drug substances and drug products in accordance with the ICH Q2(R1) guidelines. This SOP ensures that the method developed is capable of accurately detecting stability-related changes over time.

2) Scope

This SOP applies to all personnel involved in the development, validation, and application of analytical methods for stability testing of drug substances and drug products.

3) Responsibilities

Analytical Development Team: Responsible for developing and validating stability-indicating methods according to ICH Q2(R1) guidelines.

Quality Assurance (QA) Team: Responsible for reviewing and approving method validation reports and ensuring compliance with regulatory requirements.

Regulatory Affairs Team: Responsible for ensuring the stability-indicating method meets the requirements of target markets.

4) Procedure

4.1 Method Development

4.1.1 Define the objectives for developing a stability-indicating method,

including the specific analytes, degradation products, and matrix components to be tested.

4.1.2 Conduct a literature review to identify existing methods and potential analytical techniques suitable for the target analytes.

4.1.3 Develop a preliminary method using appropriate analytical techniques (e.g., HPLC, GC, UV-Vis spectroscopy) and optimize the parameters to achieve the desired sensitivity, selectivity, and accuracy.

4.2 Method Validation

4.2.1 Validate the method according to the ICH Q2(R1) guidelines, covering parameters such as specificity, linearity, accuracy, precision, limit of detection (LOD), limit of quantitation (LOQ), robustness, and stability.

4.2.2 Perform forced degradation studies to confirm that the method is stability-indicating and can separate degradation products from the active ingredient.

4.2.3 Compile a validation report documenting all results, calculations, and conclusions, and submit it to the QA Team for review.

5) Abbreviations, if any

ICH: International Council for Harmonisation
HPLC: High-Performance Liquid Chromatography
GC: Gas Chromatography
UV-Vis: Ultraviolet-Visible Spectroscopy
QA: Quality Assurance
LOD: Limit of Detection
LOQ: Limit of Quantitation

6) Documents, if any

Method development records, method validation report, validation protocol, analytical data sheets.

7) Reference, if any

ICH Q2(R1): Validation of Analytical Procedures: Text and Methodology.

8) SOP Version

Version 1.0