How to do the forced degradation test of medical devices?

What should be done for stress degradation test? How to perform the specific operation details? What are the specific steps to establish a stability indicator method that meets FDA requirements? This is a question that many quality researchers want to understand. The article development of forced degradation and stability indicating studies of drugs-a review gives the answer.

1. Preface

The chemical stability of drug molecules is a very important issue, because it will affect the safety and effectiveness of drug products. Understanding the molecular stability is helpful to choose the appropriate formula and packaging, and to provide the appropriate storage conditions and expiration date. Forced degradation test is a method to study the degradation pathway and degradation products of drugs under more severe conditions than accelerated test conditions, so as to determine the chemical stability of molecules. ICH guidelines state that stress degradation tests are designed to identify potential degradation products, establish degradation pathways, clarify the chemical stability of molecules, and verify the selected stability indicator method (1). However, these guidelines are only a general discussion, and do not provide the details of the specific operation.

In the new drug application, it is required to submit the stability data of long-term test (12 months), accelerated test (6 months) or intermediate conditions (6 months), so it will take a long time for the separation, identification and quantitative research of degradation impurities. In the forced degradation test, degradation impurities can be produced in a short time, such as a few weeks, which is helpful to the study of impurities. Stress degradation test can be used to develop stability indicator method for accelerating long-term test. In this paper, some important suggestions on the design of stress degradation test and its application in the development of stability indicator method are put forward, which are worth learning and thinking.

2. What is the purpose of stress degradation test?

Establishment of degradation pathway of API and preparation

Distinguish between formulation related and unrelated degradation products

Clarify the structure of degradation products

To determine the internal stability of the API in the prescription

To reveal the degradation mechanism of raw materials and preparations such as hydrolysis, oxidation, pyrolysis or photolysis (1,2)

Establish stability indicator method

Understand the chemical properties of drug molecules

Identify more stable prescriptions

A degradation impurity mass spectrum similar to ICH official stability test was generated

Solving problems in stability test (3)

3. When was the forced degradation test conducted