Forced degradation testing studies

Forced degradation testing studies are those undertaken to degrade the sample deliberately. These studies, which may be undertaken in the development phase normally on the drug substances, are used to evaluate the overall photosensitivity of the material for method development purposes and/or degradation pathway elucidation. 

The reaction databases let scientists easily and quickly retrieve information about the chemistry of known substances, some of which might be similar to the investigational compounds under study in forced degradation testing. Many of the readers of this book will already be acquainted with these informatics resources on their desktop computers. 

Procedure or forms for investigating, reporting, corrective action Forced degradation/stress studies Material to be tested Conditions Extent of degradation Identification of degradants Switch to ICEI conditions Allowable circumstances Procedure... 

Forced degradation studies are carried out either in the solution state and/or in the solid state. Usually the forced degradation testing is carried out on one batch of drug substance and/or one formulation blend (capsules and tablets). This forced degradation testing should not be part of a formal stability program. 

Recent publications on the topic of stress testing/forced degradation studies reveal that there is still a tremendous variability in the conditions... 

As described in the PhRMA Available Guidance and Best Practices article on forced degradation studies (12), stress testing should include condi-... 

As mentioned in the Introduction, ICH describes two kinds of tests for drug photostability determination (1) forced degradation studies and (2) confirmatory studies . ICH describes two options for light sources for use in confirmatory studies (1). 

Table 1 General Protocol for Forced Degradation Studies (Stress Testing) of Drug Substance and Drug Products...

Some firms are satisfied when no degradation is observed under the chosen forced degradation conditions and consider this evidence that the API is inherently stable. It should be emphasized, however, that the main purpose of forced degradation studies is to generate degradation products, not to test the stability of the product, thus if the conditions initially chosen do not result in degradation, the severity of the conditions (i.e., time, temperature, and/or concentration) should be increased. If the substance does not react because it is insoluble, organic cosolvents should be used to solubilize the material. 

The temperature/humidity conditions used may be more severe than the typical accelerated stability testing conditions in order to generate potential degradation products in a reasonable time. The typical forced degradation conditions include thermolytic, hydrolytic, oxidative, photolytic (in excess of ICH conditions), high pH (alkaline conditions), and low pH (acidic conditions). Outlined in Table 9-25 and Table 9-26 are some solid-state and solution forced degradation studies, respectively, that could be conducted. In the following... 

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