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A Forced Degradation Study: Overview of Stress – Testing Program

Fidelta introduces a generic approach for conducting stress testing on drug substances and drug products.

The established strategy is evaluated and verified according to the regulatory guidance documents (ICH guidelines, FDA Guidance for Industry, FDA Reviewer Guidance, European Pharmacopoeia, etc.), with emphasis on what should be considered during early development as well as for late-clinical phases and for registration application dossiers. Stress testing of the drug substance can help identify the likely degradation products, which examination can be useful in establishing degradation pathways, the intrinsic stability of the molecule and validate the stability-indicating potential of analytical method used.

This results could be helpful by generation of more stable formulations and can be used for development of manufacturing processes or to select proper packaging and conditions for long-term storage.

Forced Degradation Study Design

Stability-stress testing will be performed in different pH environment, in the presence of oxygen and ID65 light and at elevated levels of temperatures and humidity, in a solid form and / or in solution.

 

The observed degradation is classified into three categories: minor degradation of the main compound lead to degradation not more than 1 area%, moderate degradation of the main compound lead to degradation between 1 – 10 area% and significant degradation with more than 10 area% degradation of the main compound.

Testing of samples will be performed at defined sampling points using specific developed stability-indicative analytical method. All degradation products and impurities ≥ 0.1 area% will be considered in summarized overview of results.

Isolation and identification of degradation products by means of NMR spectroscopy, high resolution mass spectrometry (HRMS) and multiple stage mass spectrometry (MSn) can be performed at request.

Conclusion

Forced degradation is one of the biggest challenges of early method development; critical and selective leading of the study and understanding of mechanisms will be greatly rewarded in the efficiency of your further drug substance or drug product development.

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