Speakers

Presentation Title: The Power of Forced Degradation

Abstract: Forced degradation (FD) studies are intended to increase the rate of chemical degradation or physical change of an active drug substance or drug product under stressed conditions. Such testing is undertaken to elucidate the intrinsic stability of the active (bio-)pharmaceutical ingredient and is part of the drug development process including formulation and packaging. Even though FD studies are performed at relatively harsh conditions within a short time period, the information gathered will provide highly relevant data of the drug substance to predict effects of real time environmental conditions. The experimental conditions of the stress testing will depend on the individual drug substance and the type of drug product involved but should include acid and base hydrolysis, thermal degradation, photolysis, oxidation and may include freeze–thaw cycles(1). There is no specification in regulatory guidelines regarding the conditions of pH, temperature and specific oxidizing agents to be used(2). Moreover, the design of photolysis studies is left to the applicant's discretion although Q1B specifies that the light source should produce combined visible and ultraviolet (UV, 320–400 nm) outputs, and that exposure levels should be justified.


It is encouraged to perform FD studies early in the development during pre-clinical phase or phase I of clinical trial, in order to provide sufficient time for identifying degradants, structure elucidation and eventually fine-tuning of the stress conditions. Performing FD studies at an early stage will facilitate further drug development and reduce the risk for additional costs and loss of time at later stages of the development.


AnaBioTec offers full stress testing of (bio-)pharmaceuticals according ICH guidelines including structure elucidation of degradation products using a LC-UV-HRMS analytical platform. We provide support in all required steps starting at setting up stress testing studies including: elevated temperatures, humidity, oxidation and pH according to Q1A (R2) & photolysis (Q1B), over LC-UV-HRMS development to fully characterize the resulting degradants, to finally establish proposed degradation pathways.





(1)ICH, Final Guidance on Stability Testing of Biotechnological/Biological Products Availability, International Conference on Harmonization. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM073466.pdf, 1996.

(2)ICH Guidance for Industry, Q1B: Photo stability Testing of New Drug Substances and Product, International Conference on Harmonization. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073373.pdf, 1996.

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