Poster Presentations
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In Silico Drug Degradation Assessment in Early Phase Development
Ash Ali , Senior Scientist, Lhasa Limited
There is increasing interest in stability or forced degradation studies that lead to the identification of degradation products (and pathways) of an active pharmaceutical ingredient (API). Stability assessment is crucial as API impurities can appear due to its chemical breakdown. The FDA and ICH guidelines require performance of stability testing which include long-term (12 months) and accelerated (6 months) investigations with further studies on degradation products. This latter aspect overlaps with the ICH M7 guideline (risk posed by mutagenic degradants). Stability assessment impacts on the already heavy time constraints of API development and therefore an in silico approach to support and streamline this part of the development process is desirable.
Our group is concerned with encapsulating drug degradation knowledge (from pharmaceutical reports, chemistry literature, consultation with experts) within a knowledge base as a series of transformations that can be accessed through the in silico tool Zeneth. The transformation dictionary (what reaction could occur) in combination with a reasoning engine (how likely this is) can generate a full degradation profile under various environmental conditions (pH, oxidation, light, temperature, humidity) that can assist in the identification of potential degradants. We detail the diverse range of chemistries in the knowledge base and illustrate how pre-existing knowledge and reactivity rules can make valuable drug degradation predictions during the development cycle.
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