In several recent posts1,2 we highlighted the usefulness of an expert review of potentially reactive features. This is particularly important when an out-of-domain result is returned or when an area of the test chemical is not being considered by the computational model. The US Food and Drug Administration (FDA) recently published a paper showing that …
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The application of in silico toxicology is constantly increasing as we better understand how such methods can support different applications (such as the assessment of genotoxic impurity, extractables and leachables, chemicals requiring classification and labelling, and so on). Position papers are critical to support this expansion. We have reported in some recent blog posts progress …
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In silico toxicology has its established place in the assessment of therapeutics and is used routinely to assess toxicity endpoints with application in research, discovery, and regulatory submissions. During the pandemic we have gotten a glimpse of innovative therapeutics and the public now has an appreciation for how important these are in advancing patient care. …
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The ability to predict organ toxicity directly from a chemical structure would support many applications throughout the product life cycle, from screening candidates to formulating testing strategies and assessing non-genotoxic impurities. A recent cross-industry working group, as part of the in silico toxicology protocol project1, was initiated to understand the needs and challenges for in …
QSAR 20211 is around the corner and after last year’s cancellation, we are excited to be in attendance. We are pleased to be contributors to this year’s program through participation in two platform sessions in addition to poster presentations. If you are a frequent reader of this blog, you have read about our work on …
A recent FDA guidance for industry, titled “In Vitro Drug Interaction Studies – Cytochrome P450 Enzyme- and Transporter- Mediated Drug Interactions”1 includes the following statement: “A lower cut-off value for the metabolite-to-parent AUC ratio may also be considered for metabolites with structural alerts for potential mechanism-based inhibition (Orr, 2012; Yu, 2013; Yu, 2015)” Today, a …
We have been really happy to contribute to a number of chapters in an important new book edited by Dr. Andrew Teasdale: “Mutagenic Impurities: Strategies for Identification and Control”1 This will be an essential read for students and professionals in the field of genotoxic impurities (GTIs) assessment covering topics including a history of the regulatory …
We are pleased to be attending this year’s virtual GTA meeting1 and will be presenting on several topics throughout the course of the event. On Thursday May 6th, Dr. Kevin Cross will be presenting “Predicting N-Nitrosamine Activity from Structure-Activity Relationships” as part of a Symposium on “The 3Rs and in Silico Modeling”. This presentation addresses …
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One of the more challenging outcomes from a (Q)SAR model is the out-of-domain (OOD) result. This result is possible since (Q)SAR models are, in many situations (such as the ICH M7 guideline), required to perform an applicability domain analysis to satisfy OECD validation principles1. Although a (Q)SAR model may still generate a prediction, the OOD …
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Computational tools offer a rapid, cost-saving advantage to toxicologists assessing the hazard of chemicals. The predictivity of a model for a group of structures is one aspect to be considered in a computational assessment. However, given the universe of chemicals, there are structural classes which a model will predict with a higher level of reliability …
Continue reading “The use of chemical analogs in expert reviews”
