In 2016, we initiated a new project to develop a standardized procedure for in silico experts performing assessments, similar to in vitro or in vivo test guidelines. This would streamline the application of in silico methods, ensure best practices are adopted, and defend its use to colleagues, peers, and regulators. The general framework paper1 was …
Tag archives: SAR
The Leadscope bacterial mutagenicity expert alerts journey to universal regulatory acceptance
It has taken over 10 years, but now Leadscope’s expert rule-based methodology is used every day to support submissions to regulatory agencies around the world, including pharmaceutical impurity assessments aligned with the ICH M7 guideline1, assessment of extractable and leachables, along with other applications. The following blog reviews this journey. The first step in this …
Improving the prediction of bioactivation in relation to drug-drug interactions using proprietary data
The bioactivation of drugs may result in the generation of reactive metabolites that irreversibly inactivate cytochrome P450 (requiring synthesis of new enzyme for recovery of activity). This process is referred to as mechanism-based inhibition (MBI) or time-dependent inhibition and is often involved in damaging drug-drug interactions (DDIs). Within the FDA guidance “In Vitro Drug Interaction …
In silico toxicology project 2021 review
The in silico toxicology project objective is to support the acceptance and implementation of in silico toxicology through working groups and publications covering: (1) protocols, (2) position papers, (3) case studies, (4) fit-for-purpose evaluations, and (5) structure-activity relationships. As we look back at 2021, it’s been another great year of progress. So far this year, …
New posters and papers
We recently published a blog describing four new publications.1 Since this post, we have received news that 2 more papers, submitted earlier this year to the Journal of Computational Toxicology, have been published: Evaluating Confidence in Toxicity Assessments Based on Experimental Data and In Silico Predictions2 Reliability, relevance, and confidence are defined within the context …
Four papers accepted for publication
Over the last couple of weeks, we have received news that four papers, submitted earlier this year to the Journal of Computational Toxicology, have been accepted for publication. Developing Structure-Activity Relationships for N-Nitrosamine Activity1 This paper outlines N-Nitrosamine carcinogenic potency ranges and describes specific structural features that have clear effects on these ranges. It highlights …
US FDA collaborations – predicting mutagenicity and beyond…
This week, we are pleased to welcome Dr. Kevin P. Cross, Instem’s Principal Investigator with U.S. FDA Collaborations and VP of Product Engineering and Production, as a guest contributor to the blog. Over the last 15 years I have been working closely with the US Food and Drug Administration (FDA) as a principal investigator on …
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Using in silico approaches to assess abuse liability
In part fueled by the Opioid crisis, the assessment of abuse liability is an area of increased scrutiny. An FDA guidance outlines some recommendations on how to assess abuse potential1. Several recent publications have illustrated how in silico approaches could be applied to this problem.2,3 Such an assessment could be used as part of early …
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An expert review of potentially reactive features
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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Expanding the use of in silico toxicology
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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