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 …

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 …

Streamlining ICH M7 analyses with an implemented protocol

A major focus of our work over the last few years has been on the development and publication of in silico toxicology protocols, discussed in previous blog posts1. This has resulted in a paper outlining a framework for such protocols2  as well as two published protocols in the areas of genetic toxicology3 and skin sensitization4. …

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 …

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 …

Predicting organ toxicity

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 …

New book on Mutagenic Impurities

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 …

Instem’s Computational Toxicology and Genetic Toxicology Groups at GTA 2021

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 …

N-nitrosamine SAR Working group

Leadscope, Inc. (an Instem company), in collaboration with Lhasa Limited are leading a working group of pharmaceutical toxicologists and consultants investigating the carcinogenic potency and structure-activity relationships of N-nitrosamines. This is in response to the recent discovery of N-nitrosamines in marketed pharmaceuticals and the regulatory changes that have resulted. The working group is run by …