Novel application of in silico methods in the assessment of Extractables and Leachables

New therapeutic modalities play a critical role in our health and safety. Novel therapeutics may be comprised of biologically based molecules including peptides, monoclonal antibodies, and genetic materials. The quality and safety of these products can be assessed using experimental systems; however, it is important to ask whether in silico methods can add value to …

In silico applications in the assessment of Extractables and Leachables

The Product Quality Research Institute (PQRI) recently published on their recommendations for safety thresholds and best practices for extractables and leachables (E&L) in Parenteral Drug products1. The publication describes, and addresses, issues related to the definition and procedures for defining safety thresholds. Within the document, areas of application for in silico methods are also defined. …

In Silico Methods for Predicting Drug Toxicity, Second Edition

In Silico Methods for Predicting Drug Toxicity, edited by Emilio Benfenati1 addresses new in silico methodologies, their integrated use, and regulatory implications for the assessment of pharmaceuticals. The second edition contains both updated and new chapters, reflecting advancements in computational toxicology.  Each chapter covers specific areas such as the use of modeling a pharmaceutical in …

Leadscope database update process and statistics

The development of databases is fundamentally important to in silico toxicology. As part of our yearly release, we update Leadscope’s databases to capture either new or existing information in the public domain or data received from our collaborative partners. The process involves careful curation of chemical structures by normalization, registering the structures and resolving any …

In silico toxicology vis-à-vis new therapeutics

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. …

How an expert-review could be used to resolve out-of-domains

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 …

The use of chemical analogs in expert reviews

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 …

Endocrine activity in silico protocol

The in silico toxicology protocol consortium has been working on developing in silico protocols across various endpoints. While there are existing frameworks for identifying endocrine disrupting chemicals, there remains a lack of guidance on the usefulness and limitations of predicting relevant effects and mechanisms using in silico methodologies and how to combine relevant information inclusive …