The Use of In Silico Models Within a Large Pharmaceutical Company

Brigo, Alessandro; Muster, Wolfgang

doi:10.1007/978-1-4939-3609-0_20

Cited by 4 publications

(2 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Leadscope Model Applier and CASE Ultra include both methodologies. All of the most relevant and widely used in silico systems have been evaluated in extensive validation exercises. , Derek Nexus is a knowledge-based expert system, which applies structural alerts (SAs) and expert knowledge rules (derived from both public and proprietary data by scientists at Lhasa Ltd.) for a wide range of toxicological end points, to predict the toxicity of chemical entities. Sarah Nexus is a QSAR system that utilizes a self-organizing hypothesis network (SOHN) model to generate predictions for mutagenicity.…”

Section: Risk Assessment Approach Based On the “Aware–avoid–assess” P...mentioning

confidence: 99%

“…Brigo and Muster showed that the use of two in silico systems in combination, one knowledge- and one statistic-based system, significantly increased the sensitivity toward experimental Ames test data sets . The performance was satisfactory for numerous chemical classes, such as alkyl chlorides, azides, nitro-aromatic compounds, and others.…”

Section: Risk Assessment Approach Based On the “Aware–avoid–assess” P...mentioning

confidence: 99%

See 1 more Smart Citation

Genotoxicity Assessment of Drug Metabolites in the Context of MIST and Beyond

Zeller

Brigo

Brink

et al. 2019

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

While there are dedicated guidelines for industry regarding the assessment of the genotoxic potential of new pharmaceuticals and impurities, and the general safety assessment of major drug metabolites, only limited guidance exists on the assessment of potential genotoxic minor drug metabolites. In this Perspective, we discuss challenges associated with assessing the genotoxic potential of human metabolites and share five case studies within the context of an "aware−avoid−assess" paradigm. A special focus is on a class of potentially genotoxic carcinogens, aromatic amines (arylamines and anilines). This compound class is frequently used as building blocks and may show up as impurities, metabolites, or degradants in pharmaceuticals. We propose several recommendations that should help project teams at different stages of pharmaceutical development. In most cases, proactive interactions with the relevant health authority should be considered to endorse the proposed genotoxicity assessment strategy for minor drug metabolites.

show abstract

Section: Risk Assessment Approach Based On the “Aware–avoid–assess” P...mentioning

confidence: 99%

Section: Risk Assessment Approach Based On the “Aware–avoid–assess” P...mentioning

confidence: 99%

Genotoxicity Assessment of Drug Metabolites in the Context of MIST and Beyond

Zeller

Brigo

Brink

et al. 2019

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

show abstract

Early Drug Development

Valerio¹

2018

Early Drug Development

View full text Add to dashboard Cite

Considerations for the Use of Mutation as a Regulatory Endpoint in Risk Assessment

Klapacz

Gollapudi

2019

Environ and Mol Mutagen

View full text Add to dashboard Cite

Assessment of a chemical's potential to cause permanent changes in the genetic code has been a common practice in the industry and regulatory settings for decades. Furthermore, the genetic toxicity battery of tests has typically been employed during the earliest stages of the research and development programs of new product development. A positive outcome from such battery has a major impact on the chemical's utility, industrial hygiene, product stewardship practices, and product life cycle analysis, among many other decisions that need to be taken by the industry, even before the registration of a chemical is undertaken. Under the prevailing regulatory paradigm, the dichotomous (yes/no) evaluation of the chemical's genotoxic potential leads to a conservative, linear no‐threshold (LNT) risk assessment, unless compelling and undeniable data to the contrary can be provided to satisfy regulators, typically in a number of different global jurisdictions. With the current advent of predictive methods, new testing paradigms, mode‐of‐action/adverse outcome pathways, and quantitative risk assessment approaches, various stakeholders are starting to employ these state‐of‐the‐science methodologies to further the conversation on decision making and advance the regulatory paradigm beyond the dominant LNT status quo. This commentary describes these novel methodologies, relevant biological responses, and how these can affect internal and regulatory risk assessment approaches. Environ. Mol. Mutagen. 61:84–93, 2020. © 2019 Wiley Periodicals, Inc.

show abstract

The Use of In Silico Models Within a Large Pharmaceutical Company

Cited by 4 publications

References 37 publications

Genotoxicity Assessment of Drug Metabolites in the Context of MIST and Beyond

Genotoxicity Assessment of Drug Metabolites in the Context of MIST and Beyond

Early Drug Development

Considerations for the Use of Mutation as a Regulatory Endpoint in Risk Assessment

Contact Info

Product

Resources

About