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The Consultancy Activity on In Silico Models for Genotoxic Prediction of Pharmaceutical Impurities

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In Silico Methods for Predicting Drug Toxicity

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1425))

Abstract

The toxicological assessment of DNA-reactive/mutagenic or clastogenic impurities plays an important role in the regulatory process for pharmaceuticals; in this context, in silico structure-based approaches are applied as primary tools for the evaluation of the mutagenic potential of the drug impurities. The general recommendations regarding such use of in silico methods are provided in the recent ICH M7 guideline stating that computational (in silico) toxicology assessment should be performed using two (Q)SAR prediction methodologies complementing each other: a statistical-based method and an expert rule-based method.

Based on our consultant experience, we describe here a framework for in silico assessment of mutagenic potential of drug impurities. Two main applications of in silico methods are presented: (1) support and optimization of drug synthesis processes by providing early indication of potential genotoxic impurities and (2) regulatory evaluation of genotoxic potential of impurities in compliance with the ICH M7 guideline. Some critical case studies are also discussed.

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Author information

Authors and Affiliations

  1. S-IN Soluzioni Informatiche SRL, via Ferrari 14, Vicenza, 36100, Italy

    Manuela Pavan, Simona Kovarich, Arianna Bassan, Lorenza Broccardo & Elena Fioravanzo

  2. Molecular Networks GmbH, Erlangen, Germany

    Chihae Yang

  3. Altamira LLC, Columbus, OH, USA

    Chihae Yang

Authors
  1. Manuela Pavan
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  2. Simona Kovarich
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  3. Arianna Bassan
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  4. Lorenza Broccardo
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  5. Chihae Yang
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  6. Elena Fioravanzo
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Corresponding author

Correspondence to Simona Kovarich .

Editor information

Editors and Affiliations

  1. Mario Negri Inst for Pharm Rsrch, IRCCS, Milan, Italy

    Emilio Benfenati

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Pavan, M., Kovarich, S., Bassan, A., Broccardo, L., Yang, C., Fioravanzo, E. (2016). The Consultancy Activity on In Silico Models for Genotoxic Prediction of Pharmaceutical Impurities. In: Benfenati, E. (eds) In Silico Methods for Predicting Drug Toxicity. Methods in Molecular Biology, vol 1425. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3609-0_21

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  • DOI: https://doi.org/10.1007/978-1-4939-3609-0_21

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3607-6

  • Online ISBN: 978-1-4939-3609-0

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