title: Establishing best practise in the application of expert review of mutagenicity under ICH M7.
abstract: The ICH M7 guidelines for the assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals allows for the consideration of in silico predictions in place of in vitro studies. This represents a significant advance in the acceptance of (Q)SAR models and has resulted from positive interactions between modellers, regulatory agencies and industry with a shared purpose of developing effective processes to minimise risk. This paper discusses key scientific principles that should be applied when evaluating in silico predictions with a focus on accuracy and scientific rigour that will support a consistent and practical route to regulatory submission.
authors.affiliation: Lhasa Limited, Leeds, UK. Electronic address: chris.barber@lhasalimited.org.
authors.forename: Chris
authors.initials: C
authors.lastname: Barber
authors.affiliation: Sanofi-Aventis Deutschland GmbH, DSAR Preclinical Safety, Frankfurt, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Amberg
authors.affiliation: Bristol-Myers Squibb, Drug Safety Evaluation, New Brunswick, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Custer
authors.affiliation: Pfizer, Drug Safety Research and Development, Groton, CT, USA.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Dobo
authors.affiliation: Novartis Institutes for Biomedical Research, Department of Preclinical Safety, Basel, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Glowienke
authors.affiliation: Janssen, Drug Safety Sciences, Beerse, Belgium.
authors.forename: Jacky
authors.initials: J
authors.lastname: Van Gompel
authors.affiliation: Unilever, Safety and Environmental Assurance Centre, Colworth, Beds, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Gutsell
authors.affiliation: GlaxoSmithkline, Computational Toxicology, Ware, Herts, UK.
authors.forename: Jim
authors.initials: J
authors.lastname: Harvey
authors.affiliation: National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Honma
authors.affiliation: Pfizer, Drug Safety Research and Development, Groton, CT, USA.
authors.forename: Michelle O
authors.initials: MO
authors.lastname: Kenyon
authors.affiliation: FDA Center for Drug Evaluation and Research, Silver Spring, MD, USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kruhlak
authors.affiliation: F. Hoffmann-La Roche Ltd., Pharma Research and Early Development, Basel, Switzerland.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Muster
authors.affiliation: FDA Center for Drug Evaluation and Research, Silver Spring, MD, USA.
authors.forename: Lidiya
authors.initials: L
authors.lastname: Stavitskaya
authors.affiliation: AstraZeneca, Macclesfield, Cheshire, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Teasdale
authors.affiliation: Lhasa Limited, Leeds, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Vessey
authors.affiliation: Bayer, HealthCare, Genetic Toxicology, Berlin, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Wichard
mesh_terms: D003198:Computer Simulation / Q000592:standards; D004247:DNA / Q000737:chemistry; D004340:Drug Contamination / Q000517:prevention & control; D009152:Mutagenicity Tests / Q000379:methods* / Q000592:standards*; D009153:Mutagens; D021281:Quantitative Structure-Activity Relationship
chemical_list: D009153:Mutagens; D004247:DNA
keywords: Ames; Expert rule-based; Genotoxicity; ICH M7; In silico; Mutagenicity; Statistical