The importance of expert review to clarify ambiguous situations for (Q)SAR predictions under ICH M7

Genes and environment

Adrian Fowkes¹  Robert S. Foster¹  Chris G. Barber¹  Steven Kane¹  Grace Kocks¹  Alex Cayley¹  Rachael E. Tennant¹  Richard V. Williams¹  Susanne A. Stalford¹  Andrew Thresher¹  Anne-Laure D. Werner¹ 

[1] Lhasa Limited, Granary Wharf House, 2 Canal Wharf, LS11 5PS, Leeds, UK;

关键词: (Q)SAR;    ACEM;    Ames;    Derek Nexus;    ICH M7;    In silico;    JEMS;    Lhasa Limited;    Mutagenicity;    Sarah Nexus;   

DOI  :  10.1186/s41021-020-00166-y

来源: Springer

【 摘 要 】

The use of in silico predictions for the assessment of bacterial mutagenicity under the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) M7 guideline is recommended when two complementary (quantitative) structure-activity relationship (Q)SAR models are used. Using two systems may increase the sensitivity and accuracy of predictions but also increases the need to review predictions, particularly in situations where results disagree. During the 4th ICH M7/QSAR Workshop held during the Joint Meeting of the 6th Asian Congress on Environmental Mutagens (ACEM) and the 48th Annual Meeting of the Japanese Environmental Mutagen Society (JEMS) 2019, speakers demonstrated their approaches to expert review using 20 compounds provided ahead of the workshop that were expected to yield ambiguous (Q)SAR results. Dr. Chris Barber presented a selection of the reviews carried out using Derek Nexus and Sarah Nexus provided by Lhasa Limited. On review of these compounds, common situations were recognised and are discussed in this paper along with standardised arguments that may be used for such scenarios in future.

【 授权许可】

CC BY