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Current approaches and future role of high content imaging in safety sciences and drug discovery

van Vliet, Erwin and Danesian, Mardas and Beilmann, Mario and Davies, Anthony and Fava, Eugenio and Fleck, Roland and Julé, Yvon and Kansy, Manfred and Kustermann, Stefan and Macko, Peter and Mund, William and Roth, Adrian and Sachse, Christoph and Shah, Imran and Uteng, Marianne and van de Water, Bob and Hartung, Thomas and Leist, Marcel (2014) Current approaches and future role of high content imaging in safety sciences and drug discovery. Alternatives to Animal Experimentation (ALTEX).

Abstract

High content imaging combines automated microscopy with image analysis approaches to simultaneously quantify multiple phenotypic and/or functional parameters in biological systems. The technology has become an important tool in the fields of safety sciences and drug discovery, because it can be used for mode-of-action identification, determination of hazard potency and the discovery of toxicity targets and biomarkers. In contrast to conventional biochemical endpoints, high content imaging provides insight into the spatial distribution and dynamics of responses in biological systems. This allows the identification of signaling pathways underlying cell defense, adaptation, toxicity and death. Therefore high content imaging is considered a promising technology to address the challenges for the Toxicity testing in the 21st century approach. Currently high content imaging technologies are frequently applied in academia for mechanistic toxicity studies and in pharmaceutical industry for the ranking and selection of lead drug compounds or to identify/confirm mechanisms underlying effects observed in vivo. A recent workshop gathered scientists working on high content imaging in academia, pharmaceutical industry and regulatory bodies with the objective to compile the state-of-the-art of the technology in the different institutions. They defined technical and methodological gaps, addressed the need for quality control, suggested control compounds and acceptance criteria, highlighted cell sources and new readouts and discussed future requirements for regulatory implementation. This review summarizes the discussion, proposed solutions and recommendations of the specialists contributing to the workshop.

Item Type: Article
Keywords: High Content Imaging, Toxicology, Drug development, Toxicity pathways, Mechanistic safety screening.
Date Deposited: 02 May 2016 23:45
Last Modified: 02 May 2016 23:45
URI: https://oak.novartis.com/id/eprint/21597

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