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Review
. 2025 Apr;99(4):1271-1285.
doi: 10.1007/s00204-024-03922-z. Epub 2025 Feb 13.

Bridging imaging-based in vitro methods from biomedical research to regulatory toxicology

Monica Piergiovanni #  1 , Milena Mennecozzi #  2 , Erio Barale-Thomas  3 , Davide Danovi  4 , Sebastian Dunst  5 , David Egan  6 , Aurora Fassi  2 , Matthew Hartley  7 , Philipp Kainz  8 , Katharina Koch  9   10 , Sylvia E Le Dévédec  11 , Iris Mangas  12 , Elena Miranda  13 , Jo Nyffeler  14 , Enrico Pesenti  15 , Fernanda Ricci  16 , Christopher Schmied  17 , Alexander Schreiner  18 , Nadine Stokar-Regenscheit  19 , Jason R Swedlow  20 , Virginie Uhlmann  21 , Fredrik C Wieland  22 , Amy Wilson  23 , Maurice Whelan  2
Affiliations
Review

Bridging imaging-based in vitro methods from biomedical research to regulatory toxicology

Monica Piergiovanni et al. Arch Toxicol. 2025 Apr.

Abstract

Imaging technologies are being increasingly used in biomedical research and experimental toxicology to gather morphological and functional information from cellular models. There is a concrete opportunity of incorporating imaging-based in vitro methods in international guidelines to respond to regulatory requirements with human relevant data. To translate these methods from R&D to international regulatory acceptance, the community needs to implement test methods under quality management systems, assess inter-laboratory transferability, and demonstrate data reliability and robustness. This article summarises current challenges associated with image acquisition, image analysis, including artificial intelligence, and data management of imaging-based methods, with examples from the developmental neurotoxicity in vitro battery and phenotypic profiling assays. The article includes considerations on specific needs and potential solutions to design and implement future validation and transferability studies.

Keywords: 3Rs; Artificial intelligence; High content imaging; Imaging-based in vitro methods; Regulatory toxicology; Validation.

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Conflict of interest statement

Declarations. Conflict of interest: Erio Barale-Thomas, David Egan, Katharina Koch, Elena Miranda, Enrico Pesenti, Fernanda Ricci, Alexander Schreiner, Nadine Stokar-Regenscheit, Fredrik C. Wieland and Amy Wilson are employed by the respective companies. Elena Miranda holds shares in GSK. Amy Wilson holds shares in AstraZeneca. Nadine Stokar-Regenscheit holds share in F.Hoffmann-La Roche Ldt. Katharina Koch holds share in DNTOX. Philipp Kainz is a director and shareholder of KOLAIDO GmbH. David Egan is a director and shareholder of Core Life Analytics BV. Iris Mangas contributed in particular to the section “Developmental neurotoxicity in vitro battery” of this publication. The views expressed, and arguments employed in this article are those of the authors and do not necessarily reflect the official views or policies of their companies or institutions of employment or of the governments of its member countries.

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