Perspectives on Validation of High-Throughput Pathway-Based Assays Supporting the 21st Century Toxicity Testing Vision

In vitro, high-throughput screening (HTS) assays are seeing increasing use in toxicity testing. HTS assays can simultaneously test many chemicals, but have seen limited use in the regulatory arena, in part because of the need to undergo rigorous, time-consuming formal validation. Here we discuss streamlining the validation process, specifically for prioritization applications in which HTS assays are used to identify a high-concern subset of a collection of chemicals. The high concern chemicals could then be tested sooner rather than later in standard guideline bioassays. The streamlined validation process would continue to ensure the reliability and relevance of assays for this application. We discuss the following practical guidelines: (1) follow current validation practice to the extent possible and practical; (2) make increased use of reference compounds to better demonstrate assay reliability and relevance; (3) deemphasize the need for cross-laboratory testing, and; (4) implement a web-based, transparent and expedited peer review process.

JUDSON Richard;  KAVLOCK Robert;  MARTIN Matt;  REIF David;  HOUCK Keith;  KNUDSEN Thomas;  RICHARD Ann;  TICE Raymond;  WHELAN Maurice;  XIA Menghang;  HUANG Ruili;  AUSTIN Christopher;  DASTON George;  HARTUNG Thomas;  FOWLE III John R.;  WOOGE William;  TONG Weida;  DIX David; 

2018-03-15

SPEKTRUM AKAD VERLAG

JRC69205

1868-596X,   

https://publications.jrc.ec.europa.eu/repository/handle/JRC69205,