Acceptance criteria for new approach methods in toxicology and human health-relevant life science research – part I

Holzer Anna-Katharina, Dreser Nadine, Pallocca Giorgia, Mangerich Aswin, Stacey Glyn, Dipalo Michele, van de Water Bob, Rovida Costanza, Wirtz Petra H., Van Vugt Barbara, Panzarella Giulia, Hartung Thomas, Terron Andrea, Mangas Iris, Herzler Matthias, Marx-Stoeling Philip, Coecke Sandra, Leist Marcel
DOI: 10.14573/altex.2310021
PMID: 37889190
Keyword: BenchMarks series · GIVIMP · NAM · in vitro · methods · quality control · validation


Every test procedure, scientific and non-scientific, has inherent uncertainties, even when performed according to a standard operating procedure (SOP). In addition, it is prone to errors, defects, and mistakes introduced by operators, laboratory equipment, or materials used. Adherence to an SOP and comprehensive validation of the test method cannot guarantee that each test run produces data within the acceptable range of variability and with the precision and accuracy determined during the method validation. We illustrate here (part I) why controlling the validity of each test run is an important element of experimental design. The definition and application of acceptance criteria (AC) for the validity of test runs is important for the setup and use of test methods, particularly for the use of new approach methods (NAM) in toxicity testing. AC can be used for decision rules on how to handle data, e.g., to accept the data for further use (AC fulfilled) or to reject the data (AC not fulfilled). The adherence to AC has important requirements and consequences that may seem surprising at first sight: (i) AC depend on a test method’s objectives, e.g., on the types/concentrations of chemicals tested, the regulatory context, the desired throughput; (ii) AC are applied and documented at each test run, while validation of a method (including the definition of AC) is only performed once; (iii) if AC are altered, then the set of data produced by a method can change. AC, if missing, are the blind spot of quality assurance: Test results may not be reliable and comparable. The establishment and uses of AC will be further detailed in part II of this series.