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

Main Article Content

Anna-Katharina Holzer, Nadine Dreser, Giorgia Pallocca, Aswin Mangerich, Glyn Stacey, Michele Dipalo, Bob van de Water, Costanza Rovida, Petra H. Wirtz, Barbara van Vugt, Giulia Panzarella, Thomas Hartung, Andrea Terron, Iris Mangas, Matthias Herzler, Philip Marx-Stoelting, Sandra Coecke, Marcel Leist
[show affiliations]


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.

Article Details

How to Cite
Holzer, A.-K. (2023) “Acceptance criteria for new approach methods in toxicology and human health-relevant life science research – part I”, ALTEX - Alternatives to animal experimentation, 40(4), pp. 706–712. doi: 10.14573/altex.2310021.

Aschner, M., Ceccatelli, S., Daneshian, M. et al. (2017). Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: example lists and criteria for their selection and use. ALTEX 34, 49-74. doi:10.14573/altex.1604201

Balls, M., Blaauboer, B. J., Fentem, J. H. et al. (1995). Practical Aspects of the Validation of Toxicity Test Procedures. Altern Lab Anim 23, 129–146. doi:10.1177/026119299502300116

Bal-Price, A., Hogberg, H. T., Crofton, K. M. et al. (2018). Recommendation on test readiness criteria for new approach methods in toxicology: Exemplified for developmental neurotoxicity ALTEX 35, 306-352. doi:10.14573/altex.1712081

Bernasconi, C., Langezaal, I., Bartnicka, J. et al. (2023). Validation of a battery of mechanistic methods relevant for the detection of chemicals that can disrupt the thyroid hormone system. Publications Office of the European Union.

EMA (2008). Qualification of novel methodologies for drug development: guidance to applicants. EMA/CHMP/SAWP/72894/2008.

EMA (2016). Guideline on the principles of regulatory acceptance of 3Rs (replacement, reduction, refinement) testing approaches. EMA/CHMP/CVMP/JEG-3Rs/450091/2012.

Hartung, T. (2007). Food for thought … on validation. ALTEX 24, 67-80. doi:10.14573/altex.2007.2.67

Hartung, T., Hoffmann, S., Stephens, M. (2013). Mechanistic validation. ALTEX 30, 119-130. doi:10.14573/altex.2013.2.119

Hewitt, M., Ellison, C. M., Cronin, M. T. et al. (2015). Ensuring confidence in predictions: A scheme to assess the scientific validity of in silico models. Adv Drug Deliv Rev 86, 101–111. doi:10.1016/j.addr.2015.03.005

Hoffmann, S., Hartung, T., Stephens, M. (2016). Evidence-Based Toxicology. Adv Exp Med Biol 856, 231-241. doi:10.1007/978-3-319-33826-2_9

Krebs, A., van Vugt-Lussenburg, B. M. A., Waldmann, T. et al. (2020). The EU-ToxRisk method documentation, data processing and chemical testing pipeline for the regulatory use of new approach methods. Arch Toxicol 94, 2435-2461. doi:10.1007/s00204-020-02802-6

Krebs, A., Waldmann, T., Wilks, M. F. et al. (2019). Template for the description of cell-based toxicological test methods to allow evaluation and regulatory use of the data. ALTEX 36, 682-699. doi:10.14573/altex.1909271

Lanzoni, A., Castoldi, A. F., Kass, G. E. et al. (2019) Advancing human health risk assessment. EFSA J 17(Suppl 1), e170712. doi:10.2903/j.efsa.2019.e170712

Leist, M., Efremova, L. and Karreman, C. (2010). Food for thought … considerations and guidelines for basic test method descriptions in toxicology. ALTEX 27, 309–317. doi:10.14573/altex.2010.4.309

Leist, M., Hasiwa, N., Daneshian, M. et al. (2012a). Validation and quality control of replacement alternatives – current status and future challenges. Toxicol Res 1, 8–22. doi:10.1039/C2TX20011B

Leist, M., Lidbury, B. A., Yang, C. et al. (2012b) Novel technologies and an overall strategy to allow hazard assessment and risk prediction of chemicals, cosmetics, and drugs with animal-free methods. ALTEX 29, 373-388. doi:10.14573/altex.2012.4.373

Leist, M. and Hengstler, J. G. (2018) Essential components of methods papers ALTEX 35, 429-432. doi:10.14573/altex.1807031

Marx-Stoelting, P., Rivière, G., Luijten, M. et al. A walk in the PARC: developing and implementing 21st century chemical risk assessment in Europe. Arch Toxicol 97, 893-908. doi:10.1007/s00204-022-03435-7

OECD (2005). Guidance document on the validation and international acceptance of new or updated test methods for hazard assessment.

OECD (2018). Guidance Document on Good In Vitro Method Practices (GIVIMP). OECD Publishing, Paris. doi:10.1787/9789264304796-en

Pamies, D., Leist, M., Coecke, S. et al. (2022). Guidance document on Good Cell and Tissue Culture Practice 2.0 (GCCP 2.0). ALTEX 39, 30-70. doi:10.14573/altex.2111011

Pallocca, G. and Leist, M. On the usefulness of animals as a model system (part II): Considering benefits within distinct use domains. (2022) ALTEX 39, 531-539. doi:10.14573/altex.2207111

Pallocca, G., Rovida, C. and Leist, M. (2022) On the usefulness of animals as a model system (part I): Overview of criteria and focus on robustness. ALTEX 39, 347-353. doi:10.14573/altex.2203291

Pamies, D., Leist, M., Coecke, S., et al. (2022) Guidance document on Good Cell and Tissue Culture Practice 2.0 (GCCP 2.0). ALTEX 39, 30-70. doi:10.14573/altex.2111011

Patterson, E. A., Whelan, M. P., Worth, A. P. (2021). The role of validation in establishing the scientific credibility of predictive toxicology approaches intended for regulatory application. Comput Toxicol 17, 100144. doi:10.1016/j.comtox.2020.100144

Schmeisser, S., Miccoli, A., von Bergen, M. et al. (2023). New approach methodologies in human regulatory toxicology - Not if, but how and when! Environ Int 178, 108082. doi:10.1016/j.envint.2023.108082

Schmidt, B. Z., Lehmann, M., Gutbier, S. et al. (2017). In vitro acute and developmental neurotoxicity screening: an overview of cellular platforms and high-throughput technical possibilities. Arch Toxicol 91, 1-33. doi:10.1007/s00204-016-1805-9

Most read articles by the same author(s)

<< < 3 4 5 6 7 8 9 10 11 12 > >>