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Review
. 2022 Nov;96(11):2865-2879.
doi: 10.1007/s00204-022-03365-4. Epub 2022 Aug 20.

A framework for establishing scientific confidence in new approach methodologies

Anna J van der Zalm  1 , João Barroso  2 , Patience Browne  3 , Warren Casey  4 , John Gordon  5 , Tala R Henry  6 , Nicole C Kleinstreuer  7 , Anna B Lowit  6 , Monique Perron  8 , Amy J Clippinger  9
Affiliations
Review

A framework for establishing scientific confidence in new approach methodologies

Anna J van der Zalm et al. Arch Toxicol. 2022 Nov.

Abstract

Robust and efficient processes are needed to establish scientific confidence in new approach methodologies (NAMs) if they are to be considered for regulatory applications. NAMs need to be fit for purpose, reliable and, for the assessment of human health effects, provide information relevant to human biology. They must also be independently reviewed and transparently communicated. Ideally, NAM developers should communicate with stakeholders such as regulators and industry to identify the question(s), and specified purpose that the NAM is intended to address, and the context in which it will be used. Assessment of the biological relevance of the NAM should focus on its alignment with human biology, mechanistic understanding, and ability to provide information that leads to health protective decisions, rather than solely comparing NAM-based chemical testing results with those from traditional animal test methods. However, when NAM results are compared to historical animal test results, the variability observed within animal test method results should be used to inform performance benchmarks. Building on previous efforts, this paper proposes a framework comprising five essential elements to establish scientific confidence in NAMs for regulatory use: fitness for purpose, human biological relevance, technical characterization, data integrity and transparency, and independent review. Universal uptake of this framework would facilitate the timely development and use of NAMs by the international community. While this paper focuses on NAMs for assessing human health effects of pesticides and industrial chemicals, many of the suggested elements are expected to apply to other types of chemicals and to ecotoxicological effect assessments.

Keywords: Framework; Human health; NAMs; New approach methodologies; Regulatory; Validation.

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Conflict of interest statement

The views expressed in this article are those of the authors and do not necessarily represent the views or policies of their respective employers. Mention of trade names or commercial products does not constitute endorsement for use. The authors declare no financial conflicts of interest. The manuscript was conceived and developed solely by the authors. This paper is intended to bolster scientific confidence in NAMs and not set policy for any regulatory agency. This project was funded in part by federal funds from NIEHS, NIH under IRP project: ES103318-06 (2021) Biomolecular Screening and Alternative Approaches for the Division of the National Toxicology Program.

Figures

Fig. 1
Fig. 1
Schematic illustrating the interconnectedness of the five essential elements for establishing scientific confidence in NAMs for assessing human health effects
Fig. 2
Fig. 2
Schematic showing some of the questions relevant to determining the fitness for purpose of a NAM
See this image and copyright information in PMC

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