New Approach methodology (NAM) is an overarching term and as described by the Organisation for Economic Co-operation and Development (OECD) can include in vitro (e.g. omics, cell-based, tissue-based, etc.) assays, in silico (e.g. [Q]SARs, expert systems, etc.) models, and other biotechnological and computational approaches such as physiologically based kinetic (PBK) models. NAMs can serve as (replacement, reduction or refinement) alternatives to animal testing.
NAMs may play a crucial role in safety assessment of agrochemicals as they have the potential to provide an efficient, biologically relevant and cost-effective way to assess the potential toxicity of chemical compounds without the need for animal testing. NAMs are key components of Integrated Approaches to Testing and Assessments (IATAs), described by the Organisation for Economic Co-operation and Development (OECD) in 2020. IATAs represent a flexible framework for carrying out an assessment and reaching a regulatory conclusion with the purpose of evaluating risk to human health and the environment from chemical exposure.
Many NAMs have been developed and been subject to international validation procedures via the OECD. Many regulators are also looking to increase the use of NAMs to phase out and replace mandatory vertebrate testing, and several research and regulatory groups are actively proposing strategies to facilitate this. In the United States of America, the Environmental Protection Agency (US EPA) and Food and Drug Administration (US FDA) intend to reduce animal testing, and in Europe, the European Food Safety Authority (EFSA), European Chemicals Agency (EChA) and European Medicines Agency (EMA) are also developing strategies to include NAMs in regulatory safety assessments.
Data requirements on the mandated use of NAMs vary by region and endpoint. This raises the practical question of what to use when there is uncertainty about regulatory acceptance of the data. NAMs have been frequently used in the assessment of human relevance, such as hepatocellular proliferation in vitro and effects on the thyroid axis however, with variable regulatory impact and acceptance.
The CropLife Europe ‘in vitro in vivo extrapolation’ (IVIVE) subgroup has defined key focus areas related to NAMs including addressing recurring issues occurring in in vitro assays used for safety assessment, contributing to the review of guidelines and draft guidelines, and reviewing appropriate techniques for exposure assessment utilizing NAMs.