Dr Letizia Carramusa of Yordas overviews the growing use of New Approach Methodologies As regulatory agencies, industry leaders and the scientific community push for innovation and public pressure rises over ethical concerns for animal welfare, the chemical sector’ s regulatory compliance landscape is undergoing a significant transformation. One of the most pivotal developments is the emerging New Approach Methodologies( NAMs).
REGULATION & COMPLIANCE
The evolving role of NAMs in regulatory compliance
Dr Letizia Carramusa of Yordas overviews the growing use of New Approach Methodologies As regulatory agencies, industry leaders and the scientific community push for innovation and public pressure rises over ethical concerns for animal welfare, the chemical sector’ s regulatory compliance landscape is undergoing a significant transformation. One of the most pivotal developments is the emerging New Approach Methodologies( NAMs).
These are alternative testing methods and strategies designed to reduce, refine and replace( commonly referred to as the 3Rs) traditional animal testing, which has long been the cornerstone of chemical safety assessment. The evolving role of NAMs represents a paradigm shift, not only in how chemicals are evaluated but also in how regulatory frameworks will evolve to accommodate these novel methods.
Table 1- Examples of NAMs
What are NAMs?
Although a legal definition is not currently available, NAMs are defined as any technology, methodology, approach or combination that can provide information on chemical hazard and risk assessment without the use of animals. 1 They encompass cutting-edge technologies, including in vitro testing, in silico tools and‘ omics’ approaches, and frameworks that integrate these technologies into regulatory decision-making.
NAMs are not always newly developed methods; rather, what is new is their use in regulatory decision-making or as alternatives to traditional animal testing requirements. Table 1 summarises examples of NAMs with their descriptions.
Two main motivations lie behind the development and adoption of NAMs: to prevent animals from experiencing significant suffering and to develop more reliable models than those obtained using laboratory animals. Humans are not simply large mice, however. While animal models have been valuable for studying biology, they can never fully represent the physiological complexity of the human body.
NAMs aim to provide regulatory chemical risk assessments that are more accurate, human-relevant and cost-effective than traditional animal models. Innovations such as in vitro models, high-throughput screening( a method for testing many compounds at once to identify biological activity) and advanced computational methods
NAM Category Description Example In vitro assays
Cell-based assays, tissues or organs to evaluate biological responses to chemicals under controlled conditions.
Reconstructed Human Epidermis( RHE) 3D cultures validated for the assessment of skin irritation & corrosion
In silico models
Computational models
Use of mathematical models to establish relationships between the chemical structures of compounds and their biological activity or property to predict missing data
Use of data-driven computer simulations to predict the concentration-time profiles of substances in various tissues and organs & analyse chemical data
( Quantitative) Structure-Activity Relationship(( Q) SAR) toolbox, a free software for chemical hazard assessment
Physiologically-based kinetic( PBK / TK) models are mathematical equations that simulate how a chemical or drug is absorbed, distributed, metabolised & excreted( ADME) in an organism.
‘ Omics’ technologies Studying the complete set of specific factors within a cell, tissue or organism. It examines the full range of biological changes at a molecular level after exposure to chemicals
Genomics( complete set of DNA), transcriptomics( set of all the RNA), proteomics( set of all proteins) & metabolomics( set of all small molecules called metabolites)
Organ-on-chip( OoC)
Adverse Outcome Pathways( AOPs) framework
Defined Approaches( DAs) framework
Integrated Approaches to Testing & Assessment( IATA) framework
Small-scale device that simulates key properties of human physiology by combining human cell culturing with dynamic microfluidic flow, providing a dynamic 3D model to study the systemic effects of substances
Framework that describes the sequence of causally linked molecular key events required to produce an adverse effect when a biological system is exposed to chemicals
Framework that combines in vitro, in silico and in chemico data to improve prediction accuracy
Flexible framework that uses diverse sources of information in a weight-of-evidence basis to conclude on the toxicity of a chemical
Review of commercially manufactured OoC devices
OECD Guideline No. 168 on AOP for Skin sensitisation
OECD Guideline No. 497 on DA for Skin Sensitisation
IATA for serious eye damage and eye irritation hazard identification
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