The development and use of reliable New Approach Methodologies (NAMs) is becoming increasingly central to modern drug development. As part of a broader regulatory shift, the U.S. Food and Drug Administration (FDA) has prioritised efforts to reduce and replace animal testing while promoting more predictive, human-centric toxicology methods. This transition reflects both ethical considerations and the scientific need for models that better translate to human outcomes.
A key focus of this shift is the encouragement of NAMs in regulatory submissions, particularly when these approaches demonstrate improved predictivity, reliability, and human relevance compared to traditional non-clinical tests. While new drug-enabling studies have historically relied on animal models, the Center for Drug Evaluation and Research (CDER) routinely receives and reviews data generated using NAMs. Importantly, such data is considered acceptable when it is supported by robust methodology and demonstrates sufficient reliability and confidence.
This is not without precedent. CDER has previously accepted data from skin sensitisation tests and in vitro reconstructed human epidermis assays, signaling a growing openness to scientifically validated alternatives that can enhance regulatory decision-making.

To support their use in regulatory contexts, NAMs must meet clearly defined validation criteria. Four key features are central to how these methodologies are evaluated:

1. Context of Use
The intended use and regulatory purpose of the NAM must be clearly defined. The methodology should address a specific scientific or drug development question that directly supports a regulatory decision. For example, a NAM may be used to provide mechanistic understanding of an adverse event observed during development.
2. Human Biological Relevance
Establishing human relevance is critical. This includes describing the physiological features of the model, such as the cell types used, and demonstrating how findings can be meaningfully evaluated. For instance, in assessing liver toxicity, the assay might measure albumin and urea production over time. Additionally, the biological mechanisms captured by the NAM should be applicable to human clinical outcomes.
3. Technical Characterisation
NAMs must be technically robust and aligned with established guidance, such as OECD principles for good in vitro method practices. This involves demonstrating predictive performance, such as sensitivity and specificity alongside thorough documentation of the system, including cell types and control compounds used in the assay.
4. Fit-for-Purpose
A NAM is considered fit-for-purpose when it effectively contributes to regulatory decision-making. This includes demonstrating that it performs at least as well as traditional methods, while clearly outlining its benefits and limitations. A NAM may serve one or more of the following roles:
• Replacing or offering an alternative to traditional methods (e.g. replacing animal studies)
• Filling data gaps by providing additional safety information
• Confirming or complementing findings from established approaches

The Alcyomics Skimune® assay is a human, immune-competent in vitro platform designed to test the immunotoxicity of novel pharmaceuticals. It combines autologous immune cells with matched skin explants from the same donor to evaluate adverse immune-mediated events. Our assay aligns with each of the FDA criteria outlined above.
1. Context of use – the assay is specifically designed to evaluate immune-mediated toxicity risk during preclinical drug development, enabling more confident candidate selection and de-risking drug pipelines;
2. Human biological relevance – the platform is a completely human system using skin biopsies and human immune cells, capturing complex immune-tissue interactions that is not possible in simple in vitro models;
3. Technical characterisation – the assay incorporates a reproducible and standardised workflow to ISO9001 standards, has been fully validated across multiple drug modalities in various peer-reviewed publications and has been used in regulatory applications; 4. Fit for purpose – Skimune® can reduce or replace animal studies and successfully predicts immunotoxicity observed in humans in the clinic enabling more translational insights into safety of novel therapeutics.

The integration of NAMs into regulatory frameworks marks a significant evolution in how drug safety and efficacy are assessed. By focusing on human-relevant biology and scientifically robust validation, these methodologies have the potential to improve the predictivity of non-clinical testing while supporting regulatory confidence.
As regulatory bodies continue to encourage their adoption, NAMs are positioned to play a critical role in shaping a more efficient, ethical, and human-focused future for drug development.


Reference: U.S. Food and Drug Administration (2026). General Considerations for the Use of New Approach Methodologies in Drug Development: Draft Guidance for Industry. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-considerations-use-new-approach-methodologies-drug-development (Accessed: 5 May 2026).