Drug development is entering a new phase of nonclinical testing. New Approach Methodologies (NAMs) are creating opportunities to generate more human-relevant evidence while reducing or replacing the use of animals in certain areas of development.
Regulatory agencies are increasingly developing frameworks, guidance, and pathways for understanding how NAM-generated evidence can be used in drug development and regulatory submissions. At the same time, AI, computational models, organoids, organ-on-chip systems, and other advanced approaches are expanding the NAM ecosystem.
For pharmaceutical companies, the key challenge is therefore moving from whether an alternative method exists to whether it is scientifically credible, appropriately validated, and fit for a defined regulatory purpose.
Why NAMs are Moving from Scientific Innovation to Regulatory Strategy
NAMs are becoming increasingly relevant to nonclinical drug development and safety assessment because they can provide human-relevant evidence that complements, reduces, or in some cases replaces traditional animal studies.
This shift is increasingly visible in regulatory activity. In March 2026, the US FDA issued draft guidance outlining a validation framework and general considerations for using NAMs in drug development, particularly where they can improve the predictive value of nonclinical studies.
EMA is also developing pathways for regulatory interaction around NAMs, including Innovation Task Force discussions, scientific advice, qualification procedures, and voluntary submission of NAM-derived data.
What Counts as a New Approach Methodology?
New Approach Methodologies (NAMs) is a broad term covering innovative methods and combinations of methods used to generate evidence relevant to drug development.
Depending on the intended application, NAMs can include:
- In vitro human-based systems, including advanced cell-based models
- Organoids and micro physiological systems
- Organ-on-chip technologies
- In silico and computational models
- AI and machine-learning approaches
- Integrated combinations of different methodologies
EMA describes NAMs as methods that can generate data with similar or improved value compared with current approaches and that may help replace, reduce, or refine animal use. The important consideration is not simply whether a technology is innovative. Its value depends on what regulatory question it is intended to address and whether the evidence generated is fit for that purpose.
FDA, EMA and MHRA: How Regulatory Acceptance is Evolving
Regulatory approaches to NAMs are developing across major markets, although each agency is establishing its own mechanisms for evaluating their scientific and regulatory relevance.
FDA: The FDA’s 2026 draft guidance provides general recommendations for validating NAMs used in drug development and focuses on scientific principles for study design and reporting. The agency has also established resources showing examples of NAM use in FDA application reviews.
EMA: EMA provides several routes for NAM developers to engage with regulators, including Innovation Task Force meetings, scientific advice, qualification, and voluntary data submission. EMA emphasises the importance of a defined methodology, context of use, and sufficient evidence supporting regulatory relevance.
MHRA: The UK MHRA published its approach to medicines using non-animal methods in March 2026. It recognises the potential of alternative methods while emphasising that their ability to predict human effects still needs to be appropriately considered.
Together, these developments indicate a broader regulatory movement toward scientifically justified, fit-for-purpose alternatives, rather than automatic acceptance of every new technology.
AI is Not the Alternative: It is Part of the NAM Ecosystem
AI is often discussed as though it represents a separate alternative to conventional nonclinical testing. In practice, AI can form part of a broader NAM strategy. AI and machine learning can support areas such as predictive modelling, toxicity assessment, biological response prediction, image analysis, and integration of complex datasets. They can also be combined with experimental NAMs to generate a broader evidence package.
For sponsors, this means AI should not be treated as a regulatory shortcut. Its value depends on the quality of the underlying data, model performance, validation approach, applicability domain, interpretability where relevant, and defined regulatory purpose.
The Real Barrier: Scientific Innovation vs Regulatory Acceptability
Developing a promising NAM is only one part of the process. The greater challenge can be demonstrating that the method is sufficiently reliable, reproducible, relevant, and fit for its intended regulatory use.
A scientifically sophisticated model may still face regulatory challenges if its context of use is unclear, its performance has not been adequately characterised, or the evidence package does not demonstrate sufficient relevance to the regulatory question.
This is why NAM validation and early regulatory engagement are becoming important elements of development strategy. EMA specifically encourages developers to consider regulatory readiness and engage early when developing NAMs for regulatory use.
A NAM Regulatory Readiness Framework for Pharma
For pharmaceutical companies considering NAMs in drug development, regulatory readiness can be viewed through five connected areas:
What NAMs Mean for the Future of Nonclinical Drug Development
NAMs are not simply replacing one test with another. They are contributing to a broader transformation in how nonclinical evidence is generated, integrated, and evaluated.
As FDA, EMA, MHRA, and other regulators develop their approaches, sponsors will increasingly need to think about NAMs as part of an integrated evidence strategy rather than as isolated technologies. For pharmaceutical development, the future is likely to involve greater use of human-relevant models, computational approaches, AI, and integrated evidence packages, supported by clearer expectations around validation and regulatory use.
The competitive advantage will not come simply from adopting new technology. It will come from understanding where that technology can generate meaningful evidence, how it should be validated, and how that evidence can be positioned within a regulatory strategy.
How Can DDReg Support NAM Regulatory Strategy?
As new approach methodologies (NAMs) become more relevant to drug development, sponsors need to understand not only the scientific potential of a method, but also how it fits into the broader regulatory pathway. This requires a clear view of the intended use, evidence expectations, validation considerations, and regulatory engagement strategy.
Through its Regulatory Affairs Services, DDReg can support pharmaceutical companies in translating NAM-related development into a structured regulatory strategy.
This can include:
- Regulatory strategy: Assessing how NAMs may fit within the development program and applicable regulatory pathways.
- Regulatory gap analysis: Identifying evidence or regulatory considerations that may need to be addressed before NAM-generated data can support a development objective.
- Evidence strategy: Helping align the intended use of NAM-generated evidence with the relevant regulatory question and development stage.
- Regulatory intelligence: Monitoring evolving expectations and approaches to NAMs across key regulatory markets.
- Regulatory engagement strategy: Supporting planning for appropriate interactions with regulatory authorities where scientific advice, qualification, or other regulatory pathways may be relevant.
- Submission and lifecycle strategy: Helping position relevant NAM-generated evidence within broader eCTD regulatory submissions and product lifecycle planning.
The goal is not simply to introduce an alternative testing method, but to ensure that the evidence it generates has a clear purpose within the regulatory strategy. By connecting scientific innovation with regulatory requirements, DDReg helps sponsors approach NAM adoption with greater clarity and structure.
Conclusion
NAMs are changing how the pharmaceutical industry approaches nonclinical evidence. Human-relevant models, computational approaches, AI, organoids, and other emerging technologies are creating new opportunities to generate meaningful evidence while reducing reliance on traditional animal testing where scientifically appropriate.
But technological innovation alone does not determine regulatory acceptance. Scientific validity, context of use, validation, evidence quality, and early regulatory planning will shape how NAM-generated evidence can contribute to drug development.
As FDA, EMA, MHRA, and other regulators continue to develop their approaches, sponsors will need to focus not only on adopting new technologies, but on demonstrating how those technologies can generate credible evidence for a defined regulatory purpose.
The future of nonclinical drug development will depend on connecting scientific innovation with evidence that can stand up to regulatory scrutiny.
Frequently Asked Questions
New Approach Methodologies (NAMs) are innovative approaches used to generate evidence relevant to drug development and safety assessment. They can include in vitro human-based models, organoids, organ-on-chip systems, computational models, and AI-based approaches, among others.
NAMs can support different stages of drug development by providing evidence on areas such as drug safety, biological activity, toxicity, and human response. Depending on the method and its intended use, NAM-generated evidence may complement, reduce, or potentially replace certain traditional approaches.
A NAM regulatory strategy defines how a new approach methodology fits within a drug development program, including its context of use, evidence requirements, validation considerations, and potential regulatory pathway.
NAMs may reduce, replace, or complement certain animal studies, depending on the methodology, intended use, scientific evidence, and applicable regulatory expectations.
FDA, EMA, and MHRA are developing approaches to support the evaluation and potential regulatory use of NAMs. Their frameworks differ, but common considerations include scientific validity, context of use, evidence quality, and the ability of a method to address a defined regulatory purpose.