Overview
New Approach Methodologies (NAMs) are non-animal methods used to support the development of therapeutic products. These methodologies are primarily used in nonclinical studies and can support the replacement, reduction, or refinement (the 3Rs) of animal use in drug development and regulatory assessment.
The use of NAMs in the development of therapeutic goods is increasing globally as advances in science provide new ways to generate relevant safety and efficacy data.
The TGA already considers data from non-animal studies when evaluating the safety, quality, and efficacy of therapeutic goods during pre-market assessments. However, sponsors intending to use data from a novel NAM to support a clinical trial application or market authorisation application are strongly encouraged to engage with the TGA early in the development process.
Why do NAMs matter
While the primary goal of NAMs is to reduce reliance on animal testing for new and existing therapeutic goods, they can also provide data that are more directly relevant to human biology. In addition, many NAMs may offer faster and more cost-effective ways to generate evidence, helping to streamline the development and assessment of therapeutic products.
Our position on the use of NAMs
The TGA supports the scientifically justified use of NAMs where they are fit for their intended regulatory purpose. NAMs can strengthen the evidence base used to assess therapeutic goods while helping to reduce reliance on animal studies.
Regulatory acceptance of a NAM depends on the quality of the evidence supporting the method and its proposed context of use. Where uncertainty remains, NAMs may need to be used alongside traditional animal studies before they can be more broadly adopted as alternatives. When assessing the safety and efficacy of therapeutic goods, the TGA applies a weight-of-evidence (WoE) approach. This means that data generated using NAMs is considered alongside all other relevant evidence, considering factors such as the intended use of the method, its biological relevance, technical performance, limitations, and any remaining uncertainties.
At present, NAMs are generally not able to replace animal studies on a one-for-one basis. Many NAMs are designed to answer specific scientific questions and may not capture whole-body effects or interactions between multiple organs and biological systems. However, when used in combination with traditional animal models, NAMs can enhance scientific understanding and support regulatory decision-making, particularly in situations where animal models are limited, unavailable or have poor predictive value for humans.<
NAMs also have the potential to accelerate drug development and support applications for clinical trials or inclusion of therapeutic goods in the Australian Register of Therapeutic Goods (ARTG). To be used for regulatory purposes, however, the evidence generated from them must be scientifically robust, reliable, and appropriate for the decision being considered.
Globally, the adoption of NAMs continues to evolve. Key challenges include the limited number of methodologies that have been fully validated for regulatory use, a rapidly developing regulatory landscape, and the fact that acceptance is often dependent on the specific context in which a method is applied rather than being universally accepted. As a result, broader uptake of NAMs by regulators and industry is expected to occur progressively as the scientific evidence base and regulatory experience continue to grow.
TGA initiatives and activities
The TGA is supporting regulatory science research and the responsible adoption of NAMs through a range of activities. These include participation in national symposia and conferences, engagement with academic researchers and NAM developers, and the provision of regulatory advice to stakeholders.
The TGA also works closely with domestic and international partners to support the development and regulatory acceptance of NAMs. This includes collaboration with other regulatory authorities and participation in:
- The International Medicines Regulators’ Working Group on 3Rs (IMRWG3R), where regulators from Australia, the European Union, Switzerland, the United States, Canada, and Japan work together to promote the internationally harmonised use of NAMs and support the principles of replacement, reduction, and refinement (the 3Rs) in medicines regulation.
- The NSW Ministry of Health Office for Health and Medical Research's Non-Animal Technologies Regulation Working Group, which brings together stakeholders to advance the regulatory understanding and application of non-animal technologies.
Through collaboration, data sharing, mutual learning, and international harmonisation initiatives, the TGA aims to strengthen regulatory preparedness and support greater international alignment in the assessment and use of NAMs.
Regulatory requirements and guidance
Requirements for regulatory acceptance of NAMs
When proposing a NAM for a specific context of use, sponsors should provide evidence demonstrating that the method is suitable, reliable, and feasible for its intended regulatory purpose. The level of validation required should be proportionate to the regulatory significance of the data and the potential consequences of an incorrect conclusion. Regulatory expectations may vary depending on how the data will be used, for example, to support primary pharmacology claims or to provide safety information.
In general, the validation of NAMs should address four key considerations:
- Context of Use (CoU): Clearly define the purpose of the NAM, including the scientific rationale for its use and the regulatory question it is intended to address.
- Human Biological Relevance: Demonstrate how the information generated by the NAM relates to human biology and supports the assessment of a therapeutic product.
- Technical Considerations: Define the test method, endpoints, and performance characteristics, and provide evidence that the method produces reliable and scientifically credible data.
- Fit for Purpose: Demonstrate that the method is sufficiently robust, reliable, and appropriate for its intended use, while clearly describing its strengths, limitations, and any associated uncertainties.
Together, these considerations help establish confidence that a NAM can generate data that are appropriate and reliable for regulatory decision-making.
The following resources provide additional detail on the application of these principles:
- Regulatory acceptance of new approach methodologies (NAMs) to reduce animal use testing | European Medicines Agency (EMA)
- General Considerations for the Use of New Approach Methodologies in Drug Development
- Validation, Qualification, and Regulatory Acceptance of New Approach Methodologies: A Report of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Validation Workgroup.
NB. These guidance documents have not been formally adopted by the TGA.
Submissions to the TGA
The TGA has adopted a range of internationally recognised scientific guidelines that support the quality, nonclinical, and clinical evaluation of medicines and biologicals. You can access these here International scientific guidelines adopted in Australia. These guidelines provide an important framework for the generation, and assessment of data submitted in support of therapeutic goods.
While these guidelines inform regulatory expectations, the TGA does not prescribe specific nonclinical or clinical studies. Sponsors may submit data generated in accordance with relevant guidelines, as well as alternative scientifically justified approaches, provided the evidence is appropriate to support the application.
The TGA already considers data from non-animal studies when assessing the safety, quality, and efficacy of therapeutic goods during both pre-market evaluation and post-market monitoring. For example, in silico methods are currently used to support genotoxicity assessments and impurity safety read-across evaluations and are becoming increasingly common in regulatory submissions.
All NAM-based evidence is assessed on a case-by-case basis. This assessment considers factors such as the method's performance, biological relevance, limitations, and the overall body of supporting evidence. Consistent with the TGA's weight-of-evidence (WoE) approach, NAM data are evaluated alongside all other relevant information to determine their suitability for regulatory decision-making.
The evidence required to support a NAM will depend on several factors, including its proposed context of use, the potential impact of an incorrect result, the maturity of the method, and the extent of independent scientific experience with its application. Regulatory expectations are also likely to evolve over time as NAMs become more widely validated, internationally recognised, and accepted for specific uses.
Consistent with current Organisation for Economic Co-operation and Development (OECD) quality assurance principles for toxicity studies, NAM studies submitted for regulatory purposes are generally expected to be conducted in accordance with Good Laboratory Practice (GLP) requirements.
Sponsors intending to rely on NAM data in support of a clinical trial application or marketing authorisation are strongly encouraged to engage with the TGA early in the development process.
General principles and guidance for the use of NAMs
Some general points to consider before submitting a NAM as supportive evidence have been included in Table 1.
| Key principle | Explanation | Points to consider before submitting NAM data |
|---|---|---|
| Context of Use (CoU) | Clearly define the intended context of use - explain how the NAM data supports regulatory decision-making e.g., as a replacement for an existing requirement, or as part of a weight-of-evidence approach. |
|
| Establishment of Human Biological Relevance (HBR). | HBR refers to the relationship between the information generated by the NAM and how that information could impact the assessment of the drug in the context of human testing and prediction of toxicities that cannot be measured in clinical trials. Adequate demonstration of the biological relevance of a NAM provides confidence in the methodology. |
|
| Technical Considerations of the Defined Test Methodology | Explain how the NAM is run and controlled with enough detail that others can understand and repeat it. Include clear procedures, quality checks, and evidence that the method gives consistent results within and across laboratories. |
|
Fit-for-Purpose/ Reliability and robustness | Provide evidence to show it is suitable, reliable, and feasible for the proposed regulatory use. The strength of validation evidence should be proportionate to the regulatory importance of the method and the consequences of an incorrect conclusion. Regulatory requirements will differ depending on purpose e.g., primary pharmacology evidence versus safety data. For example, requirements for validation of models will be high when it comes to methods used to demonstrate safety. |
|
Clinical trial regulation in Australia
Clinical trials conducted in Australia are subject to a range of regulatory requirements designed to protect the safety, rights, and wellbeing of participants.
The TGA administers the Clinical Trial Notification (CTN) and Clinical Trial Approval (CTA) schemes, which provide pathways for the use of unapproved therapeutic goods in Australian clinical trials. The TGA also conducts inspections of clinical trial sites to verify compliance with regulatory requirements and Good Clinical Practice standards.
Sponsors intending to use data generated from a novel NAM to support a clinical trial application under either the CTN or CTA scheme are strongly encouraged to engage with the TGA early in the development process.
Early engagement allows the TGA to consider whether the proposed NAM is scientifically valid and fit for its intended purpose, and whether the data generated are appropriate to support the proposed clinical investigation and related regulatory decisions.
More information on clinical trials and unapproved therapeutic goods can be accessed here How we regulate Australian clinical trials that use unapproved therapeutic goods. In addition, the Australian clinical trial handbook provides guidance to clinical trial sponsors, Human Research Ethics Committees (HRECs), investigators, and approving authorities (institutions).
Related Guidance
The following resources have been provided for further reference and may not represent the views of the TGA.
Currently adopted guidance by the TGA
- ICH M3 (R2) Non-clinical safety studies for the conduct of human clinical trials for pharmaceuticals - Scientific guideline | European Medicines Agency (EMA)
- Other TGA-adopted guidance is available from the TGA website: International scientific guidelines adopted in Australia
- ICMRA statement
International regulator guidance on NAMs
European Medicines Agency
- Guidance for individual laboratories for transfer of quality control methods validated in collaborative trials with a view to implementing 3Rs
- Regulatory acceptance of new approach methodologies (NAMs) to reduce animal use testing | European Medicines Agency (EMA)
- Essential considerations for successful qualification of new methodologies
- EMA/56850/2025/Rev. 1 New Approach Methodologies EU-IN Horizon Scanning Report February 2025
Medicines and Healthcare products Regulatory Agency (MHRA)
U.S. Food and Drug Administration
- New Approach Methodologies (NAMs) | FDA
- General Considerations for the Use of New Approach Methodologies in Drug Development
Pharmaceuticals and Medical Devices Agency (PMDA; Japan)
[1] 9 November 2017 EMA/CHMP/CVMP/3Rs/94436/2014 Guidance for individual laboratories for transfer of quality control methods validated in collaborative trials with a view to implementing 3Rs
Other useful information
- CSIRO Futures, 2023. Non-animal models. A strategy for maturing Australia’s medical product development capabilities. Non-animal models - CSIRO
- Comprehensive in vitro proarrhythmia assay (CiPA) initiative to improve cardiac safety assessment without animal testing
- Interagency Coordinating Committee on the Validation of Alternative Methods, 2024, Validation, Qualification, and Regulatory Acceptance of New Approach Methodologies: A Report of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Validation Workgroup, https://ntp.niehs.nih.gov/sites/default/files/2024-03/VWG_Report_27Feb2024_FD_508.pdf.
- Nonanimal Models for Preclinical Safety and Efficacy Workshops in Australia https://globalforum.diaglobal.org/issue/april-2025/nonanimal-models-for-preclinical-safety-and-efficacy-workshops-in-australia/
- An evaluation framework for new approach methodologies (NAMs) for human health safety assessment - ScienceDirect
NAM databases
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