Concept of New Approach Methodologies (NAMs) use in quasi-drug applications — PMDA Early Consideration Summary

In Plain Language

The document addresses how methods other than animal testing may be developed and used in non-clinical studies supporting quasi-drug applications in Japan. It describes a need for more alternatives, since some types of non-animal safety evaluation have not yet been established and methods for assessing systemic effects after repeated administration remain a challenge. PMDA plans to continue assessing NAMs in individual product applications and to work with stakeholders on developing and using them. Its proposed activities include collecting data on NAM studies and considering new methods when needs are confirmed. The broader aim is to support more rational and efficient development and assessment while addressing limitations of animal testing, including differences between species.

What This Guidance Covers

The document sets out PMDA’s direction on evaluating New Approach Methodologies (NAMs) as alternatives to animal-based testing for non-clinical studies required in quasi-drug applications. It is focused on applications for quasi-drugs in Japan, and on ways to develop and use NAMs in that setting. The document describes NAMs broadly: they include newly developed tests and assessment tools and systems that combine evaluation methods. They are not limited to tests validated by public institutions such as the Organisation for Economic Co-operation and Development (OECD).

The document does not provide a list of accepted NAMs, a general testing protocol, or a single detailed assessment framework for all quasi-drug products. Instead, it describes PMDA’s initiative and intended areas of work, while stating that PMDA will continue to assess NAMs in each product application and publish guidance on individual NAMs in cooperation with stakeholders. The document does not specify a product-by-product scope beyond non-clinical studies required for quasi-drug applications.

It also does not establish one internationally agreed definition of NAMs. It notes that the term is used in different ways and describes definitions or examples from sources including the European Medicines Agency (EMA), the U.S. Food and Drug Administration (U.S. FDA), and the European Commission’s Scientific Committee on Consumer Safety (SCCS). These references illustrate the varied uses of the term; they are not presented as a single definition adopted by this document.

Why It Matters

The document places the development of non-animal methods in the context of animal welfare and long-running efforts to develop alternatives for non-clinical studies. It describes movements in Europe and other countries since the early 2000s to prohibit animal testing in the development of cosmetic products, as well as companies related to quasi-drugs in Japan declaring the abolition of animal testing.

Japan has published 13 guidance documents concerning alternatives to animal testing, including for skin irritation, ocular mucosal irritation and skin sensitization. The document says these were prepared through collaboration among government, industry and academia to support the use of alternatives, including OECD guidelines, in quasi-drug safety evaluation. PMDA contributed to their development.

However, the document identifies continuing gaps: non-animal evaluation methods have not been established for some tests, and further alternatives and evaluation systems combining multiple methods are needed. It specifically notes that NAMs capable of assessing systemic toxic effects after repeated administration, among other effects, had not been developed at the time the document was prepared. PMDA’s stated response is to work with stakeholders to promote further NAM development and support rationalisation of quasi-drug approval reviews in Japan.

Key Recommendations

The document describes PMDA’s direction and planned activities rather than prescribing a single test strategy for sponsors. Its main points are:

1. Continue assessment in individual applications. PMDA says it will continue conducting assessment of NAMs in each product application. This means the document does not state that a method’s suitability for one application automatically settles its use in another.

2. Develop guidance on individual NAMs with stakeholders. PMDA will continue publishing guidance on individual NAMs in cooperation with stakeholders. The document frames this work as one way to indicate points to consider for developing and using NAMs.

3. Collect data on NAM studies. PMDA plans to collect raw and other data on NAM studies performed in Japan and other countries. The document presents this data collection as part of the effort to support stakeholder development of NAMs for quasi-drug development in Japan.

4. Consider methods when needs are confirmed. PMDA plans to initiate consideration of novel NAMs promptly after confirming the needs. The document says this consideration should keep in view both newly emerging methods and existing methods, giving Microphysiological Systems (MPS) as an example of an existing method.

5. Work toward a scientific advice framework. PMDA states that its activities are intended to help establish a new scientific advice framework for using NAMs to obtain regulatory approval. The document describes this as an aim; it does not set out the framework’s procedures or eligibility criteria.

These activities are intended to help create an environment in which quasi-drugs can be developed rationally and efficiently, and to address limitations of animal-based testing, including differences in reactivity due to species differences.

Practical Implications

Interpretation: For sponsors and non-clinical scientists, the document signals that NAMs can be considered in quasi-drug applications, but it does not offer a blanket assurance that any particular method or combination will be suitable. PMDA’s stated approach remains assessment in each product application. In planning a non-animal strategy, teams may therefore need to describe the methods used and the data supporting their evaluation in the context of the product application. This is an interpretation of the product-specific assessment approach, not a separate PMDA requirement stated in the document.

Interpretation: The planned collection of raw and other study data makes the quality and availability of study information relevant to the shared development effort described by PMDA. The document does not specify what data sponsors must submit for this purpose, how they should be formatted, or whether particular datasets will be requested in an application. It therefore should not be read as introducing a new data-submission checklist.

Interpretation: The document’s support for combined evaluation systems suggests that developers may consider how multiple methods could contribute to an assessment, rather than treating each test as the only possible source of information. However, the document does not describe a particular combination, define how methods should be weighted, or set decision criteria for combining results. Those specifics are left to future consideration and guidance on individual NAMs.

For regulatory teams, the document is useful context for understanding PMDA’s planned engagement with stakeholders and its intention to develop a scientific advice framework. It does not explain how to access that framework or provide a timeline. For investigators and method developers, its call to consider both emerging and existing NAMs indicates a broad area of interest, while the need for methods addressing currently unmet assessment areas remains an important context.

Technical Details

This document does not present statistical methods, equations, numerical decision rules, or a technical validation procedure. Its technical content is mainly about the meaning and breadth of NAMs, the types of methods that may be included, and the limitations identified at the time of publication.

To illustrate the range of meanings, the document reports that EMA describes NAMs as novel methods compliant with the 3Rs principles: Refinement, Reduction and Replacement. It says the U.S. FDA describes them as alternatives to traditional animal testing and emphasises that method validity and reliability should be established. It also reports that the SCCS notes NAMs may include in vitro, ex vivo, in chemico and in silico methods, as well as grouping, Read-Across and combinations of these approaches, particularly in hazard identification. These are descriptions attributed in the document to the named sources, rather than additional technical criteria specified by PMDA here.

The document distinguishes between methods that exist and areas where further development is needed. It identifies methods for some evaluations, including skin irritation, ocular mucosal irritation and skin sensitization, as subjects of existing Japanese guidance. At the same time, it identifies the assessment of systemic toxic effects after repeated administration as a challenge for NAM development. The text does not give a test-by-test inventory of remaining gaps, nor does it define what evidence would resolve each gap.

Structurally, the document has three parts: an introduction describing the purpose and terminology; a background section on existing alternatives and remaining needs; and a section setting out PMDA’s initiative. Its central practical distinction is between continuing to evaluate methods in individual applications and developing broader guidance and advice activities in collaboration with stakeholders.

Who Should Read It

This document is relevant to professionals involved in non-clinical safety assessment and quasi-drug applications in Japan, including:

• Regulatory affairs staff seeking to understand PMDA’s stated direction on NAMs and planned scientific advice activities.
• Non-clinical scientists and toxicologists developing or assessing alternative methods, including methods used in combination.
• Statisticians and data scientists supporting the evaluation of study data generated by NAMs, particularly where data from methods or studies need to be considered together.
• Clinical research and medical writing professionals who need context on the non-clinical evidence supporting quasi-drug applications.
• Industry, government and academic stakeholders involved in NAM development, data collection, or the preparation of guidance on individual methods.

It is especially relevant when a team is considering non-animal approaches for a quasi-drug application, is working in an area where methods remain under development, or wants to understand the collaborative work PMDA says it intends to undertake.

Official PMDA Source

• Official title: Concept of New Approach Methodologies (NAMs) use in quasi-drug applications (Early Consideration)
• Issuing body: Pharmaceuticals and Medical Devices Agency, Office of OTC / Quasi-drugs
• Date on the cover: September 25, 2025
• PMDA PDF: Official PMDA document (PDF)
• PMDA list page: PMDA Early Consideration documents

Source: Pharmaceuticals and Medical Devices Agency (PMDA) website, PMDA Early Consideration documents. This page was created by editing and summarising the PMDA document.

Consult the official document for the complete text; this summary does not replace it. PMDA provides the English version for reference purposes, and the Japanese original prevails if the two differ. PMDA describes Early Consideration documents as reference information reflecting the Agency’s views at the time of publication; those views may change as scientific knowledge develops.

Related Clinical Biostats Resources

• All Clinical Biostats tutorials — Browse other educational tutorials, including summaries of PMDA Early Consideration documents.
• Statistical Calculators — Access calculators that may support statistical work related to research and evidence assessment.