The regulatory conversation around non-animal methods is moving beyond whether these approaches can generate scientifically credible data. The more difficult question is how regulators can evaluate that evidence consistently and determine where it can contribute to regulatory decision-making.
The European Medicines Agency (EMA) has taken a practical step in this direction with its Voluntary Data Submission (VDS) pilot, launched in September 2026. The pilot allows companies, contract research organisations, method developers, academic laboratories and other stakeholders to voluntarily submit data generated using New Approach Methodologies (NAMs) outside a marketing authorisation application.
EMA's NAM Voluntary Data Submission Pilot: Why It Matters Now
NAMs are becoming increasingly relevant across non-clinical development, encompassing approaches such as complex in vitro systems, organoids, microphysiological systems, computational and in silico models, and combinations of methodologies.
While the scientific case for NAMs is developing rapidly, regulatory experience has not always kept pace. Limited real-world regulatory experience can make it challenging to establish consistent expectations around their reliability, relevance and appropriate use. EMA’s VDS pilot is designed to help address this evidence gap.
The pilot enables participants to submit and discuss NAM-derived data outside a marketing authorisation application. Feedback is individual, non-binding and non-decisional; it does not constitute a marketing authorisation decision, formal qualification or guarantee of acceptance in a future regulatory submission.
Its value therefore lies in building regulatory experience and confidence, supporting more consistent assessment approaches and informing future regulatory acceptance of NAMs. For sponsors, 2026 marks an important step toward NAMs regulatory acceptance—from broad encouragement of innovative methods toward more structured consideration of how specific NAMs can address defined regulatory questions.
What is the EMA Voluntary Data Submission Pilot?
The VDS pilot is a voluntary mechanism for submitting and discussing data generated using NAMs, independently of a marketing authorisation application. The pilot applies to both human and veterinary medicines and is not limited to pharmaceutical companies. Companies, method developers, CROs, academic laboratories, consortia and other stakeholders can participate where their data fall within the pilot’s defined scope.
EMA has limited the pilot to predefined contexts of use (CoUs) and broader Regulatory Applicability Areas (RAAs). This is important because the acceptability of a NAM cannot be considered independently of what the method is intended to demonstrate. The process begins with an expression of interest using the EMA application form. EMA then performs an initial validation and prioritisation. Selected applicants are invited to submit a full briefing package for scientific assessment.
The briefing package is expected to provide a structured description of the methodology, its performance, proposed context of use and regulatory relevance. EMA indicates that the package should, where appropriate, be aligned with the format and level of detail of a written summary corresponding to eCTD Module 2.4.
The submission should clearly define:
- The regulatory problem, applicability area and proposed context of use
- How the NAM will be used, including independently, in a battery or within a weight-of-evidence approach
- The relevant endpoint, biological mechanism and safety endpoint
- The development stage and validation/characterisation status
- Biological relevance, robustness, reproducibility and supporting in vivo or external validation data
- Limitations, uncertainties and intended regulatory application
- Compatibility with existing regulatory guidance and the regulatory gap analysis it could address
Even a technically sophisticated NAM can be difficult to evaluate if its intended regulatory question and context of use are not clearly defined. The pilot was launched in September 2026, with applications expected to remain open until September 2027. EMA plans to publish a lessons-learned report after the pilot, while participating organisations will receive individual informal feedback within the pilot timeframe.
What Does EMA Actually Want to Learn from NAM Data?
The VDS pilot is not simply an exercise in collecting examples of innovative technologies. EMA is looking to understand how NAM evidence can function within regulatory decision-making.
Several themes are particularly important:
| Key Consideration | What to Demonstrate | Regulatory Relevance |
|---|---|---|
| Context of Use | Define where, how and for what purpose the NAM will be used. | Link the NAM to a defined regulatory question and decision. |
| Biological Relevance | Show its relevance to the human safety question and underlying biology. | Establish scientific justification for using the method to address the regulatory concern. |
| Performance & Reliability | Demonstrate reliability, reproducibility and appropriate validation. | Support confidence in the method's results for the intended context of use. |
| Evidence Integration | Explain how NAM data complement other evidence within a WoE approach. | Show how the combined evidence supports a scientifically justified regulatory conclusion. |
| Limitations & Uncertainty | Clearly identify limitations and remaining uncertainties. | Enable transparent interpretation of results and assessment of residual uncertainty. |
What Should Sponsors Assess Before Submitting NAM Data?
A sponsor considering the VDS pilot should assess the regulatory case before assembling the submission package.
- Define the regulatory question
Clearly state the regulatory decision the NAM is intended to support and why it is relevant. - Define the context of use
Specify what the NAM is intended to do, including the endpoint, biological system, conditions and regulatory decision. - Characterise the method
Document the model, endpoints, controls, performance, reproducibility, robustness, data quality and known limitations. - Establish biological relevance
Explain how the NAM reflects relevant human biology and supports the specific safety question. - Determine the evidence approach
Define whether the NAM will be used independently, in a battery or within a weight-of-evidence (WoE) approach, with a clear rationale for combining evidence. - Assess validation and comparative evidence
Use available internal or external validation, established-method comparisons and relevant in vivo data to support confidence in the NAM. - Identify the regulatory gap
Explain what the NAM adds—for example, greater human relevance, mechanistic insight, reduced animal use or evidence where existing approaches are limited. - Define the regulatory application
Explain how the NAM or WoE approach could be used in development or regulatory submissions, considering the product, development stage and regulatory pathway.
VDS vs ITF vs Scientific Advice vs Qualification Advice
The VDS pilot does not replace existing EMA procedures. In fact, one of its purposes is to help identify when another regulatory interaction may be more appropriate.
| Route | Primary Purpose | Best Suited To |
|---|---|---|
| VDS Pilot | Obtain individual, non-binding feedback on NAM data and regulatory readiness within the pilot scope. | NAM data requiring regulatory experience and assessment outside an MAA. |
| Innovation Task Force (ITF) | Early informal dialogue on innovative technologies, methodologies and regulatory/scientific issues. | Early-stage innovation and regulatory uncertainty. |
| Scientific Advice | Obtain formal scientific guidance on development strategy, studies or methodology. | Product-specific or development-specific regulatory questions. |
| Qualification Advice | Support development of an innovative methodology for a specific intended use/context. | Sponsors or developers seeking a formal qualification pathway for a methodology. |
The distinction matters because a sponsor should not automatically choose VDS simply because a programme involves a NAM. EMA’s VDS process allows for the possibility that an alternative procedure may be more appropriate. During initial validation, applications can be redirected toward established routes such as ITF briefing, scientific advice or qualification advice where relevant.
The VDS pilot is therefore best understood as one component of the EMA regulatory ecosystem for innovative methodologies, not a new universal approval route for NAMs. For sponsors, selecting the right interaction early can prevent an evidence package from being developed around the wrong regulatory question.
What FDA and MHRA Are Doing Differently
The global regulatory direction is converging around greater use of scientifically justified non-animal methods, but the mechanisms being used by regulators are different.
The US FDA issued draft guidance in March 2026 on the general considerations for using NAMs in drug development. The draft provides a validation-oriented framework covering areas such as context of use, human biological relevance, technical characterisation and fit-for-purpose considerations. The guidance is non-binding and remains in draft form but provides a framework for developers considering NAMs for regulatory use.
In September 2026, FDA also updated its broader NAM activities and introduced a NAM Database of Use Case Examples based on publicly available FDA application review materials. The database provides practical examples of NAMs used in specific regulatory applications. Importantly, FDA states that these examples are illustrative and do not constitute guidance, approval of a method for future use or a recommendation that a method will be acceptable in another submission. Acceptability remains context-specific and depends on factors such as the method, endpoint, product, data package and application.
The MHRA has taken a different but complementary approach. Its March 2026 guidance explains that non-animal methods can be submitted as part of applications and that the agency will assess the overall evidence package rather than expecting a one-to-one replacement of individual animal studies. It also states that applications are assessed individually and that scientifically justified departures from existing expectations can be considered where alternative approaches adequately address safety.
Viewed together, the three approaches illustrate three complementary regulatory perspectives:
EMA VDS creates a structured opportunity to submit NAM and weight-of-evidence data independently of a marketing authorisation application. Its immediate value is regulatory learning, scientific dialogue and feedback on readiness within defined contexts of use and regulatory applicability areas.
FDA’s NAM framework places significant emphasis on validation principles that establish confidence in the method and its intended regulatory application. The March 2026 draft guidance is not final or legally binding, while the new use-case database provides practical examples of how NAMs have appeared in specific FDA reviews.
MHRA’s approach focuses strongly on the totality of evidence presented in a specific application. The agency does not expect one non-animal method to replace one animal study on a direct one-to-one basis and instead considers whether the overall data package supports the proposed clinical or marketing decision.
The same NAM may therefore require different documentation, validation evidence, contextual justification or regulatory engagement depending on where it is intended to support development. A global NAM regulatory strategy should consequently consider regulatory expectations early rather than treating EMA, FDA and MHRA submissions as interchangeable.
From NAM Data to Regulatory Acceptance: What's Next?
The VDS pilot should not be interpreted as the final stage of NAM regulatory acceptance. Its immediate purpose is to generate experience and structured feedback. The longer-term objective is to help regulators understand which types of NAM evidence can support regulatory decisions and what criteria are needed to evaluate those approaches consistently.
EMA expects the pilot to contribute to lessons learned and support future work on context-of-use-based acceptance criteria. A sponsor receiving positive or useful feedback from the VDS pilot should not automatically describe its method as qualified, authorised or generally accepted. The feedback is non-binding and non-decisional.
That may involve:
- Refining the context of use
- Strengthening validation
- Generating additional reproducibility data
- Addressing identified limitations
- Improving the weight-of-evidence rationale
- Conducting additional regulatory interactions
- Adapting the development programme
- Preparing a stronger future regulatory submission
NAMs in drug development are moving toward a model in which regulatory acceptance depends on defined use, scientific confidence, biological relevance, data quality and the ability of the evidence package to support a specific decision. The transition is therefore unlikely to be a simple move from animal studies to NAMs. It is more likely to involve increasingly sophisticated evidence strategies in which NAMs, mechanistic data, computational approaches, clinical information and other evidence sources are combined according to the scientific question and regulatory purpose.
How does DDReg Supports the approach
DDReg can support sponsors in translating emerging regulatory expectations into practical development `and regulatory considerations. This can include assessing the regulatory relevance of NAM approaches, mapping the intended context of use, reviewing available scientific and regulatory evidence, identifying potential gaps and evaluating appropriate regulatory engagement pathways.
Support can also include comparative assessment of EMA, FDA and other regulatory expectations, development of NAM regulatory strategies, preparation of briefing materials and support for interactions with health authorities.
Conclusion
The EMA VDS pilot marks an important development in the regulatory evolution of non-animal methods. Its significance lies not in creating a shortcut around conventional regulatory requirements, but in giving regulators greater exposure to real-world NAM data and giving stakeholders a structured opportunity to discuss how those data can support regulatory questions.
A strong approach starts by defining the regulatory question and context of use, understanding the biological relevance of the method, characterising its performance and limitations, determining how it fits within a broader evidence package, and selecting the regulatory interaction that best matches the objective.
The EMA pilot, FDA’s emerging validation framework and use-case examples, and the MHRA’s case-by-case evidence assessment demonstrate that global regulatory expectations are evolving but are not yet identical. Sponsors developing NAMs should therefore treat regulatory engagement as part of evidence generation itself. The objective is not simply to demonstrate that a method can produce data. It is to demonstrate why those data are relevant, reliable and fit for the regulatory decision they are intended to support.
Frequently Asked Questions
The EMA VDS pilot, launched in September 2026, allows stakeholders to voluntarily submit and discuss NAM data outside a marketing authorisation application. Participants receive individual, non-binding and non-decisional feedback on the regulatory readiness of the NAM or weight-of-evidence approach.
No. Participation does not constitute formal qualification, approval or authorisation of a NAM. The pilot is intended to build regulatory experience, support scientific dialogue and inform potential next steps for regulatory acceptance.
Selected applicants submit a structured briefing package covering the regulatory applicability area, problem statement, context of use, methodology, endpoints, biological relevance, validation and performance, limitations, intended regulatory application and compatibility with existing guidance. The package should also explain whether the NAM is used independently, in a battery or within a weight-of-evidence approach.
The pilot is open to stakeholders including companies, method developers, CROs, academic laboratories, consortia and other organisations. Applications are expected to remain open until September 2027, subject to the pilot's defined eligibility, regulatory applicability areas and contexts of use.