A new era of drug development: Comparing regulatory roadmaps to reduce animal testing

Introduction

The poor translatability of animal models where interspecies differences limit their predictability, alongside the need for more ethical and sustainable science, has led to recent regulatory roadmaps to reduce animal testing from the United States (US) FDA, the United Kingdom’s (UK’s) Government and on June 1st 2026, the European Commission (EC).  These highlight their respective commitments to phasing out animal testing where possible in favour of innovative non-animal approaches, known as New Approach Methodologies (NAMs).

We now stand at a pivotal moment in drug development. Following these announcements, regulators are signaling a future where NAMs such as in silico models, AI and microphysiological systems (MPS), are more than just peripheral tools. They will become increasingly central to defining how new medicines are discovered, evaluated, and approved.

In part one of this blog series, we will explore:

• How animal reduction roadmap announcements from the US, UK and EC compare
• Why NAMs have moved from promise to regulatory reality.
• New guidance for NAMs-use in drug development and how we can support your transition by changing the game, together.

How does the EC announcement compare to the US FDA and UK governments?

The EC announcement commits to phasing out animal testing entirely for chemical safety assessments “as soon as scientifically possible”, framing it as both ethically imperative and as fostering innovation and competitiveness. Its ambitious roadmap cites cross-sector regulatory transformation across 15 legislative domains, including:

• Chemicals (REACH)
• Pharmaceuticals
• Pesticides/ biocides
• Food/feed additives
• Medical device compatibility

The roadmap sets out clear objectives and the steps required to transition, stating that non-animal approaches must offer the same level of protection as currently established methods. It is built around a three-pillar implementation model: #1 Making change happen #2 Keeping Europe at the forefront of research and innovation by aligning institutional efforts and resources, and #3 Working together in Europe and beyond. An accompanying Staff Working document (SWD(2026)114) provides the evidence supporting the proposed actions.

The announcement cites the gradual transition to a new scientific framework as a “paradigm shift”, with initial efforts focusing on “recognizing knowledge gaps, prioritizing future funding and identifying any needs for possible change”. The EU states a move from observing adverse effects in animals towards Next Generation Risk Assessment (NGRA) using alternatives to deliver mechanistic, human-relevant biology that provides a molecular-level understanding of toxicity.

Their timeline for change represents a managed transition that is organized into:

• Short-term actions: centered around implementing existing alternatives and removing redundant animal tests
• Medium-term: validating and adapting new methods for implementation
• Long-term: Redefining non-animal safety assessment frameworks to allow the “switch to animal-free regulatory assessments” and performance criteria for future NAMs

It is backed by regulatory infrastructure change across decentralized EU agencies (EMA, EFSA, ECHA) to provide regulatory exploration spaces for prioratizing regulatory need, and “safe spaces” for companies to test the acceptability of alternative approaches with regulators, “without regulatory consequences”. Furthermore, significant funding has been allocated to keep Europe at the forefront with an ecosystem push of investment into research and development, and to support non-animal method validation, qualification and standardization.

Their proposal, of more than 30 concrete and targeted recommendations to replace, reduce, and refine animal testing in the short to long-term, sets the EU up as the strongest regulatory driver for NAMs across the entire chemicals industry. For human health assessments, these include the areas of acute toxicity testing, genotoxicity, carcinogenicity, repeat dosing toxicity, developmental neurotoxicity (DNT), reproductive toxicity (DART) and endocrine disruption.

The Commission aims to implement short-term actions into legislation and guidance by the end of 2029, have a supporting organizational structure to steer roadmap implementation in 2026, publish an EU report on key areas of regulatory need by 2027 and provide access to the experimental facilities and expertise of EURL ECVAM (EU Reference Laboratory for Alternatives to Animal Testing) to promote the development and validation of non-animal approaches.

Focusing on the EMA for pharmaceuticals, current guidelines for the regulatory acceptance of 3R testing approaches remain unchanged from 2017. Requirements for primary pharmacology are not strictly defined, but are more stringent for toxicology. Guidance states that developers should consider how NAM data will be used in the context of regulatory decision-making. The NAM can replace an existing regulatory requirement, or it can contribute to a ‘weight of evidence’ approach. Regulatory acceptance is currently handled on a case-by-case basis.

The US positions adoption of NAMs as a scientific modernization effort to improve predictive accuracy and reduce development costs in pharmaceutical development. The US roadmap is strongly driven by the FDA through federal legislation, notably:

• FDA Modernization Act 2.0 (2022) explicitly allowed NAMs for IND/BLA submissions and removed animal testing requirements for biosimilars.
• FDA’s roadmap (announced April 10, 2025), which outlines a strategic, stepwise approach to reduce and replace animal testing across drug development
• FDA Modernization Act 3.0, approved by the Senate in Dec 2025, aims to formally update FDA regulations so animal tests are no longer the implied default.

The FDA is initially prioritizing regulatory certainty and caution, noting that NAMs must be “ready for prime time”, but has stated that it envisions animal studies will become “the exception rather than the default” within nonclinical safety testing. Their strategic stepwise approach begins with monoclonal antibodies (mAbs) as the first test case, with other drug types to follow.

Read more about the reasons behind the US animal testing phase out for mAbs – including the shortcomings of animal models, plus practical considerations around “skyrocketed” costs in our blog.

To facilitate and accelerate the validation of NAMs, the FDA is collaborating with federal agencies such as the NIH and VA via the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). In 2025, the NIH demonstrated its commitment to change by ceasing funding opportunities for purely animal-based projects and, in 2026, announced more than $150 million to develop and scale research methods that better simulate human biology and reduce reliance on animal models. The first funding awards under the Complement Animal Research in Experimentation (Complement-ARIE) program have now been granted to set up new Technology Development Centers, which facilitate the development of NAMS in the areas of greatest scientific and regulatory need.

Alongside this, the FDA’s CDER Group has provided industry with regulatory guidance (draft guidance released March 2026) encouraging the use of NAMs within nonclinical data packages. The draft guidelines emphasize context-of-use, human biological relevance, technical characterization, and fit-for-purpose criteria for their use in regulatory submissions, which is explored in additional detail below.

By comparison, the UK frames its roadmap (launched in Nov 2025) as an ethical, economic, and scientific transformation. Driven by a government manifesto commitment, the plan aims to phase out animal testing by utilizing emerging technologies and reducing regulatory barriers. The manifesto covers the Home Office, DEFRA, DSIT, and MHRA, signalling cross-government policy alignment.

The UK’s roadmap is predominantly led by the MHRA and supported building capacity, infrastructure, and national accelerator programs. A total of £75 million in funding has been allocated to accelerate NAM innovation and validation via a new UK Centre for the Validation of Alternative Methods (UKCVAM), alongside funding to advance new in vitro models of the liver, brain, cancer, pain and blood vessels for use as more human-relevant alternatives to animals within five UK-based teams.

The UK’s plans are prescriptive and timeline-driven, signaling a push for the rapid adoption of animal alternatives. The long-term goal is to eliminate animal use in “all but exceptional circumstances.” The UK’s roadmap is categorized into distinct baskets. Basket 1 focuses on areas with potential for rapid NAMs transition, including:

• End of 2026: eliminate animal regulatory tests for skin/eye irritation and sensitisation.
• 2027: end Botox potency tests on mice and use only DNA-based lab methods for adventitious agent testing
• End of 2025: rabbit pyrogen test phased out.

Basket 2 includes tests that require further development in the medium term. One goal is to reduce the use of dogs and non-human primates in dedicated pharmacokinetics (PK) studies for human medicines by at least 35% by 2030.

Basket 3 covers instances where no suitable alternative methods currently exist, e.g. reducing the use of fish in assessing endocrine disruption by the end of 2035.

Read more about the UK’s plans to phase out animal testing faster in favor of alternative methods in our blog

The UK has now moved on to the early execution phase, building the systems, skills, and funding mechanisms required to execute its roadmap. The MHRA has just released new guidance outlining how it will assess applications for medicines that use alternative methods to replace animals in science, which will be explored in more detail below.

Why NAMs are moving from promise to regulatory reality?

Despite significant scientific progress, drug developers continue to face the same core challenges that have limited preclinical decision‑making for decades: unclear or conflicting animal data, late‑stage clinical failures, and a need for mechanistic clarity. Regulatory expectations will continue to evolve, and pressure will increase to strengthen data packages. MPS and other complementary NAMs provide human‑relevant insight that traditional models often miss. Specifically, they can be applied to three major areas; ADME/PK, safety assessment and efficacy, plugging gaps where traditional models offer limited predictability.

Unsurprisingly, these regulatory roadmaps focus on derisking safety assessments and/or more accurately predicting a drug’s PK ahead of Phase I studies. This is where regulators most closely examine nonclinical packages. These are also the areas where NAMs deliver the most impact, as model development and validation is well underway.

For safety pharmacology, off-target toxicity, dose-response characterization, organ-specific liability and PK/ADME, the scientific and regulatory environment is shifting. We are seeing wider acceptance of validated non-animal approaches in nonclinical packages achieved through a structured, stepwise and manageable transition. This approach is crucial as it does not immediately disrupt the status quo. Instead, it asks sponsors to begin compiling data packages that answer the specific questions reviewers need, using the best available tool for the job, animals, NAMs, or both animals and NAMs.

Regulatory guidance for NAMs use in drug development

Whilst we wait for further regulatory guidance updates from the EMA, the MHRA has recently published new guidance for the use of NAMs in nonclinical packages, and the FDA has published draft guidance.

The FDA highlights that while most investigational novel drug-enabling studies have traditionally been performed in animals, CDER routinely receives and reviews NAM-based data. It actively encourages the use of NAMs where they improve predictivity, reliability, and human relevance compared with traditional animal studies. Their draft guidance for the use of NAMs is short, concise and easily digestible. It clarifies that full validation is not always required for a NAM to support a drug application. It specifies four pillars to consider when integrating NAMs into drug development and regulatory submission packages to “improve predictive toxicology in humans and move away from reliance on animal testing”. These are: human biological relevance, technical characterization, context of use and fit‑for‑purpose.

Reassuringly for CN Bio as an MPS provider, the best practices that we adhere to when developing, characterizing and validating our MPS models are perfectly aligned with these pillars. Our focus here at CN Bio has always been to show how MPS enhances workflows and overcomes limitations for specific contexts of use. While it is important to note that this document remains a draft until May 18^th, 2026, when the public comment process closes, it gives insight into where the FDA considers NAMS to be fit-for-purpose. They are best used when:

• Replacing an animal study
• Filling a data gap that animal models cannot address
• Confirming or complementing existing data within a weight of evidence framework.

These align with what our Contract Research Services Team is already seeing through our work with the industry. Clients frequently ask for confirmatory data or have real-world late-stage drug development questions, including mechanism of action queries from clinical observations, that can’t be answered using any other means.

While the FDA’s draft guidance sets out the principles for evaluating NAMs, it doesn’t specify scenarios where they might apply, and instead leaves it to the sponsor’s discretion to justify their choices. In contrast, the approved MHRA guidance released on March 25^th, 2026, is more prescriptive. It provides a consolidated document with guidance on the use of non-animal methods using specific example scenarios in medicine development. These scenarios illustrate how the MHRA may evaluate applications that include or omit animal studies:

1. Novel systemically administered small molecules
2. Vaccines and other biological products with platform or component similarity
3. mAbs and other modalities with limited animal relevance
4. Advanced Therapy Medicinal Products where animal testing is not expected

The MHRA says it does not “expect that specific non-animal methods can be used to replace specific animal studies on a 1:1 basis.” Clarifying that “Alternative assays should provide data on which to make a decision and the MHRA review will focus on whether the data package, overall (with or without data from animal studies), supports safe and scientifically justified use of the product.

They encourage developers to submit NAMs data alongside information about their robustness and relevance to humans. This data can be obtained in parallel with conventional animal studies, and will be assessed as part of the total weight-of-evidence for each application.

What is clear is that the FDA and MHRA both emphasize the same goal of better-informed decisions based on robust, human-relevant mechanistic evidence with a clearly defined context-of-use, rather than only using animal models as the default. Neither agency expects a 1:1 replacement. Instead, they prioritize a clearly defined context-of-use. This doesn’t completely resolve regulatory uncertainty, but it is a meaningful step towards clarity and alignment that is starting to take shape in a practical and meaningful way. This gives developers a much clearer framework for integrating MPS data into nonclinical packages with greater confidence.

For a detailed document-level comparison, read our blog: Do MHRA and FDA guidelines on non-animal drug development align?

Summary

Regulatory momentum across the globe is shifting towards NAMs-based data in nonclinical packages. Even though each region has chosen a slightly different route, they are all moving towards more ethical, human translatable, NAMs-based science.

Against this backdrop, MPS are moving from promise to practice. By addressing known gaps in predictivity, mechanistic insight and translatability, especially where interspecies differences can “muddy the waters”, in areas such as safety, ADME and disease modeling, these systems align well with evolving regulatory expectations. With regulators now encouraging early engagement, parallel submission, and weight‑of‑evidence approaches, the opportunity for sponsors is clear: by integrating validated, human‑relevant NAMs today, they can build stronger, future‑ready regulatory packages and support a more efficient reduction in animal use.

Greater regulatory clarity means pharmaceutical and biotech companies can confidently use MPS to build stronger regulatory packages. Progress is accelerating, and the industry is ready for change. Contact us here to discuss how we can support your transition.

Part two of this blog series explores some of the contexts of use where MPS are aligned with regulatory roadmaps. And we share a case study on validating an MPS-based Drug-induced liver injury assay through the FDA’s ISTAND program. Continue reading part 2: For which contexts of use are microphysiological systems regulatory roadmap aligned?

Related resources:

1. Read more about the reasons behind the US animal testing phase out for mAbs – including the shortcomings of animal models, plus practical considerations around “skyrocketed” costs in our blog.
2. Read more about the UK’s plans to phase out animal testing faster in favor of alternative methods in our blog

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