FDA and MHRA Move Away From Animal Testing: What the New Approach Methodologies (NAMs) Shift Means for Regulatory Affairs Professionals in 2026

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The FDA NAMs roadmap for reducing animal testing is now over a year into implementation, and the Medicines and Healthcare products Regulatory Agency (MHRA) has published its own parallel guidance on non-animal methods. Together, these changes affect any sponsor preparing nonclinical safety data for an Investigational New Drug (IND) application, a Clinical Trial Authorisation (CTA), or a Marketing Authorisation (MA) in the US or UK. As of September 2026, developers who can justify a New Approach Methodologies (NAMs)-based package — using tools such as physiologically based pharmacokinetic (PBPK) modelling and quantitative structure-activity relationship (QSAR) models — may reduce, refine, or in some cases omit, certain animal studies, provided the scientific rationale is robust.

FDA NAMs roadmap and MHRA non-animal methods guidance — overview of nonclinical regulatory science in 2026

Contents

1. At a Glance

2. Background: Why Nonclinical Regulatory Science Is Being Rewritten Now

3. The FDA's Roadmap to Reducing Animal Testing in Preclinical Safety Studies

4. MHRA's Approach to Medicines Using Non-Animal Methods

5. PBPK Modelling and QSAR: The Science Behind the NAMs Shift

6. Where EU, UK, US and ICH Requirements Still Diverge

7. Deepen Your Knowledge: Regulatory Affairs Training on This Topic

8. Practical Implications for Regulatory Affairs Professionals

9. Key Takeaways

10. Take the Next Step in Your Regulatory Affairs Career

11. Frequently Asked Questions

12. Further Reading and Reference Sources

At a Glance

- The **FDA** issued its **Roadmap to Reducing Animal Testing in Preclinical Safety Studies** on **10 April 2025**, targeting monoclonal antibodies first.

- On **20 April 2026**, the FDA published a **Year One progress report** confirming draft guidance releases, an alternative-methods database, and its first qualified AI tool.

- The **MHRA** published **"MHRA approach to medicines using non-animal methods"** on **25 March 2026**, covering both **CTA** and **MA** applications.

- Draft FDA guidance **"Monoclonal Antibodies: Streamlined Nonclinical Safety Studies"** (Docket **FDA-2025-D-4634**) sets out when toxicology studies may be shortened or waived.

- Both agencies frame this around the **3Rs principle** — replace, reduce, refine — not an outright ban on animal studies.

- **ICH M3(R2)** remains the default international standard for animal study duration unless a sponsor justifies a NAMs-based deviation.

- Regulatory teams fluent in **PBPK** and **QSAR** methodology are ahead of a genuine industry skills gap.

Background: Why Nonclinical Regulatory Science Is Being Rewritten Now

For decades, nonclinical safety packages built on animal studies were the default under **ICH M3(R2)**, which sets minimum toxicology study durations ahead of human trials. That default is now challenged scientifically — **FDA Commissioner Marty Makary, M.D., M.P.H.**, notes over 90% of drugs clearing animal studies still fail in humans — and politically, since the US and UK have committed to reducing animal testing on ethical grounds.

Interested in building a career in regulatory affairs and working with frameworks like the FDA's NAMs roadmap or MHRA's non-animal methods guidance? The Introduction to Regulatory Affairs Course at Entry to Regulatory covers nonclinical and CMC regulatory strategy, including emerging science such as PBPK modelling and QSAR models, giving you the practical knowledge, real work experience and job search support to break into or advance within regulatory affairs. - 50+ CPD-accredited hours of expert-led training - Up to 3 months of real regulatory work experience - Mentoring and job search support until you are employed - Covers EU, UK and US pharmaceutical regulations - Taught by a regulatory affairs expert with 10+ years at MHRA, GSK, MSD and Bayer - Study online, part-time, just 6 hours per week View the course

This traces back to the **FDA Modernization Act 2.0** (December 2022), which removed the statutory animal-testing requirement in certain circumstances, enabling the FDA's April 2025 roadmap. The **MHRA** has moved in parallel, publishing its own guidance on 25 March 2026 linked to the UK government's **"Replacing Animals in Science"** strategy. Neither agency abandons animal data: existing dossiers remain acceptable, and NAMs are being layered in through pilots, not mandated overnight.

Understanding how the **3Rs principle** — replace, reduce, refine — has moved from an ethical guideline into an operational regulatory framework is a core component of the Entry to Regulatory regulatory affairs training programme, which covers nonclinical strategy and toxicology data interpretation as part of its practical curriculum for EU, UK and US regulations — see the full course details at https://pages.entrytoregulatory.com/courses/

Timeline of FDA and MHRA non-animal testing policy milestones, 2022-2026

The FDA's Roadmap to Reducing Animal Testing in Preclinical Safety Studies

On **10 April 2025**, the FDA released its **Roadmap to Reducing Animal Testing in Preclinical Safety Studies**, announcing that animal testing for monoclonal antibodies and other drugs would be "reduced, refined, or potentially replaced" using **New Approach Methodologies (NAMs)** — AI toxicity models, cell-line/organoid testing, and organ-on-a-chip systems.

> "This initiative marks a paradigm shift in drug evaluation." — Marty Makary, M.D., M.P.H., FDA Commissioner, 10 April 2025

On **20 April 2026**, a follow-up report, **"Reducing Animal Testing in Nonclinical Studies: Year One Progress and the Path Forward,"** confirmed:

1. Draft guidance reducing or eliminating non-human primate (NHP) testing for monoclonal antibodies.

2. Updated guidance moving away from horseshoe crab-derived endotoxin testing, sparing over one million animals annually.

3. Draft guidance expanding **weight-of-evidence** approaches across more safety endpoints.

4. Qualification of the FDA's first AI-based drug development tool.

5. A searchable database of currently acceptable alternative methods.

The centrepiece document is draft guidance **"Monoclonal Antibodies: Streamlined Nonclinical Safety Studies"** (Docket **FDA-2025-D-4634**), issued by the FDA's **Center for Drug Evaluation and Research (CDER)**. It recommends streamlined approaches for monospecific antibodies, describing when toxicology studies may be shortened, framed around avoiding unnecessary NHP use "in furtherance of the 3R principles."

Regulatory professionals wanting practical training in how draft guidance becomes operational strategy will find relevant assignments on toxicology and CMC strategy in the Entry to Regulatory course. Full details at https://pages.entrytoregulatory.com/courses/

FDA Center for Drug Evaluation and Research nonclinical guidance for monoclonal antibody safety studies

MHRA's Approach to Medicines Using Non-Animal Methods

The MHRA published **"MHRA approach to medicines using non-animal methods"** on **25 March 2026**, setting out how it will assess **Clinical Trial Authorisation (CTA)** and **Marketing Authorisation (MA)** applications relying on non-animal data. The guidance does not extend to animal use in quality control batch release testing.

The MHRA will continue accepting applications built on animal studies under existing **ICH** guidelines, stating that "refusing such applications because they include animal studies is not in the best interests of UK patients." Where a sponsor shows that omitting an in vivo study poses no risk to human health for the proposed use, the MHRA is open to that proposal — case-by-case, not blanket policy.

PBPK Modelling and QSAR: The Science Behind the NAMs Shift

Two computational tools sit at the centre of most NAMs-based nonclinical strategies:

- **Physiologically based pharmacokinetic (PBPK) modelling** simulates how a drug is absorbed, distributed, metabolised and excreted in the human body, using mathematical representations of human physiology rather than relying solely on animal pharmacokinetic data.

- **Quantitative structure-activity relationship (QSAR) models** predict a compound's toxicity or biological activity from its chemical structure alone, flagging safety concerns before extensive laboratory testing begins.

Method	What It Replaces or Supports	Regulatory Status (Sept 2026)
PBPK modelling	Animal pharmacokinetic/distribution studies	Encouraged in FDA roadmap; case-by-case MHRA acceptance
QSAR models	Early chemical toxicity screening	Referenced in FDA weight-of-evidence guidance
Organ-on-a-chip / organoids	Organ-specific toxicity studies (liver, heart, immune)	Named in FDA roadmap; not yet standardised across agencies
Non-human primate (NHP) studies	—	Draft FDA guidance recommends reduction for monoclonal antibodies

Neither tool replaces animal testing wholesale; both agencies use a **weight-of-evidence** approach, combining computational and in vitro data with any available human or animal data rather than accepting NAMs data alone.

Where EU, UK, US and ICH Requirements Still Diverge

Do not conflate these frameworks. The **FDA's** roadmap and draft guidance are US-specific instruments issued by CDER. The **MHRA's** guidance is a separate UK instrument, developed independently post-Brexit, though it references shared **ICH** guidelines, notably **ICH M3(R2)** and **ICH S5(R3)**. The **European Medicines Agency (EMA)** has not, as of publication, issued an equivalent standalone NAMs document, though the European Commission has signalled a similar direction. Sponsors running parallel US and UK submissions should justify NAMs-based deviations separately to each agency, since ICH guidelines remain non-mandatory recommendations regulators have historically chosen to follow.

Deepen Your Knowledge: Regulatory Affairs Training on This Topic

Interpreting a NAMs-based package requires fluency in toxicology fundamentals, ICH guideline structure, and the language agencies use to signal how much flexibility a weight-of-evidence argument gets. Most life science degrees do not teach this, hence the gap between traditionally trained professionals and NAMs-literate reviewers.

The Entry to Regulatory **Introduction to Regulatory Affairs Course** builds this into its curriculum: marketing authorisation submissions, variations, clinical trial applications, CMC strategy, and nonclinical/toxicology interpretation across EU, UK and US frameworks, plus NAMs, PBPK and QSAR content. This suits graduates needing applied knowledge beyond their degree, toxicology-background scientists transitioning in, and pharmacy professionals needing a structured nonclinical introduction.

TRAINING SPOTLIGHT BOX Course: Introduction to Regulatory Affairs Course Provider: Entry to Regulatory Relevant to this topic: Nonclinical and toxicology data interpretation, CMC regulatory strategy, ICH guideline application, NAMs/PBPK/QSAR emerging science content, EU/UK/US marketing authorisation and clinical trial application frameworks Format: Online, part-time | 6 hours per week | 3 months Includes: Up to 3 months real work experience, job mentoring, CV review, mock interviews, industry-recognised certificate Suitable for: Life science graduates, pharmacy professionals, career changers, scientists seeking regulatory transition Start here

Practical Implications for Regulatory Affairs Professionals

The table below reflects what sponsors and MAHs are actively asking as they revise nonclinical strategies.

Key Question	Previous Situation	What Changes Now
Can we omit NHP toxicology studies for a mAb?	Default under ICH M3(R2)	FDA-2025-D-4634 sets conditions for reduction or omission
Will the MHRA accept a submission with no animal data?	Case-by-case, limited precedent	MHRA's 25 March 2026 guidance offers a clearer route, still case-by-case
Do EU and UK requirements move together?	Aligned via shared ICH adoption	MHRA has its own guidance; EMA has not published an equivalent
Is PBPK data alone sufficient for an IND submission?	Typically supportive, not primary	FDA encourages PBPK data within a weight-of-evidence package
What happens to existing animal-based applications?	Animal data was the accepted standard	Both agencies confirm they remain fully acceptable
How is horseshoe crab endotoxin testing being phased out?	Limulus amebocyte lysate (LAL) testing was default	FDA guidance now supports transition to recombinant alternatives
Where can we check if an alternative method is accepted?	No centralised reference existed	FDA has launched a searchable database of accepted methods

Key Takeaways

1. **Review your nonclinical strategy against Docket FDA-2025-D-4634** before finalising a mAb IND package.

2. **Engage early with the MHRA** on CTA/MA applications with reduced animal data — the 25 March 2026 guidance supports pre-submission dialogue.

3. **Do not assume EU-UK alignment.** Track EMA's position separately, since no equivalent EMA guidance exists yet.

4. **Build weight-of-evidence documentation habits now**, combining PBPK, QSAR and in vitro data with any available human/animal data.

5. **Monitor the FDA's alternative methods database** and update nonclinical SOPs as new methods are added.

6. **Prepare for horseshoe crab endotoxin testing transition** if your portfolio includes injectable biologics relying on LAL testing.

7. **Invest in PBPK and QSAR literacy within your regulatory team now**, ahead of a widening skills gap.

Regulatory affairs professional studying NAMs, PBPK and QSAR training online — career development in pharmaceutical regulatory science

Take the Next Step in Your Regulatory Affairs Career

The shift towards NAMs, PBPK modelling and QSAR models is a genuine career opportunity, not just a scientific one. Regulatory teams and sponsors are looking for professionals who can defend a weight-of-evidence nonclinical package, and there are more open roles requiring this literacy than trained candidates. This is becoming a core skill at every level.

If you are new to the field or looking to advance, the Introduction to Regulatory Affairs Course at Entry to Regulatory is a practical next step, and a free introductory webinar is available as a low-commitment way to see whether the course fits your goals.

Explore the full course details and register for a free introductory webinar at Entry to Regulatory: https://pages.entrytoregulatory.com/courses/

Frequently Asked Questions

What are New Approach Methodologies (NAMs) in drug development?

NAMs are non-animal testing tools used in nonclinical safety assessment — PBPK and QSAR models, human cell-based assays, organ-on-a-chip systems — intended to predict human responses more accurately than animal studies.

Has the FDA banned animal testing?

No. The FDA's April 2025 roadmap describes a phased reduction where validated alternatives exist, not a ban. Existing animal-data submissions remain fully acceptable.

Does the MHRA's non-animal methods guidance apply to medical devices?

No. The MHRA's 25 March 2026 guidance covers Clinical Trial Authorisation and Marketing Authorisation applications, not quality control batch release testing.

How do PBPK modelling and QSAR models differ?

PBPK modelling simulates how a drug moves through the body, supporting pharmacokinetic predictions. QSAR models predict toxicity from chemical structure, typically used earlier for safety screening.

How can I build the skills to work with NAMs, PBPK and QSAR data as a regulatory affairs professional?

Structured training is the fastest route, since most degrees do not cover applied regulatory interpretation of NAMs data. The Introduction to Regulatory Affairs Course at Entry to Regulatory includes this content alongside core EU, UK and US training and real work experience — full details at https://pages.entrytoregulatory.com/courses/

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