Convergence: Global acceptance of NAMs concerns sponsors who want to use them

CHARLOTTE, NC — While new approach methodologies (NAM) offer a path to reduced reliance on animal testing, experts say global regulators need to agree on their use to give sponsors predictability and regulatory assurance.

Interest and regulatory support for NAMs have increased in recent years, with the European Medicines Agency (EMA) explicitly stating that it supports their acceptance across the EU and the US Food and Drug Administration (FDA) issuing draft guidance on their use in drug development in March, and more recently publishing a database of NAMs referenced in publicly available application review materials. (RELATED: FDA to remove ‘animal testing’ terminology from its regulations, Regulatory Focus 21 September 2026)

However, a panel of experts who spoke at the RAPS Convergence 2026 noted that there are still significant challenges and unpredictability in their use, though they expressed hope that regulators will work together to develop a harmonized approach to NAMs.

Tyler Vandivort, regulatory affairs lead at UCB Pharma, said that animal studies are still relied upon because they use intact organisms and capture the total of an organism's biological processes. There are decades of animal and corresponding clinical data to support interpretation of data from such studies, and there are well-established global regulatory requirements and expectations for their use, he said.

He added that ethical considerations regarding animal welfare are driving a shift toward NAMs, and that NAMs may provide greater clinical relevance and predictability, reduce research costs, and offer certain mechanistic insights that animal studies may not yield.

While NAMs are currently in use, Vandivort noted that they aren't guaranteed to yield positive outcomes at the regional level, let alone the global level, which is why the context of their use is very important to consider.

"Assay developers and regulatory reviewers are often misaligned on the type and amount of data needed to justify using NAMs in place of a particular traditional study," said Vandivort.

"Sponsors, of course, are often accused, with some truth, in defaulting to traditional studies to preserve timelines and costs," he added. "And likewise, regulatory reviewers have been known to require traditional studies out of an abundance of caution, even sometimes when they're not necessarily scientifically justified."

When using NAMs, Vandivort said, it may be challenging to model some complex multi-organ and multi-dose processes, various developmental stages, disease progression, and chronic toxicity. He also noted that developing new assays in such situations requires significant investment of time and money.

Uncertainty about regulatory acceptance across regions, technical limitations, difficulties in modeling complex processes, and a preference for testing batteries in animal models have slowed the adoption of NAMs, Vandivort said.

Despite some differences in across regions, Vandivort noted that there is significant alignment on how NAMs can be adopted.

He noted that in some jurisdictions, the drive to support NAMs is rooted in environmental protection legislation or ensuring that cosmetics are cruelty free, whereas the US is the only jurisdiction that is proposing to offer sponsor incentives for using NAMs.

"There are a number of existing mechanisms that sponsors can use to ensure alignment," said Vandivort. "EMA has perhaps the most options currently available between their innovative task force and other scientific meetings, their qualification procedure, their safe harbor program, and their recently announced voluntary data sharing pilot program.

"The FDA is probably next with their critical path innovation meetings and their ISTAND [Innovative Science and Technology Approaches for New Drugs] DDT [drug development tool] qualification program, as well as their general INTERACT meetings for early development considerations," he added. "But new mechanisms are being introduced in other regions on a regular basis, including China's recent announcement of their Pioneer Program to promote adoption among both developers and sponsors, and of course, many regions also explicitly encourage the use of existing meeting mechanisms."

Corinne de Vries, EMA liaison to FDA, said that NAMs are seen within the context of Europe's efforts to reduce, refine, and replace animal testing, also known as the 3Rs, and have been effective for several years. For example, she noted that batch potency testing has declined by 57%, pyrogenicity testing by 53%, and skin sensitization testing by 76% in Europe between 2015 and 2022.

De Vries also noted that EMA has worked with standards organizations such as the International Council for Harmonization (ICH) to adopt several standards that reduce reliance on animal testing and promote NAMs. She noted that EMA reviews the use of NAMs on a case-by-case basis, and its evaluation is based on scientific merit and relevance to the medicinal product and target indication. Furthermore, she said regulators are using a qualification procedure for NAMs based on reflection papers that they have published.

"These reflection papers I'm very proud of because they give you the legal basis for the animal testing, the alternative method that we already know works and is in our guidance or in ICH guidelines," said de Vries.

De Vries said EMA is also working with other regulators through the International Medicines Regulators' Working Group on 3Rs (IMRWG3R) to achieve harmonization on issues such as acceptance criteria for NAMs, batch release requirements, phasing out obsolete tests, and issuing regulatory position statements that can lead to new standards.

"We really want to make sure that if one agency agrees that a non-animal method is acceptable, then it only works if everybody agrees," she added. "In terms of reference, we recognize we have different legal frameworks, but we say, 'Okay, can we harmonize our regulator acceptance criteria?'"

Marie Lemper, head of US toxicology at UCB, echoed the need for global harmonization.

"I think one of our fears is often that even if we engage in early regulatory interactions, we know it might be accepted by the FDA or the EMA, but how can we ensure that it will be globally accepted and we won't have to do animal studies later on, leading to a huge delay in our program and potentially even more animals to be used," said Lemper.

"If the sponsor has some kind of reassurance that what works for one country might work globally, we will be more confident in using innovative methods to answer questions," she added. "I think more and more, we'll see NAMs in weight of evidence, specific target organs, and mechanistic insights."