In recent years, there has been a strong global push to evolve the way researchers conduct preclinical testing, with government organisations, industry members and life science bodies alike campaigning to move away from animal testing in a bid to prioritise potentially more human-relevant, animal-free methods.
At the forefront of this shift from animal testing are new approach methodologies (NAMs), which the NC3Rs describes as assays used to fully or partially replace animal models when assessing the toxicity of a drug or chemical. While several types of NAMs are available to developers, approaches like organoids, organs-on-chips and predictive computational toxicology models are creating a buzz within the industry.
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During the ‘Transitioning to non-animal methods in science and regulation’, keynote seminar held by the Westminster Health Forum, experts were keen to discuss the role of NAMs in preclinical toxicology – with many explaining their grounded optimism towards these approaches amid their rapid rise to notoriety.
UK government pushes for NAM implementation
As key life sciences players make a concerted push towards the reduction of animal testing, the UK government has also devised some approaches to cut down its use in the preclinical setting.
During the seminar, William Reynolds, head of the animals in science regulation unit at the Home Office, outlined the main shifts in the government division’s “managed transition” approach. The Home Office, in this context, is responsible for creating the legal framework to regulate how, where and by whom animal research is conducted.
At the foundation of this approach is the Animal Scientific Procedures Act (ASPA) of 1986, which is still relevant in this transitional context, Reynolds noted, as the flexible nature of the policy allows it to evolve with the science.
That being said, the shifting scientific landscape calls for a renewed approach, Reynolds caveated, which the Home Office aims to achieve through a sharpened focus on risk-based regulation to shift the agency’s focus to the most high-risk cases. It is also introducing a shift away from project-level to systemic assurance to drive consistency in outcomes, and a move from static to data-driven oversight that facilitates a proactive approach to risk management. The Home Office is also placing a keen interest in real-world outcomes instead of just process adherence.
However, it’s important to consider that regulation doesn’t operate in isolation, Reynolds commented. “This is certainly a whole system effort depending on coordination across government, organisations and key partners in the system,” he added.
This collaborative mindset should also extend internationally, experts agree.
NAMs: complementary or dominant players?
In a previous conversation with Clinical Trials Arena, Charles River’s CVP and Chief Scientific Officer for Safety Assessment, Steve Bulera, noted that NAMs will dominate in time, but the change will not happen overnight.
However, both Kirk Leech, executive director of the European Animal Research Association (EARA) and Robin Lovell-Badge, principal group leader at the Francis Crick Institute, agree to a point. During the seminar, both Leech and Lovell-Badge expressed their beliefs that NAMs are unlikely to replace animal testing for a “long time” and that they should serve as a complementary approach, rather than a replacement tool.
This is because they aren’t currently able to replicate real human biology in complex areas such as the brain, reproductive, endocrine or immune systems, Lovell-Badge says.
Leech echoed this sentiment, noting that the loss of scientific expertise and infrastructure associated with animal testing in the UK could disadvantage the UK life sciences sector and its ability to form international partnerships, while potentially risking its pandemic preparedness, as NAMs are not able to effectively replicate the complex human systems mentioned by Lovell-Badge.
Tempering expectations to retain trust
With experts in this seminar determining that the role of NAMs should primarily be an ‘and’ rather than an ‘instead of’ approach in preclinical toxicology, Leech stressed the importance of communicating this reality to the UK public as the government looks to replace animal testing where appropriate.
In their current state, Leech says that NAMs are not, and will not be, an all-round suitable alternative to animal testing any time soon. “The reality is much more complex,” he asserted.
With the government and industry collaborating to actively reduce animal testing, Leech believes that clear communication about the complementary role of NAMs is crucial as the space reaches an inflexion point. This is because telling the public that NAMs will soon replace animals in preclinical toxicology, which is broadly infeasible for now, he says, threatens to undermine trust and promote a “broader cynicism” towards regulation and science.
A cautionary tale from Europe
In the context of shaping NAMs policy, Leech noted that the UK could learn from Europe’s mistakes in phasing out animal testing, as the continent grapples with conflicting and incompatible definitions of ‘NAMs’ laid out by the EU and the European Medicines Agency (EMA).
According to the EU Biotech Act, NAMs should act as a total replacement for animal testing in any area in which one exists, regardless of the its validation for the endpoint in question. Meanwhile, the EMA’s guidance acknowledges the complementary role of NAMs and animal testing in preclinical toxicology.
This regulatory incoherence, Leech says, can “repel investment and delay science”, so the UK should avoid the same fate as it pushes the reduce animal testing. “What the US is doing, and what the UK should emulate, is adding optionality; the toolbox gets bigger, and science determines what approach you use,” Leech added.
With some cite the US Food and Drug Administration’s (FDA) Modernization Act as proof that NAM adoption leads to a reduction in the scale of animal testing, Leech warns that the UK should “resist this framing” due to its misleading nature in the context of Europe. This is because the US regulatory baseline is “incomparable to Europe”, as mice, rats and zebrafish are not counted in its animal use statistics, whereas Europe counts even zebrafish larvae.
Finding common ground
As discourse around the shift towards wider NAM use continues to garner attention, Lovell-Badge notes that many experts in animal research are fearing for their jobs as they wonder if their services will soon become defunct – despite their continued role in research moving forward.
However, Lorna Ewart, CSO of in vitro model developer Emulate, argued that this is also the case for many in her line of work – especially in the UK – due to the high and continual investment needed to validate in vitro systems.
As each side contends with its own challenges, Ewart voices the importance of finding common ground between the two areas. According to her, instead of the polarisation of each side, there is a need for “more discussion about how we centralise and balance” between the two. Ewart added that funding obtained by players in the for in vitro space still represents a “drop in the ocean” compared to the capital allocated towards animal model testing.
