Non-human primates (NHPs), such as macaques and cynomolgus monkeys, have long served as a cornerstone in preclinical drug development due to their close genetic, anatomical and physiological resemblance to humans. Their unique suitability has made them valuable for evaluating pharmacokinetics, toxicology and safety in drug candidates before human clinical trials. But growing ethical scrutiny, supply shortages, cost burdens, scientific innovation and regulatory shifts like the FDA’s new alternative methods roadmap are bringing the continued reliance on live NHPs into question — and opening the door to next-generation solutions that could eventually replace them altogether.
Despite their biological relevance, using live NHPs in research poses several major challenges:
1. Ethical Concerns
NHPs, due to their advanced cognition and social behavior, are at the center of ongoing ethical debates. Animal rights groups, policymakers and the public are increasingly vocal in opposing their use in research. Litigation and regulatory interventions have intensified in recent years. For instance, the USDA has faced lawsuits over inadequate oversight of primate research facilities,[1] and federal rulings have called for improved welfare standards.[2]
This ethical spotlight translates into practical implications for research institutions and sponsors, including the need for more robust justification protocols, heightened compliance measures and increased risk of reputational harm or funding loss.
2. Rising Costs and Regulatory Hurdles
Ensuring NHP welfare comes at a significant financial and operational cost. Institutions must invest in secure housing, specialized veterinary care and rigorous training for handlers. Research using NHPs often requires detailed justification, approval by ethics committees and regular inspections. [3-5] These layers of regulation, while essential for animal welfare, make NHP-based studies complex, expensive and time-consuming.
3. Supply Chain Disruptions
Availability is a critical bottleneck in NHP-based research. Since 2021, institutions like the National Primate Research Centers (NPRCs) have reported their inability to meet up to two-thirds of requests for research monkeys.[6] Geopolitical factors, import restrictions (especially involving China) and breeding challenges have made NHPs a scarce and volatile resource. This scarcity disrupts research timelines and limits the ability to replicate results across studies.
In April 2025, the U.S. Food and Drug Administration (FDA) announced a major regulatory shift with its plan to phase out the requirement for animal testing in the development of monoclonal antibodies and other drugs, when scientifically appropriate.[7] This initiative is part of a broader effort to modernize drug development and align regulatory expectations with emerging New Approach Methodologies (NAMs), including human cell-based assays, artificial intelligence models and organ-on-chip platforms.
The FDA’s plan introduces a phased strategy that begins with a pilot program for monoclonal antibody developers, allowing them to submit safety data generated from non-animal methods.[7] If successful, the findings from this pilot will inform expanded regulatory guidance and potentially lead to a broader adoption of animal-free approaches across drug categories.
The shift is not only ethical but also pragmatic: the agency cited goals such as lowering research and development costs, accelerating time to market and improving translational relevance between preclinical and clinical outcomes.[7] For sponsors and drug developers, this opens the door to integrating more scalable and reproducible alternatives while reducing dependence on difficult-to-source and ethically sensitive animal models like NHPs.
Importantly, this roadmap complements earlier FDA initiatives supporting the use of NAMs,[8] signaling a sustained federal commitment to reducing animal use in science without compromising patient safety.
For industry, this is a call to action: Those who invest early in validated, human-relevant systems — such as induced pluripotent stem cell (iPSC)-derived models — are likely to gain an advantage in navigating regulatory approvals and meeting evolving ethical expectations.
NHPs have long been considered indispensable, especially in immunology, neuroscience and cardiovascular safety studies. But the last decade has seen a gradual reduction in their use, driven by tightening animal welfare regulations and scientific advances.[9]
The COVID-19 pandemic also created both a surge in NHP demand and an unprecedented supply crisis, pushing researchers to rethink their dependence on live primates. Since then, pharma and biotech firms have increased investment in alternatives, including computational models, organ-on-chip systems and stem cell technologies.
While some therapeutic areas still rely heavily on NHPs — like biologics and gene therapies — many others are exploring models that offer better scalability and ethical acceptability.
Several alternatives to live NHPs are now in development or early use:
As exciting as they are, these alternatives are a far cry from what many sponsors are currently doing to evaluate preclinical safety, especially cardiotoxicity.
There is a new wave of alternatives emerging that will bridge the translational gap and support a smoother transition toward more human-relevant, ethical and scalable research methods.
Ncardia has pioneered Ncyte® NHP-C vCardiomyocytes, the first-ever cardiomyocytes derived from cynomolgus monkey iPSCs.
These cells address several long-standing concerns in preclinical safety testing[13]:
Conventional models often fail to predict cardiac side effects, especially with biologics. NHP-C cardiomyocytes offer a more predictive and ethical platform, especially for drugs intended to advance from animal testing to first-in-human trials.
While it is unlikely that live NHPs will disappear from research entirely in the near term, their role is becoming more selective. In many areas — especially cardiovascular safety, where alternatives like NHP-derived iPSCs now exist —traditional NHP use may no longer be justified.
The path forward involves continued validation, regulatory engagement and industry collaboration to accelerate this transition and navigate several significant challenges of NHP alternatives:
To overcome these hurdles, stakeholders must invest in collaborative research, transparent data sharing and regulatory science. Cross-disciplinary efforts —combining pharma, academia, regulators and tech developers — will be essential to fully phase out NHP reliance.
The use of NHPs in preclinical research stands at a turning point. Mounting ethical concerns, operational inefficiencies and regulatory reforms are pushing the industry toward a new era of more humane, efficient and predictive science.
Alternatives like Ncardia’s NHP-derived iPSC cardiomyocytes are leading the way, offering a solution that retains the biological advantages of NHPs without the burden of live animal use. As regulatory bodies like the FDA open the door to novel testing platforms, the industry has a clear incentive to embrace innovation.
In the future, the most effective and ethical research won’t rely on tradition — it will be driven by technology, transparency and trust.
Mariana Argenziano, PhD
Associate Director Manufacturing Technologies
Mariana holds a PhD in molecular biology from the University of SanMartin (Buenos Aires) and has worked at several universities in the US for more than eight years, specializing in stem cell biology. Throughout her experience in academic research, she gained distinct knowledge and expertise in both disease modeling and biobank building and in the differentiation of iPSCs into cardiac and neuronal cell types.
In 2022, Mariana joined the manufacturing team at Ncardia, where she pursues new iPSC manufacturing procedures and scale-up processes to support their application in regenerative medicine and drug discovery.
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