The world of drug discovery is witnessing a seismic shift as researchers and institutions move away from traditional animal models toward innovative human-based in vitro systems, driven by a pressing need to address the staggering failure rate of drug candidates in clinical trials, which exceeds 90% when transitioning from animal testing to human subjects. Over 90% of drugs that show promise in animal testing ultimately fail when tested in humans, revealing a critical gap in translation due to fundamental differences in genetics and physiology across species. This persistent challenge has not only delayed the development of effective therapies but also escalated costs and prolonged timelines in an already complex process. Human-based models, such as organoids and organ-on-chip technologies, are emerging as powerful tools to bridge this divide, offering a closer approximation of human biology. Beyond the scientific imperative, ethical concerns and sweeping policy changes are further accelerating this transition, signaling a new era in biomedical research. The urgency to adopt these alternatives is palpable, as the industry seeks solutions that are both more accurate and aligned with modern values.
Revisiting Preclinical Foundations
Unpacking the Flaws of Animal Testing
The long-standing dependence on animal models in drug discovery has been a fundamental approach for decades, yet the cracks in this methodology are increasingly evident as data reveals its limitations. A staggering statistic underscores the issue: more than 90% of drug candidates that succeed in animal studies fail during human clinical trials, largely due to species-specific differences in biological responses. Variations in genetics, immune system behavior, and tissue composition often render animal data unreliable when applied to human contexts. This translational disconnect has led to countless setbacks, with promising therapies faltering at the final hurdle, costing billions in wasted resources. The scientific community is now grappling with the reality that these models, once considered the gold standard, are no longer sufficient for the precision required in modern medicine. This growing awareness has sparked a critical reassessment of preclinical strategies, pushing researchers to seek alternatives that better reflect human physiology.
Beyond the scientific shortcomings, the ethical dimension of animal testing adds another layer of complexity to its continued use in research. Public sentiment and advocacy have increasingly called for a reduction in animal experimentation, highlighting concerns over welfare and questioning the moral justification of such practices when alternatives exist. Simultaneously, the scientific argument for moving away from these models aligns with ethical pressures, as the inaccuracies in predicting human outcomes diminish their practical value. Regulatory bodies worldwide are beginning to respond to this dual challenge, setting stricter guidelines and encouraging the exploration of non-animal methods. This convergence of ethical and scientific imperatives is reshaping the landscape of drug discovery, creating a fertile ground for innovation. As the field evolves, the focus is shifting toward systems that not only address these moral concerns but also deliver more reliable data for therapeutic development.
Drivers Behind the Shift
The push to abandon traditional animal models is fueled by a combination of technological advancements and a deeper understanding of their inherent limitations in mimicking human biology. Historically, these models were indispensable for assessing drug safety and efficacy, but their inability to replicate complex human responses—such as nuanced immune interactions or organ-specific reactions—has become a significant barrier. The advent of sophisticated in vitro systems offers a promising alternative, capable of simulating human tissue environments with unprecedented accuracy. These innovations are not merely stopgap solutions but represent a fundamental rethinking of how preclinical research should be conducted. The drive to improve success rates in clinical trials is a key motivator, as stakeholders recognize that better early-stage predictions can save time and resources. This momentum is further amplified by a cultural shift within the scientific community, which increasingly prioritizes precision and relevance over outdated conventions.
Global policy changes are also playing a pivotal role in hastening the transition away from animal-based research toward human-centric approaches. Major institutions, including the US Food and Drug Administration (FDA) and the National Institutes of Health (NIH), have initiated steps to phase out animal testing requirements for certain drug approvals while investing heavily in alternative technologies. Similar efforts in regions like Australia, where initiatives support non-animal research frameworks, reflect a broader international consensus on the need for change. These regulatory shifts are not merely symbolic; they provide tangible incentives and funding for labs to adopt new methods. The alignment of policy with scientific goals underscores a shared recognition that animal models often fail to predict human outcomes effectively. As these directives take hold, they are reshaping the operational priorities of research institutions, encouraging a faster pivot to systems that promise greater translational success.
Innovations Paving the Way
Emergence of Advanced In Vitro Systems
Human-based in vitro models are rapidly gaining ground as transformative tools in drug discovery, offering a level of biological accuracy that traditional methods cannot match. Technologies such as organoids, spheroids, and organ-on-chip systems are designed to replicate the intricate architecture and functionality of human tissues, providing insights into cellular interactions and disease mechanisms. Unlike animal models, these systems can simulate specific human responses, such as immune reactions or tissue-specific drug effects, with remarkable precision. While they are not without challenges—such as the need for improved scalability—they represent a significant leap forward in bridging the gap between preclinical research and clinical outcomes. The potential of these models to reduce the high failure rate of drug candidates is driving intense interest and investment across the biomedical field. Their ability to mirror human biology is setting a new benchmark for how therapies are developed and tested.
The practical application of these advanced models is already yielding impressive results, demonstrating their value in real-world research settings. For instance, at a recent SLAS event, scientists presented 384-well-compatible 3D models tailored for pancreatic ductal adenocarcinoma (PDAC), a particularly aggressive form of cancer. These models successfully preserved key tumor biology characteristics while enabling high-throughput screening with minimal variability, a critical factor for efficient drug testing. Such developments highlight the operational feasibility of in vitro systems, showing they can integrate seamlessly into existing workflows. Industry experts argue that combining disease relevance with reproducible data is essential for advancing therapeutic discovery, and these examples provide concrete evidence of progress. As refinements continue, the focus remains on ensuring these tools can handle the demands of large-scale studies without sacrificing accuracy or consistency.
Overcoming Technical Hurdles
Despite the promise of human-based in vitro models, significant technical challenges must be addressed to fully realize their potential in drug discovery. Organoids, while biologically precise, often prove difficult to scale for widespread use due to inconsistencies in production and growth. Similarly, organ-on-chip systems offer remarkable complexity in mimicking organ functions but frequently lack the throughput needed for extensive screening processes. These limitations can hinder their adoption in high-volume research environments where efficiency is paramount. Addressing these issues requires ongoing innovation to standardize protocols and enhance the reproducibility of results across different labs. The scientific community is actively working to refine these technologies, recognizing that overcoming such obstacles is crucial for integrating them into mainstream drug development pipelines. The goal is to create systems that are both cutting-edge and practical for routine application.
One promising solution to these challenges lies in the development of bioengineered 3D scaffolds, particularly when combined with bioprinting techniques, which aim to balance complexity with operational consistency. These scaffolds can be tailored to replicate specific human tissues while maintaining uniformity, making them suitable for larger-scale experiments. Their design allows for controlled environments where cell behavior can be studied with precision, addressing some of the scalability issues seen in other models. Additionally, bioprinting enables the creation of consistent structures, reducing variability that often plagues organoid production. This approach is gaining traction as a way to merge the detailed biological insights of in vitro systems with the practical needs of drug discovery workflows. As these technologies mature, they are expected to play a central role in overcoming the current limitations, paving the way for broader adoption and more reliable preclinical outcomes.
Shaping the Future Through Policy and Practice
Regulatory Momentum for Change
The transition to human-based in vitro models is being significantly bolstered by a wave of regulatory changes that prioritize alternative research methods over traditional animal testing. Agencies like the FDA and NIH are leading this charge by revising guidelines to reduce reliance on animal data for drug approvals and channeling resources into human-centric technologies. Across the globe, similar movements are evident, with countries like Australia launching dedicated programs to support non-animal research initiatives. These policy shifts are grounded in the understanding that animal models often fail to accurately predict human responses, leading to inefficiencies in drug development. By providing funding and clear directives, regulators are creating an environment where innovation can thrive, encouraging research institutions to adopt new approaches. This structural support is proving to be a catalyst for change, aligning scientific progress with evolving societal expectations.
The impact of these regulatory changes extends beyond mere policy, as they are actively reshaping the priorities and capabilities of research communities worldwide. Labs and pharmaceutical companies are now incentivized to invest in human-based models, knowing that compliance with updated standards can streamline approval processes and enhance credibility. This shift also reflects a broader acknowledgment of the ethical concerns tied to animal testing, aligning regulatory frameworks with public sentiment. The tangible backing from major institutions sends a clear message: the future of drug discovery lies in systems that better mirror human biology. As these policies continue to evolve, they are expected to drive even greater adoption of in vitro technologies, ensuring that research practices keep pace with scientific advancements. The momentum created by such support is a key factor in accelerating the transition to more predictive and humane research methodologies.
Industry Adoption and Insights
Industry leaders are increasingly vocal about the need for human-based in vitro models that deliver both accuracy and reliability in drug discovery workflows. Cameron Ferris, PhD, COO and co-founder at Inventia Life Science, has emphasized the importance of systems that provide reproducible, disease-relevant data across diverse research settings. This perspective is echoed in practical demonstrations, such as the PDAC 3D models showcased at SLAS 2025, which proved their compatibility with high-throughput screening while maintaining biological fidelity. Such examples highlight the growing feasibility of integrating these models into existing pipelines without requiring extensive overhauls. The industry’s focus is on ensuring that these tools can meet the rigorous demands of large-scale therapeutic development, balancing innovation with practicality. This alignment of vision and application is critical for driving widespread acceptance among stakeholders.
The enthusiasm for human-based models within the industry is tempered by a recognition of the challenges that accompany their implementation, particularly in terms of standardization and resource access. Ensuring consistent data interpretation across different platforms and labs remains a hurdle, as does securing patient-derived materials for personalized research. However, pharmaceutical companies and biotech firms are actively collaborating with technology developers to address these issues, investing in solutions that enhance model accessibility and reliability. The collective push toward operational integration signals a maturing field, where the emphasis is on refining these systems for everyday use rather than treating them as experimental novelties. As partnerships strengthen and best practices emerge, the industry is positioning itself to fully leverage the advantages of in vitro models, aiming to transform the efficiency and success rate of drug development processes.
Expanding Horizons in Biomedical Research
New Frontiers in Experimental Design
Human-based in vitro models are unlocking unprecedented opportunities for researchers to explore complex biological questions that were once beyond reach with animal testing. These systems enable detailed studies of cell interactions within specific microenvironments, offering insights into mechanisms like immune responses in tumor settings or drug resistance in chronic diseases. Their capacity to replicate human-specific conditions allows for a deeper understanding of how therapies might perform in real patients, a critical factor in fields like precision oncology. Unlike traditional models constrained by species differences, in vitro technologies provide a platform to investigate nuanced aspects of human biology with greater relevance. This shift is redefining the scope of preclinical research, empowering scientists to ask bolder questions and pursue innovative solutions. The potential to accelerate discoveries in targeted therapies is a driving force behind the growing adoption of these advanced tools.
The flexibility of human-based models also facilitates research into patient-specific variability, a cornerstone of personalized medicine that has long been limited by the constraints of animal studies. By using cells derived from individual patients, researchers can examine how genetic or environmental factors influence treatment outcomes, tailoring therapeutic strategies to unique profiles. This approach is particularly impactful in areas like cancer research, where understanding resistance mechanisms or identifying optimal drug combinations can significantly improve patient prognosis. The ability to simulate such individualized scenarios marks a departure from the one-size-fits-all methodologies of the past, ushering in an era of customized healthcare solutions. As these models become more refined, their role in bridging the gap between laboratory findings and clinical applications is expected to expand, offering hope for more effective and tailored interventions.
Building a Path to Scalable Solutions
Looking back, the journey toward integrating human-based in vitro models into drug discovery reflects a determined effort to address the shortcomings of animal testing through innovation and policy reform. Regulatory bodies and industry pioneers collaborated to establish frameworks that supported the development and validation of technologies like organoids and organ-on-chip systems. Their commitment to reducing the over 90% failure rate of drug candidates in human trials drove significant investments in scalable, reproducible models. Examples such as the PDAC 3D models presented at scientific gatherings demonstrated early successes, proving that these systems could handle the demands of high-throughput research. This collective push not only validated the scientific merit of human-centric approaches but also highlighted the ethical alignment with societal values, marking a pivotal chapter in biomedical history.
Reflecting on those strides, the next steps involve a focused effort to tackle remaining barriers like standardization and widespread access to these cutting-edge tools. Enhancing collaboration between researchers, technology providers, and regulatory agencies will be essential to develop universal protocols that ensure consistency across studies. Additionally, expanding training programs for scientists to master these systems can accelerate their integration into routine practice. Investment in infrastructure to support large-scale production of patient-derived materials is another critical area, ensuring that personalized research is not limited by resource constraints. By prioritizing these actionable initiatives, the field can build on past achievements to create a future where human-based models are the cornerstone of drug discovery, ultimately delivering therapies that are both more effective and closely aligned with human needs.
