The Federal Food, Drug, and Cosmetics Act of 1938 mandated animal testing for all new drug development protocols. This approach was initially aimed at ensuring safety and efficacy before human trials, but is facing increased scrutiny. Ethical concerns regarding animal welfare and questions about the effectiveness of these methods in accurately predicting human responses drive the search for alternatives.
Recent advancements in research technology have led to the development of "fashionable models" including organoids and organ-on-chip (OoC) models, which provide reliable safety and efficacy assessments for therapeutics without animal testing (1,2).
The development of viable alternatives to animal testing led to a significant legislative shift, culminating in the signing of the FDA Modernization Act 2.0 in December 2022, which permits non-animal testing methods for drug and biological product applications. This shift in legislation marked the beginning of an ongoing transformation in the landscape of drug discovery towards innovative, more ethical approaches. Here, we will further explore organoid and OoC technologies, including their potential, challenges, and future perspectives.
Organoids
Central to this revolution are organoids: Three-dimensional structures typically derived from stem cells that closely mimic human organs (1). The development of organoids has been a game-changer in understanding complex diseases and testing potential treatments, but these complex models are not without challenges. Variability in organoid development, due to different sources of stem cells and variablility of growth conditions, presents a hurdle (3). Scaling up organoid production to meet the demands of high-throughput drug screening also remains a significant challenge.
OoC systems
OoC are microfluidic chips that simulate the microenvironments, mechanical properties, and biological functions of human organs (2). The evolution of OoC systems has been rapid, but they are still in the early stages of development. OoC systems were initially focused on single-organ models, but now integrated systems that can mimic inter-organ interactions, known as body-on-chip models, are being developed (4). These systems are poised to revolutionize our understanding of systemic responses to drugs and the interplay between different organ systems in health and disease.
Conclusion and Future Perspectives
Organoids and OoC systems offer a closer approximation of human physiology compared to traditional animal models, potentially leading to more accurate drug efficacy and safety predictions. As these technologies continue to be refined, their potential to revolutionize drug development and personalized medicine will become increasingly evident.
If you are interested in keeping up-to-date with the latest trends poised to revolutionize drug discovery —don’t miss our latest whitepaper. We continue our discussion of the fashionable models currently on the rise in the pharmaceutical field and explore other fascinating emerging trends in the world of drug discovery.
Bibliography
- Zhao Z, Chen X, Dowbaj AM, et al. Organoids. Nature Reviews Methods Primers. 2022;2(1):1-21. doi:10.1038/s43586-022-00174-y
- Clapp N, Amour A, Rowan WC, Candarlioglu PL. Organ-on-chip applications in drug discovery: an end user perspective. Biochemical Society Transactions. 2021;49(4):1881-1890. doi:10.1042/bst20210840
- Quadrato G, Nguyen T, Macosko EZ, et al. Cell diversity and network dynamics in photosensitive human brain organoids. Nature. 2017;545(7652):48-53. doi:10.1038/nature22047
- Sung JH, Wang YI, Narasimhan Sriram N, et al. Recent Advances in Body-on-a-Chip Systems. Analytical Chemistry. 2018;91(1):330-351. doi:10.1021/acs.analchem.8b05293