Advancing Organoid Technologies for Drug Development
The continued need for drug discovery requires extensive R&D to bring these products to market. Many drugs that make it through drug development ultimately do not pass clinical trials. The expense of screening and developing drug candidates necessitates cost-effective technologies for drug candidate screening that are more accurate to human physiology.
Currently, screening potential candidates is primarily accomplished through 2D culture bioassays and animal models, which provide information on drug safety, toxicity, efficacy and pharmacokinetic action. However, the failure rate of drugs in clinical trials remains high:
- High Clinical Trial Failure Rates – Preclinical models often produce data that don't accurately reflect human physiological responses
- Limited Human Relevance – 2D and animal models lack the complexity of human biology, reducing relevance and reliable data
- High Cost – Animal studies are expensive and resource-intensive
- Need for Better Models – The need for more relevant data earlier in drug development highlights a need for preclinical models that enable high-throughput screening of multiple candidates
Human organoids are 3D cell cultures that develop into structures, modeling the complex structure and function of tissues and organs. They are derived from stem cells, iPSCs or cancerous tumor tissues¹'². Following cell isolation and culture under 2D conditions, the cells are embedded in an extracellular matrix, such as Matrigel, which provides an environment for them to grow and organize into 3D structures.
Combined with maintenance and monitoring, these processes can take multiple weeks, making organoid cultures more time-consuming compared to 2D studies. Nevertheless, organoids offer several key advantages:
- Improved physiological relevance – Accurately represents human physiology and pathology better than 2D cell cultures
- Ethical and practical benefits – They are more logistically accessible and socially acceptable than animal studies³
- Regulatory recognition – Recognized as New Alternative Methods in drug development by the FDA Modernization Act 2.0
- Versatile applications – Serve as a valuable platform for small and large molecule testing, high-throughput drug screening and long-term toxicity screening of small molecules⁴
The biopharmaceutical industry is eagerly adopting organoid systems, using cerebral and lung organoids to mimic characteristics of diseases such as Alzheimer's or cystic fibrosis, respectively. These 3D systems are also implemented in cancer research, where the biopsies collected from patients can be cultivated into ‘tumoroids’. These can be used to develop personalized oncology treatments.
While the markets for drugs such as small molecules are mature, using organoids for screening is still in development and currently faces several limitations, including reproducibility, standardization and scalability³:
-
Manual Handling - Most 3D cultures are still handled manually, which can lead to possible variations in the function and quality of organoids
-
Inconsistent Characteristics - The characteristics of organoids at different stages of culture or organization can vary, adding complexity to consistent and reproducible results
-
Lack of Standardization - Standardization protocols and culture methods differ across studies and labs, making comparing organoid results challenging and potentially limiting the broader acceptance in drug development
-
Scalability Issues - Scaling up organoids at a large scale while maintaining quality standards is both time and resource-consuming
-
Dependence on Expertise - Manual handling relies heavily on individual expertise, further complicating the mass production of organoid cultures
-
Quality Control Challenges – Ensuring the quality of 3D cell cultures also presents challenges
- The need for real-time imaging required for monitoring
- Long sample preparation times
- Processing a vast amount of data can be time-intensive
These challenges must be addressed for organoids to become a reliable and scalable solution in drug screening workflows.
The Life Sciences companies of Danaher offer solutions for automating 3D cell culture, real-time data analysis and tracking organoid cultures, speeding up decision-making and enhancing the accuracy of preclinical small molecule drug screening. To learn more about improving your workflows by bringing organoid models and 3D cell culture processes into your lab, visit our Human Relevant Model and Spatial Profiling solutions or contact an expert from the Life Sciences companies of Danaher.
Bridging the Gap: Advancing Human-Relevant Models for Real-World Impact Webinar
References
- 1. Vandana JJ, Manrique C, Lacko LA, et al. Human pluripotent-stem-cell-derived organoids for drug discovery and evaluation. Cell Stem Cell 2023; 30(5):571–91.
- Miranda CC, Cabral JMS. Organoids for cell therapy and drug discovery. In: Precision Medicine for Investigators, Practitioners and Providers [Internet]. Elsevier; 2020. p. 461–71.
- Matsui T, Shinozawa T. Human Organoids for Predictive Toxicology Research and Drug Development. Front Genet 2021; 12:1–14.
- Co JY, Klein JA, Kang S, Homan KA. Toward Inclusivity in Preclinical Drug Development: A Proposition to Start with Intestinal Organoids. Adv Biol 2023; 18 2200333:2200333.