The pursuit of safer, more effective drugs continues to be one of the most pressing challenges in the pharmaceutical industry. While toxicology testing is crucial in this process, current models often fall short in terms of predictive accuracy, human relevance, and ethical standards. Commonly used approaches such as primary human hepatocytes, animal models, and immortalized cell lines each have their own limitations that can lead to inefficiencies, unreliable results, and delays in drug development. This is why we created a new model, Opti-HEP – a next-generation platform for human hepatocyte-based toxicology screening that directly addresses these challenges and provides pharmaceutical researchers with a more robust, ethical, and accurate alternative.
Primary human hepatocytes are considered the gold standard model for drug toxicity testing due to their ability to closely mimic human liver metabolism. However, these cells have a limited lifespan, high donor variability, and are difficult to culture in large-scale, reproducible systems. The limited lifespan and batch-to-batch variability makes them unreliable for long term, high-throughput screening, which is often necessary in modern drug discovery workflows.
Despite their widespread use, animal models are now increasingly viewed as inadequate due to significant species differences in drug metabolism and toxicity pathways. Results from animal testing do not always translate to human outcomes, leading to costly late-stage drug failures and poor predictability in clinical trials. Additionally, ethical concerns and the regulatory push towards reducing animal testing make this approach increasingly unsustainable.
While immortalized cell lines are widely used in toxicity screening, they often fail to accurately recapitulate human liver function. Their altered metabolic pathways, differences in expression for key markers, and inability to model long-term toxicity make them less suitable for reliable human screening. Not only do these cell lines have a cancerous origin, they also present with mutations not observed in healthy populations and have low expression of Phase I enzymes and metabolically relevant enzymes such as urea.
Opti-HEP are iPSC-derived human hepatocytes that offer a highly accurate and reproducible alternative to traditional models. Unlike primary hepatocytes, Opti-HEP can be produced in scalable, consistent batches ensuring no donor or batch variability, providing researchers with a more reliable system for toxicology screening. Here’s how Opti-HEP overcomes the limitations of existing models:
Opti-HEP are derived from induced pluripotent stem cells (iPSCs), which enables them to exhibit human-specific liver metabolism and drug response profiles. This human relevance is essential for understanding how a drug will behave in a clinical setting. Furthermore, Opti-HEP display robust drug-metabolizing enzyme activity, including both Phase I and Phase II metabolism. This allows researchers to evaluate not only the acute toxic effects of a compound but also its long-term metabolic fate, something animal models or immortalized cell lines often fail to achieve.
Leveraging the expansion capacity of the iPSC system, Opti-HEP offer a scalable and reproducible alternative to primary hepatocytes, which are difficult to source in large quantities. Since Opti-HEP are sourced from a single donor unlike primary cells, they can be scaled to meet your needs ensuring consistent performance across experiments. This scalability is a significant advantage in drug discovery pipelines, where high-throughput screening is essential for evaluating large compound libraries. Crucially, our expanded iPSC library derived from a variety of healthy donors with diverse genetic backgrounds allows us to additionally investigate population diversity in a fully-controlled manner.
As the pharmaceutical industry moves toward more ethical, animal-free testing methods, Opti-HEP align with these evolving expectations. By using human-derived cells rather than animal models, researchers can avoid the ethical concerns surrounding animal testing while meeting regulatory requirements that favor human-relevant data. This makes Opti-HEP a preferred choice for companies aiming to demonstrate their commitment to ethical practices and stay ahead of regulatory trends that increasingly favor human-based models.
Unlike primary hepatocytes, which lose functionality over several days, Opti-HEP maintain a functional liver phenotype over several weeks, enabling researchers to observe chronic toxicity, drug-drug interactions, and metabolic changes that occur during prolonged drug exposure. This long-term assessment is crucial for identifying potential hepatotoxicity early in the drug development process, reducing the risk of late-stage failures. Additionally, Opti-HEP have been shown to accurately predict toxicity risk for a broad set of compounds with known DILI liability. Our data shows that Opti-HEP can accurately predict DILI across a dose-response range using both cell viability and albumin secretion as endpoint assays.
Opti-HEP represent the next step in the evolution of toxicology testing. By combining the advantages of human-derived liver cells with scalability, reproducibility, and accuracy, Opti-HEP offer pharmaceutical researchers a reliable, ethical, and efficient way to assess drug toxicity. As the industry continues to push for better predictive models, Opti-HEP is the solution that will help researchers stay ahead of the curve and drive more successful drug development efforts.