Standardising human organoid-based drug permeability assays

With the Modernization Act 2.0 signed in early 2023, the FDA paves the way for more new drug applications without animal testing. This decision puts researcher and drug developers back into the drivers seat to quickly bring non-animal-based pre-clinical studies to a level of trust, validation and broad acceptance by the public and regulatory authorities. To meet at least a small part of this demand, this project aims to develop a validated and standardised assay based on human cells, focusing on predicting drug absorption in the gut and permeability to the brain—key aspects covered by current animal tests in DMPK (Drug Metabolism and Pharmacokinetics) studies. Based on recent advancements in human organoid in vitro assays, coupled with in silico modeling, such tests may even address patient-specific differences and enable personalised predictions of clinical outcomes. Guided by Swiss and EU regulatory authorities and pharma industry experts, the main objective for the team is to standardise a drug permeability assay on a Swiss-developed platform. We plan to create a Standard Operating Procedure (SOP) and qualify this assay using clinically validated reference drugs. To refine the model, we feed our data into in silico modeling software for in vitro – to - in vivo extrapolations and assess its predictive validity using clinically relevant parameters. This project aligns with Swiss-wide and international efforts to establish new regulatory guidelines for animal-free drug testing assays. We intend to secure additional funding from pharmaceutical industries and international consortia because we realize that this task will take co-ordinated efforts and input from all stakeholders to replace current animal testing, faster!