Scientific Contributions
Exhibitor-Hosted Session
Baseline Characterization as a Key Foundation to Qualification of NAMs
The emergence of complex in vitro models (CIVM), including 3D multicellular tissues and microphysiological systems (MPS) offers new opportunities to better mimic human physiology and improve toxicity predictions in pharmaceutical research. Integrating CIVM into testing pipelines presents challenges, such as the need for specialized expertise, evolving protocols, and sensitive biomarker detection. Careful characterization of baseline function, clear definition of context of use (COU), and rigorous qualification are essential for reliable toxicological assessment.
Presenter: Rhiannon N. Hardwick, PhD, DABT, Scientific Director, Bristol Myers Squibb
Date: Monday, March 23
Time: 12:15 - 1:15 PM
Room: 23C
Poster A128
Integration of HLA-Typed PBMC into a Long-term, Functional Hepatocyte Co-culture, HEPATOPAC®, for Detection of Immune-Mediated Drug-Induced Liver Injury
Preclinical prediction of idiosyncratic drug induced liver injury (iDILI) is important in drug development both to safeguard patients from serious adverse outcomes and to reduce late-stage candidate drug failure. Standard preclinical in vitro models fail to identify DILI potential for several reasons including lack of relevant immune cell types in the model and/or factors that are specific to particular patient populations. Retrospective studies have identified compound interaction with T-cells in patients with specific human leukocyte antigen (HLA) types as a contributing factor for iDILI in some compounds which showed liver toxicity in the clinic. Based on these observations, we developed a co-culture model which incorporates human PBMC into a long-term micropatterned hepatocyte co-culture model (HEPATOPAC) in order to better model peripheral immune system contribution to DILI development. In these studies, culture conditions were optimized to maintain both hepatocyte and PBMC viability and function for up to 7 days. To investigate the utility of this model for immune DILI studies, HEPATOPAC cultures with and without HLA-typed PBMC were treated with amoxicillin-clavulanate (AC), which is known to cause DILI in patients having specific risk associated HLA-types (DRB1*15:01-DQB1*06:02). The TC50 in cultures with and without PBMC was compared to determine if the presence of PBMC increased toxicity as indicated by ashift of the concentration-response curve.
Presenter: Karissa Cottier, PhD, Manager of R&D, BioIVT
Date: Tuesday, March 24
Time: 9:15 - 11:45 AM
Location: Hall B
Poster A150
Novel Machine Learning Algorithms Allow Fast and Accurate Automated Counting of Primary Hepatocyte Samples
Primary hepatocytes are a critical cell type in toxicity and drug metabolism workflows. Given the sensitive nature of these experiments, accurate and precise hepatocyte counts are essential for achieving reproducible results for downstream applications. We have developed a machine learning-based model for counting hepatocytes and determining viability on an automated cell counter to 1) help standardize results across laboratories and 2) reduce user to user variability. This study aims to test if an automated machine learning model can provide the same level of counting accuracy for hepatocyte quantification against the established gold standard method of manual hemocytometer counts by trained scientists.
Presenter: Dan Schieffer, Scientific Director, DeNovix Inc.
Date: Tuesday, March 24
Time: 9:15 - 11:45 AM
Location: Hall B
Poster A117
Trends in Intrinsic Clearance of Drugs in In Vitro Liver Test Systems: Insights from a CRO’s Microsome and Hepatocyte Data
Drug developers have long aimed to design molecules with low metabolic turnover. In vitro assays, such as metabolic stability studies, are commonly used as an initial approach to assess how rapidly compounds are metabolized and to estimate turnover rates to guide early drug development. We therefore used in vitro metabolism study data to examine whether there has been a shift over time toward drug candidates with lower turnover.
Presenter: Tina Mueller, PhD, Scientific Advisor, ADMET Services, BioIVT
Date: Tuesday, March 24
Time: 9:15 - 11:45 AM
Location: Hall B