CellASIC has developed a novel microfluidic technology to integrate 32 bioreactors on a standard 96-well plate for multiplexed perfusion culture of primary human hepatocytes with demonstrated long-term viability and liver-enzymatic function. This Phase 1 SBIR will utilize this technology to develop and validate an in vitro screening platform for liver-specific drug metabolite profiling. Model compounds will be used to assess metabolic activities, with analysis via LC-MS/MS with our collaborators at BD Biosciences. Once the validation is complete, the company positioned to quickly make the product available to the marketplace. Drug metabolite profiling using primary human hepatocytes has gained more importance in the past decade as it has become recognized that drug metabolism is closely related to drug safety. The FDA has recently issued guidance on drug-drug interaction tests as well as drug safety testing of drug metabolites. Additionally, there is a strong movement in the US as well as in Europe to reduce animal trials and develop improved in vitro technologies. However, the state-of-the-art in vitro drug metabolism models only predict around 50% of the in vivo metabolites, partly because primary hepatocytes rapidly degrade in culture and lose their liver-enzymatic functions.
Public Health Relevance: CellASIC is developing a microfluidic liver array (MLA) system that will allow biopharmaceutical companies to more accurately predict the adverse effects of new drug compounds on human liver prior to clinical and animal studies. Key benefits include safer drugs in the clinic, reduced cost per data point, more clinically relevant data at an earlier stage, reduced reliance on animal testing, and improved understanding of toxicity mechanisms.
Public Health Relevance Statement: CellASIC is developing a microfluidic liver array (MLA) system that will allow biopharmaceutical companies to more accurately predict the adverse effects of new drug compounds on human liver prior to clinical and animal studies. Key benefits include safer drugs in the clinic, reduced cost per data point, more clinically relevant data at an earlier stage, reduced reliance on animal testing, and improved understanding of toxicity mechanisms.
Project Terms: 4,4'-Diaminophenyl Sulfone; 4,4'-Sulfonylbisbenzeneamine; 4,4'-Sulfonyldianiline; 4H-Imidazo(1,5-a)(1,4)benzodiazepine, 8-chloro-6-(2-fluorophenyl)-1-methyl-; 7-ethoxycoumarin; Acetamide, N-(4-ethoxyphenyl)-; Acetophenetidin; Adverse effects; Animal Testing; Animals; Area Under Curve; Arts; Avlosulfon; Benzeneacetic acid, 2-((2,6-dichlorophenyl)amino)-; Biologic Products; Biological; Biological Agent; Biological Products; Bioreactors; Bis(4-aminophenyl)sulfone; Cell Count; Cell Number; Cell Survival; Cell Viability; Cells; Clinic; Clinical; Clinical Evaluation; Clinical Testing; Collaborations; Croysulfone; Culture Media; DADPS; DDS; DXM; Dapsone; Data; Development; Devices; Dextromethorphan; Diaminodiphenylsulfone; Diaphenylsulfone; Dichlofenal; Diclofenac; Dicrofenac; Diphenasone; Disulone; Drug Compounding; Drug Interactions; Drug Preparation; Drugs; Dumitone; Eporal; Europe; Fungi, Filamentous; Grant; Height; Hepatic Cells; Hepatic Parenchymal Cell; Hepatocyte; Human; Human, General; In Vitro; Industry; Length of Life; Letters; Life; Liver; Liver Cells; Longevity; Man (Taxonomy); Man, Modern; Marketing; Measures; Medication; Metabolic; Methods; Microfabrication; Microfluidic; Microfluidics; Midazolam; Modeling; Molds; Monitor; Morphinan, 3-methoxy-17-methyl-, (9alpha,13alpha,14alpha)-; Movement; Novophone; Perfusion; Pharmaceutic Preparations; Pharmaceutical Preparations; Phase; Phenacetin; Position; Positioning Attribute; Problem Solving; Process; Production; Publishing; Reagent; Reliance; Research Resources; Resources; Running; SBIR; SBIRS (R43/44); Safety; Savings; Screening procedure; Services; Si element; Silicon; Simulate; Small Business Innovation Research; Small Business Innovation Research Grant; Staging; Sulfona-Mae; Sulfonyldianiline; Sulphadione; System; System, LOINC Axis 4; Technology; Testing; Thick; Thickness; Time; Toxic effect; Toxicities; Treatment Side Effects; Undolac; Validation; Variant; Variation; Voltaren; Work; base; biopharmaceutical; biotherapeutic agent; body movement; body system, hepatic; clinical relevance; clinical test; clinically relevant; commercialization; cost; d-Methorphan; design; designing; drug discovery; drug metabolism; drug/agent; enzyme activity; growth media; improved; in vivo; in vivo Model; life span; lifespan; meetings; novel; organ system, hepatic; prototype; public health relevance; research clinical testing; safety testing; screening; screenings; side effect; therapy adverse effect; tool; treatment adverse effect
