In vitro models of animal liver tissues are of great interest to drug developers and regulatory agencies because of their potential to reduce costs and in vivo animal use during drug development. Furthermore, drug metabolism and toxicity studies in vitro across human and animal species are utilized for selection of the appropriate animal species for in vivo testing. Primary monkey hepatocytes are widely considered to be the most suitable for drug metabolism and toxicity studies; however, these cells display a precipitous decline in phenotypic function when kept in suspension or plated in a sandwich of extracellular matrix. The development and validation of a Cynomolgus monkey HepatoPac™ liver model is described. Several liver-specific functions were measured over four a week period including urea synthesis, cytochrome P450 activities, and formation of functional bile canaliculi. Results indicate that Cynomolgus HepatoPac displays higher levels of measured functions for at least 4 weeks as compared to traditional cell culture models making it a valuable in vitro tool for refining and reducing testing in live monkeys during drug development.