The discovery of a new chemical entity (NCE) suitable for CNS drug development is a challenging endeavor as many different properties require simultaneous optimization. One of these properties, metabolic stability, is a surrogate for in vivo clearance (CL). A common practice of discovery project teams is to select NCEs with the greatest metabolic stability for further evaluation. With NCEs that exhibit low or no turnover in in vitro systems, it becomes very challenging to project human CL and the plasma profile of the compound (i.e., half-life; T 1/2) creating development challenges. In addition, the low turnover of an NCE complicates the characterization of metabolites. Here, a retrospective analysis was done to compare the HepatoPac™ with various in vitro methods to determine human clearance of ELND006, a low turnover compound, and to characterize the in vitro metabolic profiles of ELND006 with HepatoPac.