CHARACTERIZING THE PHARMACOKINETICS AND BIODISTRIBUTION OF THERAPEUTIC PROTEINS: AN INDUSTRY WHITE PAPER

Characterization of the pharmacokinetics (PK) and biodistribution of therapeutic proteins (TPs) is a hot topic within the pharmaceutical industry, particularly with an ever-increasing catalog of novel modality TPs. Here, we review the current practices, and provide a summary of extensive cross-company discussions as well as a survey completed by International Consortium for Innovation and Quality (IQ consortium) members on this theme. A wide variety of in vitro, in vivo and in silico techniques are currently used to assess PK and biodistribution of TPs, and we discuss the relevance of these from an industry perspective, focusing on PK/PD understanding at the preclinical stage of development, and translation to human. We consider that the ‘traditional in vivo biodistribution study’ is becoming insufficient as a standalone tool, and thorough characterization of the interaction of the TP with its target(s), target biology, and off-target interactions at a microscopic scale are key to understand the overall biodistribution at a full-body scale. Our summary of the current challenges and our recommendations to address these issues could provide a guide to the implementation of best practices in this area of drug development, and continued cross-company collaboration will be of tremendous value