Assessment of the metabolism of therapeutic proteins and antibodies.

INTRODUCTION: In the last decade, our increased knowledge of factors governing the pharmacokinetics and metabolism of biologics (recombinant therapeutic proteins) has driven, and will continue to support, biological engineering and the design of delivery systems for more efficient biologics. Further research in analytical methods for assessing their in vitro and/or in vivo metabolism will also support these developments. AREAS COVERED: In this review we will discuss the main components affecting the metabolism of biologics, and try to demonstrate how novel analytical evaluations will facilitate their future development. We will focus on the use of radiolabeled drugs, ligand-binding assays and mass spectrometry. EXPERT OPINION: Future marketed biologics will be complex structures, such as glycoengineered, fused, or chemically modified proteins. Their in vivo efficiencies will be strongly dependent on their metabolic stabilities. Similarly to small molecular drugs, for which in vitro and in vivo biochemical platforms and analytical techniques have helped to rationalize preclinical and clinical developments, we would expect this also to translate to effective approaches to study the metabolism of biologics in the near future. Mass spectrometry should emerge as a standard technique for in vivo characterization of the biotransformation products of biologics.