Disposition of biologics

Abstract

Drug development is a complex process, requiring scientific and regulatory input at almost all stages from multiple groups of expertise. Small molecule development issues are covered in other parts of this volume. This chapter is devoted to discussing the large molecules, or biologics, and the particular nuances involved in developing these molecules as medicines. Our definition of biologic, for the purposes of this chapter, differs from that described by the regulatory bodies. Where regulators state that a biologic is a molecule produced by a living organism, be it a mammalian, insect, yeast or bacteria cell, or whole animal, we prefer to include molecules such as oligonucleotides and peptides here, which are usually chemically synthesized. So our definition is that of a molecule whose composition mostly entails naturally occurring amino acids, sugars or nucleotide bases. There are modifications made chemically to oligonucleotides and peptides to improve their drug-like properties, but for this volume, we class them as biologics. The aim of this chapter is to describe some of the differences, complexities and paradoxically, simplifications in the pharmacokinetics and ADME sciences during drug development of biologics when compared to the more familiar small molecule drug development process. The impact of the particular pharmacokinetics and ADME sciences of biologics on toxicological and pharmacological end points will be discussed.