Overview of Biopharmaceuticals and Comparison with Small-molecule Drug Development

Recombinant DNA technology enables the manufacture of proteins and antibodies with a defined specificity and uniformity, which is a vast improvement over previous methods of production by extraction and purification from human or animal blood and tissues. This chapter introduces the various classes of therapeutics that are produced using recombinant DNA technology, and provides background on the history and evolution of therapeutic hormones, enzymes, cytokines, and monoclonal antibodies from an early understanding of their value in the treatment of disease to present day production of genetically engineered human proteins and novel constructs designed to improve uniformity, safety, efficacy, or duration of effect. While this customization bears some resemblance to optimization of chemical scaffolds during lead optimization of low molecular weight chemical compounds (i.e. small molecules), there are unique considerations for the nonclinical safety evaluation of biopharmaceutical drug candidates. This chapter will describe key features of biotechnology-derived molecules, how they compare to traditional chemical compounds, and the impact these features have on preclinical safety testing during their development as medicines.