Chapter 2. Comparative Drug Development of Proteins and Genes versus Small Molecules

Summary

The pharmaceutical industry spends several billon dollars each year in research to transform novel chemicals and biologics into medicinals that are safe and effective for human use. This translational research and drug development has benefited from billons of dollars allocated annually by the United States government through the Department of Health and Human Services (HHS), the Public Health Service (PHS), and the National Institutes of Health (NIH) to support research aimed at understanding disease mechanisms and finding therapeutic solutions. To ensure that a new drug candidate is proved effective and safe before it reaches the US market, all of the information that has been gathered about the new drug candidate is rigorously scrutinized by the Food and Drug Administration (FDA) and by independent experts called upon to assist the agency in its evaluation. Whether a drug candidate is a protein, nucleic acid, or small molecule, manufactured in the United States or abroad, the same regulations apply. In general, traditional drugs (i.e., small organic molecules) are reviewed through the new drug application (NDA) process, while macromolecules (biopharmaceuticals); including proteins, peptides, genes, and recombinant products, are reviewed under the biologic license application (BLA) process. The Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER), within the FDA, are responsible for the review of NDAs and BLAs, respectively. However, in September 2002, the FDA announced its intention to consolidate review of most new biotechnology products under its drug division CDER. Regardless of whether the drug candidate is a small chemical entity or macromolecule, transformation of a new molecular entity into a marketed drug product takes about 12 years on average, and costs about $200–350 million. This chapter provides an overview of the drug development process, followed by a discussion of key differences between development of biotechnology products of macromolecules and chemical products. Perspectives on current trends in integration of expertise, technology and personnel to accelerate the drug development process are also included.