The drug development process

FIGURE I The phases of drug development from a clinical perspective. 

Biopharmaceuticals Biochemistry and Biotechnology, Second Edition by Gary Walsh John Wiley Sons Ltd ISBN 0 470 84326 8 (ppc), ISBN 0 470 84327 6 (pbk) 

In other cases, the widespread application of a biopharmaceutical may be hindered by the occurrence of relatively toxic side effects (as is the case with tumour necrosis factor a (TNF-a), Chapter 5). Finally, some biomolecules have been discovered and purified because of a characteristic biological activity which, subsequently, was found not to be the molecule s primary biological activity. TNF-a again serves as an example. It was first noted because of its cytotoxic effects on some cancer cell types in vitro. Subsequently, trials assessing its therapeutic application in cancer proved disappointing, due not only to its toxic side effects but also to its moderate, at best, cytotoxic effect on many cancer cell types in vivo. TNF s major biological activity in vivo is now known to be as a regulator of the inflammatory response. 

In summary, the discovery of biopharmaceuticals, in most cases, merely relates to the logical application of our rapidly increasing knowledge of the biochemical basis of how the body functions. These substances could be accurately described as being the body s own pharmaceuticals. Moreover, rapidly expanding areas of research, such as genomics and proteomics, will likely hasten the discovery of many more such products, as discussed below. 

While biopharmaceuticals are typically proteins derived from the human body, most conventional drugs have been obtained from sources outside the body (e.g. plant and microbial metabolites, synthetic chemicals, etc.). Although they do not form the focus of this text, a brief overview of strategies adopted in the discovery of such non-biopharmaceuticaF drugs is appropriate, and is summarized later in this chapter. 

Pharmaceutical biotechnology concepts and applications Gary Walsh 2007 John Wiley Sons, Ltd ISBN 978 0 470 01244 4 (HB) 978 0 470 01245 1 (PB) 

Fundamentals cf Industrial Chemistry Pharmaceuticals. Polymers, and Business, First Eidition. John A. lyrell. 2014 John Wiley Sons, Inc. Published 2014 by John Wiley Sons, Inc. 

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The partition coefficient and aqueous solubility are properties important for the study of the adsorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) of drugs. The prediction of the ADME-Tox properties of drug candidates has recently attracted much interest because these properties account for the failure of about 60 % of all drug candidates in the clinical phases. The prediction of these properties in an early phase of the drug development process could therefore lead to significant savings in research and development costs. 

The metabolism ofa potential drug has to be considered at an early phase of the drug development process. 

Walgren JL, Thompson DC. Application of proteomic technologies in the drug development process. Toxicol Lett 2004 149 377-85. 

The tools for in silico toxicology are broadly applied in the drug development process. The particular use of the tools is clearly context-dependent, which includes the quality of the prediction and the applicability domain of the model. 

DiMasi JA. The value of improving the productivity of the drug development process faster times and better decisions. In The cost and value of new medicines in an era of change. Pharmacoeconomics 2002 20(Suppl 3) 1-10. 

The Drug Development Process Increasing Efficiency and Cost Effectiveness, edited by Peter G. Welling, Louis Lasagna, and Umesh V. Banakar... 

Physiologically based pharmacokinetic models provide a format to analyze relationships between model parameters and physicochemical properties for a series of drug analogues. Quantitative structure-pharmacokinetic relationships based on PB-PK model parameters have been pursued [12,13] and may ultimately prove useful in the drug development process. In this venue, such relationships, through predictions of tissue distribution, could expedite drug design and discovery. 

Braxton S et al. The integration of microarray information in the drug development process. Curr Opin Biotechnol 1998 9 643-649. 

The emphasis at this stage of the drug development process is upon assessing safety. Satisfactory pharmacological, and particularly toxicological, results must be obtained before any regulatory authority will permit commencement of human trials... 

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