DRUG DEVELOPMENT AND PRECLINICAL STUDIES

5 Animal Tests, In Vitro Assays, and In Silico Methods 158 

Drugs From Discovery to Approval, Second Edition, By Rick Ng Copyright 2009 John Wiley Sons, Inc. 

In earlier chapters, we discussed the discovery of new drugs. After a lead compound has been identified, it is subjected to a development process to optimize its properties. The development process includes pharmacological studies of the lead compound and its effects on toxicity, carcinogenicity, mutagenicity, and reproductive development. These data are important for determining the safety and effectiveness of the lead compound as a potential drug. 

An ideal drug is potent, efficacious, and specific that is, it must have strong effects on a specific targeted biological pathway and minimal effects on all other pathways, to reduce side effects. In reality, no drugs are perfectly effective and absolutely safe. The aim of pharmacological studies is to obtain data on the safety and effectiveness of the lead compound. Many iterations of optimization of the lead compound may be necessary to yield a potential drug candidate for clinical trial. 

Exhibit 5.1 FDA 21 CFR Part 58, Good Laboratory Practice for Nonclinical Laboratory Studies Table of Contents 

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Before entering into a clinical evaluation program, a drug candidate is subjected to a number of preclinical studies to further define and characterize its safety profile. The results from the pharmacology, developability, and preclinical studies are documented in technical reports or scientific publications and used to prepare the IND submission. All of the preclinical studies, described in the section below, and nonclinical studies, discussed in the following section, need to be conducted according to GLP regulations. 

Alios Therapeutics Inc. was then able to proceed through a phase-one study on the basis of the basic and preclinical studies for only 2 million. This is perhaps a record for a new drug. The following graph prepared by the former Alios CEO, Stephen Hoffman, compared the cost of development of RSR 13 to the blood substitute companies that also sought to increase oxygen delivery in vivo (Figure 17.4). 

Dombey (1990) commented that the concept of qucility is the basis of cill drug development and creates confidence in product safety and efficacy. The drug substance has to be of sufficient quality to interpret the preclinical studies and the drug product has to be of sufficient quality to link all the human studies together and to provide confidence in the marketed product . 

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