Modern Industrial Microbiology and Biotechnology

Drug Discovery in Microbial Metabolites 497named the process Combinatorial Genomics in mimic of combinatorial chemistry wherenumerous compounds are prepared, in the same manner as numerous recombinationsmay occur between the host organisms and the unknown DNA isolated from theenvironment.Growth is on agar plates and the colonies selected are tested for i) their furthercharacterization in additional antibiotic tests employing a wider range of indicatormicrobial species, ii) their anti-cancer activity in a battery of malignant cell lines, and iii)their agonist or antagonist activity in a relevant central nervous system (CNS). Thosebioactive agents which display promising activity as antibiotic agents, as anti-canceragents or as pharmacologically relevant materials are then purified and subjected tochemical structural analysis. Novel bioactive agents are examined for their safety andtoxicology properties.28.4 APPROVAL OF NEW ANTIBIOTIC AND OTHERDRUGS BY THE REGULATING AGENCYDiscovering and developing safe and effective new medicines is a long, difficult andexpensive process. The US system of approval for new drugs is perhaps the most rigorousin the world. In the US the regulatory agency for certifying new medicines as safe andeffective is the Food and Drug Administration (FDA). In EU countries drugs are regulatedby the European Medicines Agency (EMEA) which was established in 1993.In the US which is a major producer of new drugs, it takes 12 years on average for anexperimental drug to travel from the laboratory to the medicine chest. It is also anexpensive process and takes on the average about $360 million to get a new medicinefrom the lab oratory to the medicine cupboard. Where a new medicine is a life saving onefor which few or no equivalent exists it can be put on fast track and may be approved insix months.Prior to submission for pre-clinical trial by the FDA, the firm itself would have carriedout tests. Subsequently the firm submits its product for testing by the FDA. Only five in5,000 compounds that enter preclinical testing make it to human testing. As shown in thetable below, one of these five tested in people is approved. The processes of drug progressare as follows beginning with the work of the firm. (see Table 28.2)28.4.1 Pre-Submission Work by the Pharmaceutical Firm28.4.1.1 Synthesis and extractionThe process of identifying new molecules with the potential to produce a desired change ina biological system (e.g., to inhibit or stimulate an important enzyme, to alter a metabolicpathway, or to change cellular structure).The process may require: 1) research on the fundamental mechanisms of disease orbiological processes; 2) research on the action of known therapeutic agents; or 3) randomselection and broad biological screening. New molecules can be produced throughartificial synthesis or extracted from natural sources (plant, mineral, or animal). Thenumber of compounds that can be produced based on the same general chemicalstructure runs into the hundreds of millions.