Number of new Chemical Entities

The 1990s was a decade of fruition because the computer-based drug discovery work of the 1980s yielded an impressive number of new chemical entities reaching the pharmaceutical marketplace. We elaborate on this statement later in this section, but first we complete the story about supercomputers in the pharmaceutical industry. 

Over the last four decades, we have witnessed waves of new technologies sweep over the pharmaceutical industry. Sometimes these technologies tended to be oversold at the beginning and turned out to not be a panacea to meet the quota of the number of new chemical entities that each company would like to launch each year. Experience has shown that computer technology so pervasive at one point in time can almost disappear 10 years later. 

On the question of technical efficiency, results are also mixed. The productivity of pharmaceutical research funds has receded sharply in recent years, at least when measured by the number of new chemical entities introduced and the cost of discovering and developing these products has correspondingly increased. The promise of a science-based research process has not led to the greater efficiency that was projected by its early proponents. 

The number of new chemical entities (NCEs) approved by the U.S. FDA has dropped in the last decade (41) and the average success rate, from the first-in-human studies to registration, is only 11% (42). The lack of drug efficacy and safety account for around 30% of the failures in the clinic (42). Thus, the ability to determine drug safety and efficacy early in the discovery process should help in reducing the failure rate during the costly development studies, and in the end it would produce better and safer drugs (43). 

All the points just described match the requirements of medicinal chemistry the opportunity to synthesize a large number of new chemical entities in very short times, in high purity, in a reproducible way, and making use of scarcely reactive species. The following examples might better illustrate the advantages of the application of MAOS in organic synthesis. 

Many of the advances discussed in this chapter have been implemented to improve the quality of assay hits, shorten discovery timelines and increase the number of new chemical entities (NCEs) the number of NCEs recorded by the US Food and Drug Administration s Center for Drug Evaluation and Research (CDER) dropped from 53 in 1996 to just 17 in 2008.1... 

Technological advances in both biotechnology and molecular biology have yielded a surge in the number of new chemical entities that are produced to treat specific diseases or ailments. However, a growing portion of these new chemical entities display poor aqueous solubility, leading to poor oral bioavailability and an inability to form intravenous formulations. Nanoparticle formation has been proposed and utilized as a method to improve oral bioavailability of poorly soluble drugs and as a method for delivery of particles via parenteral, pulmonary, and topical administration. 

In addition, a more efficient primary drug screening and hit validation is necessary to minimize the costs. In total, for the discovery, development and the introduction of a new drug to the market including the costs for discontinued development projects about 300 to 500 million have to be estimated [350]. On the other hand, the number of new chemical entities (NCE, ca. 50 per year) is nearly constant since 1983 while the costs increased more than three times [351]. 

When taking into account the number of new chemical entities approved for each decade, the rale at which new drugs are being withdrawn due to safely concerns has decreased steadily [2]. 

Fig. 43.1 Numbers of new chemical entities (NMEs) launched worldwide and in the United States 1980-2000 and United States plus Europe R D pharmaceutical R D expenditure at 1998 prices.

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