New molecular entity

New drug application (NDA), 165 New 1UPAC naming system, 177 New molecular entity (NME), number of, 164... 

The rapid physical maturation that occurs between birth and adulthood is well known. Logically, it would be anticipated that these changes would result in altered responses to xenobiotics. Within the first 5 years of life 95% of children have been prescribed medications. Yet in 1977 only one third of the new molecular entities that have potential usefulness in pediatric patients had pediatric labeling at the time of approval. 

The FDA Modernization Act of 1997 contains a requirement for public disclosure and congressional reporting by October 2001 of Phase IV studies. FDA intends to meet the public disclosure requirement by posting Phase IV study commitments, the projected end of the study, and the current status of the study on their web site [102]. Sponsors whose new drug was approved with a Phase IV study requirement must submit an initial status report to FDA within one year of approval. According to data compiled by Public Citizen s Health Research Group [103], not one of the Phase IV study commitments for 107 new molecular entities approved between January 1995 and December 1999 had been completed as of December 1999. 

Under different types of agreements, short- and long-term projects are undertaken in close alignment to customer needs. Joint projects are meant to discover and synthesize new molecular entities designed for specific functions, discovery new and more efficient approaches to the synthesis of target molecules, and characterization of components of complex organic mixtures. 

FIGURE 1.1. Attrition during the development of new molecules with a promise of therapeutic potential. Over the course of taking a new molecular entity through scale-up, safety and efficacy testing, and, finally, to market, typically only one out of every 9000 to 10,000 will go to the marketplace. 

Second, as many as 60% of new molecular entities developed as potential therapeutic agents, when assayed for hERG blocking liability, test positive and are thus abandoned early in development, although their true torsadogenic potential is unknown. 

Ten-year trends in NME submissions to FDA and U.S. pharmaceutical research spending. The figure shows 10-year trends in U.S. pharmaceutical research and development (R D) investment (PAREXEL s Pharmaceutical R D Statistical Sourcebook 2002/2003) and the number of submissions to FDA of new molecular entities (NMEs), defined as drugs with novel chemical structure. (Redrawn from http //www.fda.gov/ oc/initiatives/criticalpath/whitepaper.html.)... 

Caco-2 cells have been valuable in the estimation of drug absorption potential, transport mechanisms, and effect of permeation enhancers on transepithelial transport.35,39,53,67-69,78-81 Owing to the sensitivity of the cells and the limited solubility of new molecular entities, Caco-2 permeability studies are routinely done with relatively low concentration of compounds. One way to increase the solubility of these compounds is to use organic solvents. The low tolerability of Caco-2 cells to organic solvents limits the use of this approach in permeability studies. 

With all these positive indicators, the expectation has been that a large number of new products will become available. That was the belief in the mid-1990s. But Figure 34.3 shows what has happened over time New product submissions have basically remained flat for the last 20 years. Figure 34.3 depicts new molecular entities submitted to the FDA since 1983, and there is no trend toward increasing submissions. In fact, concern has been raised lately about the downturn since the late 1990s. Whether or not this is a real trend or simply a fluctuation is not known the point is that there has not been a huge increase in the submission of new producfs. 

For the accumulated costs and resources devoted to the development of a new chemical entity (NCE) or new molecular entity (NME) to make sense financially, the commercial potential of the compound must be evaluated in a rigorous manner. Compounds whose expected financial performance does not warrant these high investment costs must be abandoned or out-licensed as soon as possible so as to direct resources toward more profitable endeavors. By operating effectively, a well-designed drug discovery and development process can focus its efforts to operate efficiently on the compounds that will maximize cash flow to the pharmaceutical firm. 

Harmonization has three essential values. The first is the facilitation of international eommeree. The second is facilitation of product registration processes in multiple nations. The third is to reduce duplicative testing costs. Facilitation of registration is for any new molecular entity a one-time event for each country, whereas the facilitation of international commerce and reduction of duplicative testing remains throughout the lifetime of the product. 

The term exploratory development (ED) can be defined as the first part of clinical drug development in which tolerabihty, pharmacokinetics and pharmacod)mamic activity are defined in man and in which an early indication of therapeutic efficacy is often obtained. A new molecular entity (NME) can be defined as an unlicensed new chemical or biological entity with activity in biological systems whose therapeutic potential is under investigation. The overall aim of ED should be to select appropriate NMEs for full development (ED), that is, commitment to licence application and to reject those that will not make useful medicines, as early as possible. 

What is the company s strategic goal for this new molecular entity (NME) ... 

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