New chemical entity

In contrast to prescription dmgs, OTC dmgs and cosmetics are not subject to preclearance in the United States. However, the rules covering OTC dmgs preclude introduction of untested dmgs or new combinations. A "new chemical entity" that appears suitable for OTC dmg use requires work-up via the new dmg appHcation (NDA) process. In contrast, the use of ingredients in cosmetics is essentially unrestricted and may include less well known substances. 

The development of a single enantiomer as a new active substance should be described in the same manner as for any other new chemical entity. Studies should be carried out with the single enantiomer, but if development began with the race-mate then these studies may also be taken into account. Chiral conversion should be considered early on so that enantiospecific bioanalytical methods may be developed. These methods should be described in chemistry and pharmacy part of the dossier. If the opposite enantiomer is formed in vivo, then it should be evaluated in the same way as other metabolites. For endogenous human chiral compounds, enantiospecific analysis may not be necessary. The enantiomeric purity of the active ingredient used in preclinical and clinical studies should be stated. 

Structural information chemical formula and stereochemistry in the case of a New Chemical Entity (NCE) or amino acid sequence and glycosylation sites in the case of a biotech product... 

The authorisation of veterinary medicines containing a new chemical entity for use in food-producing animals involves a two-stage application process (i) an application to establish MRLs and (ii) an application for a marketing authorisation. 

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. 

For non-prescription and generic dmgs, the documentation required is simplified and is mostly concerned with chemical and pharmaceutical data. In general, the documentation required for registering products containing new chemical entities is more extensive than that for products in other categories (see Table 8.2). Countries that have the capacity to make an independent assessment of the safety, efficacy and quality of products, such as Australia, Estonia and the Netherlands, do not request the WHO-recommended Certificate of Pharmaceutical Product. Only Cyprus and Tunisia request price information. 

Does workload affect the time taken for assessment and registration Since the registration of products containing new chemical entities requires the most extensive review and expertise, it is used for this analysis. The data are the same as those presented in Figure 8.5. 

P. A. Experimental and virtual physicochemical and pharmacokinetic profiling of new chemical entities. 

Galland, A. Towards the validation of in silica models and physicochemical filters to identify and characterize new chemical entities, PhD Thesis, University of Lausanne, 2004. 

Research on the identification of vanilloid antagonists has been pursued more intensively in industry than in academia. Thus, a SciFinder search for new chemical entities endowed with this type of activity pulled out 34 entries from the proprietary literature, and only 14 from journal articles during the period January 2004 June 2006. The patent literature can be difficult to evaluate and compare with the published data. Bioactivity is often not disclosed (or commented), and activity can be broadly claimed for a series of lead structures without specifying their optimal substitution. On the other hand, analysis of the patent literature does not only complement the published data, but also offers a preview of information that will be eventually disclosed and detailed in journals. Given the relevance of proprietary literature in the realm of vanilloids research, the main trends emerging from its analysis will be briefly summarized. 

Based upon a review of the physical chemical properties of marketed drugs, Lipinski and coworkers have proposed an empirical rule of 5 (20). This rule may help pharmaceutical scientists in reaching an early decision about the potential candidacy for further development of a new chemical entity. The rule states that a chemical candidate is likely to display poor absorption or poor membrane permeability if... 

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