Drug discovery shortening

Figure 3.10 The drug development process. The timeline for drug discovery and development is long, adding to the high cost of drug development. Computational methods have helped to shorten this timeline.

The pharmaceutical industry now faces compelling demands to improve the productivity of analyses and shorten drug discovery and development time cycles. An impressive number of drug candidates generated by modern synthesis and combinatorial libraries requires screening of many samples. Some examples of the usefulness of the IPC strategy will be discussed below. 

All drug discovery projects depend on luck to be successful, but research and careful planning can improve chances of success and lower the cost. Project teams can streamline the discovery process by using the tools that can lead to a discovery most directly. These tools are drawn from the repertoires of modem biology, chemistry, robotics and computer simulations. In comparison with older processes of in vivo screening of huge numbers of molecules, however, these innovations have not been associated with shortening of the development... 

Optimization of drug discovery strategies is driven by the actual patent situation (drug discovery and development 10 to 12 years term of patent 20 years expiry of important patents in the next few years will cause drastic drops in turnover) forcing the companies to shorten the time taken to bring a drug onto the market. 

Because of the time and effort needed to develop immunoaffinity methodology (4 to 8 weeks typically needed to generate a purified antibody), immunoaffinity separations are usually reserved for the more difficult separation problems in analytical chemistry. The shortened time scale of drug discovery precludes their routine day-to-day use. The power of immunosepara-tions in combination with mass spectrometry could see wider use as clever solutions to difficult problems are needed. 

These automated assays can be used for high-throughput ADME screening in early drug discovery. The double-sink PAMPA permeability assay mimics in vivo conditions by the use of a chemical sink in the acceptor wells and pH gradient in the donor wells. The use of the pION gut-box integrated on the deck has shortened the PAMPA assay incubation time to 30 minutes. The permeability coefficient and rank order correlate well with data obtained using the in vitro Caco-2 assay and in vivo permeability properties measured in rat intestinal perfusions. 

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