Chiral Drug Discovery and Development – From Concept Stage to Market Launch

What do the complexities and challenges look like in the pharmaceutical industry of today and how are they addressed? This straightforward question summarizes very well the major theme of this chapter. The once so successful and admired drug business is going through a demanding and troublesome period in the beginning of the twenty-first century. A key concern in this regard is the declining productivity expressed as new products on the market and ways to improve on the attrition level that remains at an ‘unhealthy’ industrial average of around 90%. Part of the answer is most likely that more complex and insufficiently understood diseases from a mechanistic point of view are being pursued but also in parallel to constantly increasing pressure to supply comprehensive documentation on every new product, especially in the areas of safety and efficacy. Thus, many companies are grappling with these issues by trying to come up with more efficient and efficacious ways of working as well as encouraging their staff to be creative in finding new best modes of operation. There is a widespread recognition that in order to maintain development, production, and marketing of new and innovative medicines sustainable business changes will be required, in certain areas maybe even dramatic ones. Looking at the industry from a molecular perspective, a wealth of information is available on distinguishing features between compounds that have been proven successful as drugs (the small minority) and those that have failed (the vast majority). The gold mine that these data provide is now used regularly when designing new structures with a hopefully better survival rate. In stereochemical terms the shift from the racemic domain into the enantiomeric counterpart has been concluded – including also the relatively few cases of chiral switches – and today only a very small percentage of racemates are taken forward as new chemical entities. A raft of technologies has been developed and improved to match higher and higher demands on accuracy and productivity in areas such as asymmetric synthesis and stereospecific analysis. Numerous success stories have given testimony to what Medicinal Chemistry, Process R&D, and Analytical Development are capable of handling when challenged with increasingly complex target molecules. However, now and in the future it will not suffice simply to manage the technical problems, no matter how complicated, but it will also be necessary offer the desired product at a competitive and attractive cost in response to the strong price pressure exerted by the authorities and the public. There is no doubt a fairly large number of areas on which pharmaceutical companies are already focusing to better serve society with innovative medicines to improve single individual's quality of life. Being mindful of the highly complex environment in which the drug manufacturing firms operate, the task is formidable, but nonetheless one that has to be faced without fear and successfully solved.