Process R&D under the magnifying glass: organization, business model, challenges, and scientific context

Abstract

Initially, the aim is to provide the big picture illustrating the as is situation in the pharmaceutical industry: a lack of productivity resulting in too few products reaching the market; a loss of billions in revenue over the next few years as some of the major megabrands go off patent; a spiraling cost for developing new drugs and taking them through clinical and safety studies. Following on, a look deeper into the organization will offer an insight into the state-of-the-art in a technical function accountable for chemical Process R&D (with a remit to develop scalable, robust, and cost efficient processes for small molecules). The vast majority of compounds already launched in the form of drug products on the market or still being pursued through the phases of discovery and development, fall within the category of small molecules (as opposed to biopharmaceuticals, e.g., proteins, monoclonal antibodies). This typically means molecular weights of <1000Da and puts organic synthesis in the widest sense of the word at the forefront of technologies needed to support R&D programs in the pharma industry. Understandably, the demands on Medicinal Chemistry are quite different to what applies in a Process R&D (PR&D) organization. In the former, making large numbers of potentially interesting molecules, many of which are discarded after testing, is a key driver and for this virtually any synthetic methodology will suffice. For PR&D, however, homing in on selected compounds there is an expectation that the best synthetic routes will be delivered that meet a number of tough criteria, for instance from an environmental and safety point of view, allowing operation on large scale, offering cost competitiveness, avoiding patent infringements, showing sustainability for long-term production, etc. The intention is to focus on issues to be addressed during this transition by providing examples of changes that had to be put in place in order to make the supply of larger amounts of material feasible. At the end some forward looking conclusions will be shared.