ABSTRACT
For those readers unfamiliar with how things operate in the pharmaceutical industry, a brief description is in order. The goal of the medicinal, or drug discovery, chemist is to identify a new drug candidate to treat or prevent some particular medical indication. Once a new drug candidate has been selected, the next important step is the filing of an Investigational New Drug Application (IND) with the Food and Drug Administration (FDA). On approval of the IND, the compound can be administered to humans for the first time in Phase-I clinical studies. Studies which are reported in an IND include animal toxicology studies, pharmaceutical and formulation studies, drug substance and drug product stability studies, metabolic studies, and pharmacokinetic studies. This work, of course, requires relatively large amounts of the drug substance, substantially more than was prepared during the course of the medicinal chemistry program. Generally, it becomes the responsibility of a process chemistry group to produce this material, within, of course the shortest feasible timeframe. Pharmaceutical process chemistry groups are organized in different ways. The Bristol-Myers Squibb paradigm allocates this function among Process Research, Process Development, and Manufacturing. Process Research is responsible for providing the supplies of bulk drug substance required for an IND filing, including the initial clinical batch (or batches). Typically, the initial supplies are prepared by some combination of a modified medicinal chemistry synthesis and new, alternative synthetic processes more suitable for scale up. At Bristol-Myers Squibb, this responsibility is shared by process research chemists and Kilo Lab chemists, the Kilo Lab being responsible for the scale up of processes provided by the process research chemists. Kilo Lab scale up work typically is performed in up to 22-L glassware. Process Development, on the other hand, is responsible for further scale up in the Pilot Plant and typically takes over the preparation of bulk drug substance beyond the initial Phase-I clinical supplies.
