(758g) An Integrated Management System to Optimize Process Operations Within the Pharmaceutical Industry

One of the major challenges in developing a pharmaceutical process is the need to supply material of a quality representative to the final product, and at the same time, develop a safe and scalable process that can evolve into the final manufacturing process.  In order to overcome this challenge, requires careful integration of process chemistry development, analytical techniques and process engineering of the chemical synthetic route.  Historically, process safety has been regarded as a manufacturing concern, leaving the collection and analysis of process safety information, such as thermal stability and thermo-chemistry to the latter stages of process development.  Since, other constraints such as product impurity was developed earlier in the process, this introduced the need for engineering solutions to process safety problems later in the process.  This could have been avoided by straightforward changes in process chemistry, had these problems been identified and determined earlier in development.  In addition, the process safety information that is obtained from physical experiment to address the process safety problems, can also provide valuable insight into, inter alia, process robustness and optimum operating conditions.  Thus, the opportunity to leverage this information is lost by separating process safety from process chemistry and regarding it as an independent compliance function.

 It is proposed here, to integrate the activities generally associated with process safety, such as thermal stability testing, reaction engineering and safety management into the development process for pharmaceuticals and fine chemicals.  This will enable the data generated by the process safety function to be part of the dossier of process information that can be utilized by chemists and engineers in developing the “operating envelope”.  In addition, companies can avoid the delay and expense due to process changes that result from safety recommendations at latter stages in the process, and which conflicts with the process declarations in regulatory filings.  This paper presents a novel integrated  management system that can optimize process operations within the pharmaceutical industry.