Critical Concerns for Implementing Process Analytical Technologies in the Pharmaceutical Industry

tion to a series of columns that will describe key elements in the practice of implementing process analytical technology (PAT). Process Analytical Technology is defined by the United States Food and Drug Administration (FDA) in the document Guidance for Industry: PAT – A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance as “a system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and inprocess materials and processes with the goal of ensuring final product quality.” Process Analytical Technology promises to provide benefits to both manufacturers and consumers of pharmaceutical products. Such technology will improve manufacturing efficiency, while enhancing process understanding. The advances in pharmaceutical manufacturing that are possible from enhanced process understanding will augment the quality of pharmaceuticals, while reducing the cost of manufacturing, and ultimately play an important role in controlling the price of healthcare. One of the potential outcomes from the implementation of PAT is the replacement of conventional quality assurance/quality control methods for product release with a new approach, termed Real-time Release (RTR). RTR is a system that ensures a product is of the intended quality, while reducing or eliminating traditional end-product testing. PAT methods, including monitoring and control of process parameters, provide a platform for RTR. Published investigations of PAT applications often focus on the selection of sensor technology, and the development and validation of predictive calibrations. While these are essential aspects of a PAT application, a suitable infrastructure must be in place to support the deployment, operation and maintenance of the PAT method in a real-time manufacturing environment. The development of this infrastructure comprises another important phase of PAT method development. Critical issues to be considered during any PAT method development project include the following: ■ Risk analysis ■ Experimental design ■ Sensors ■ Model development and transfer ■ Process sampling ■ Information management