What is the goal of the Process Analytical Technology (PAT) initiative?
In October 2003, FDA released a draft guidance that introduced PAT to the pharmaceutical manufacturing industry . PAT is a science based approach that focuses on the improvement of manufacturing efficiency and product quality. PAT tools perform real-time, on-line measurements of evolving quality parameters to ensure optimal processing conditions are maintained throughout the manufacturing process. PAT tools provide the means to gain new understanding and knowledge of the process critical control points and facilitate better control of process variation further upstream. The variability of inputs to the process may still exist, but knowledge of their existence and impact allows the process to be accommodating to these differences resulting in a more robust process and hence more consistent end product.
Why monitor blend uniformity on-line?
Powders are normally blended together to produce pharmaceutical products and the consistency of those powders is critical to the quality and the efficacy of that product. Typically a blender is charged with four or more individual components and they are blended using parameters of fixed time and speed. A fixed blending process does not take into account the variability of the components and this can lead to variation in the product. Despite the fact that a lot of effort has been committed to reduce the lot to lot variability of the components, the industry is still facing the problem that slight variations in the chemical or physical properties of these components can potentially have a huge impact on the final product. Variation of the components could be attributed to several factors. Some of these include: environmental conditions, humidity, feedstock grade, and particle size distribution. Presently the blending is validated as a fixed process (e.g. blend for ten minutes). If variation is introduced into a fixed process, the only possible outcome is product variability. Fixed processing conditions do nothing to dampen or buffer the influence of incoming variability.
On-line monitoring of a blending process uses a somewhat different approach. Real time measurements and feedback provide a "process check" operation that occurs within the actual unit operation being performed. The knowledge gain during the process does not in itself improve the incoming variability, but by measuring and modifying a process in response to measured fluctuations of incoming materials, it is possible to achieve processing, and hence, product consistency. On line measurements also add the benefit of eliminating thieving time and bias.