Optimal handling of Highly Active Pharmaceutical Ingredients during milling and blending operations

Abstract

This thesis investigates best practices for Highly Active Pharmaceutical Ingredient (HAPI) milling and blending. We utilize a qualitative analysis centering on a benchmarking study and quantitative analyses using a probabilistic capacity simulation and tradeoff methodology. The analyses indicate that the growing number of HAPI products in a manufacturer's portfolio may result in capacity constraints. Therefore, we recommend that manufacturers pursue process improvement technologies. Suggested process improvements include implementing online particle size measurement and Wash in Place (WIP) and Clean in Place (CIP) cleaning systems. Online particle size measurement allows for better process control and eliminates the need for HAPI blending for homogenization. Automated WIP and CIP systems decrease changeover time and allow for higher equipment availability. Additionally, the results of the analyses suggest that manufacturers consider standardizing transportation containers with the upstream vendors and downstream consumers. Lastly, from an organizational standpoint, we recommend that manufacturers include both subject matter experts and operations personnel when developing and implementing internal guidelines so as to ensure the guidelines are practical and uniformly applied.