The sources of particulate contamination are often not easy to identify. To control manufacturing processes, the measurement of particle concentration and size is necessary and has been routinely performed for many years. Technology has been developed to increase the information available for the immediate evaluation of particles. The method analyzes airborne particles or particles isolated from liquids automatically according to their number, size, and chemical composition. The analysis of thousands of particles enables users to locate the major sources of contamination in various manufacturing processes. The analytical tool provides rapid determination of particulate contamination, thus allowing for a quick, efficient response. Over time, the ability to compare analytical result data sets assists in detecting trends and implementing the appropriate quality management. Routine use of the technology contributes to ongoing supervision and optimization of production processes. This study reports on the use of the technology to analyze foreign particles associated with oral, inhalable, and nasal drug products (OINDP) and parenterals. Applications for troubleshooting and identifying latent contamination sources are discussed through several examples.
A variety of nitrogen-containing drugs used to treat heart disease were separated on ZORBAX Rapid Resolution (RR), 3.5 μm, and Rapid Resolution High throughput (RRHT), 1.8 μm, columns of differing dimensions. All three column configurations produce satisfactory results, creating the luxury of deciding which column configuration to choose for finalizing a method. Speed, resolution and sensitivity are primary goals in method development and column selection. When using RR or RRHT technology, these three factors can be quickly achieved using more than one column configuration. In this application we can compare three RR and RRHT columns, considering speed, sensitivity, and resolution to make a column choice. Additionally, with the primary goals met, we demonstrate how high temperature can be used to alter selectivity and further improve resolution of critical pairs in the chromatogram.
Pharmaceutical manufacturing is undergoing radical changes in response to challenges being faced by the industry. Science-based tools and Quality Risk Management (QRM) are increasingly being used to improve the efficiency of manufacturing operations. With the support of regulatory agencies, the industry is investing in developing the knowledge base of manufacturing and establishing the design space. There is a strong business case for the use of QRM throughout the product lifecycle. Use of QRM tools such as Risk Ranking & Filtering and Failure Mode Effect Analysis is discussed. A case study discussing the use of QRM to optimize the preventive maintenance program in the Quality Control laboratory is presented.