QbD – Quality by Design
The FDA’s emphasis on drug applications that include Quality by Design (QbD) data has sparked a surge in activity for protein therapeutics R&D teams. The overarching goal of Quality by Design is to improve biological therapeutics safety and efficacy, while additional benefits include increasing the efficiency of manufacturing process, which reduces cost, and the potential for faster regulatory approval of new drugs.
The FDA has stated that “Quality by Design means that product and process performance characteristics are scientifically designed to meet specific objectives, not merely empirically derived from performance of test batches.” As a direct consequence, one of the core tenets of QbD is the requirement of detailed knowledge of the critical quality attributes (CQAs) of the biological product and the critical process parameters (CPPs) that can be used to control overall product quality. Gathering the raw data needed for this endeavor can be prohibitively time, labor, and cost intensive without employing Design of Experiment (DOE) approaches, also known as Factorial Experimental Design (FED). Even with DOE, a significant number of samples need to be processed, which has created a need for next generation Process Analytical Technologies that provide robust, high throughput, predictive results for critical quality attributes such as titer, purity, aggregation, fragmentation, and size.
The LabChip GXII, an automated platform for rapid analysis of proteins and nucleic acids, has proven to be an enabling technology for QbD programs. As an automated replacement technology for SDS-PAGE gels, the LabChip GXII provides high throughput analysis of titer, sizing, and purity analysis of proteins. When compared to traditional capillary electrophoresis for screening monoclonal antibody product quality, microfluidics provides “sufficient resolution and sensitivity for this purpose but on a time scale approximately 70 times faster (41 s vs. 50 min)”1. The speed of microfluidics enables a 96-well plate to be analyzed in just over an hour, compared to several weeks for traditional gel electrophoresis or capillary electrophoresis. Consequently, researchers can perform experiments that explore several parameters in detail in a process that has been described as “reduces cost and time while increasing throughput, making possible what-if experiments that, up to now, had been either prohibitively expensive or too complex to perform.”2
The LabChip GXII can also be coupled with the Twister II Plate Handler for longer walk away time and can be integrated into a Staccato Workstation for complete automation of sample preparation and analysis.
