Best Practices of Downstream Protein Purification and Product Concentration

Downstream protein purification and product concentration is known to be the most challenging part of the process development. It is also known that the Downstream process development is critical to ensure protein drug’s quality, safety & efficacy meet regulatory expectations. When initiating the development, the Chemistry, manufacturing and controls considerations for process development and manufacturing must include molecule complexity. Raw materials, process development. Equipment and manufacturing, Quality and Regulatory affairs. The critical factors for development and manufacturing is performing stage-wise assessment on Product development, analytical and process development and not the least, the manufacturability assessment. The expected qualities of a superlative process shall include increased capacity, flexibility, cost-effectiveness, controllability, scalability, and efficiency. However, general challenges exist in downstream process development involving, Balancing higher cost chromatography resins and solvents Constrained purification space for molecules prone to degradation at wide range of pH and temperature Process fit to multi-product facility, PAT availability to accelerated processing Adaptation of new technologies one of smarter way to address the challenges: Non-Protein A process use of next-generation chromatography resins Continuous processing for capture, intermediate purification, Viral clearance