Optimization of ultrafiltration/diafiltration processes for partially bound impurities.
ABSTRACT Ultrafiltration and diafiltration processes are used extensively for removal of a variety of small impurities from biological products. There has, however, been no experimental or theoretical analysis of the effects of impurity- product binding on the rate of impurity removal during these processes. Model calculations were performed to account for the effects of equilibrium binding between a small impurity and a large (retained) product on impurity clearance. Experiments were performed using D-tryptophan and bovine serum albumin as a model system. The results clearly demonstrate that binding interactions can dramatically reduce the rate of small impurity removal, leading to large increases in the required number of diavolumes. The optimal product concentration for performing the diafiltration shifts to lower product concentrations in the presence of strong binding interactions. Approximate analytical expressions for the impurity removal were developed which can provide a guide for the design and optimization of industrial ultrafiltration/diafiltration processes.
Article: Bioprocess membrane technology[show abstract] [hide abstract]
ABSTRACT: Membrane processes play a critical role in the purification of biotechnology products. Early membrane systems were adopted from technology originally developed for other industrial applications. During the last 2 decades, new membranes and modules have been developed specifically to meet the requirements of the biotechnology industry. This includes applications of membranes for sterile filtration, clarification, initial harvest, virus removal, protein concentration, buffer exchange, and protein purification. This manuscript provides an overview of recent developments in membrane technology, focusing on the special characteristics of the membrane systems that are now used for the commercial production and purification of recombinant protein products. Future developments in membrane technology are also discussed that may be able to meet the growing needs for higher productivity, lower cost of production, and increased development speed in the biotechnology industry.Journal of Membrane Science.