Filtration is one of the most commonly used unit operations in biopharmaceutical manufacturing. Available formats include direct or normal flow filtration (NFF) and cross or tangential flow filtration (TFF). These methods are used for sterilization and virus filtration, depth filtration or ultrafiltration, and diafiltration applications. Some common objectives include:
This article is the fourth in the "Elements of Biopharmaceutical Production" series and will be published in two segments. In this first segment, Anurag Rathore and Alice Wang present development and scale-up of a depth filtration step, and Jerold Martin discusses development and validation issues for a viral clearance filtration step.Anurag S. Rathore and Alice Wang, Amgen Inc.
Process Development and Scale-up for Depth Filtration The following shows the development of a robust depth filtration step for clarification.1 We wanted to design a robust and scaleable depth filtration step that could maximize product recovery (in this case, a protein expressed in Pichia pastoris) and that could handle varying % solids content in the feed stream from the preceding centrifugation step. First, we performed a screening study using various depth filters available on the market that met our manufacturing process criteria. Second, we chose filters based on the screening data; we directly and thoroughly compared those filters to determine the best performing filter. Then, we performed characterization studies on the chosen filter to ensure robust performance at scale. Finally, we scaled the filtration step up to pilot scale and compared its performance under these conditions.