One of the biggest challenges in the production of therapeutic proteins, monoclonal antibodies, and vaccines is the clarification and separation of the product (typically a protein) from the cell culture or fermentation broth. The desired product is present in low concentrations and must be efficiently separated from the other components present in the bioreactor fluid. An overall objective in developing a clarification process is to achieve the highest level of product recovery (yield) and contaminant removal with the fewest number of unit processes. Understanding how each operational step affects the performance of the next step downstream is the challenge at hand. Centrifugation, in combination with depth filtration, is gaining acceptance as the preferred method for the removal of cells, cell debris, colloids, insoluble precipitants, aggregates, and other materials found in mammalian cell culture and bacterial fermentation fluids. In today's bioreactor-based processes, increased cell concentrations and longer culture times result in higher product titers. However, these bioreactor conditions also reduce cell viability, increase cell debris, and raise concentrations of organic constituents in the bioreactor fluid. The primary step of the recovery process should be designed to remove the bulk of large particles, whole cells, and cell debris. This step must also minimize additioanl cell lysis before and during separation to avoid the release of unwanted soluble proteins from the whole cells. Primary recovery goals include achieving maximum yields, product consistency, process scalability, adequate product concentration, adequate product stability, cost of production targets, and compliance with current regulatory guidelines. The primary recover step is commnly performed by centrifugation due to cost and space advantage over other methods. Centrifugation has proven effective at minimizing shear damage to cells while achieving the primary recovery goals. High speed disc stack centrifuges are most commonly applied in the removal of cells and cell debris. What makes disc centrifuges unique is the way they combine the benefits of high G-force and surface area to enable high-throughput fine particle separation. Centrifugation for primary recovery is typically able to handle relatively high concentrations of insoluble material in the feed, but has limitations in its ability to remove all the particles below a certain size at a practical flow rate. This means that some form of secondary clarification will be needed to remove the remaining particulates before final purification. Centrifuges can generally concentrate the cell mass to > 70 percent by volume and offer flexibility because the major optimization parameters, flow rate and rotor speed, can be altered without changing hardware. Recent improvements to the acceleration zone of newer centrifuges have reduced the mechanical stress to the cells and the subsequent release of cell fragments and intercellular release of materials associated with cell lysis. High-performance and economical cell culture clarification can be achieved by combining centrifugation and depth filtration technologies. The unique characteristics of these two technologies enhanced by recent product improvements provide benefits such as: ·Fast processing of large volumes ·Consistent clarified fluid quality, regardless of bioreactor fluid variability ·Enhanced product yield ·More robust manufacturing process