Linear scale ultrafiltration

Abstract

Tangential flow filtration has traditionally been scaled up by maintaining constant the filtrate volume to membrane surface area ratio, membrane material and pore size, channel height, flow path geometry and retentate and filtrate pressures. Channel width and the number of channels have been increased to provide increased membrane area. Several other parameters, however, have not been maintained constant. A new comprehensive methodology for implementation of linear scale up and scale down of tangential flow filtration processes has been developed. Predictable scale up can only be achieved by maintaining fluid dynamic parameters which are independent of scale. Fluid dynamics are controlled by operating parameters (feed flow rate, retentate pressure, fed batch ratio and temperature), geometry (channel length, height, turbulence promoter and entrance/exit design), materials (membrane, turbulence promoter, and encapsulant compression), and system geometry (flow distribution). Cassette manufacturing procedures and tolerances also play a significant role in achieving scale independent performance. Extensive development work in the aforementioned areas has resulted in the successful implementation of linear scale up of ultrafiltration processes for recovery of human recombinant DNA derived pharmaceuticals. A 400‐fold linear scale up has been achieved without intermediate pilot scale tests. Scale independent performance has a direct impact on process yield, protein quality and product economics and is therefore particularly important in the biotechnology industry. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 737–746, 1997.

Downstream processing of monoclonal antibodies—Application of platform approaches

“…Following the completion of downstream purification, the product is buffer exchanged into the formulation buffer [42]. This is best accomplished by the use of an ultrafiltration/diafiltration setup.…”

Scale-up of monoclonal antibody purification processes

“…ultrafiltration, may be necessary to make a process fit into a facility. Ultrafiltration operations are readily scaled-up [23] but they can result in increased levels of product aggregation. This is particularly critical when scaling up high titre processes and may require challenging concentration conditions.…”

Bioseparations

“…They are also the method of choice for concentrating either cells or true solutions when only the desired species is retained by the membrane. Moreover, membrane filtrations are much cheaper than chromatography, and available selectivity is rapidly increasing (Christy et al, 2002;van Reis et al, 1991van Reis et al, , 1997avan Reis et al, , 1997bvan Reis and Saksena, 1997;. Membranes have already largely replaced gel permeation chromatography (Kurnik et al, 1995), and further encroachments can be expected.…”

“…Our primary concerns here are with micro-and ultrafiltration, and both equipment design and operation are covered in readily available references (Belfort et al, 1994;van Reis et al, 1997a;Zeman and Zydney, 1996). These are designed to provide high ratios of filtration rates (mass transfer) to pressure drop, or drag, in the fluid flowing past the membrane.…”

“…The most recent applications, which seem to be expanding rapidly are in the discrimination between proteins of similar size, a family of processes known as high performance tangential flow filtration (Christy et al, 2002;van Reis and Saksena, 1997;, van Reis et al, 1997a, 1997b, 1997c. As already indicated above this process seems poised to compete with chromatography.…”