- 9:20 AM

Membrane Development for the Production of Biopharmaceuticals

Anthony Allegrezza, Gabriel Tkacik, and Willem Kools. Porous Structures & Chemistries, Millipore Corporation, 80 Ashby Road, Bedford, MA 01730

Biopharmaceutical producers have become more knowledgeable, sophisticated and demanding as the development and production of biopharmaceutical drugs has grown. Membrane manufacturers have responded to these demands by developing membranes tailored not only to the standard requirements (i.e., flux and rejection) but also to secondary needs. In this talk, we will discuss microporous membranes used for clarification and sterile filtration, ultrafilters used for concentration and purification, and ultrafilters used for virus removal.

The early biopharm industry used symmetric microporous membranes for clarification after the centrifuge step, for in process filtration, and for final aseptic filtration. These membranes are still the workhorse of the industry. But the demand for increased speed and process efficiency required by larger plants has led to the development and use of asymmetric microporous membranes, particularly polyethersulfone (PES). Equally important biopharm producers want higher capacity, that is, the ability to filter longer. To meet this latest requirement, the latest membranes in this field are multilayered composite membranes designed for specific steps in the process train.

Ultrafiltration (UF) for protein concentration and buffer exchange requires very high yields due to the high cost of the protein products being filtered. For monoclonal antibodies especially, composite cellulose UF dominate because of their high rejection capabilities, low protein binding, and robustness. The development and use of these membranes will be described. For applications requiring harsh chemical cleaning, or where protein binding is of less concern, PES UF membranes are used. In these applications, the use of membranes with no macrovoids has shown increased productivity. Most applications use flat sheet cassettes, but the use of hollow fibers will be discussed.

Ultrafilters used in a final virus clearance step have the most difficult requirements in this field. They must have very high retention of virus particles, down to 20nm diameter, and pass well over 90% of the product protein. There are several competitive products in the field, ranging from hollow fibers to flat sheet composites to symmetric membranes. These will be discussed and compared.