Membranes have been used for bioseparations for nearly 100 years, although the commercial development of ultrafiltration technology didn’t really occur until the work by Alan Michaels and his colleagues at Amicon in the 1960’s and 1970’s. However, the general rule of thumb through most of the next 20+ years was that membranes could only be used to separate species that differ in size by at least a factor of 10, severely limiting applications of membranes in bioprocessing. Recent advances in membrane science and technology have led to the development of membranes / processes that can accomplish much finer separations, opening up exciting opportunities for using membrane technology for the purification of high value biotherapeutics. This talk will provide an overview of the key historical developments enabling these membrane processes, building directly on the pioneering efforts of Alan Michaels. Emphasis will be placed on how new advances in membrane science coupled with an improved understanding of the underlying transport phenomena have led to exciting new applications of membrane technology in bioprocessing. This includes the use of virus removal filtration in the production of monoclonal antibodies, which can provide selectivities of more than 1000-fold even though the small parvoviruses are only about twice the size of a monoclonal antibody. Recent work in our group has demonstrated that ultrafiltration can be used for the purification of conjugated vaccines and pegylated proteins, enabling the removal of very similarly-sized impurities (e.g., unreacted polysaccharides in the production of polysaccharide-based vaccines). It is even possible to separate different plasmid DNA isoforms, in this case by exploiting differences in the elongational flexibility of biomolecules with nearly identical size but different topological structures. These developments are likely to have a major impact on the downstream processing of novel biopharmaceuticals for many years to come.

Michaels Award: Membranes in bioprocessing: From Alan Michaels to the present

2019 Spring National Meeting

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