Microbial Culture Processes
Bacteria have long been used to manufacture protein therapeutics, with recombinant insulin being the first protein manufactured this way in large-scale production. Pall® filters are used to sterilize the large volumes of air or oxygen needed to support bacterial growth at the start of the process, harvesting the bacteria and purifying the resulting extracted product all the way through to sterilizing the bulk drug.
Although some bacteria are now being engineered to express protein into the culture medium, or into the periplasmic space, in most cases proteins, plasmids, polysaccharides and other biotechnology molecules are formed and remain within the bacterial cell – often as insoluble Inclusion Bodies, from which they have to be extracted before downstream purification.
Bacteria tend to be more robust and more amenable to large volume high density culture than animal cells. However, in most cases, the proteins produced need further processing to render them suitable for use, as they may not be folded or glycosylated in the same way that mammalian proteins are. Chemical processes are then used to refold the proteins as required. Advances in bacterial genetic engineering are starting to address some of these shortcomings.
Bacteria are widely used to produce recombinant vaccine components (proteins and polysaccharides), as well as allergens and many other molecules used for therapeutic, prophylactic, diagnostic and cosmetic uses.
Some yeasts are used in the same way. Bacteria and fungi cultured for the production of small molecules such as antibiotics are covered in the Active Pharmaceutical Ingredients section.