BioPharm International-03-10-2006

Anyone who has ever hoisted a glass of a local microbrew has experienced the results of the oldest form of biotechnology?fermentation, the process by which living cells obtain energy through the breakdown of glucose and other molecules. The basic technique of brewing has not changed much in the past 6,000 years, but it is still an excellent illustration of the principles that underlie some of today's most sophisticated biotech production.

To learn more about the processes of fermentation and cell culture used in the production of biopharmaceuticals, you can refer to our advertisers or to the following publications, organizations, and web sites.

Fermentation is an industrial process, but it's probably easier to understand it as something more familiar: raising a living creature. Every fermentation process has to answer several basic questions: Where will the cells live and grow? What will they nourish themselves with? Will the cells live suspended in a mix of water and nutrients (the medium) or do they need to be contained or allowed to attach themselves to a solid base? How will food and air be distributed so all the individual cells get their share? Should all the nutrients the cells need be added at one time, or should the cells be fed additional food as fermentation progresses? How will the progress of fermentation be monitored to ensure the best possible results?

At the heart of modern biotechnology is the ability to manipulate DNA, the astonishing molecule that contains the genetic code of all life on earth. But fermentation and cell culture are also the practical art of keeping cells alive and growing in an artificial environment. As a result, the science of cell culture also includes a healthy focus on the natural processes that keep cells alive.

Many of these terms have more general definitions as well. Those given here are specific to their application in cell culture and fermentation.

As we've shown, biopharmaceutical companies have many options when they choose an expression system: bacteria, yeasts, insect or mammalian cells, and transgenics. Each system has its advantages and disadvantages. Company decision makers must ask themselves several important questions: How much product must be made? How complex is the molecule? Does it require posttranslational modifications to be biologically active? The expression system determines what kind of contaminants will be present and in what quantities. It also determines economic factors: the time scales involved, expression levels obtained, and various regulatory issues. Each potential expression system must be evaluated for its ability to produce economically the maximum amount of biologically active product. Purification methods may be different for products that come from the different host systems. And regulators are more familiar with some systems than with others.