Chapter 3 - Fermentation and downstream processing: Part 2

Abstract

The need to exclude all microorganisms except the one being cultivated is a unique challenge in the design and operation of aseptic fermentation vessels. The fermenter, along with all associated piping and sterile feed tanks, must be sterilizable, and post-sterilization, all foreign organisms must be denied entry. Required features include the absence of crevices, gross imperfections, and rough surfaces that are difficult to sterilize, a sterility barrier (either a steam seal or sterilizing filter) at each transition away from the aseptic environment, and pipes, valves, fittings, and sensors that have smooth surfaces and are free draining. Other important design considerations for aerobic fermenters are also discussed, including vessel geometry, air sparger details, and types of heat transfer surface. (Mixing is covered mainly in Chapter 2.) Sensors and control approaches are reviewed for all parameters of interest, notably temperature, pressure, pH, dissolved oxygen, level, foam, and exit gas composition. While most fermenters are mechanically agitated, airlift fermenters are also an option. In lieu of a mechanical mixer, these rely on the energy of rising air bubbles for agitation. Airlift fermenters are particularly useful for very large vessels, where the huge mixers that would be required would be impractical. Although not common in industry, continuous fermentation processes offer higher productivity when compared to their batch counterparts. Key aspects are discussed, including relevant mathematics, operation with and without cell recycle, examples of commercial implementation, and the use of the continuous fermenter as a research tool. Lastly, downstream processing operations are reviewed in light of two representative fermentation processes, with available options considered for each processing step, along with comments on how the various steps fit together to deliver acceptable product in a cost-effective manner. Cell rupture, crossflow membrane filtration, centrifugation, evaporation, crystallization, rotary vacuum precoat and pressure leaf filtration, drying, hydrophobic resin adsorption/elution, liquid-liquid extraction, and distillation are covered.