A next generation, pilot-scale continuous sterilization system for fermentation media

Junker, B., Lester, M., Brix, T., Wong, D., & Nuechterlein, J. (2006). A next generation, pilot-scale continuous sterilization system for fermentation media. Bioprocess And Biosystems Engineering, 28(6), 

Advantages

Advantages of continuous sterilization have been outlined in several reports [3, 7, 10, 30, 60, 84]. By far the most noted benefit is energy conservation since continuous sterilization consumes up to 60–80% less steam and cooling water for large-scale fermenter media volumes. This economy lies at the high end of this range when continuous sterilization utilizes heat recovery via indirect heat exchange to pre-heat incoming cold medium with hot medium leaving the sterilization hold loop. It thus requires less energy (as well as generates a more uniform demand without peak draws [7]); than the alternative batch sterilization process involving sterilizing the fermenter vessel and its non-sterile contents together.

Batch sterilization becomes less efficient with scale since heating and cooling portions of the cycle are longer than the constant hold temperature portion [54,83], and heat transfer coefficients decrease with scale up[34]. Prior to receiving continuously sterilized medium, the fermenter is sterilized empty or with a small volume of water covering the pH and dissolved oxygen probes. Heat up/cool down times are substantially shorter, decreasing overall turn-around time [96].Continuous sterilization results in gentler treatment of medium compared to batch sterilization, which tends to overheat medium to ensure that vapor space vessel internals achieve sterilization temperatures [1]. Sterilization at higher temperatures for a shorter time generates less degradation of heat-sensitive medium components since spore destruction rates increase fasterthan nutrient destruction rates as temperature rises [15].The activation energy for nutrient degradation ranges from 50 to 150 kJ/mol, which typically is smaller than activation energies for the thermal death of microorganisms, which range from 250 to 350 kJ/mol [67].Consequently For increases more than Ro as temperature rises [1, 52]. Similarly, amino carbonyl or   reactions, which form objectionable color and tastes to consumers for pasteurization and adversely affect medium quality (destroy growth factors) for fermentation, are minimized [12, 54]. In the case of polymerizedpoly (L-lactide) rod implants, lower molecular weight decreases also have been found for autoclavecycles at higher temperatures and shorter times [88].Continuous sterilization results in more uniform heat treatment of medium than batch processes since the system operates at steady state [15]. Proteins and carbohydrates can be separately sterilized in multiple sections using several mix tanks with a sterile water flush between them [96]. Since there is no need to agitate unaerated (ungassed) large liquid volumes during batch sterilization, fermenter agitator design can be based on drawing full load during gassed conditions [96]. Some feel that continuous sterilization offers a lower contamination rate relative to batch sterilization since fermenter internals are more easily sterilized in an empty rather than full fermenter [96]; others believe that batch sterilization has a lower risk since there is no need to transfer aseptic media [97]. HTST systems have a high degree of flexibility since a large range of time/temperature combinations can be selected within equipment design limits. Scale up is linear with media flowrates of10–100,000 L/h reported for HTST systems [36] and up to 30,000–50,000 L/h for pasteurizers [38]. Time/temperature exposure profiles accurately reflect sterilization conditions for the media of interest and can be readily modeled. Finally, the ability to design heat exchange equipment to minimize fouling reduces cleanability and maintenance concerns. Disadvantages of continuous sterilization primarily are that process control performance is critical since it is necessary to immediately divert flow of any inadequately sterilized medium, halt any further medium sterilization, and resterilize the system. In contrast, for a batch sterilization system upset, often additional hold time can be readily added to the sterilization. Continuous sterilizer systems also use dedicated equipment that usually is not well suited for other purposes.