Question

discuss in detail scale-up issues in bioreactors

Answer 1

Bioreactors are manufacturing devices that has a closed environment suitable for a biological process to take place. The process can either be aerobic or anaerobic. The mode of operation may vary: batch fed (input given at the beginning of the process) or continuous (fresh medium is continuously added). Bioreactors must maintain closely controlled conditions such as ph, temperature, humidity, sterility, etc to give the cells or tissues a homeostatic environment so that they can perform the necessary activities at an optimum efficiency.

Upscaling in bioreactors is an essential step in the production of desired therapeutic proteins such as monoclonal antibodies. Starting from cell culture flasks or petridishes, Upscaling requires a step by step increase in the production. The most important thing to remember in such upscaling is maintaining the same exact conditions. Apart from the temperature, ph and such parameters, it must be planned to use similar gassing strategies, similar pipes to deliver the gas in the culture, etc.

It must be taken care to maintain constant vessel ratios while gradually upscaling the process, for example, the ratio of height to diameter must be similar in both the small and large bioreactors. Similarly, components such as the kLa (mass transfer coefficient), power input per volume, must be kept similar in all bioreactors while upscaling. All these parameters must be monitored from time to time by employing proper sensors and computer softwares.

A major issue in upscaling is contamination. Production processes such as microbial metabolites’ production, proteins’ production, any cells cultivation, etc, all processes when performed at a higher capacity are susceptible to unwanted infections. Though a careful monitoring of optimum conditions is precautionary, contamination may yet take place. It remains important to quickly identify the source and nature of the contamination and only then, can a strategy be developed to reduce the contamination.