Single-Use Technology for Microbial Fermentation

Equipment utilization will be much greater due to the faster turnover between runs. Single-use avoids post-run CIP, cleanliness validation, sterilization and pressure testing. The risk of cross-contamination is virtually eliminated. The consumption of water in CIP and sterilization is tremendous. Maintenance is almost non-existent by comparison; with no seals, O-rings or gaskets to replace between runs; not mechanical seals service, etc.

This will depend on the process. We have customers running fermentation at 1000L today. We evaluate all such cases individually to be certain of the applicability of single-use fermentors. Mainstream application of single-use fermentation, however, ranges between 50L and 500L; with 500L being an upper boundary right now.

With respect to the process contacting parts, which is the bioreactor/fermentor bag, there is nothing to clean as nothing gets reused from that assembly. This is one of the main benefits of single-use bioprocess technology as a whole. And, specifically, for fermentation, single-use technology eliminates cross-contamination previously associated with O-rings, gaskets, diaphragms and mechanical seals. The process piping from the stainless steel equivalent has been replaced by elastomeric tubing. No cleaning necessary, just discard similar to other process waste.

Single-use technology is a good option for new and existing processes. There may be more to evaluate for existing processes because is it already operational. Consider that single-use technology shortens the turnaround time thereby, effectively, increasing equipment utilization. The industry remains very competitive and saving time had direct benefit to the bottom line. Also consider the amount of time and, if nothing else, the water associated with cleaning a fermentor between runs. Water is a valuable resource with daily headlines trumpeting its scarcity. Consider, too, footprint…and not just the footprint at the fermentor. Single-use fermentors do no rely on piping skid adjacent to the vessel; nor do they require clean or plant steam sources.

Application of single-use technology does not relieve the process owner from assessing any and all appropriate risks. The infectiousness or toxicity of a process, process intermediate or end-product should be considered, with operator safety being paramount. Unlike stainless steel fermentors, single-use fermentors rely on plastic films, tubing, etc. There are risks, though low, of breaches in the integrity of the film or tubing or failures due to miss use.

Very definitely…the flexibility imparted to fermentation, like in cell culture, is analogous. If I interpret your question further, might I also say that dual-purpose systems, systems capable of either cell culture or fermentation by switching reactor bags and some accessories are available. This type of dual-purpose product provides another level of flexibility, especially for development and pilot operations. With respect to implementing a flexible manufacturing environment, a comprehensive approach to the owner’s business is recommended, if not required. Single-use technology provide a catalyst for implementing changes necessary to be competitive today and into the future where biologics production is concerned. Single-use technology suppliers, especially for the unit operations become a much deeper “partner” in the business. The more information that can be shared, the better the supplier is able to support business continuity, for things like facility layout/design, operational efficiency, supply chain integration, just-in-time materials delivery and many more. As mentioned in an earlier topic response, footprint, utility requirement and water consumption all change for the better. Personnel skills and training may need augmentation. The technology really provides an excellent opportunity to align a manufacturing entity with specifics of today’s biomolecule while equipping them with ability to handle the changes so often associated with our industry.

In steam sterilizable, or conventional fermentors, we have had the ability to deliver more horsepower to the agitation system and oxygen to the sparging system than was sometimes needed; an overabundance of capacity, at times. With single-use fermentors, efficiency, especially in the process is the premium. Single-use fermentors are capable of controlling dissolved oxygen with the typical cascade control elements: air & oxygen gas flow, agitation and substrate feed. Pressure is all that is missing. Gas flow rates between 1 and 2 vessel volumes per minute are available. And, with agitation systems equipped with one or more Rushton impellers capable of supporting oxygen transfer rates in the 500-1100 range, single-use fermentor performance is comparable to conventional fermentors. Ensuring sufficient cooling to handle metabolic heat loads while overcoming the insulative properties of the bag film has been achieved. Like the application of technology in any area, there are boundaries. Within those boundaries, or design space, the user obtains the associated benefits. Necessity will help push and expand current boundaries.

Batch an fed-batch processes have been run with success. Be sure culture media is filter sterilizable. As with the application of any new technology, training and familiarity will ease the transition.

Simulated process modeling, using current known process data typically provides the necessary feasibility information. About the technologies, for processes that are transferable, single-use offers an equivalent platform to stainless. There may be unique processes not suited for single-use. Media and additives cannot be sterilized in the bag, but rather externally. Consider your motivation for implementing single-use fermentor technology. Outline your process and go through it, on paper, to maximize your success. Planning and preparation is crucial, especially considering how quickly a system can be turned around. Single-use fermentors can play an essential role in modern-day process environments...development and production.