Are Single-Use Bioreactors (SUBs) the Future of the Pharmaceutical Industry?

Jonas Bisgaard, PhD

Within the pharmaceutical industry, solving major challenges of lowering operating costs, reducing contamination risks & lengthy downtime, and ensuring scalability of processes seems a daunting task. Single-use bioreactors (SUBs) function by using disposable bags rather than traditional steel vessels, and can promote efficient ways of making start-up and development of production faster and safer for pharmaceutical companies. Because of the advantages, SUBs offer attributes relevant for both large- and small-scale production, meaning wide-spread adoption is of collective interest for the pharma-industry.

What are single-use bioreactors?

SUBs are disposable bioreactors that are constructed using plastic materials, making the bags scalable, consistent in quality, and cheaper in maintenance. As these bioreactors are produced to be ready-for-use, they are delivered pre-sterilized, usually through gamma-sterilization. Conversely, traditional bioreactors made of glass or steel are sterilized before and steam-cleaned after use, meaning SUBs comparatively reduce cleaning and sterilization demands.

As single-use bags are pre-sterilized, all necessary hardware such as stirrers or sensors for measuring temperature, glucose, or pressure are often installed into the bags prior to delivery, meaning additional calibration or assembly is not intended. If additional sensors or probes are required to install after delivery of the bag, it will incur compromising the integrity of the bag, with increased risks of leakage and contamination. Firms should therefore consider whether their SUB needs can be met without installing sensors post-delivery, in order to preserve bag integrity as much as possible. SUBs can usually be custom-produced by suppliers in order to fit firm demands, making issues of post-delivery modification less prevalent with some additional cost.

Advantages of SUBs

As opposed to traditional steel vessels, single-use bags are replaced between each cycle, reducing downtime and cleaning.

The most distinctive advantage of single-use technology in bioreactors, is significant reduction in process and maintenance costs via less downtime. Cleaning traditional bio-vessels between cycles is extensive & time-consuming, as the risk of cross-contamination must be kept to a minimum. Conversely, transitions between single-use bags can be done in short order and with less maintenance required for the next cycle- saving both time and operational costs for companies.

However, replacing the SUB bag after each use does increase the chance of operational risks related to bag installation. Mitigating such risks requires additional training in order to ensure proper compliance and quality, but also means that employees become well-versed in using differing types of single-use technology.

Having high configurability of the single-use reactors makes them viable in nearly all biopharmaceutical processes, from cell cultivation to microbial batches. Both newer and established pharmaceutical companies can apply the lower costs and higher configurability & scalability to test and develop new or existing processes more quickly.

Developing processes more quickly also has the substantial benefit of reducing time to market, contributing to giving firms an edge over competitors. Generally, replacing traditional bioreactors with SUBs will allow firms to have lower initial capital expenditure, as a singular, high-cost vessel is replaced with low-cost, replaceable ones. Conversely, using SUBs may incur higher operational expenditure per cycle, depending on the operational costs associated for each bag.

Even though the SUB bags can include a higher ongoing cost than reusing a steel reactor, the lower cleaning and maintenance costs may actually outweigh the value of a steel reactor in the longer term. Having a quicker turnaround can also contribute to firms hitting their financial targets faster, providing a good business case benefit for SUB systems.

Safety, lower costs, and reduced downtime are prominent reasons for expanding single-use bioreactors in the pharmaceutical industry.

When considering the faster time to market, more expedient process cycles, and occasional need for sensor installation post-delivery, it can raise concerns about lower standards for quality control. However, there are reasons that SUBs should be considered dependable for use in pharmaceuticals.

By combining pre-sterilization before delivery and substitution of bags between process cycles, the main risk of contamination arises only from probes or sensors being installed post-delivery. For firms using fully-assembled bags, risks of contamination is thereby significantly reduced compared to conventional bioreactors. This not only contributes to dependability of processes, it also adds financial value by lowering risks of costly or time-consuming delays.

The future of the pharmaceutical industry?

Considering its attributes and advantages, there are a multitude of reasons that single-use bioreactors are applicable for pharma-related firms. If bags are used as delivered, most prominent advantages are improvements within lowering cycle downtime, reducing operating costs, minimizing risks of cross-contamination, and offering reconfigurable reactors for a large selection of bioprocesses.

They are not a perfect technology, however, also requiring additional training for operational handling and possible operational expenditure. Deciding on whether to incorporate SUBs thereby becomes a matter of weighing pros and cons for each process. Taking into account elements of quality, costs, and productivity, there are clear advantages to further incorporation of SUBs into the pharmaceutical industry, as a valuable alternative to traditional bio-vessels.

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