The bioreactor market’s first disposable and scalable solution.
The single-use bioreactor market generated $202.5 million last year, according to Markets and Markets.1 Its market research points to an 18.4 percent increase, reaching $470.9 million by 2019. Single-use technologies primarily include disposable bioreactors, mixers, containers, tubing, connectors, sampling systems, purification devices and columns, and probes/sensors. There are many single‑use options existing, each with its advantages and disadvantages—although, scalability is often pushed as one of the biggest overall confines.
With scalability comes the need for sealing solutions to be able to accommodate the larger sized single-use bioreactor bags. For the larger bags, innovative sealing solutions that have been specially engineered and tested are required to meet rigorous demands.
Adopting & Implementation
The growing adoption by the pharmaceutical industry of single-use process steps come in the form of media and buffer preparation, cell harvesting, filtration, purification, and virus inactivation. The preference for single-use bioreactors over conventional stainless steel in the global market is showing huge growth—with 66 percent of pharmaceutical companies preferring this disposable arrangement.2 Single-use technologies reduce cleaning and sterilization demands. In pharmaceutical production, the procedures for a sophisticated qualification and validation process can become simpler and deliver significant cost reductions in the long run.
The rate of implementation of single-use technologies is probably slower than we would like—mostly due to the time it takes to conduct full comparative studies with conventional stainless steel bioreactors. There is currently considerable focus on obtaining more clarity of understanding in the regulatory requirements for single-use bioreactor technology.
The FDA’s CBER (Center for Biologics Evaluation and Research) regulates a vast array of compliance and surveillance undertakings during the lifecycle of biological products, which may have an impact on suppliers. They conduct activities such as pre-license and pre-approval inspections of manufacturing facilities, products under clinical study, monitoring of the safety, purity, and potency of biological products, and product recalls or potential adverse events. CBER also monitors research conducted on biological products and assesses the protection of the rights, safety, and welfare of human research subjects as well as the quality and integrity of research data.
However, CBER cites that a key advantage of single‑use bioreactor bags is flexibility. Often multi‑drug facilities require the production of different drugs using the same facility. By doing this, they aim to minimize time and cost without compromising the quality of the drug. In such scenarios, the principal manufacturing challenge is product line clearance and cleaning validation to safeguard any carryover from prior batches. Such downtime reduces the number of batches produced in a given period of time.
Advantage of Single-Use Products
The advantages of single-use products in these situations are as obvious, as they are wide-ranging. They include lower cleaning and sterilization costs due to shorter downtimes. Other advantages include a lessened cross-contamination risk, as well as the capability for lower volumes per batch. Overall, the increased operational flexibility and shorter lead times can lower capital expenditure costs.
The disposable-bioreactor market has become quite dynamic, with new entrants and variants continually being tested as alternatives to stainless steel for commercial applications. Single-use technologies today comprise a large percentage of small- and mid-scale biopharmaceutical manufacturing, particularly in clinical testing and research and development (R&D), but that is expected to grow as more manufacturers are seeing it as a competitive edge.
International suppliers of integrated solutions for the biopharmaceutical industry have to deal with fermentation, cell cultivation, filtration, and purification. The growing demand for single-use bioreactors have led biotech companies to develop a bag that meets all the design criteria offered by conventional stainless steel reactors, giving birth to the first completely disposable and scalable solution on the bioreactor market. In essence, a chamber optimized for cell cultivation using stirred motion mixing technology, as in reusable bioreactors, and suitable for a large variety of cell types, such as mammalian and insect cells.
A Question of Scale
While such disposable bags are often found on the lab bench holding as little as ten liters of liquid, bioreactor bags have now been scaled up to hold a total volume exceeding 2,000 liters. This naturally incurs some technical challenges.
For example, the aim to retain the adequate geometry and impeller design as well as the tip speed and power input per volume. However, on a scale-up of this size, a huge amount of torque is applied to the stirrer inside the reactor and a new drive assembly for the mixing technology inside the bag is needed.
Particular attention has to be paid to specifically targeting the assembly requirements without jeopardizing quality and compliance. A conventional planar coupling is not sufficient, but a radial magnetic coupling with an assembly incorporating a special bearing provides an excellent solution. The complete assembly—consisting of the radial magnetic coupling and a polyethylene port, which is welded onto the bag—ensures a hermetical sealing between the bag and the external environment. This eliminates the risk of contamination.
Difficulties with Single-Use Products
One of the difficulties usually encountered is the much higher force that the assembly has to withstand in the large-scale bioreactor bag compared to a smaller one. The development of the 2,000-liter bioreactor lasted several years and involved true global cooperation to complete an efficient solution.
In series production, parts are produced with injection molding tools in order to guarantee a cost-effective production process. Assurance of supply and business continuity is of the utmost importance to the market served by the manufacturer. Therefore, a long-term partnership ensures stable supply of the radial magnetic coupling with defined safety stock levels.
On-site testing of several mechanical evaluation prototypes proved that the radial magnetic coupling is very stable with no rocking or tilting, even when subjected to high forces. The final design has bioreactor bags resulting in a complete surface area greater than 13 square meters/140 square feet. Following successful trials that confirmed the biological performance and mechanical robustness of the new product, the bioreactor bag was ready to go into mass production.
The Future of Single-Use Technologies
As single-use technologies such as disposable bioreactor bags, mixers, and other disposable vessels, start to proliferate the market, expect to see more manufacturers look at methods and technologies to differentiate. There will be enhanced supply chain security, cleanliness, integrity testing (to avoid leaks), visibility (have it be crystal clear), and delivery programs for on-time delivery.
In the future, single-use technologies will be seen as an enabler that will support the expansion of drug development and manufacturing applications on a global scale for varied disease treatments. As developing economies strengthen, their population will influence the need for accessing medications that were not available to them previously. This will help drive the growth of single-use technologies. Companies can benefit from single-use bioreactor bags because it enables more manageable processes—allowing them to be flexible and adapt to changing product needs.
About Luis Tissone
Luis Tissone is the Director of Life Sciences at Trelleborg Sealing Solutions. Luis has worked as a Regional Sales Manager for Helix Medical and prior to that in positions ranging from supply chain operations to marketing and sales. He has a Bachelor of Science degree in Industrial Engineering from Argentinean Catholic University and a Business Administration and Management degree from Harvard University.