In some form, single-use bioprocessing (SUS) tools are now used for about 85% of pre-commercial scale manufacturing, including both preclinical and clinical operations. In addition, it is increasingly being adopted for portions of commercial manufacturing as well. With these single-use systems becoming more and more common, it can make one wonder if the basic large scale fixed stainless steel equipment-based bioprocessing facilities are becoming extinct?
While “disposable” items such as filter cartridges, silicone tubing, and sanitary gaskets have been used in the industry since the early days, the concepts behind modern SUS were being developed throughout the 1980’s in the form of small disposable bioprocessing containers and through the 1990’s with 2D and 3D product bags in much larger volumes. It continued the evolution through the 2000’s with tubing advancements and development of welding technologies. Even then, the offering was limited and adoption was small as compared to today; most of the significant growth has happened over the past 10 years as more companies become comfortable with the concept. Standards are being developed within the ASME BPE and BPSA (amongst others) which continue to build confidence in SUS as a viable option where stainless steel was previously utilized.
Today, even as single-use becomes more prevalent there remain limitations based on volume, chemistry, or pressure requirements in particular processes. While most manufacturers employ SUS in some form even in their commercial facilities, a significant portion of the industry will continue to use fixed stainless metal systems as it is more economically viable at larger scales. However, we are confident that single-use processes will continue to take a larger share of the market as technology continues to improve. New materials, new methods of handling pressure, new types of instrumentation, and new methods of validating sterility all represent areas that will spur single-use segment growth.
SUS (Single-use systems) refers to biopharmaceutical manufacturing tools designed to be used once and then discarded. SUS equipment is typically composed of plastic elements that have been sealed and sterilized using gamma irradiation.
There are several important advantages of SUS versus basic stainless steel:
- The equipment arrives pre-sterilized, avoiding cleaning and sterilization prior to usage. It also reduces the requirement for complex Clean-in-place (CIP), Steam-in-Place (SIP), large WFI, and other systems that are required for facilities to clean large permanent stainless steel components.
- Much less facility infrastructure is required and bioprocessing suites can be as simple as empty rooms filled with a SUS-assembled process line.
- The facility footprint has the potential to be a lot smaller, construction costs can be much lower, and new processes come online faster versus stainless steel.
- A properly implemented SUS program can speed up the turnaround time between batches, saving ample amounts of time that no longer has to be spent cleaning and sterilizing.
- Flexibility as manufacturing needs change can be a substantial benefit.
While there are obvious benefits to considering a Single Use strategy, there are several challenges that must be considered:
- The ongoing expense to purchase new SUS equipment after each use can be considerable.
- There remains a risk that the bag or tubing can fail resulting in a major loss of product.
- Leachables and Extractables (L&E’s) can adversely impact process. Improper Gamma Irradiation can impact the integrity of the films, and affect the degree of L&E’s that are produced in process.
- Waste is a concern as there is a lot of material that must be properly disposed.
- Supply chain can also be a concern. Disruption in raw material or finished goods can mean that a validated process cannot be operated.
- Size limitations can mean that SUS is not an option. Consider moving and handling a 2000L bag and installing it into a tote or reactor. Also consider moving it when full; it may weigh in excess of 5000lbs.
- Conversely, new processes that are being developed may require extremely small diameter tube sets which present problems with joining and end connection option.
- Measuring process variables such as flow, pressure, volume and others in a SUS system may be challenging.
- Chemistry and/or pressures may be limiting factors for single use products.
In the previous 10 years we have seen the adoption of SUS equipment and process lines as an alternative to stainless steel-based structures, largely in pre-commercial manufacturing. Pre-commercial manufacturing is a good fit for SUS as it is executed intermittently, and typically entails smaller quantities and smaller manufacturing vessels.
However, the total quantity of products manufactured using SUS remain relatively small in contrast to stainless steel-based manufacturing. Approximately 97% of the world’s complete bioprocessing capacity (which, as of 2018 is estimated at about 16.7 million liters) is at facilities that utilize capacities in excess of 2,000 L. So, despite sub-2,000 L bioreactors being dominant in terms of number of reactors, they remain a very small element of overall global bioprocessing capacity. As noted earlier, because larger volumes and vessel sizes can limit the use of SUS, a significant portion of manufacturing is still done in stainless steel systems.
With that being said, we still see increased adoption of single use, particularly in upstream processing. Larger product titers mean that processes are becoming substantially more efficient which is bringing volumes more in-line with SUS capability. In addition, processes can be run with multiple SUS systems in parallel which can still be economically viable.
SUS and the Purification Industry
Despite the adoption of SUS to most of the pre-commercial manufacturing industry, the downstream purification industry has not been able to successfully capitalize to the degree that upstream has. Downstream pressures can be higher. Chromatography columns, resins and other purification methods are rarely cost-effective as SUS, with columns and resins generally reused/recycled a few times. Protein A resin used for initial recombinant antibody capture at any larger scale can cost millions of dollars, which is far too costly to be discarded when it can be reused. The purification industry may have to wait for technologies that are more suitable for single-use to have better options for downstream SUS bioprocessing. Until then, most chromatography and other downstream processing will continue to involve permanent systems rather than single-use.
A Look Into The Future
Our industry continues to evolve with single use technologies. Things that were not available in the early years have been developed and are stretching SUS capabilities and extending the range of application. Supporting equipment such as totes, tubing management systems, and automated pinch valves are helping make SUS more practical in crowded manufacturing spaces. While SUS may never fully displace Stainless Steel systems in larger facilities, the future is bright as material science evolves and new products hit the market.
Click here to learn more about the single use systems Acuity Process recommends.