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Randi Hernandez was science editor at BioPharm International from September 2014 to May 2017.
The author explores various biocontainers-both old and new-in the single-use space.
Selection of single-use containers is process-dependent, and different fluids within the course of drug development have different storage needs. Biocontainers can support process intermediate storage, as well as various other bioprocessing activities, such as long-term stability studies, compatibility studies, adsorption studies, freezing studies, and leachable studies, according to Joe Capone, global product manager, biocontainers and hardware, Pall Life Sciences. Single-use containers offer cost benefits over time, perhaps even more than reusable containers. “Though a reusable container is one initial capital investment for many uses, added costs and labor requirements come with it in the form of cleaning, validation, facility costs, and storage,” adds Capone.
Single-use storage options: Legacy systems
Single-use fluid storage systems have been in use for quite some time and in the fast-moving biotechnology industry could be considered legacy systems. Pall’s Allegro plastic totes can be used for buffer (or other media) preparation and storage, bulk harvest storage, product pooling, and bulk intermediate hold. The Allegro totes can be easily moved via forklift, even when fully loaded. They are compatible with 100-L, 200-L, and 500-L Allegro single-use systems.
Many 2D fluid storage solutions require biocontainers on trays, while 3D biocontainers are typically held in larger tanks instead of palletanks. Allegro bioprocessing workstations feature a shelf of high-molecular-weight polyethylene biocontainer trays that can store fluid products. In addition, these multipurpose modular workstations on lightweight wheeled stainless-steel frames can also be used to handle materials and transport them throughout a facility. 2D trays can be loaded onto the frame at an angle to maximize product recovery, and the stackable design reduces facility footprint. In addition to multiple storage applications, the workstations can be used for buffer filtration, chromatography fraction collection, and sterile filtration with in-situ testing.
Once a product is finished and needs to be transported, 3D tanks can be used to ensure containment of the product as it travels to its final destination. Pall’s Allegro 3D transportation totes contain numerous safeguards to keep a product protected from environmental ingress and movement-related disturbances. Gaskets, straps, foam protection pad systems, clamps, and a sealed chamber are among the tools used to prevent liquid surges of biopharmaceutical products within the totes.
Buffer storage vessels and bags
As Challener points out, buffer solutions are required for most downstream biopharmaceutical processing steps, such as filtration, capture, and chromatography operations; buffers are necessary to maintain a stable pH in a biopharmaceutical product (1).
Because buffers are the “largest constituents by volume in the downstream processing of biotherapeutics,” the storage of large quantities of buffers in a facility must be carefully arranged (1). For a typical 2000-L monoclonal antibody (mAb) downstream process with product titer 5 g/L, Kappel et al. estimate a total buffer volume of more than 25,000 L is required (2). High-protein formulations demand durable materials, and products to store buffers and other related media take up valuable real estate within a facility.
There are a variety of different options for buffer bags, and bag selection is dependent on buffer volume needs. Buffer hold bags can be single use or stainless steel, and in some cases, can even be a hybrid of both systems (2). “Hybrid systems are gaining popularity, as the industry looks at the most effective ways to integrate single-use technologies--many times in facilities with previously existing stainless equipment,” notes Capone.
There are many pros to single-use bags for liquid hold. Clean in place (CIP) and steam in place (SIP) are generally not required, and small volumes of product can be transported to point of use without the use of auxiliary equipment (1). For hybrid buffer storage and distribution systems with stainless-steel parts, however, CIP and SIP will still be required for steel parts and transfer lines (2). “When it comes to distribution, hybrid systems are ideal,” says Capone. “The added single-use technologies enable smoother transportation via a robust, certified, fluid containment system.” Another benefit of single-use storage biocontainers is that the small sizes can be transported to point of use without the use of auxiliary equipment.
New releases in the disposable space
There have been few releases in the solution storage product space in recent years. Those that are being released, however, are highly specialized, such as the LabPure fluorinated ethylene propylene (FEP) bags from Saint-Gobain. The LabPure bags are manufactured with a proprietary laser-sealed process that ensures safe storage of fluid materials. Extractable profiling is crucial to qualify the bags in a single-use system, and LabPure’s bags are associated with low extractables. They are also certified to meet the industry standard of no particulates larger than 50 microns in size and are animal-derived component-free. An added bonus is the LabPure bags come attached to Tygon tubing, which can be used for sterile-docking applications. The company also produces standard fluid-transfer assemblies, a line of fluoropolymer containers, and FEP overwraps for cryopreservation.
Also new in the field is Meissner’s recently released single-use biocontainers. The company’s TepoFlex polyethylene biocontainer is available in a range of sizes (50 mL to 1000 L) and can either be designed to be compatible with customer-specific tubing lengths, connectors, and end fittings, or paired with Meissner’s BioFlex tubing systems. Scale-up efforts are made easier by the fact that all sizes of Meissner’s products are made with the same materials.
The importance of container testing
The safety of biocontainers, both for processing and storage, has recently come into question. According to Marghitoiu et al., single-use bioreactors and containers are more susceptible to problems associated with extractables leaching into the bioprocessing fluid (3). A 2013 study concluded leachables in single-use biocontainers were detrimental to cell growth, and in this study, the reduced cell growth was attributed to a gamma radiation-induced degradant of Irgafos 168, an additive used to prevent process-induced degradation and extend the performance of primary antioxidants (4). Martin points out in a separate editorial, however, that the real culprit in the study was an excess amount of Irgafos 168, a detail that the storage container manufacturer disclosed at an industry event (5). To avoid cytotoxicity events in biocontainers, Martin suggests end users “screen all new cell lines or media formulations with their intended or potential biocontainer(s) and bioreactor film(s) prior to initiating production.” According to Martin, biocontainer suppliers should provide evaluation kits to facilitate this testing (5), though this is not yet standard practice.
References 1. C. Challener, BioPharm Internat. 28 (2), pp.24–27 (2015). 2. W. Kappel et al., Pharm. Eng. 34 (1), pp. 1–9 (January–February 2014). 3. L. Marghitoiu et al., PDA J Pharm. Sci. Technol. 69 (1), pp. 49–58 (January–February 2015). 4. M. Hammond et al., PDA Journal of Pharm. Sci. and Technol. 67 (2), pp. 123–134 (March–April 2013). 5. J. Martin, BioPharm Internat. 27 (2), pp. 16–18, 48 (February 2014).