Disposable bioprocess equipment has achieved a level of acceptance that was largely unanticipated a decade ago. Single-use bags, tubing, connectors, and related products have profited from rising protein titers that have caused many processes to shrink in size. Disposables have become particularly attractive among contract manufacturers operating at up to the 500 L scale.
But disposables have their limitations. One senses reluctance to use process bags above 500 L in working volume. Bags much larger than that become difficult to work with, require mechanical support, and present disposal problems. Additionally, many biomanufacturers owe their accountants full amortization on their substantial investments in stainless steel fermentors, plumbing, and cleaning systems.
While new plants, particularly those of contract manufacturers, are specifying disposables as part of their facility plans, many more companies are incorporating single-use equipment as part of process and facility retrofits, says Denise DeTommaso, global technical support manager for SAFC Biosciences.
“Companies are looking for spots where they can adapt a single-use product for part of a process,” she says. “Everyone is looking for a way to reduce contamination, changeover time, and generally to make things faster.” Other factors driving disposables are trends toward lean manufacturing, cost-cutting, and sustainability.
Vendors no longer need to trot out the benefits of disposables to bioprocessors, says Chris Mach, product manager for single-use products at Pall. “At this point, customers are more interested in the specific advantages to them and what technologies vendors can offer.”
Vendors increasingly design disposable equipment around specific applications, as users seek to duplicate the functionality of fixed-tank systems in flexible, single-use plastic. One emerging application, says Mach, is bioreactor sampling using disposable bags, which he describes as “an application within an application” for single-use products.
Tubing and fittings represent a critical component for integrated disposable processing, yet few vendors offer robust connection products. For example, Pall’s KleenPak™ connectors allow sterile connections of two fluid pathways while maintaining the sterility of both.
Another recent introduction is the Allegro™ Biocontainer, a storage bag available in 2-D and 3-D formats. The pillow-shaped 2-D containers are available in sizes from 50 mL to 50 L; the cubic 3-D bags range from 100 L to 500 L. Allegro biocontainers address problems of leakage, folding, and improper filling of process bags. Both versions unfold cleanly and predictably on filling without the need for operator manipulation, provide improved drainage, and utilize a highly transparent plastic material that allows operators to look inside for misfolding or precipitates, the company reports.
According to Mach, small molecule drug manufacturers are beginning to show interest in disposable containers. Problems of chemical compatibility with organic solvents remain, particularly at elevated temperatures, but the idea that chemical/pharmaceutical processors would even consider plastic process equipment is intriguing.
Vendors Making Improvements
Mani Krishnan, director for process systems at Millipore, agrees that customers do not require a hard sell to adopt disposables, adding that end-users are beginning to think of single-use equipment for critical as well as non-critical applications. “It’s not just for buffers any more. People have gone beyond that,” he reports.
Millipore’s acquisition of Newport Biosystems has given the company entry into markets that integrate process bags (Newport’s specialty) with connectors and filters. Millipore’s Lynx® ST (steam-to) and Lynx S2S (sterile-to-sterile) connectors are two enabling products that allow custom integration based on users’ specific applications, Krishnan adds.
While chromatography remains a difficult adaptation for disposables, Krishnan believes that a good case could be made, in many instances, for single-campaign utilization (vs. truly single-use or single-batch) for even the most expensive resins. A manufacturing campaign might entail five or six batches, for example. Krishnan mentions pre-packed chromatography columns as products that might tip the balance in favor of single-campaign use. Another such product is Millipore’s Prosep® Ultra Plus protein-A chromatography media, a resin with high binding capacity and high linear velocities—attributes that are desirable for high-productivity, small-footprint unit operations.
These products are just a start. Operating in disposable or single-campaign manner will require that vendors continue to innovate and that industry change its mindset regarding chromatography, Krishnan says.
For example, Millistak+® filters were first developed to be used in large stainless steel housings that required large CIP loops. Millipore launched the fully disposable Pod format containing the same filter media, which significantly minimizes the demands of the CIP loop.
Vendors also need to do a better job of making their single-use products more user-friendly, he says. “When customers take a disposable assembly out of the box it is a ‘spaghetti’ of piping and tubing. The more complex the process, the more complex the ‘spaghetti’.”
At a recent IBC conference, Millipore exhibited a Tangential Flow Filtration process skid that simplifies the task of unraveling and utilizing the bags, tubing, and connectors. The skid features supports and connectors of its own that enable the various components to be installed in the correct location making the numerous components more accessible and enabling easier use of single-use processing systems.