Vendors can attest to the increasing acceptance of single-use equipment in biopharmaceutical manufacturing. For instance, the Bioprocess Solutions Division of Sartorius Stedim Biotech, Goettingen, Germany has posted a double-digit increase in orders over the last nine months, largely due to demand for single-use products in such manufacturing. Meanwhile, GE Healthcare Life Sciences, Chalfont St. Giles, U.K., has gotten an order for the first plant to use its new modular approach for biopharmaceutical production.
The significant growth in the demand for single-use technology stems from the major advantages it offers over traditional stainless-steel solutions, says Christel Fenge, Sartorius Stedim Biotech's vice president, marketing and product management, fermentation technologies. "As cleaning in place is not required due to the fact that single-use bags or bioreactors are disposed of after use, significantly less steam and water is required. This, in turn, reduces the investment cost for new facilities, both in terms of the process equipment needed for these utilities but also the space. So overall you are saving cost, time, space and utilities," she contends.
Fenge also emphasizes the benefits in terms of speed of product changeovers: "With single-use technologies you can increase the number of campaigns by more than 25% with the same number of operators. A typical changeover takes just 3–4 hours, or even less, and decontamination procedures are obsolete as the bags used are disposed of or incinerated."
Single-use bioreactors also have played their role in this development, especially as biopharmaceutical companies are under significant cost pressures to generate pre-clinical and clinical materials such as monoclonal antibodies (MAbs) needed for trials.
One of Sartorius Stedim Biotech's latest innovations is the FlexAct family of standardized configurable disposables (Figure 1). These trolley-based units can be adapted to carry out a range of biopharmaceutical production steps, including buffer and media preparation, manifold bag filling, cell harvesting, ultrafiltration and diafiltration, and low pH virus inactivation. The trolley includes mixing tanks, filters, pumps, sensors and an integral control unit. "It is an important product because it replaces a lot of bespoke solutions put together by companies that often weren't very streamlined and which required a lot of labor to use and maintain. Because of its automation, it also frees up operators to do other tasks," says Fenge, who boasts, "in terms of the development of single-use technology, bags were the first wave, bioreactors the second and FlexAct the third."
The cumulative effect of all this single-use development is that the concept of a "process in a box'" has become a reality, she notes. "I prefer to call 'process in a box' 'industrialized pre-clinical and clinical supplies,' but a number of companies have already established very standardized processing concepts — notably with antibody development where, as with drug development, you are dealing with lots of leads and need to select the right cell lines. So speed is crucial here, as is the ability to make as many different candidates as possible. You might also use this concept when using protein engineering to improve the potency of a drug."
She cites WuXi, Shanghai, China, as one company that operates single-use-only processes. At the end of October, WuXi announced the completion of a cell-culture capacity expansion, including two 2,000-L disposable bioreactors that are ready for cGMP manufacturing. The company says its new plant is the largest disposable bioreactor facility in the world that is able to support phase-III clinical manufacturing and initial commercial launches of therapeutic antibody and recombinant protein drugs.
Fenge also points to a veterinary vaccine supplier in France that operates a single-use-only facility. "There are many other customers, both in the U.S. and Europe, which are using legacy stainless steel plants, but also investing into entirely single-use facilities for MAb [monoclonal antibody] manufacture. Most companies looking at single-use today are making MAbs, recominbant proteins and vaccines," she adds.
Sartorius Stedim Biotech now is turning its attention to process analytical technologies — using intelligent bags with single-use sensors to further automate production or support the development of better, more robust processes, or to add additional information that today comes from an offline measurement. "For example, single-use biomass measurement might be used to control a nutrient feed rate, while single-use pressure and flow sensors could be used in downstream unit operations such as cross flow."