Last month, the 2012 Parenteral Drug Association’s (PDA) annual meeting highlighted issues involved in the application of single-use disposable biopharmaceutical processing equipment. Several tracks focused on single-use issues, not only lessons learned from upstream implementations and buffer operations projects at Shire, Grifols and other drug manufacturing companies, but discussion of extractables and leachables. In addition, an entire workshop was devoted to the topic of single-use systems during the last day of the program, Wednesday, April 18th.
One standout presentation for anyone interested in manufacturing was a case study presented by Chuck Hart, director of manufacturing operations at Shire, in which he discussed the implementation of single-use systems at a new Massachusetts facility. The plant is using 100% disposable equipment in upstream operations, including cell initiation and expansion, production using perfusion via centrifuges. In addition, the facility is using hybrid single use and stainless steel in its chromatography and ultrafiltration recovery, purification and media and buffer makeup holding operations.
Benefits, Hart said, include a reduction in facility size and initial capital costs, as well as an 87% reduction in water and 95% reduction in chemical use. Hart also reports “significant reduction” in plant steam and clean steam requirements. Another benefit has been elimination of equipment turnaround time. “There’s no need for changeover, and quicker decontamination,” he said.
However, he warned, there were also challenges involved in applying single-use equipment. For one thing there is no flexibility for pressurization, for process transfers. Peristaltic pumps are required with single use, and they are much slower than the positive displacement, mag or other pumps used with stainless steel equipment. In addition, he said, heat transfer operations take longer and mixing capabilities are limited, since impellers are much smaller.
Logistics can be a bit more complicated as well, Hart said, especially where material transfer and hold operations are concerned. “Prepare to buy a lot of totes, especially for smaller scale buffers, for instance, for chromatography.
The simplest of every day procedures must be rethought, even things as simple as the opening of boxes in the warehouses, since simply ripping open a box containing the equipment, can cause potentially fatal equipment damage. The bags are susceptible to punctures, so special care must be taken during handling and operations, he said.
Tubing design is critical, he said, since the plastic tubing can be vulnerable to wear, for instance with peristaltic pumps, shedding and wear can be problems.
Critical to Shire’s recent implementation, he said, was end user input. In addition, he said vendor partnerships were essential, and he suggested that any potential user of single-use devote sufficient time on educating the vendor on the potential cost of their product failure. Like other presenters on this topic, Hart advocated the use of additional supply sources, where possible.
