John Milne, Ph.D., technical manager at Biouetikon, discussed his company's experiences with single-use technologies in the contract manufacturing of biologics. “In principle we would anticipate lower initial capital expenditures, shorter facility development time, lower validation costs and expenditure of time resources, and fewer constraints on the existing facilities layout,” Dr. Milne indicated.
Every step in downstream processing has separate challenges for single-use technologies. For buffer preparation, magnetically coupled stirrers allow the system to remain closed and sterile. Single-use bioreactors are now available in sizes up to 2,000 L. These are highly complex systems, as many parameters must be monitored in the course of a run.
“Many case studies have now shown that single-use stirred tank bioreactors can mimic reusable bioreactors in geometry, design, cell growth, viability, and specific product expression. The technology has advanced to the point that a completely disposable process manufacturing train is now possible.”
In membrane chromatography, single-use technologies can offer some dramatic advantages, such as 95% less buffer consumption, simple setup protocols, and higher throughput for trace impurity removal than traditional packed columns. There is no packing, no regeneration, and no re-use validation required.
However, concerns have been voiced regarding a number of aspects of disposable implementation, such as high cost and a lack of continued innovation within the industry.
There is also the issue of extractables and leachables, compounds that could migrate from the disposable unit into the biologic material being processed. A thorough evaluation of all the materials that the product comes in contact with is difficult in earlystage development, given time requirements and the rapid turnover of different artificial materials. It is an ongoing issue that will require analytical expertise and the use of a stringent risk-assessment framework.