But Will It Play in GMP Land?
To Lorraine Attridge, ReadyToProcess™ business leader at GE Healthcare Life Sciences, the industrialization of single-use equipment is a matter of GMP-worthiness for late clinical and market manufacturing rather than scale. “As our manufacturing becomes more sophisticated even greater industrialization will follow.”
Attridge believes that end-to-end disposable processing is already here, including for separations. Today’s smaller batches, higher titers, and higher capacity resins are well suited to the use of single-campaign resins and columns. GE Healthcare’s ÄKTA™ ready chromatography systems and ReadyToProcess columns, which were introduced several years ago, are designed for such applications.
A significant component of industrialization is standardization, which GE Healthcare has addressed with standardized, off-the-shelf assemblies for cell culture harvest and tangential flow filtration, disposable, aseptic, genderless, universal connectors, and nonproprietary films and materials of construction for its bags, connectors, and tubing.
Attridge believes that controls and sensors will become significant concerns in the industrialization of single-use bioprocessing. While supervisory and control systems are usually proprietary, their ability to communicate through industry-standard OPC clients will further drive industrialization.
In September 2011, GE Healthcare and Sartorius Stedim Biotech signed an agreement by which GE will sublicense patents held by the University of Maryland and spinoff Fluorometrix, to which Sartorius Stedim Biotech had enjoyed exclusive commercialization rights. This intellectual property covers bioreactors with at least two optical sensors for process monitoring. Similarly, GE Healthcare granted Sartorius Stedim Biotech sublicensing rights that it had with SciLog, which specializes in disposable sensors for bioprocessing.
One cannot mention GMPs without discussing validation as well, particularly for new technologies “There is less need today for validation or testing on the customer’s end for single-use products,” Hutchinson said. Increasingly, top-tier manufacturers are creating redundant, worldwide supply chains and facilities to maintain consistent, reliable supply for critical customer and partner processes.
Bill Hartzel, product manager for medication delivery solutions at Catalent Pharma Solutions noted that the progression of single-use bioprocessing, at least for CMOs, has been based on risk management and risk progression. “Single-use technologies are now beginning to take hold downstream.” Hartzel noted that “some issues” remain with purification, and that faster, higher-titer upstream processing will continue to create downstream bottlenecks.
“True single-use market leaders are those that could assemble systems and supply a finished product,” noted Hartzel. “The true value is in the suppliers’ validation packages, their understanding of validation, their auditability, and consistency.”
Paul Priebe, director for fluid management technologies at Sartorius Stedim Biotech North America, noted that industrialization is a “provocative” way to describe the state of single-use bioprocessing. “To me, the term means growing up, maturing to the point where it’s more mature, robust, and repeatable.”
From the end-user side that means larger scales and GMP adoption beyond pilot and clinical scales, which forces suppliers to employ more mature technologies, more automation, and greater standardization of unit operations. Vendors face a great demand to evolve single-use along these lines, Priebe said, and to create the proper balance of flexibility and “platforming,” while maintaining a strong supply chain and recognizing the uniqueness of every process.