Change is coming to the way biopharmaceutical products are manufactured, said industry thought leaders at the ISPE national meeting in Washington, DC in November 2013. Although how quickly change will occur is uncertain, the manufacturing paradigm is shifting from large, single-product facilities to smaller-scale, flexible, multiproduct facilities that may even be moved to different locations as the need arises. New facility designs that enable flexible, multiproduct production include single-use technologies, the use of controlled nonclassified (CNC) spaces with closed systems, modularization, and continuous processing.
Single-use systems face hurdles, such as a conservative industry mindset and existing investments in stainless-steel facilities, but some companies are moving ahead with increasingly complex systems, such as single-use bioreactors and other single-use unit operations, said Joshua Hays, associate director for upstream sales development at EMD Millipore, in a presentation. Single-use components are an enabling technology for smaller-scale production of biopharmaceuticals as well as cell therapies, such as stem cells, which would otherwise be much more difficult to produce. Because revalidation is costly, the majority of single-use systems are being employed for new products, and many companies choose hybrid facilities with both stainless-steel and single-use components. Hays predicted a big move to single-use components, estimating that as much change would occur in the next three to five years as it has in the past 15 years.
CNC multiproduct ballroom facilities, which have most unit operations in one room, are not monitored to a specific environmental classification, but are GMP facilities that must use demonstrably closed systems and have other appropriate controls (e.g., quality systems), noted Paul Smock, senior director of quality assurance at AstraZeneca's MedImmune, speaking as a member of the Area Classification team of the Biophorum Operations Group, which is a collaborative community of biopharmaceutical industry experts who meet to establish best practices. Other important considerations for a successful multiproduct manufacturing facility, said Smock, are understanding the process, using advanced controls and testing, and having a flexible organization with good communication.
Modular manufacturing designs, which add flexibility by using prefabricated modules that can be arranged as needed and in the location where they are needed, continue to grow in use in biomanufacturing. Modularization reduces capital cost compared to conventional construction and is also advantageous for construction in developing countries.
The rate of change in biomanufacturing is increasing, and the new value driver is flexibility, said Parrish Galliher, founder and CTO of Xcellerex, a GE Healthcare Life Sciences company, in a presentation at the meeting. Blockbuster-drug facilities are not flexible enough for the future, which is moving to smaller, multiproduct facilities made "in market, for market". Future technologies, such as cell and organ therapy and personalized medicine, will require even smaller-scale manufacturing, predicts Galliher. These facilities would need to be located "at clinic, for clinic" to have the proximity needed to deliver live products with short shelf-lives. Such technologies have high treatment costs and it is uncertain if they will make a viable business, but the technology is in development. Peering even further into the future, Galliher painted a vision of "on patient, for patient" manufacturing that could include noninvasive real-time diagnostics and real-time, microfluidic laboratory-chip drug synthesis.
Continuous biomanufacturing is a game-changing technology for smaller-scale, flexible, multiproduct production that is emerging even now. Sanofi's Genzyme is developing a closed, continuous manufacturing process with the vision of a universal platform for all its protein biologics, said Robert Snow, senior project engineer in Sanofi’s Biologics Development Group, in a presentation at the meeting. The continuous process integrates upstream and downstream unit operations into one process train. Similar to its solid-dosage counterpart, continuous biomanufacturing offers a smaller footprint when compared to traditional perfusion or batch-type systems, and capacity is increased by increasing the number of process trains rather than their scale. The combination of closed, continuous processing and platform approach will result in smaller and more flexible multiproduct manufacturing facilities that can take full advantage of CNC ballroom-type facilities. The concept is being developed using mainly single-use components, but would also work with more traditional stainless steel process equipment, commented Snow.For further reading:
Flexibility in Biopharmaceutical Manufacturing, by Simon Chalk of the Biophorum Group in the June 2013 issue of BioPharm International.