|Email Newsletters from Pharmaceutical Technology and Pharmaceutical Technology Europe|
News from Europe's pharmaceutical manufacturing industry coupled with upcoming events, and exclusive articles and interviews from industry experts.
Advances in Continuous Biopharmaceutical Manufacturing
Continuous manufacturing, regardless of the application, can result in more consistent processes and products. Advantages include reduced energy, water, raw material consumption, waste generation, product losses, and downtime, in addition to lower capital and operating expenses. For the pharmaceutical industry, additional benefits include reduced human intervention. The biopharmaceutical industry is taking steps towards the realization of integrated, continuous manufacturing of biologic drugs with two changes. First, perfusion has moved from concentrations of 10–15 million cells/ml a decade ago to a now well-established upstream process at concentrations of 50-80 million cells/ml. Second, simulated moving-bed chromatography is in the adoption phase for downstream separation and purification. Some of the challenges include the large existing batch-based infrastructure, the traditional separation of upstream and downstream operations, and the need to develop new technologies for downstream processing steps.
Integrating upstream and downstream
The biggest notable achievements, according to John Bonham-Carter, vice-president of business development with Refine Technology, come from CMO companies such as Gallus and Rentschler and from end users such as Genzyme, who have shown that continuous processing is possible today using existing equipment in a reliable setting. “It is the integration of different technologies that is novel, rather than any new technology itself,” he notes.
Peter Tiainen, a senior scientist with Novo Nordisk’s Biopharm Research Unit, adds that the work done at companies like GE Healthcare, Genzyme, and Novo Nordisk has helped demonstrate that continuous processing is not overly complex. “We have shown that going from batch to continuous is achievable and manufacturable. The technologies are available today; what is required is a fresh approach (and some guts) to switch to continuous processing.”
Hurdles do exist
With respect to technology on the upstream side, Genzyme has come to appreciate the crucial importance of media formulations and has invested in finding optimal solutions, according to Johnson. The perception of increased process complexity is another issue, but as the number of companies exploring continuous processing increases and wider application of this knowledge occurs, this issue is gradually diminishing, according to Bonham-Carter. Tiainen adds, however, that there is not enough down-scaled and laboratory-sized equipment to enable wider exploration of continuous processing, particularly with respect to downstream processes.
Once the needed technology is developed on the downstream side, the issue of integration of upstream and downstream operations for fully continuous production lines will need to be addressed, which will involve managing the impacts that changes in one process step have on other steps down the line, according to Bonham-Carter. Tianen agrees that the interdependency of unit operations is currently a potential issue for product quality.
This particular hurdle leads to another key challenge–overcoming the divide between upstream and downstream groups within biopharmaceutical companies. “Implementation of integrated continuous manufacturing projects requires collaboration between groups. There is definitely much more communication internally at Genzyme than previously existed, and the traditional boundaries of the organization are beginning to subside,” Johnson comments. He also notes that two-way collaboration with supplier of materials, equipment, sensors, and automation and control systems is necessary for achieving effective solutions for continuous processing.
— Cynthia A. Challener, PhD, is a contributing editor for Pharmaceutical Technology and BioPharm International. Further discussion on this topic will appear in Pharmaceutical Technology’s May 2014 Bioprocessing & Sterile Manufacturing e-book.