Continued Focus on Continuous Processing
As we construct the editorial calendar each year for the coming year, the editors of Pharmaceutical Technology consult just about everyone with an opinion on what topics we should be covering. We ask you, our readers in our annual Reader Assessment Survey, we ask our editorial board members, and other industry experts what topics and technologies will emerge as important in the coming year. Usually, we get suggestions as broad as our coverage, from novel catalysis for API synthesis, to innovative excipients, to novel process analytics, emerging regulations, new drug-delivery paradigms, and novel aseptic approaches to process and fill/finish operations. So it caught us somewhat by surprise when last year these usually disparate opinions converged on a single topic: Continuous processing.
While continuous manufacturing technologies have been a topic kicking around for years now, this year it seemed everyone—regulators, academics, and industrial scientists—were certain that continuous processing would start to become a reality. Yesterday, I attended a meeting hosted by the New Jersey chapter of the International Society of Pharmaceutical Engineers (ISPE) where once again, continuous processing was the topic. Bernhardt Trout, director of the Novartis-MIT Center for Continuous Manufacturing, presented the results from the Center’s ongoing academic work developing the equipment and chemistry that will someday enable end-to-end continuous manufacture of small-molecule solid dosage forms in a paradigm Trout called “ultra-lean, ultra-QbD manufacturing.” Alton Johnson, vice president for Global Manufacturing Services, Marketed Products at Pfizer followed with a presentation describing Pfizer’s ongoing initiatives to implement continuous manufacture for several unit operations.
If the attendance and the Q&A session are any indication, continuous processing is indeed a topic to watch. So much so in fact that Pharmaceutical Technology will be hosting an afternoon of panel discussions and interviews on the topic as part of its Signature Series program at Interphex. We will kick off the presentations on Tuesday, March 29, at 1:30 pm on the Main Stage in the Exhibit Hall, where I will be moderating a panel in which FDA’s Moheb Nasr joins Fernando Muzzio from Rutgers and Alex Cheuh of Pfizer to explore the challenges and benefits of continuous processing as seen by regulators, academics, and industry professionals.
Following the panel presentation, we will continue to explore the topic in one-on-one interviews with James Evans, associate director for the Novartis-MIT Center for Continuous Manufacturing, who will discuss the prospects for developing a start-to-finish manufacturing line for small-molecule pharmaceuticals. Next, in my interview with Invetech’s Vice President for Business Development, Bob Speziale, I’ll explore the prospects for developing a continuous processing line for the large-scale manufacture of therapeutic stem cells. I hope you’ll join us for these presentations.
1:30-2:30: Panel Discussion: Challenges for Continuous Processing
Panelists: Moheb Nasr, Director, Office of new Drug Quality Assessment, CDER, FDA; Alex Cheuh, Director/Team Leader of the Technology, Science and Operations Group, Pfizer Global Supply Division, Pfizer Inc.; Fernando Muzzio, Professor Chemical Engineering, Rutgers University and President, Mixing Consultants, Inc.; Moderator is Michelle Hoffman, Editorial Director, Pharmaceutical Technology
2:30-3:30: Interviews
The Future for a Fully Integrated Platform with James Evans, Associate Director Novartis-MIT Center for Continuous Manufacturing.
Automating Stem-Cell Manufacturing with Bob Speziale, Vice President Business Development, Invetech.
The main obstacle to continuous processing of solid dosage forms seems to be that it requires an interdisciplinary approach that is hardly in its infancy, involving formulators, engineers, regulators, and now academics, all of whom have incomplete and sometimes contradictory understanding of what is needed. Pharmacist formulators are not trained in the engineering aspects, neither engineers nor formulators are adequately trained in formulating for effective continuous processing, and regulators have overly imaginative expectations of how it should all operate. Added to this is that the pharmaceutical batch granulating processing itself is being done essentially the same way it was done a hundred years ago. Beyond the introduction of high shear granulators, fluid bed dryers and granulators, (utilized in a way that would be laughable in the food processing industry), little advance has been made in the basic dry and wet granulating processes, and nothing has occurred that could be called revolutionary in the way of simplification or cost reduction other than the introduction of some direct compression excipients and disintegrants. If anything, the equipment has become more costly and complex, but without a concomitant increase in quality or throughput. Taking these technologies and “continuizing” them is like making a stretch limousine or baja race car out of a Model T Ford – it can be done, but why not start with a leaner and more rational process? (MADG is a promising approach) It is time to question those unit operations that inherently make oversized agglomerates that then have to be correctly sized, and those that overwet the material using excess water that then has to be removed to the correct level by costly drying equipment, before leaping into converting them into continuous processes.
Ya learn somtnehig new everyday. It’s true I guess!