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Issue link: https://lifescienceleadermag.epubxp.com/i/161331
Pharma Manufacturing mulation process, a cell-growth profile). But because it is in a LSL: WHAT ABOUT A HYBRID MANUFACTURING PROCESS THAT UTILIZES THE BEST OF BOTH BATCH batch, the sweet spot isn't maintained. With CM you have the AND CONTINUOUS AS A MEANS OF IMPROVING possibility of being able to maintain the process at that sweet EFFICIENCIES AND MANAGING BOTTLENECKS? spot for a long period of time, which can be more effective than KN: That is what we've evolved to. I don't know that this was batching. However, you need to be concerned with how long it an intentional, planned evolution, but it's where we are now. takes you to get to that sweet spot, since there can be quite a We have evaluated CM for most unit operations that we exelot of auxiliary equipment and processes necessary to maintain cute in both large and small molecule areas of pharmaceutical the environment around one processing step. That's one of manufacturing. There are some unit operations that are really the challenges with a CM process. The other challenge that we effective and carry a very strong business case. As the business have seen concerns linking multiple unit operations together case justifies it, we are deploying CM for those products or for in one CM process. This is the approach the Novartis MIT multiple products for that unit operation within our manufacproject has taken with great results. Using creative engineering turing network. and sophisticated control systems technology, they were able As of yet, we don't have any situations that are true end-toto match each process step, each unit operation, to the rest of end continuous whereby you start with a raw material on one the process to avoid bottlenecks or hold points where invenend and finish with a final drug product on the other with tory might build up. Building in buffers is a technical challenge zero interruptions. We term our manufacturing approach as that can be overcome, but it takes a lot more work on the unit being a hybrid, which utilizes operations and is a potential some elements of batch and downside to CM. continuous. We may have one One of the big upsides to CM unit operation or one step in a is that you don't have a fixed four- or five-step process that batch size, so you can make is continuous, or maybe a couas little or as much as you ple that are back-to-back, but need. As the market dynamics there will also be some batch change, and we try to get into processes or batch steps witha supply model that is more in that process. The hybrid responsive to the customer approach has proven effective demands (especially as we start for us, especially when you to look at some of the emerghave one unit operation that ing markets with smaller and might be the real bottleneck in variable demands that need a process. For example, tablet to be satisfied very quickly in coating is a bottleneck, and order to be effective from a can be a very long process in business standpoint), CM gives a batch mode. It is often the you a lot more flexibility than rate-limiting step for a drug batch. CM lead times (from Kevin Nepveux, VP of global technology services, Pfizer Global Supply product manufacturing operapurchase of raw materials to tion. We have looked at and delivery of finished products) deployed platforms of conare typically a fraction of batch tinuous coating in those situations, which can de-bottleneck lead times — this can substantially reduce inventory carrying a process and allow your granulation and tableting, which is costs. Another basic advantage of CM is that you can get a higher in front, and your packaging, which is in back, to be better throughput on a smaller footprint for less of a capital investment utilized overall. Another example in the small molecule API as compared to a batch process. area is crystallization, which can be a variable process. This The other area where CM is really effective is when your variability can result in changes to physical properties of your process cannot tolerate much variability. In these cases, you API, which in turn can cause you problems in filtration, drying, can be more consistent and more robust using CM. This is also and formulation. There are some cases where we've looked an advantage when introducing new products, since there is at continuous crystallization as a way to get more consistent no "scale-up" — you can manufacture development, clinical, physical properties, which improves other components of the and commercial product on the same equipment by running manufacturing process. longer. "As the market dynamics change, and we try to get into a supply model that is more responsive to the customer demands, continuous manufacturing gives you a lot more flexibility than batch." 46 LifeScienceLeader.com September 2013