This is the third in a three-part series (read Part 1 and Part 2 for the complete picture).
As you approach cell therapy commercialization—having traveled what is still very much a new road in medicine—reflect on the learning and the difficult moments you’ve encountered thus far and remember the words of Robert Frost: “I took the one less traveled by, and that has made all the difference.”
If you are a cell therapy developer in Phase 3 of clinical development, or at the end of Phase 3 and ramping up manufacturing for commercial launch, you are at both the end and the beginning of a journey. Your therapy has hopefully been proven safe and effective, and you’ve learned something about quality, cost of goods, scalability and sustainability along the way. It may seem natural at this point to be ready to breathe a sigh of relief that the hard work is done, and sit back and watch success come to you. In truth, however, the hard work is just beginning—smart scale-out and manufacturing process efficiency must be considered in a whole new light when you move from making 100 or 200 patient-specific cell therapy (PSCT) products to making thousands of individual doses. Ideally, you have been laying the groundwork for this stage through careful consideration of Development by Design and the creation of a strategic commercial-focused manufacturing plan.
PSCTs offer a new and exciting challenge for process scalability, where the manufacturing process must be scaled-out, in order to produce one batch for each patient. This introduces the concept of “personalized medicine,” where the cost of production per batch cannot be reduced by exploiting an increasing economy of scale by simply producing a larger batch. Reducing the cost of these patient-specific cell therapies must therefore be achieved by a variety of means, including advances in engineering and manufacturing technology (along with the use of automation and closed-processing systems), which can reduce the number of complex, labor-intensive and open-process steps that are commonplace in cell therapy production. Given the impressive efficacy profile of a number of patient-specific cell therapies currently in clinical development, it is imperative that these processes be transferred into a commercial manufacturing setting, yielding cost-effective results so that the therapies present a reasonable value proposition for their developers, increasing the likelihood that the therapies will have a transformative impact for patients.
Additionally, lining up commercial market demand projections with required manufacturing capacity is extremely difficult and puts a lot of strain on in-house manufacturing facilities. This is where utilizing a CMO for early commercial ramp up can offer an advantage in terms of time and cost (by not over-building). Once the actual level of market demand has been established, that data can then be used to inform the long-term needs for the product’s manufacturing, possibly through the use of a blended model that incorporates some in-house manufacturing capacity and some contracted capacity.
Finally, at facilities that manufacture therapies that have received commercial approval, the FDA has the right to audit the facility at any point (and is required to inspect at minimum every other year); such audits must be carefully managed to ensure full compliance. This requires a team to manage and complete regulatory audits and the subsequent actions. Companies developing in-house manufacturing facilities and quality systems may not have the necessary experience to deal with these audits, whereas some CMOs are accustomed to coping with these audits.
In order for not just your cell therapy to be commercialized, but for the cell therapy industry as a whole to achieve long-term viability, we need an industry-wide effort in engineering and innovation, an effort that is just beginning to take root at suppliers and technology providers, small biotech companies developing cell therapies, and some contract manufacturing partners. Their efforts will enable thoughtful and staged rebuilding of unit operations for cell therapy manufacturing from the ground up, transforming manufacturing processes and test methods to achieve true scalability and business sustainability. Cell therapy manufacturing must move largely away from the clean room model to fully integrated, automated closed-processing systems that can create steps in which an entire clean room need not be dedicated to one process for a limited number of patients at a time.
Click the image below to download the complimentary article, "Mapping Success for Commercial Cell Therapy Manufacturing."
