The following is an excerpt from an article published in the April issue of BioProcess international, entitled “Factories of the Future: Can Patient-Specific Cell Therapies Get there from Here?” The article was written by PCT’s Brian Hampson, Vice President of Global Manufacturing Sciences and Technology and Jacob Ceccarelli, Biotechnology Engineer
Patient-specific cell therapies (PSCTs) are still, in many ways, the new kid on the block in medicine; researchers, therapeutic developers, manufacturers, FDA, and payers are still exploring and developing an understanding of the powerful benefits and unique challenges of this growing industry. As we all become more familiar, an evolution will need to occur—as it had to for automobiles, computers, and every technological advance in human history—in order for these therapies to become widely adopted, cost-efficient, market-scalable, and sustainable over the long-term. From where we are now as an industry, what is needed from a manufacturing perspective for us to achieve the future of patient-specific cell therapy?
From their compositional complexity to their mechanism of action to their manufacture, PSCTs are very different from traditional biologics. Some of those key differences can be grouped into two categories—product attributes and manufacturing design drivers, as noted in Table 1:
Because of these differences, manufacturing for PSCTs has inherent challenges not experienced with other biologics. For starters, as described in Table 1, failure of a production lot for PSCTs does not just incur un-reimbursable cost, but actually means failure to treat a patient who was waiting for cells to be returned to them as therapy. For PSCTs, some errors, such as delivery of the product lot to the wrong patient, can be life-threatening. Further, conventional approaches to economies of scale are limited, and a separate batch record and lot release are needed for each patient. Having such a complex product, where the manufacturing process directly impacts properties of the product itself, results in challenging comparability assessments and greater comparability risk when making process changes.
In light of these challenges, it is crucial for cell therapy developers to invest in a robust manufacturing process that leads to products of high quality, at a reasonable cost of goods (COGs), that is scalable and sustainable throughout the commercial life of the product. This strategy—planning for and implementing a manufacturing process that from the beginning takes into account quality, COGs, salability, and sustainability—is something we refer to as Development by Design (DbD). The essence of DbD is that planning for these four elements must take place well ahead of the realization of each phase of product development.
The Factory of the Future
To achieve optimal DbD-based manufacturing, the industry needs not only a manufacturing process that is vastly different from the traditional methods of manufacturing biologics, but also one that is vastly different from even the current standard of cell therapy manufacturing. In order for the cell therapy industry as a whole to truly become commercially viable, we must envision and develop the “factory of the future,” likely to have at least some of the attributes noted in Figure 1.
What we need is an industry-wide effort of innovation and engineering, an effort that is just beginning to take root at tools and technology providers, small biotechs that are developing cell therapies, and some contract manufacturing partners. This will enable thoughtful and staged rebuilding of unit operations for cell therapy manufacturing from the ground up, to transform cell therapy manufacturing processes and test methods in a way that achieves true scalability and sustainability. Cell therapy manufacturing must move largely away from the clean room model and sent to the “back of the facility,” into production spaces more suited to high-volume production. That is not to say that clean rooms have no place in cell therapy; they certainly do. However, any time that automation, integration, and close processing systems can result in steps whereby one entire clean room need not be dedicated to one process for one patient at a time, your bottom line will be in better shape for the effort.
To learn how considering five crucial elements (comparability risk, cost of goods, automation and integration, sustainability, and idle capacity) can help the industry achieve the cell therapy factory of the future, click below to download the complimentary PDF of the complete article:
