Successfully bringing cell therapies to more patients will require the development of manufacturing solutions that are efficient and cost-effective, and that allow for the stringent quality control measures that cell therapy demands. Examples of the barrier to commercial success posed by manufacturing costs are numerous. For example, Dendreon’s financial troubles were summed up were that “without a change to efficiencies in the manufacturing process, it’s really difficult to see them coming back as a standalone company”. Dendreon is now focused on ways to automate their production process to reduce the cost of goods sold (COGS) from 50% to 30%.
After Vericel’s (formerly Aastrom Biosciences, Inc.) Phase III trial for its autologous cell therapy, ixmyelocel-T, was halted in 2013 because of the quality control risks and lag times associated with manufacturing autologous products the company restructured and developed a patented manufacturing system to address the FDA’s concerns surrounding manufacturing.
One result of the high cost-of-goods associated with manufacturing has been a propensity for companies to develop a business model as close to that of traditional pharma/biotech as possible. This means developing therapeutics amenable to large-scale batch manufacturing of identical products (allogeneic solutions). However, the real value proposition of the cell therapy and regenerative medicine industry may lie instead in solutions to growing new skin, hair, neurons, retinas, and organs or curing cancer (see The CAR-T Cell Race) that need only a small number of cells to be therapeutically effective. How is small-scale manufacturing being addressed to ensure that these companies and their solutions are commercially viable?
Therapeutic Solutions Where Small-Scale Is Full-Scale
While it is difficult to determine exactly the number of companies and products where small scale fulfills manufacturing requirements, a few beyond CAR-T come to mind. Hemostemix, is developing therapies for regenerating blood vessels. Rhinocyte is developing autologous adult olfactory-derived stem cell therapies to treat spinal cord injury and neurodegenerative diseases such as Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis. RepliCel has a series of autologous therapies for various musculoskeletal and dermatological conditions and is investing in research to develop allogeneic versions of these therapies. These and other cell therapies that only require a small dose of adherent cells and are targeting a small population of patients are a few examples of the many high potential regenerative medicine companies where small-scale manufacturing is full-scale. jCyte, recently received approval from the FDA to move forward with a Phase I/II clinical trial to investigate the safety of its allogeneic cell therapy for retinitis pigmentosa (“RP”), a genetic, degenerative eye disease. ReNeuron is also developing a treatment for retinitis pigmentosa and recently received FDA approval to start its Phase I/II clinical trial in the U.S.
Industry Solutions for Small-Scale Manufacturing
The industry has begun to invest in the development of disposable, small footprint systems as well as fully enclosed, automated manufacturing systems. One of the bottlenecks associated with current cell manufacturing systems (from both a time and cost perspective) is the need to use of a single cleanroom for manufacturing runs whether it involves cells from a single donor (autologous) or cells from a master-cell bank (allogeneic). Scaling up a manual, cleanroom-based process to enable treatment of more patients involves installing additional cleanrooms, but cleanrooms are expensive to build and maintain, and simultaneous production of cells from multiple donors is impossible. Solutions exist creating partially closed manufacturing systems, from bags, stir tanks and static systems for cells in suspension to micro-carrier, hollow-fiber and new multi-plate solutions for adherent cells (see Brindley et al for recent review).
But what about a complete system that obviates the need for a cleanroom altogether? PCT and Invetech recently announced a partnership to develop a fully enclosed system for manufacturing needs where “small-scale is full-scale”. Kawasaki Heavy Industries has also developed a next-generation fully enclosed, automated system, currently available in Asia, that provides a plug-and-play alternative to building out cleanrooms. These new systems offer solutions to young companies that provides a cost-efficient manufacturing solution that can readily be transferred from an outsourcing facility to in-house manufacturing, without the high cost associated with clean room build outs.