By: Erich Bozenhardt
IPS-Integrated Project Services, LLC
Would you pay $93,000 USD to extend your life by four months and would you relocate to one of the handful of treatment centers in the US for that therapy? Questions like this continue to propagate. Innovative and effective cell therapy treatments are advancing in the R&D pipeline, but costs and logistical challenges have been limiting the commercial success of the select therapies that have been approved. The considerations on the road to commercialization for cell therapy take on a higher level of complexity than those for biopharmaceuticals. For example, cold chain logistics moves from refrigerated cases of finished product handled by a distributor to shipping individual cryogenic units of sale. Additionally, new considerations come into play like administration through a medical device or a pre-conditioning treatment that are as much part of the process as the operations in a controlled manufacturing facility.
Some companies are betting on autologous therapies as the quickest and safest route. These therapies challenge us as an industry to deliver personalized medicine in a reliable and repeatable way. While the immediate goal might be successfully completing clinical trials, developing the process for scale-up and automation early on is critical to future successes. Removing operator variability by automating manipulations is one consideration. This can be a simple jig or the process could utilize a fixed bed culture technology that has an existing scale up/automation solution like a NuncTM Cell FactoryTM or Miltenyi Biotec Prodigy®. Developing the process to use closed systems can reduce the clean room space required, as well as the cross contamination risk. Gaining a deeper understanding of culture needs and how to meet those needs without a conventional incubator can also help the commercialization. Moisture loss concerns through vent filters and CO2 control have kept several processes locked into manual operations since the culture must be loaded into a reach-in style incubator.
During the development of the process for scale up and automation, logistics need to be considered. A Fenwal AmicusTM collects and processes the donation so that the desired fraction can be shipped frozen with a significantly longer allowable storage time versus a refrigerated whole blood donation. As those donations arrive at the manufacturing facility, the management of what will become individual lots needs to be established. Barcode readers have been standard for a number of years and workarounds have been identified for frost over issues; however, cryogenic capable RFIDs can provide a simpler solution.
While autologous therapies provide a straightforward means of patient safety, specifically addressing graft versus host disease, researchers have developed allogeneic cell-based therapies that sufficiently address the safety concerns. Allogeneic therapies relieve some of the logistical complexity as a lot can provide therapy to many patients. Although donation logistics can be complex if the number of cell expansions are limited, requiring new donor material for every batch. Induced pluripotent stem cells (iPSCs) have the potential to allow for a traditional cell banking approach on human stem cell based therapies. Some allogeneic therapies take a different approach and utilize bacteria for cell therapies. One of the common commercialization considerations for all types of allogeneic therapies is the development of the culture to use