What’s Next for Commercial Cell Therapy Manufacturing?
Now it's getting serious. Panelists from bluebird bio, Juno Therapeutics and Hitachi Chemical Advanced Therapeutics Solutions (HCATS) discuss their vision for the coming era of industrialized cell therapy production.
Automation is at the heart of achieving efficiency and cost-effectiveness in cell therapy manufacturing; however, many therapy companies face barriers when it comes to introducing automation.
During a recent panel discussion at the Phacilitate conference in Miami, Invetech’s David Hodl opened the floor by highlighting that many cell therapy companies are still challenged with the ‘how’ and ‘when’, and not engaging automation from the very beginning because of funding limitations and process complexity.
“A common theme we hear is: ‘We need to first get our therapy approved, and then we’ll consider automation later’. With the approval of Yescarta and Kymriah in 2018, that ‘later’ has suddenly become ‘now’.”
Automation drives cost savings, standardization and operator safety
The panel first discussed the drivers for pursuing automation. Steve Goodman from bluebird bio addressed the need for consistency and standardization, and how achieving these by moving away from manual processes helps combat costs.
“We already deal with a tremendous amount of variation in the process just inherent to the types of cells and disease that we work with. Using automation to take out the variability that comes from the manual manipulation and having a machine that can consistently deliver against a protocol also helps with cost improvement.”
Brian Hampson from HCATS said, “We want to have our people not needing to focus on very tedious manual operations but being able to turn those over to a system that can do that. Even if you don’t take labor out completely, by reducing how many times there are quality events – that is a huge reduction in cost of goods.”
“Using automation to take the variability that comes from the manual manipulation and having a machine that can consistently deliver against a protocol, and taking that manual interface out also helps to look at cost improvement.”
Hampson added that there are lots of opportunities across quality and cost of goods with cell therapy manufacturing automation that manual processes cannot match. “Bringing it into a totally closed system as part of an automation platform will provide a huge cost-reduction in the indirect cost. There are lots of opportunities across quality and cost of goods, and scaling of these. Those are some of the reasons why we pursue automation.”
Randy Schweickart from Juno Therapeutics added, “One of the reasons that this is very important to us right now, as we are rapidly ramping up our manufacturing, is with operator safety. We are in a situation where we have employees who now have ergonomic issues with their elbows, wrists, and so forth from all the manual operations. These are operations which were repetitive and should be done exactly the same again, and again, and again. The human body is not really made to do that.”
Early implementation of automation enables seamless scaling up
Most of the cell therapies that have been developed so far have been developed in a manual process. With so much variability from the cells themselves, it is essential to get rid of variability in the process. Developing processes with automation inherent from the beginning tackles the issue of having to change when scaling up and out.
Hampson said, “What we advise our clients is that if something about the cell journey is likely to change drastically when you go to automation, let’s do that early. You got to build up as you go towards the commercial finish line, but first, start with those key core processes in getting into closed automation early.”
“Now as we’re going towards commercial, for us it’s more about how do we start integrating the individual unit operations horizontally to support greater numbers of patients as we get into commercial manufacturing.”
Goodman said, “We actually had done a reasonable amount of automation during our clinical studies. Now as we’re going towards commercial, for us it’s more about how do we start integrating the individual unit operations horizontally to support greater numbers of patients as we get into commercial manufacturing.”
Big opportunities in automating quality control and data integration
The panelists agreed that there are big opportunities in automating quality control and data integration. Goodman said, “I think there’s a huge opportunity around automating quality control, both for release testing, but also in process, moving more towards in-line analytics. I’m guessing that everyone will agree that all of those cells that we have are precious. In quality control, it consumes a huge proportion of cells that really, in the end, are better served going into the patient. The more we’re able to non-destructively analyze and learn from our process the better.”
Another key area that automation can address in a robust way is data integration. Schweickart commented, “With the data integration people understand that this is critical data that we need to get in the right place, but ultimately when you talk about a manufacturing environment, there is a much larger integration that you need to see happen.”
Goodman added, “The shift from paper batch records to electronic batch records will be huge. It opens up significant opportunities in terms of how we actually execute the process by making it less about being in the room and having potentially a control center outside of the cleanroom space.”
Approaching automation and platform solutions
The panel also discussed their overall approach to implementing automation, and how that has changed over time. Goodman described bluebird bio’s approach: “I think, like many here, getting through the clinical proof of concept has been so foreign that we’ve made incremental changes over time to our existing products. Now that we see the potential being realized across the industry, we can then make that investment for a longer-term platform solution. We are looking at it both from a ‘Is there a solution in a box?’, something that is end to end, versus optimizing specific unit operations that can then be consistently brought together and perform in a uniform fashion.”
“Now that we see the potential being realized across the industry, we can then make that investment for a longer-term platform solution.”
He added, “My design principle is, if you can design it as if you were going to run this in any hospital around the world in a decentralized fashion, then you build in the robustness that will allow you to do centralized or decentralized manufacturing. That’s from a design principle for automation in the next-gen platform, the approach we’re using. That gives us ultimate flexibility in how we implement.”
Schweickart described Juno Therapeutics’ approach, “The idea is: ‘Do we have a reconfigurable system?’ By having a flexible supervisory control layer around the automation I’m able to put the unit operations where I need them or swap in a particular unit of operation for the next therapy. That’s the approach that we’re taking.”
A fast evolution ahead of us
The panel touched on many key points and challenges in pursuing automation during their discussion. Hampson said, “I think connectivity is one of the key points being made here, and it’s even the physical connectivity of unit operations from a falling of transfer of cells from one unit operation to the next, and standardizing that. Then the other point I want to make is the standardization all the way out, from vein to vein if you will, and the standardization that has to occur in an orchestration of the whole supply chain of cells. We’re starting to see companies that are addressing those types of things and making use of standards that are already out there, like good automation practices.”
“We are going to be adapting to an incredibly fast evolution in this industry, and it’s going to be the efficacy of the therapies that’s going to drive all of the manufacturing, and all of the process.”
Schweickart summarized the panel’s final thoughts: “We are going to be adapting to an incredibly fast evolution in this industry, and it’s going to be the efficacy of the therapies that’s going to drive all of the manufacturing, and all of the process. This is an amazing industry to be in for innovation.”
Watch the panel discussion
Watch a recording of the panel discussion below for more insights into commercial-scale automation for cell therapy manufacturing.
About the Panelists
Steve Goodman, bluebird bio
As Head of Drug Product Manufacturing at bluebird bio, Steve Goodman oversees production of cellular therapies across the company’s portfolio of products and is accountable for the long-term technology strategy to expand access of these treatments to serve global patient requirements. Before joining bluebird, Steve was at GSK where he held a number of roles across research, development, manufacturing and supply chain. As Director of Manufacturing and Strategy for GSK’s CGT unit, he was responsible for the external manufacturing of the entire value chain to support GSK’s cellular therapies, and for defining and executing the vector manufacturing strategy. Steve joined GSK in 2002 following a Ph.D. and post-doctoral fellowship in organic synthetic chemistry at Harvard University.
Brian Hampson, Hitachi Chemical Advanced Therapeutics Solutions (HCATS)
Brian Hampson has over two decades of strategic and technical leadership experience driving innovative development of technologies, devices, systems, and automation for cell-based processes. He currently holds the position of Vice President, Global Manufacturing Sciences & Technology at Hitachi Chemical Advanced Therapeutic Solutions (“HCATS”, formerly PCT) where he provides executive oversight for Manufacturing Development and Innovation & Engineering teams dedicated to solving the challenges of cell therapy manufacturing.
Randy Schweickart, Juno Therapeutics
Randy Schweickart is Director of Engineering in the Cell Therapy Technology and Platforms Department at Juno Therapeutics, a wholly owned subsidiary of Celgene Corp. In this role, he is responsible for the development and implementation of equipment and automation for CAR-T and TCR therapy manufacturing processes. These activities are focused on both the transformation of current generation process equipment as well as the advancement of next-generation manufacturing plant concepts and process technologies.
White Paper: Commercializing Cell & Gene Therapies
For more action-oriented solutions to cell and gene therapy commercialization, read this white paper we co-authored with market-leading experts from AmerisourceBergen and TrakCel.