The emergence of commercially available cell therapies has been, and continues to be, an inflection point for the cell therapy industry. An initial pathway from process development to commercial manufacture has been described, yet many challenges remain along the way.
Invetech hosted a panel discussion during the recent International Society Cell & Gene Therapy (ISCT) conference in Melbourne, Australia to explore the main challenges along the pathway from process development to commercial cell therapies.
The panel, chaired by Invetech’s Jon Ellis, and comprising of Dr. Dawn Driscoll (Cell Therapies Pty Ltd), Dr. Joanne Kurtzberg (Duke University) and Dr. Wen Bo Wang (Fate Therapeutics) had an insightful discussion on the role that considered automation plays in navigating three of the biggest potholes in commercial cell therapies:
What are some of the most significant potholes along the way to cell therapy manufacturing?
Tackling the main theme first, the panel members discussed some of the most significant potholes along the pathway from process development to commercial cell therapies. Dr. Dawn Driscoll from Cell Therapies talked about two of the biggest potholes from her point of view: forward planning for companies aiming for commercialization, and regulations in different countries.
Dr. Driscoll said, “One of the biggest things that I have seen are sponsors who don’t look far enough down the track in terms of their materials and what they’re using in their cells. They don’t necessarily understand that even in the early stages, you need to keep a tight watch on the provenance of your cells.”
“Probably the second biggest pothole is people working in one country under only those regulations. At the earlier stages, they don’t look out to other large countries where they might want to do clinical trials, or ultimately launch, and then realize that there might be slightly different regulations, particularly in terms of donor testing.”
“And the challenge for us at the moment is that sometimes there isn’t even a device for us to utilize to scale up our process.”
Dr. Wen Bo Wang from Fate Therapeutics agreed and then touched on the challenge of scaling up to commercial scale in the rapidly evolving industry. Dr. Wang said, “I think the challenge, really the biggest one, is still the scaling up part of it. From a research scale to a commercial scale; that is a huge change in scale. And the challenge for us at the moment is that sometimes there isn’t even a device for us to utilize to scale up our process.”
What role can automation play?
The panel then turned to discuss the role of automation in cell therapy commercialization. Does automation help, or can it sometimes be a hindrance, if employed too early? The panel agreed that automation has many benefits and will pave the way for commercial manufacturing; however, there is still a lot of work ahead of us to make it an easy transition.
Dr. Kurtzberg said, “In general, automation is helpful because it standardizes the manufacturing. I’ll give you an easy example in the cord blood manufacturing world. When we were getting the VLA [very late antigen], we had 15 years of manual manufacturing and then we had switched to automated devices. The automated devices made our recoveries in a much tighter range and eliminated technician variability; with how they handled the product, or helped the product, or disturbed the interface. These are simple things. But in that case, the automation really made it easier and made us have a more consistently produced product.”
“On the other hand, with automation, you have to maintain your equipment, you have to make sure you validated it – and then every time something goes out of service, you re-qualify it. So, there is a whole set of different kind of work that you do that you don’t do with manual manufacturing. But I think in general, automation makes sense.”
“What I’m really looking forward to is getting to the point where we do have more automation systems, and tighter control over in-process testing.”
The panel agreed that there have been rapid developments in the industry in the recent years, however the road ahead is still long. Dr. Driscoll commented: “For us, what I’m seeing with automation is, we’ve come a long way in the past 15 years and we do have gadgets here and there. There’s quite a lot of room for improvement with some of them that do one part of the process very well, but then they become a bottleneck [because of limitations in functionality].”
“What I’m really looking forward to is getting to the point where we do have more automation systems, and tighter control over in-process testing. I think that will be very, very important. I think the regulators will be very happy with that. The payers will be happy with that.”
Where can we reduce the cost?
Discussing potential opportunities to reduce the cost of cell therapy manufacturing, the panel talked about the factors that go into the facilities – people, and the cost of disposables as a process.
In describing how to best reduce the cost of cell therapy manufacturing, Dr. Wang said, “Go closed system as much as you can, and do some automated steps as much as you can. That will definitely help to reduce the requirements for the clean room and the people, and that in turn will help to bring the cost down.”
“But I think the biggest opportunity here is still the allogeneic versus autologous [therapies]. If you are producing large kinds of lot sizes for a product – although per batch, it is still very expensive – but if you divide it by hundreds of doses then that cost will reduce quite a bit.”
“…the thing that will ultimately reduce costs of these therapies is if we can use them in patients earlier inthe treatment paradigm. So before we’ve spent a million dollars with chemo and surgery and other types of transplant. That will be the ultimate cost savings for the health care budgets.”
Dr. Driscoll agreed and added, “I think if we can move out of clean rooms at some point – Grade B and Grade C areas are extraordinary expensive to maintain. If you could have your cleanest environment be a bag, that would be wonderful. I think we will be stuck with pretty high costs for a while until we get the economies of scale so that we can enjoy lower cost vector and lower cost materials.”
She continued, “I also think for the health care system overall, the thing that will ultimately reduce costs of these therapies is if we can use them in patients earlier in the treatment paradigm. So before we’ve spent a million dollars with chemo and surgery and other types of transplant. That will be the ultimate cost savings for the health care budgets. But as far as the cost of manufacturing, we just need to get some of the components down – and the cost of clean rooms is quite atrocious.”
Is there an opportunity for technology providers and therapeutic companies to work together on automation?
The panel shared their insights on how technology providers and therapeutic companies could work together in terms of automation and commercial scale cell therapy. Dr. Kurtzberg pointed out that there could simply be cooperation – or industry standardization – between technology companies. She said, “So if one company has built a robot that fills vials and another company has built a volume reduction machine, right now most of their tubing sets don’t match and you can’t weld them – simple things like that. If those companies cooperated, then people doing manufacturing could plug and play different devices from different manufacturers into their overall system.”
“If those companies cooperated, then people doing manufacturing could plug and play different devices from different manufacturers into their overall system.”
The discussion ended by the panel summarizing their final thoughts on where we are on the pathway to commercial cell therapy manufacturing. Dr. Driscoll said, “I think once we work through the next painful two to three years and sort that out, we’ll be in a much better state. But right now we just have to slog through it and work out everything with the codes and the long-term implications, but we’ll get there. We’re just not quite there yet.” Dr. Kurtzberg added,” I think that if the products work, people will find a way”, to which Dr. Wang said, “It’s a learning curve for the field. We’ll get there.”
Watch the panel discussion
Watch a recording of the panel discussion below for more insights into the role that automation plays in navigating the biggest potholes in commercial cell therapies.
About the Panelists
Dawn Driscoll, MBA PhD GAICD, Chief Executive Officer, Cell Therapies Pty Ltd
Dawn Driscoll is the CEO of Cell Therapies. Dawn has over 20 years of experience in the biotechnology industry globally, with expertise in cell therapy, licensing, acquisitions and commercialisation. Dawn has previously managed global technical teams in clinical development, regulatory affairs, marketing and pharmaceutical product launches. Dawn has held senior roles in Johnson & Johnson, Wyeth (Pfizer) Pharmaceuticals, and managed DCi Biotech, an international consultancy focused exclusively on the commercialisation of cell & gene therapies, for over 10 years.
Joanne Kurtzberg, MD, Director, Marcus Center for Cellular Cures, and Director, Carolinas Cord Blood Bank at Duke University
Dr. Joanne Kurtzberg is an internationally renowned expert in pediatric hematology/oncology, pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation, and novel applications of cord blood in the emerging fields of cellular therapies and regenerative medicine. Dr. Kurtzberg pioneered the use of umbilical cord blood as an alternative stem cell source for unrelated hematopoietic stem cell transplantation (HSCT). Over the last two decades Dr. Kurtzberg has established an internationally known pediatric transplant program at Duke which treats children with cancer, blood disorders, immune deficiencies, hemoglobinopathies and inherited metabolic diseases. In 2012, under the direction of Dr. Kurtzberg, the Carolinas Cord Blood Bank received FDA approval for DuCord, a stem cell product derived from umbilical cord blood, for use in transplants between unrelated donors and recipients. Dr. Kurtzberg currently holds several INDs for investigational clinical trials.
Wen Bo Wang, PhD, Senior Vice President – Technical Operations, Fate Therapeutics, Inc
Dr. Wen Bo Wang is Senior Vice President, Technical Operations at Fate Therapeutics, overseeing the company’s manufacturing strategies for its pipeline of off-the-shelf cell-based cancer immunotherapy candidates and scaling the Company’s induced pluripotent stem cell iPSC platform to support late-stage clinical and commercial operations. She was formerly Senior Vice President Cell Therapy R&D at Fujifilm Cellular Dynamics Inc (FCDI), where she was responsible for developing the cell therapy R&D strategy and the iPSC based pipeline products and led the next generation production technology development efforts. Previously, she was VP Process Sciences, and directed scale up and scale out platform process development for iPSC based iCell products and MyCell products including automation and bioreactor work.
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