Fall is almost here, and that means it is Cell Therapy Bioprocessing and Manufacturing conference season. This year it started a few weeks earlier as conference organizer CHI put together a Cell Therapy BioProduction session as part of their Annual BioProcessing Summit in Boston from August 18-22. In our last post (Scale-up Production – Post 1 of 2), I summarized some of the cool technologies that vendors had on display, as well as some of the poster highlights. In this post, I want to highlight just a few talks that were focused on manufacturing, scale-up, and Cost of Goods of allogeneic cell therapies. There were several other great talks, but I just wanted to focus on these three due to topic and brevity.
Manufacturing, Cost of Goods, and Unprecedented Stem Cell Process Yields:
On the first day, we had a dynamic duo from Loughborough University give a pair of excellent talks. Experienced Manufacturing Engineer David Williams gave a great talk on precision manufacturing of living products, highlighting the challenges of working with the inherent variability that comes with primary cell culture. Dr. Williams is the Director of the Center for Innovative Manufacturing in Regenerative Medicine that “works to equip the regenerative medicine industry with manufacturing tools, technologies and platforms by considering the ‘right therapy, right patient, right time’ supply chain from end to end.” In his talk, he highlighted the need for solid quality characteristics so you know exactly what you are manufacturing – and can do it “again, and again, and again, and again….”. He points out that, without knowing what characteristics are important for your product (the identity and functional potency of your cells), you: can’t manufacture to specification, can’t scale up, can’t implement new raw materials in your process, can’t transfer manufacturing to another facility, and can’t reduce COGS through process optimization. Hearing David talk is always a reminder of how important the basics are.
The second half of the Loughborough team was recent Ph.D. graduate Mark McCall who has made a good name for himself over the past few years with his excellent Cost of Goods (CoGs) modeling. Mark’s talk was focused on the impact of the manufacturing process on CoGs, and he has recently launched a blog www.CellTherapyWonk.com where he will share much of his CoGs-related work. His presentation, that he has posted to his blog, shows the components of his very detailed cost modeling, as well as the impact of scale-up production on the cost of an example cell product. I highly recommend following Marks’s blog, as there is little detailed information out there on CoGs modeling, and it is critical to the future success of Cell Therapy as an industry.
The final talk I want to highlight is a scale-up production talk by Hari Kamaraju related to an allogeneic adherent stem cell product isolated from umbilical tissue. Dr. Kamaraju, a Process Development (PD) Scientist at Janssen(a pharmaceutical company of Johnson & Johnson), spoke about some of the development challenges that they overcame before manufacturing. Dr. Kamaraju outlined the strategic aspects of the cell source (easily accessible tissue with “early”, fast-growing cells capable of many population doublings), and the goals that his team achieved in a particular PD campaign. Like all good PD campaigns, they had quantified goals which were to 1) increase bioreactor yields by >50%, 2) increase downstream process recovery by >75%, and 3) decrease serum by 70%. All of this would dramatically increase the yield from every run and help reduce the CoGs of the overall process. Impressively, Dr. Kamaraju reported that they scaled up to 1000 L single-use bioreactors and were able to consistently achieve yields of >300 Billion (3 e11!!!) cells per run. I have been following this technology area for several years, and this is the first I have heard of any team achieving yields in the 100s of billion cells with adherent stem cells. Dr. Kamaraju also mentioned the use of TFF and kSep for downstream processing of these large volumes, but didn’t go into detail on this aspect of development. Large companies like Janssen have both extensive internal bioprocess development experience as well as the deep pockets required to run such large programs. The impact of this achievement will be broad-reaching and helps to underscore where the field is headed.
I, unfortunately, had to catch a plane and missed the last 2 talks – one by Pluristem’s VP of Development & Manufacturing Ohad Karnieli and the other by MIT/Harvard (and soon to be TED fellow) professor Jeff Karp. Both of these talks were on the scalable production of allogeneic adherent stem cells (Pluristem) or for enhancing the biofunctionality of these cells (Karp’s talk). I will look forward to seeing both of them at the upcoming Cell Therapy BioProcessing conference in DC in a couple of weeks.
A note on Autologous and Patient-specific
There were several excellent talks on Autologous and Patient-specific Manufacturing related to orthopaedics and immunotherapies. Due to the length of this post, I will not go into these, but this is another critical part of the Cell Therapy BioProcessing eco-system that will be changing how health care is practiced. The interesting aspect of this is that few, if any, vendors were marketing towards the immunotherapy companies – all of the messaging was to scale-up of adherent cells, like hMSCs. I want to underscore again that it is critical for tool companies to become committed to the area so that new tools can make it into the hands of the industry – helping the industry to develop. GE and Miltenyiare the two companies that have focused product areas that help the immunotherapy field develop – and I think these will be much more prominent at the upcoming Cell Therapy BioProcessing conference.
I want to stress that Manufacturing Matters, even when talking about stem cells and cell therapy. Improvements in Manufacturing Technologies are what drives scale-up and costs down, and when coupled with solid biology and product characterization will drive the sustainability of current industries and the development of new ones. RoosterBio is trying to help make this happen for the next generation of cell-based products and technologies.
Thanks for making it to the end of this blog post, which was more extensive than I was hoping, but I think all of the content is in need of distribution. If there are any questions about the above info I will try to answer in the comments, or send you to the right person/company that is best suited to answer you.