Cryopreservation, from starting material to point-of-care processing: an interview with Chris Wegener
Chris Wegener has been a part of Fresenius Kabi for over 12 years and has led the Cell Therapy R&D team for the past 9 years. His work in concept and feasibility have led to the development of the Lovo and Cue instruments, which have brought automation, quality improvements, and scalability to many clinical and commercial CGT workflows.
In this interview, we talk to Christopher Wegener (Fresenius Kabi, Bad Homburg, Germany) about all things cryopreservation in cell therapeutics. From automation to point-of-care processing, Christopher provides an expert insight into the challenges facing the industry for cryopreservation of starting material, as well as a sneak peak into the future of cell and gene therapy processing workflows.
Please introduce yourself and your company/institution.
Fresenius Kabi (Bad Homburg, Germany) is a global leader in healthcare with products ranging from cell processing instrumentation, medical devices, generic pharmaceuticals and nutrition products. Our competencies in cell and gene therapy (CGT) processing spurs from our longstanding experience in patient-connected apheresis systems. We leverage the know-how from decades of closed-system medical device production – everything from material science to fluid handling to embedded software design – into the robust design, manufacture and support of our CGT portfolio, notably our Lovo and Cue Cell Processing Systems.
I came to the company 12 years ago with degrees in biomedical engineering. I am proud to have been a part of the founding CGT team and now lead many of the research and development efforts going on in CGT. Some of my first work at Fresenius Kabi was improving the spinning membrane filtration technology that we employ on our plasmapheresis collection systems. With that deep experience, I have helped to build our CGT portfolio on the same separation platform.
It’s been an amazing time to be a part of the CGT community, watching it move from academic to translational to commercial production of life-changing therapies. For someone who has been forever striving to do good through innovation, my time at Fresenius Kabi has been a dream come true.
Why is cryopreservation important in cell and gene therapy?
I’m a pretty big fan of French fries; good ones, light and salty, crispy and still warm from the kitchen, can be a masterpiece. However, takeaway fries are another experience; they might be soggy or getting cold. It’s not the chef’s fault – they were prepared in the same delicious way – but they just aren’t the same when you package them up, carry them away and enjoy them even a few minutes later. It’s similar with CGT drugs.
You can make and qualify very potent therapeutic cells and source high quality starting materials, but if you can’t provide the stability of that product all the way to the manufacturing facility or back to the patient, it doesn’t matter how perfect the in-between is. Cryopreservation can help provide some semblance of stability for those cells. It certainly introduces additional complexity; it’s another set of unit operations that need to get incorporated into an already challenging manufacturing workflow.
CGT production is unlike any other manufacturing paradigm to date – it involves good manufacturing practice of biologically active products in sometimes single-dose lots, sometimes in facilities in other countries or continents from the points of collection and delivery and nuances of patient management, all while trying to juggle the logistics of labor and shipping. A good cryopreservation strategy may introduce a little bit of complexity, but in turn, helps provide a solid foundation on which to prevent getting soggy fries.
How has COVID-19 influenced the process of cryopreservation in the past few years?
I don’t know if COVID-19 has influenced the cryopreservation process itself, for example the workflows, the materials or the reagents, but certainly the logistics and labor complexities around the process have increased. Material shortages, inability to staff shifts with experienced team members and shipping inconsistencies have all highlighted the importance of using cryopreservation to build-in the ability to hold starting materials or final drug products.
What are the benefits to cryopreservation for final drug product? For starting material?
For final drug products, there are often days of quality control testing required to release the lot to the patient. These cells, being living things, begin to lose potency almost immediately post-production. Cryopreservation can help preserve the therapeutic benefit of the cells while quality control is processed and released. It also provides stability on back-end logistics and ensuring the patient is ready to receive their life-saving dose.
On the starting material side, the benefits are similar. Cell viability can be preserved despite the shipping and logistics involved in getting cells from the patient to the manufacturing location, especially if the cell collections are scheduled over multiple days.
What challenges face the industry for cryopreservation of starting material?
I think the biggest hurdle to implementing cryopreservation of starting cells is standardization of the cryopreservation process. It’s relatively easy to standardize the process on the drug product side; you have well-trained manufacturing personnel in your own facilities that have the right equipment and access to the right processes.
Starting material needs to be cryopreserved at the patient site. Geographically, patients potentially span the globe. This can put the cryopreservation process in hard-to-reach places, outside of your manufacturing purview. As a therapeutic developer, you can specify standard operating procedures (SOPs), audit and certify those locations, but this can be an incredible burden to manage. For collection sites, they must juggle separate SOPs, audits and certifications for dozens of separate therapeutic developers, some processes of which may only be performed a few times a year.
This often forces the therapeutic developer to defer to the institutional cryopreservation processes already established at the collection sites, leaving them to deal with variability in the preparation materials, methods and quality of the incoming material.
What benefits can be achieved through automation of cryopreparation operations?
The most substantial benefit to automation is standardization. A therapeutic developer can ensure their SOP is followed every time. A collection site doesn’t have to hope they targeted the right fill volume. Automation makes sure the correct freezing concentration or cell dose is targeted every time for a given therapy. Automation confirms a consistent flow rate or agitation method is followed. Automation doesn’t care at what location it’s sitting or if it’s been 7 months since the last time it performed that specific protocol.
These benefits are the reason we have developed the configurable Cue Cell Processing System. A therapeutic developer can define nearly any variation on a cryopreparation process and deploy that to dozens of sites. If those sites are already familiar and trained on the Cue system, they are instantly cross-trained on any other Cue process also deployed at their site.
We at Fresenius Kabi are very excited to enable a new level of process standardization and product quality for the industry, and allow these therapies to be more accessible to those patients they will benefit.
What does the future of cell and gene therapy processing workflows look like with ever-shortening manufacturing times?
Some of the advances in biology and manufacturing science have me at a loss for words. To see how the field can collect and analyze manufacturing and clinical data, and quickly translate that into more potent therapies, at lower cost and in a quicker timeline, is truly incredible.
So, what does the future look like? Thinking about French fries, they are just going to taste better if you eat (at least some of) them at the restaurant and avoid the complexities of packing and transporting. It’s going to be the same for CGT. Point-of-care processing, bedside manufacturing and, at some point, in vivo therapies are going to be a reality. Advances in biology, manufacturing science and Fresenius Kabi’s focus on developing new tools are going to ensure it.
How are Fresenius Kabi and ScaleReady positioned to offer solutions for the challenges in the future of cell and gene therapy production?
Fresenius Kabi and its ScaleReady partners are laser focused on providing a practical and scalable manufacturing platform to minimize process development time, decrease batch failures and get novel therapies to market faster. We’ve assembled partners with deep expertise in reagents and media, gene editing, cell culture and automation coupled with the best field support services to ensure every customer’s manufacturing workflows are simple, flexible and effective.
We’ve had the incredible opportunity to work with customers working with all different cell types and indications, at different points in their therapeutic development programs and accommodate an incredible number of workflows with the same flexible tools. We’re confident Fresenius Kabi and ScaleReady know how to support even the most novel application.
It also has given us unparalleled insights into the needs of the industry and how to fill our pipeline with the next generations of value-added products to ensure customers always have the right tools to deliver their next therapy, crispy fries and all.
Disclaimer
The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of RegMedNet or Future Science Group.
This article is part of the RegMedNet Spotlight on cryopreservation. Click here to view the full feature and discover expert insights on this >>>
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