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In this interview, Ramin Baghirzade, Senior Director, Gene Therapy at Charles River Laboratories, explores the impact off-the-shelf plasmids can have on reducing the wastage and costs associated with manufacturing cell and gene therapies.
To start with, please could you introduce yourself and tell us a little about your role?
My name is Ramin Baghirzade and I’m the Global Head of Commercial at Charles River Laboratories for Gene Therapy CDMO services. I look after our gene therapy portfolio and capabilities, which include the viral vector and plasmid DNA services.
In the current landscape, what specific challenges are therapeutic developers facing regarding the cost and wastage associated with plasmids as critical starting materials?
Since plasmids are a starting material, any delay or any availability issues has a domino impact on the rest of the manufacturing process. It’s obviously important to have this material available sooner or later to avoid any bottlenecks.
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In terms of wastage, we know that if a developer requires a certain amount of material, say 200mg, and you’re procuring a batch of plasmid material which might yield 500mg or 1g or 2g, if you only need 200mg, that means that you might not need the rest of it for many months or possibly years to come, and that material is wasted. It just doesn’t make sense.
How can these challenges be mitigated? What options do developers have for reducing costs and wastage in the therapeutic development and manufacturing process?
At Charles River Laboratories, we made a strategic decision to standardize as much as possible and to make plasmids available over the shelf to as large an extent as possible.
With this in mind, we have launched several off-the-shelf plasmids, which includes pHelper, lenti plasmids, VSV-G, Gag-Pol, and Rev, and recently, as of this week, we publicly announced that we launched five more Rep/Cap off-the-shelf plasmids for Rep/Cap 2, 5, 6, 8 and 9, and we make them available from day zero.
Can you elaborate on the impact of the supplier situation on plasmids and how the introduction of more plasmids might provide a cost-effective solution for therapy developers?
Because it’s a starting material, if we can make them available on day zero in the quantities required for a specific, say, AAV or lenti batch, it means that developers can, first of all, take the topic of availability of plasmids out of the equation because it’s already manufactured, and secondly, it allows the developers to procure the exact amount they need.
With a focus on cost effectiveness, how could a platform approach, particularly with the availability of over-the-shelf plasmids, contribute to the industry’s efforts toward standardization and reduced wastage?
It’s important to highlight that in addition to off-the-shelf plasmids, we have launched three platforms for manufacturing gene therapies: one platform called eXpDNA™ for plasmid DNA production, and two platforms for viral vectors – the nAAVigation platform for AAV and Lentivation for LVV production.
We have optimized, or a more precise word would be standardized, how we do the production, and this allows us to massively reduce the timelines from initiation to batch release. So, in combination with these platforms and with the availability off-the-shelf plasmids, it allows us to further support the development of these drug products.
Considering the trend toward standardization in the gene therapy industry, what role do proprietary technologies play in optimizing yields and, consequently, enhancing cost effectiveness for therapy developers?
We know there are a lot of plasmids out there, and there are also quite a few enabling technologies.
At Charles River, we have spent a significant amount of time and effort in understanding how we’re able to optimize the plasmids, because it’s used as a starting material, based on a lot of data we have and the experiments we’ve performed. We were able then to, by optimizing the plasmids, help with increasing and boosting the titers and yield, which essentially means that you’re getting more material.
Could you tell me a little about Charles River Laboratories’ ‘Concept to Cure’ initiative, and how it contributes to the broader goal of improving cost effectiveness and minimizing resource wastage in gene therapy development?
We have a lot of capabilities which go well beyond manufacturing, so we pride ourselves as an end-to-end provider, starting from early discovery to commercialization, and we support our customers throughout the entire journey of drug development.
Hence, we designed this concept where we have a vision that we’re able to support developers at any moment or throughout this journey, be it if they need to perform, for example, some animal studies or if they need to perform some discovery work, and ultimately going with them into clinic and to commercialization.
What impact does the availability of off-the-shelf plasmids, based on proprietary technologies, have on making gene therapies more accessible and cost-effective for a larger patient population?
We know that cell and gene therapy is no longer science fiction. We have already seen quite a few landmark approvals and I think everyone would agree that the industry has been maturing.
Having said that, they’re still only available to a fairly small patient population and we need to do a lot more in making them more accessible and affordable.
So, with that in mind, having a more standardized approach which allows, among other things, cost savings and also savings regarding the wastage of material, we’re positive that this will help the industry to mature further.
What do you see for the future of gene therapy, especially as new plasmids come to market?
It’s tied a little bit to what I mentioned earlier, where we think that, or we’re convinced that having those plasmids available means that those therapies can be made more accessible both to the clinic and beyond.
We expect to, hopefully, see more drug products available to patients in need, and also see more products making it to the finish line.
This interview was produced in partnership with Charles River Laboratories.
