We began the conversation by talking about the challenges that the cell and gene therapy industry has faced in manufacturing and commercialization. Dave described two hurdles that he sees in moving more products to commercialization. First, he discussed how most of the current cell therapies are autologous, second and third line therapies for replapse refractory patients. At this stage of disease progression, these patients may not respond as well as if they had received this treatment earlier. This makes it more challenging to get a product through the clinic and may make the entire approval process longer. The second hurdle discussed was cost. These therapies are time consuming and expensive to administer. However, companies can take steps up front to ensure quality, consistency and a scalable process with good planning. This includes using high quality reagents from reputable suppliers, implementing consistent quality control parameters, and adequately predicting the amount of time, space and material needed to meet product demand. These measures will increase the odds of successful commercialization and reimbursement from insurance companies.
Next, I asked about Bio-Techne’s new initiative to create cell and gene therapy solutions to expedite the path from bench to clinic. Dave explained that this was important to Bio-Techne because they have spent over 4 decades as a leader in immunoassays, proteins, antibodies and small molecules for research use. Now, it is time to also focus on products for cell therapy and gene therapy manufacturing. As a result of this new focus, they have made significant investments to produce reagents at the highest cGMP standards. In addition, to their existing product lines, they have made a number of acquisitions to further support this initiative.
I followed up by asking about the acquired cutting edge technologies in the cell and gene therapy space, and which they believe provide the most immediate workflow solutions. Sean described cutting edge workflow solutions.
- Cloudz – a novel polymer particle format acquired from Quad Technologies. Enables activation and expansion of T cells for autologous or allogeneic adoptive T cell therapy workflows such as CAR T or TCR.
- Ella – an automated platform for performing ELISAs developed by Protein Simple. Can be used for a variety of applications including in-process and QC ELISAs.
- GMP small molecules – used in iPSC derived cell therapies. Bio-Techne is the only company providing cGMP quality for therapeutic manufacturing.
- GMP proteins and cytokines for the cell culture step in cell therapy and gene therapy.
Then I asked Sean what new and innovative technologies are the Cell and Gene Therapy team at Bio-Techne working on and what workflow challenges do they address? He said that they focus on improving unit operations, i.e. cell separation, cell culture, etc. to try and optimize and develop products to make each unit operation most efficient. For example, the Cloudz platform allows T cell activation without the use of a magnetic bead platform. Magnetic bead platforms can cause challenges because the magenetic particles are viewed as particulates that must be removed. This requires an extra removal step in downstream, an additional qualification step, and more operator manipulations. The polymer quick gel that is the basis for the Cloudz platform is dissolvable and while it functions similar to the magnetic bead technology it doesn’t require the additional downstream challenges of magnetic particles. Sean went on to explain that they are working on using the same technology to make improvements to cell separation.
On the protein side he explained a solution that they have to help process engineers and operators introduce exogenous cytokines or proteins into culture vessels in a closed system, weldable format. This solution reduces operator error and QC risk. The product is called ProDots and it has generated a great deal of excitement as it solves a big challenge around adding cytokine cocktails to culture bags without the need for serial dilutions in biosafety cabinets.
Next, I asked Sean which workflow solutions did he find most exciting and beneficial. He explained that in-process testing is very important as it is necessary to evaluate the product as it moves through the manufacturing process. They are utilizing the Ella automated ELISA platform to create new application notes for how this can be incorporated into workflows to improve in-process understanding and QC. Another exciting application is the use of the Ella system to look at patient’s cytokine levels as it pertains to cytokine release syndrome. Dave added that they have entered a major public agreement with Micropoint in China to use Ella to develop cytokine release assays along with immunotherapies. There is a lot of interest around this application as it is the only way to generate fast, accurate data on a patient’s cytokine levels during treatment. This is a very important tool for the cell therapy industry as a whole.
I asked Dave as Bio-Techne moves forward with the initiative, what did he see as the biggest hurdles and the biggest areas of opportunity in cell and gene therapy manufacturing? He said that tools providers need the ability to scale up reagent manufacturing to meet industry demands. With so many products in clinical trials, even modest success will cause a significant growth in demand for GMP reagents. The challenge is that building capacity is capital intensive and requires long lead times. It is not as simple as brick and mortar and stainless steel. Providers must be able to scale up and still meet product quality requirements, this takes experience and financial strength. Bio-Techne is ready to scale-up production to cost-effectively produce these reagents as demand requires.
I ended the conversation by asking if either Dave or Sean had anything else to add for listeners? Dave asked researchers to stay close to what Bio-Techne is doing in this space. They are committed to developing new products and solutions to meet the evolving needs of the industry. Sean asked that those working in this industry bring them their most challenging problems because they want to work with companies to solve these industry challenges. They want to stay close to the issues as they unfold and be able to work with companies to find solutions together.
To view Bio-Techne’s Cell Therapy and Gene Therapy Manufacturing portfolio, please visit www.bio-techne.com