A journey in scaling up the world's first allogeneic injectable discogenic cell therapy
At the Cell & Gene Therapy Manufacturing & Commercialization Asia Digital Week, Isaac Erickson, Director of Bioprocess Engineering at DiscGenics, delivered a presentation on allogeneic cell therapies to treat lower back pain. Silvia Hnatova recalls the highlights.
DiscGenics is the only company developing an allogeneic cell therapy based on intervertebral disc tissue to treat lumbar disc degeneration, called injectable discogenic cell therapy (IDCT).
Dr. Erickson used his presentation to draw attention to the challenges of scaling up allogeneic cell therapy production in bioreactors. He emphasized the need to produce cost-effective cell therapy treatment for lower back pain.
Chronic back pain due to lumbar disc degeneration affects more than 250 million individuals worldwide every year and is a leading cause of disability worldwide, costing more than 100 billion per year in the US alone.
Dr. Erickson stressed that there is currently no effective treatment available, with patients not responding to early interventions having to undergo spinal disc fusion and limit pain symptoms with the use of opioids.
Dr. Erickson proceeded to explain that IDCT is an investigational, homologous, and injectable therapy, currently under investigation in clinical trials in animal studies.
It could potentially be used to treat mild to moderate adult lumbar disc degeneration. The main mechanism of action is regenerative and anti-inflammatory and is predicted to limit the disability and progression of the disc degeneration disease.
Currently, there are two double-blinded clinical studies led by DiscGenics underway in the US and Japan.
Accompanied by the efforts to complete the clinical trials, DiscGenics is focused on scalable and feasible manufacturing to increase the scale of IDCT development.
Dr. Erickson numbered the desired improvements: to increase the scale, eliminate flask culture, eliminate viscous media static culture system, and increase the ability to control the culturing environment.
After explaining the reasons for scaling up manufacturing, Dr. Erickson outlined DiscGenics’ strategy to achieve the scaling-up improvements. The first step was to move from a static to a dynamic culture, selecting the Eppendort DASbox model.
The DiscGenics team first started scaling up in 1 and 2-liter bioreactors, assessing the ability to scale up.
They found that tangential flow filtration (TFF) did not have the desired effects, having adverse effects on cell viability, prompting the return to manual media exchange and testing an ATF system instead.
To increase the scalability of their system, DiscGenics partnered with Cytiva, using their 10l Cytiva XDR-10 STR bioreactor.
Together, they designed a study to assess the best parameters for a culture, concluding that manual media exchange maintains the best cell growth.
This was compared to a DASbox 250ml culture in parallel, to assess the potential for scalability at 10l.
ATF system was also successfully adapted for the 10l reactor, and compared to 10l manual exchange and the DASbox 250ml.
Having demonstrated successes at the 10l scale, DiscGenics made efforts to scale up to 50l. Dr. Erickson highlighted the costs of scaling to this level and the importance of risk mitigation.
For this, comprehensive computational fluid dynamics (CFD) was performed by APC Ltd Dublin to confidently assess parameters at a large scale.
Dr. Erickson explained that a model was produced to create similar hydrodynamic conditions in the 50l reactor as in the DASBox system to separate out the parameters that were driving the conditions in the DASBox 250ml, to reproduce these in 50l.
Using the CFD data, DiscGenics was able to scale up culturing to 50l while demonstrating that growth was comparable to the small-scale model and the cells met critical quality attributes.
Dr. Erickson presented data to demonstrate that manufacturing at 50l was an achievable scale, and that harvesting at this scale is also feasible.
This data demonstrated that kSep 400 system was able to selectively remove dead cells from the 50l culture, increasing cell viability.
To build upon their successes, Dr. Erickson said that DiscGenics is now creating its own bioreactor, by partnering with AES to create a 50l bioreactor in their pilot lab.
Future steps of DiscGenics include procuring and installing a similar system in their manufacturing suite.
DiscGenics secured a new warehouse for the IDCT manufacturing process, including all processes as well aseptic filling.
To summarize DiscGenics’ progress up-to-date, Dr. Erickson highlighted that the company is currently completing two Phase I/II trials for IDCT for low back pain indications.
The IDCT manufacturing process has been successfully scaled up and DiscGenics built a new manufacturing facility to be able to produce hundreds of thousands of cost-effective doses for lower back pain.
