Industrializing Autologous Cell and Gene Therapy Manufacturing to Bring Quality Products to Patients

POC Technology_Oregenesis

Photo: POC Manufacturing/Courtesy of Orgenesis

Orgenesis is developing a point-of-care manufacturing platform for cell and gene and other advanced therapies to make them more widely available and significantly more affordable. The platform is based on regional point-of-care (POCenters) and Orgenesis’ mobile production units or labs (OMPULs). These pre-fabricated units contain everything needed for manufacturing or for a lab. They are pre-validated and can be up and running quickly.

Vered Caplan, CEO of Orgenesis described the point-of-care centers as manufacturing hubs that industrialize the production of advanced therapies, such as autologous cell therapies. This is because the production can be moved from hospitals or research centers that make a few such therapies to a dedicated regional facility, thus leveraging economies of scale while still delivering fresh product to patients within a few hours after they are manufactured.

“Today, many cell and gene therapies are autologous, which implies that manufacturing is personalized. A therapeutic is made patient-by-patient, which makes it so effective,” but as these therapies scale, supply becomes extremely complex, Caplan told BioSpace. “For example, every time you move the source material, you need special quality control testing and special logistics. Additionally, these products cannot be sterilized but must be produced in clean room conditions. For 10 patients, that isn’t an issue. For 50 patients, it becomes more complicated, but now you’re dealing with thousands of patients. What happens when you get to hundreds of thousands or millions of patients?”

Simultaneously, on the manufacturing side, “The industry is becoming much more efficient at reprogramming the cells and delivering them to their targets.” But, as the process scales out, building and qualifying more and more clean rooms isn’t the solution, Caplan said. Instead, “We have to come up with a different system so we can quickly scale out to make these products and very quickly bring the product lines into the market.”

The goal is to automate the process to remove as many manual steps as possible. “You want to close the system, so it’s one validated package,” she said. “Then you can quickly duplicate it.” By industrializing autologous cell and gene therapy manufacturing, it is possible to lower the cost of the therapeutic to – hopefully – one-fifth the current cost.

“Everyone wants a fresh cellular product, so you don’t want to have a manufacturing site in the middle of the country,” Caplan said. “You want fresh produce, close by, and a process that is automated, standardized and unitized. That way, success can be duplicated everywhere, in a very cost-effective manner.”

To do that, Orgenesis is setting up supply hubs to serve medical centers in about a four-hour radius. “These hubs provide everything that industrial production of cellular therapeutic processing needs. They also serve the OMPULs, which we integrate into the unitized systems in a good manufacturing practice (GMP) environment.

“The POCenters are basically the size of a standard shipping container. Inside, we place OMPUL units, so they’re replaceable. We validate a unit running the required process inside, to ensure high quality,” Caplan explained. “We place the hardware (OMPULs) and run the software (reprogramming of the cells). We can add another OMPUL to the same POCenter to provide for another hospital or can provide a similar OMPUL to another POCenter in another region. It’s like the data-centers-in-a-box concept the IT industry introduced several years ago.”

The idea, she said, came from a decade of trial and error throughout the industry. “We’re working now on data integration,” incorporating best-of-breed systems and processes to make cell therapy available for every hospital. “There’s a lot of work to be done.”

There are two use cases for these mobile production units or labs. “Usually, it’s an industrial partner developing the therapeutic, but sometimes the hospitals themselves want their own supply in an OMPUL,” Caplan said. Because the POCenters are only a few hours away from the patient, the cells don’t have to be frozen or otherwise preserved, thus enabling optimal efficacy.

Currently, Orgenesis has about 10 POCenters in various stages of deployment. “We’ve been putting a lot of focus on Europe, and now we’re advancing more into the U.S. We just announced the latest developments at Johns Hopkins University. We’re also working with the University of California - Davis and setting up in Boston and are hoping to expand to Texas,” she said. The company’s network of development and service centers are in place in the U.S., Europe, Israel and South Korea with research and industry partners in these locations.   

The company and its collaborative partners recently received a €4 million grant to industrialize the manufacturing of induced pluripotent stem cells (iPSCs) using the OMPULs.

“We want to develop a closed, automated system to make iPSCs that differentiate into any type of cell you want, and to automatically analyze those cells,” Caplan shared. Today, reprogramming cells into iPSCs and then differentiating them into the desired type of cells is an extremely manual process.

In the past decade, artificial intelligence technologies have advanced amazingly in terms of their sophistication and capabilities for medical indications. “AI is doing extremely well in image analysis,” she pointed out, so using AI to expedite microscopical work for cell reprogramming may save a lot of time and cost, and help industrialize the process.

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