From The Editor | January 22, 2025

Easing Autologous Cell Collection, Automating Manufacturing

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By Tyler Menichiello, contributing editor

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The starting point for most cell therapies, at least for CAR-T and NK cell therapies, is leukapheresis (i.e., the mechanical separation of white blood cells from a patient’s blood). While this procedure is effective for collecting therapeutic starting material, it has drawbacks like the several hours it takes, along with a handful of possible side effects (e.g., infection and anemia). Not to mention that sometimes the process can’t collect enough viable cells after one round, leading to multiple rounds, which is challenging from both a clinical and commercial standpoint.

That’s why one company is working to find an alternative. CellProthera, an autologous, regenerative cell therapy company, has developed a novel method for collecting hematopoietic stem cells without leukapheresis. The company’s therapeutic CD34-positive stem cells for cardiac tissue regeneration are purified and expanded from a single 220 mL blood draw. I met with CellProthera’s CSO, Ibon
Garitaonandia, Ph.D., to learn more about the company’s mission to simplify collection and streamline manufacturing with automation.

Ensuring A Reliable Supply Of Starting Material

Ibon Garitaonandia, Ph.D., CSO at CellProthera
CellProthera’s goal is to ensure a consistent, viable supply of starting material (CD34-positive cells) by avoiding the potential for failed leukapheresis runs entirely. This method of collection also allows for the treatment of diseases where leukapheresis is not currently being used, such as in neonates and low-weight infants. “We believe that our process can standardize the production of these cells and really make it reliable for everybody else,” Garitaonandia says.

The process starts with purifying CD34-positive cells from peripheral blood collected from patients. These cells are then expanded in incubators for nine days and purified again. This second purification is necessary because of asymmetric cell division. “Some of the cells remain stem cells,” Garitaonandia explains, “but others start differentiating into different blood cell types, so they need to be purified after expansion.”

The company’s automated expansion platform, StemXpand, is coupled with its single-use Stempack kits to optimize cell expansion and viability, Garitaonandia tells me. The platform consists of five incubators within the system, allowing for the simultaneous manufacturing of five patient samples. “It also contains an automated centrifuge controlled by a computerized system,” says Garitaonandia.

This platform has gone through several iterations, as the company is moving towards the ultimate goal of 100% automated process control. It is currently working on “Version Three,” which Garitaonandia says will likely be implemented after the Phase 3 approval of its CD34-positive stem cells (aka ProtheraCytes). “That one will contain several probes to determine the level of nutrients during expansion,” he explains. “We’ll also have machine learning (ML) and artificial intelligence (AI) with feedback-loop mechanisms to improve the yield and minimize the losses.”

Automation’s Potential To Improve Quality Control

CellProthera’s iterative process design illustrates a common theme in biotech — the adoption of new technologies as they become available. As evidenced by the FDA’s recently published guidance, AI is only gaining more traction in the world of drug development. Garitaonandia believes we will continue to see more adoption of AI and ML for enhanced decision making and the automation of complex tasks.

“I also see the expansion of smart factories and digital twins, with sensor robotics and advanced systems that will provide real-time data, enabling predictive maintenance, reducing downtime, and optimizing production lines,” he says. To complement this increasing adoption, Garitaonandia thinks the industry needs to focus on reskilling and upskilling the workforce to prepare for the new roles that will require human-AI collaboration.

According to Garitaonandia, the most immediate need for AI and ML in cell therapy manufacturing is in cell isolation and enrichment, which is very labor intensive and prone to variability. “Current methods mostly use manual handling, which can introduce inconsistencies and increase the risk of contamination,” he says. AI and ML tools can help improve speed, precision, and purity of cell isolation, all while reducing the need for human intervention.

“I also see a need in quality control systems,” he continues. “We need real-time feedback on cell viability, purity, and functionality throughout the manufacturing process.” Often, your only glimpse into product quality is at the end or at a single time point during cell culture. “Having full quality control during the process will be much, much better,” he says. Technologies like microfluidics and advanced imaging systems can be integrated into the manufacturing workflow to enable this kind of continuous, non-invasive monitoring of cell characteristics.

Ultimately, when it comes to implementing new technologies, companies need to do their due diligence, Garitaonandia says. This means assessing the potential regulatory impact and identifying any potential risks, such as operational disruptions, regulatory setbacks, and vendor reliability. “They also need to provide a risk mitigation plan that would address all these concerns,” he says. Integrating new technologies into your workflow can take a lot of work, but “it’s doable,” he says, and frankly, necessary to keep up in this competitive market.

Several months from now, on April 16 at 11 a.m. ET, Pharmaceutical Online Live will feature a live hour of discussion and Q&A on the use of AI and ML in real-time analytics and continuous manufacturing. The panel of experts will share their thoughts on smart adoption and practical applications in a conversation you won’t want to miss. It will be a great opportunity to ask SMEs some of your burning questions around AI and ML in manufacturing. Stay tuned to Pharmaceutical Online for more details to come.