Driven by recent medical advances, the field of cell manufacturing offers unique opportunities for engineers with the skills to turn these innovations and medical therapies into deliverable products with a real impact.
According to Roland Kaunas, director of graduate programs and associate professor in the department of biomedical engineering at Texas A&M University, while cell manufacturing inherently involves biology, it is necessary to understand the cell processing equipment involved, its limitations, and how to problem-solve in order to address fluid situations to maintain high quality in these living cell products.
“As automation advances in this rapidly-developing industry, we will need [engineers] who can work with robotic systems and process control software involved in bioprocessing,” he says. “You need to know biology, but what makes production reliable and economical will be engineering.”
Thomas Tubon, director of the NSF ATE Coordination Network: Advanced Manufacturing for Cell & Tissue-based Products at the School of Applied Science Engineering and Technology at Madison College in Wisconsin, says scale-up and scale-out logistics and integrated automation are current challenges facing solid tissue manufacturing. To produce a therapeutic dependent on supply chain modeling, teams must determine whether it is more cost-effective to offer a therapeutic at one site or many—the question of using a point-of-care versus a distribution type model.
For example, take Chimeric Antigen Receptor (CAR) T- cell immunotherapy in regenerative medicine. Most point-of-care therapies are focused on adult stem cells harvested from tissues, processed and administered to the patient. However, mesenchymal (adult) stem cells for treating conditions related to bone, cartilage, muscle or fat are collected at one facility, processed and then allocated to other sites in a distributed model for allogeneic applications (those derived from genetically similar donors).
As the processing efficiency at which therapeutics can be created increases, the supply chain and distribution logistics remain as potentially serious bottlenecks for production and patient delivery. “These are real-world situations that can be addressed using mathematical algorithms or modeling,” Tubon says. “The ability to generate solutions to complex issues is one of the strengths of someone coming in from an engineering background who can apply these models to problem-solve and troubleshoot.”
Collaborating with healthcare experts
According to David Smith, head of innovation and engineering at Hitachi Chemical Advanced Therapeutics Solutions, LLC, engineers are the bridge between scientists and the needs of patients and clinicians. Engineers can address how to scale up therapies and produce higher quality cells.
“Innovative thinking is crucial,” he says. “Engineers use problem-solving skills. We are going to test and find out the truth.”
The ability to communicate and learn new terminology is important for engineers to understand scientists’ specifications. “It is a much better approach to come in with those core engineering skills and then pick up the biology as you go along,” Smith says.
Cell manufacturing still relies on technologies first developed in other areas of biomedicine, such as processing blood or producing monoclonal antibodies or vaccines. The field now needs to develop new techniques to make certain procedures more cost-effective. For example, individualized cell therapies currently may cost half a million dollars per patient, according to Smith.
“In general, you want to acquire a translatable skill set to make scientists’ work more applicable in the real world,” he says. “If scientists develop a way to use 1,000 cells to treat a mouse, what is the best way to generate a million of these cells to treat a human? Could you just use 1,000 dishes or is there a better way of doing that in an affordable, efficient manner?”
For instance, t-flasks are frequently used in small-scale research in which cells must be manually removed, centrifuged and re-suspended in order to culture them. However, this method is impractical for producing the therapeutic dose needed for clinical trials. Automation is more efficient, with solutions such as a rocking platform bioreactor that uses perfusion for culture medium exchange while measuring dissolved oxygen, pH and temperature to ensure the cells are in the correct environment for optimum culture.
“For these individualized therapies, the need is scale out rather than scale up,” Smith says. “It is now a perfect time for engineers to step up and make science work on a commercial scale to treat as many patients as possible.”
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