3 Critical Considerations For Cell Therapy Manufacturing
By Trisha Gladd, Editor, Life Science Connect
The cell therapy market is certainly heating up. Over the last year, we have seen several companies, such as Fujifilm and most recently Celgene, make monumental moves to acquire companies that are making significant progress in the area of cell therapy drugs. These strategic moves are an effort to get a foot in the door of a market that is expected to reach $67.6 billion by 2020.
One company, Vericel Corporation, made its move last June when it announced the acquisition of the cell therapy and regenerative medicine business of Sanofi. Through this deal, Vericel, which was known as Aastrom Biosciences, Inc. at the time of the acquisition, obtained the rights to three cell therapy products from Sanofi: Carticel®, an autologous cellular product for articular cartilage repair; Epicel®, a cultured epidermal autograft; and MACI®, a next-generation autologous chondrocyte implantation product to treat knee cartilage defects. Carticel and Epicel are currently available for use in the U.S. Vericel intends to submit a Biologics License Application (BLA) by the end of 2015 to the FDA for marketing approval and distribution of MACI in the U.S.
While autologous cell therapies offer promise in the way of patient treatment, manufacturing them is a complex process requiring thorough understanding of the cell type(s) that a company will be providing as therapy. Ross Tubo, chief scientific officer at Vericel Corporation, has been working with cell therapy and regenerative medicine for over 25 years. He was involved in the genesis of both Carticel and Epicel when both products were under the original ownership of Biosurface Technology. He is now responsible for scientific programs leading to FDA approval and manufacturing of Vericel’s pipeline programs, including MACI and Ixmyelocel-T, an investigational complex autologous cellular therapy, which is being studied for ischemic dilated cardiomyopathy (iDCM). When it comes to ensuring the successful manufacturing of a cell therapy drug, Tubo says there are three critical areas where particular attention should be paid.
- Handle With Care
Manufacturing processes should be developed with cellular identity, potency, and purity in mind. These parameters are critical for ensuring that the therapeutic cells are present, functional, and in the right number. Once these parameters are identified, Tubo says the system and procedures used to manufacture a cellular product must be sufficiently robust to ensure the maintenance of cellular function, whether used in structural repair and tissue replacement (e.g. Epicel, Carticel) or activity expected to impact physiologic function (Ixmyelocel-T).
One particular challenge Tubo has faced when it comes to safe handling of cells is physician education, especially if treatment involves a significant shift in surgical technique. Tubo offers an example from his experience with Carticel®. “The surgical procedure for Carticel required orthopaedic surgeons to perform very fine microsurgical suturing to hold a periosteal membrane in place for delicate cells in suspension to be injected under and develop cartilage,” he explains, “The challenge is that orthopaedic practices are geared more toward repairing cartilage defects with expert ‘body carpentry’, surgically shaping and/or plugging defects with osteochondral implants. The goal of next generation cartilage repair products is to more closely meet the needs of orthopaedic practice by making implants easier to apply.”
- Establish Logistics Parameters Early
When developing a cell therapy, one must also identify early on specific shipping conditions, such as transport temperature and physiological storage solutions. “Establishing parameters for storage and shipment in the development process will ensure that the viability and function of a cell therapy are maintained, which is critical to serving patient need,” says Tubo.
He adds that shipping containers must be developed in order to maintain the proper temperature for the “shelf life” of the cell therapy. In the early days, cells had a shelf life of only a few hours; however, Epicel® can now be shipped for as long as a temperature of between 13 to23 degrees Celsius is sustained during travel. To address this, shipping containers were developed by testing extremes of temperature, for example ranging from Arizona in summer to New England in the winter. Temperature-control studies via mock shipments were then completed to test the container.
- Simplify To Save
Since acquiring the business from Sanofi, there are several things that have been done to streamline Vericel’s processes in order to maintain minimal level costs. “The level of hands-on manipulations has been reduced by modifying methods for processing patient tissue samples, methods of cell storage, and conditions for cell growth.” Handling time is a major cost factor in manufacturing cell therapy drugs. According to Tubo, reducing the number of times an individual has contact with a culture is one way to keep costs down.
“One area where some companies are looking for cost savings is the use of automation during manufacturing. However, because of the sensitive and specialized nature of the patient’s own cells, one must balance the desire for automation with the ability to manufacture a high quality product,” says Tubo. “Since these are autologous therapies—where a person’s cells are removed, altered, and administered back to the same patient—it’s important to validate the process during manufacturing in order to show that you are able to maintain the functionality of the cells from beginning to end,” he explains.
He also adds that preclinical animal model experience is key to moving toward clinical trials. “It is not a trivial point to identify a relevant pre-clinical animal model for demonstration of your cell therapies’ function in vivo prior to human clinical study,” says Tubo. He notes that identifying and addressing these specific needs early facilitates the ability to move into human clinical trials and demonstrate safety and efficacy to initiate the FDA approval process.