CHOP set to open its gene-therapy factory

UNDER WEST PHILLY — Doctors and research officers at Children's Hospital of Philadelphia and their collaborators from University of Pennsylvania's Perelman School of Medicine spent Halloween afternoon walking groups of Philadelphia CEOs and other guests a couple of stories below the level of the nearby Schuylkill, to see CHOP's newly finished clinical manufacturing facility, in the basement of the Colket Translational Research Building at its campus in University City.

The $75 million underground lab complex is airlock-doorways-protected, hydrogen-peroxide-sprayed, climate-controlled, hair-net-and-boot-net-wearing spotless — and it's designed to stay clean for its role as the newest in the chain of cell and gene-therapy testing and production facilities spreading around Philadelphia.

Over the last 10 years, CHOP has put together products for hundreds of patients in 30 clinical trials. The new lab will more than double production to 20-plus clinical-trial products a year, through four separate production suites, each with its own clean rooms, centrifuges, filters, cold storage, laboratory, and office space separated by air locks that limit access and exposure. Digital controls limit access and track what goes in and out, including how many times staff have changed their sterile scrubs and shoe covers (booties).  The chairs in the suites are color coded so staff can tell them apart at a glance.

"This place is unique in the world," said Johannes Van der Loo, director of the Clinical Vector Core program at the center. To be sure, there are gene-therapy production labs at universities and hospitals in California, Florida, and several Midwestern states; Pfizer has expanded a program started at the University of North Carolina. But "this is a much more complex manufacturing enterprise," said Van der Loo. "Nothing like this exists in Boston," Philadelphia's rival as an East Coast medical-industrial center.

The city's emerging bioscience manufacturing system includes the cell-therapy manufacturing facilities at the Hospital of the University of Pennsylvania across Civic Center Boulevard, Chinese-owned WuXi AppTec's 600-person, 380,000-square-foot commercial labs at the former Navy Yard in South Philadelphia, along with cell and gene-therapy batch production and research labs at Jefferson, Christiana, and other hospital systems, and at academic start-ups.

CHOP's chief executive, Madeline Bell, called the labs a modern update on the old factory clusters that made Philadelphia a historic manufacturing center. "Penn uses our gene-therapy vectors," the vehicles that deliver treatments, said Beverly Davidson, a professor of pathology and laboratory medicine at Penn and director of CHOP's Raymond G. Perelman Center for Cellular and Molecular Therapeutics, which operates the lab. So do scholars at other schools, start-up therapy developers, and commercial labs.

The CHOP facility engineers beneficial genes into modified viruses and other materials that deliver them to fix cancerous and other diseased cells in patients. CHOP, Penn, and other area medical centers and commercial suppliers are cranking up vector production, so new therapies can be tested, approved, and sold commercially, bringing costs down from experimental levels that can currently cost patients, insurers, and donors hundreds of thousands of dollars, or more.

Teams of CHOP and Penn doctors have produced the first FDA-approved gene therapies: Kymriah, a CAR T-cell  therapy used against leukemia, for pharma giant Novartis; and Luxturna to treat an inherited blindness — a therapy developed by Spark Therapeutics, one of the first publicly traded companies spun out by scholars at the University City gene-therapy complex.

CHOP officials said they manufacture at cost, not as a profit-making enterprise. Translational research, such as the systems developed in the CHOP lab, is designed to bring products closer to market. The Colket building was built in 2009, but the basement was left empty while researchers developed plans and raised funding for the updated lab.

Davidson said gene-therapy products aren't complete when they leave the lab. "We test that product for years to come," after it's been used in patients, she said. "Six, eight, ten years." The FDA requires follow-up testing. "Once it's out of our facility, it's never really gone."