Like many in the pharmaceutical industry, Carol Houts, Germfree’s chief strategy officer, began her career at the bench before taking on roles in regulatory affairs, pharmacovigilance, compliance, and other areas. She met Keith Landy, Germfree’s CEO at the time nearly eight years ago. At the time, the company worked largely on building modular cleanroom environments for use in healthcare but was exploring opportunities in biopharma, specifically the cell and gene therapy (CGT) space. Landy, who was battling glioblastoma and has since passed away, was particularly passionate about bringing Germfree’s cleanroom infrastructure into the cell and gene therapy space, Houts told GEN in an interview. “That drive for getting patients’ access to therapies is embedded in the fabric at Germfree.”
And the drive is now bearing fruit. This week, Germfree announced a partnership with Caring Cross focused on providing patients with affordable access to CGTs starting with CAR T-cell therapies for cancer. Caring Cross is a nonprofit with a mission to accelerate the development of advanced medicines and ensure access to cures for all patients, everywhere. The partners are creating a decentralized, point-of-care manufacturing model that combines Germfree’s mobile cleanroom units with Caring Cross’ manufacturing technologies and pipeline of cell and gene therapy products. The result is a comprehensive, end-to-end infrastructure for manufacturing cell and gene therapies at the point-of-care.
The partnership builds on three years of preparation including a pilot project with Brazil’s Fundação Oswaldo Cruz (Fiocruz). Under the terms of the agreement between the partners, Germfree will provide its modular facilities including hardware and digital platforms while Caring Cross will develop the therapies as well as workflows and manufacturing protocols. They’ll also train doctors and healthcare organizations to produce the therapies. Germfree will also install a unit at the Ohio State University that will be responsible for piloting all the processes that will be implemented at the Fiocruz unit.
At its core, the partnership is about enabling accessibility and affordability for a broad swathe of patients. CAR T-cell therapies currently start at $350,000, with some patient-specific treatments exceeding $3 million. That price point puts them squarely out of reach for most patients who need them. And costs for treatment will likely continue to rise as the field expands into new indications.
Both Houts and Boro Dropulić, executive director and co-founder of Caring Cross, believe decentralizing manufacturing is key to bringing those costs down. Dropulić has had a long and impressive career in the gene therapy space that includes founding Lentigen, a lentiviral vector manufacturing company, which was responsible for putting the first lentiviral vector into human clinical trials and establishing safety for lentiviral vectors. Now at Caring Cross, he is part of a team, many of whom have worked in the cell and gene therapy field for decades, that is working on “new models for affordability and access.”
Many of the people involved in Caring Cross have worked in the cell and gene therapy field for decades and understand how to make all of the different components as well as how to lower the costs of making the therapies. At Caring Cross, “our mission is to enable hospitals and other organizations to make CAR T and other cellular gene therapies locally, for at least a tenth of the price,” Dropulić told GEN.
Manufacturing the treatments locally is critical for keeping those costs down, which is why the collaboration between Caring Cross and Germfree is crucial. Germfree offers multiple versions of its cleanrooms that can be tailored for different manufacturing needs. The smallest option is also its mobile offering which offers about 400 square feet of space. It features a fully functional, CGMP-compliant cleanroom housed in a 53-foot tractor trailer complete with biosafety cabinets, laminar flow hoods, and other equipment required for manufacturing.
Other options are considerably larger—some are over 700 square feet—and can house more equipment. Multiple units can also be combined to create larger facilities. Germfree can also ensure that its cleanrooms meet the GMP requirements for Grade B facilities. Mobile platforms can be production-ready in 1–2 months while large units take about seven or months. All cleanrooms undergo rigorous testing and validation to ensure that the space is fully operational and meets the necessary CGMP requirements before manufacturing begins. Germfree offers both leasing and purchase options for their units.
“There are many advantages with point-of-care manufacturing,” Dropulić said. With these units, “we can reduce the cost tenfold by using a very simple manufacturing process” that is “much more economical in terms of the labor footprint and shipping logistics,” he said. Besides costs, the product is manufactured within seven days and can be produced fresh with a higher quality. Manufacturing locally also avoids potential shipping delays and other issues that can delay therapy for patients.
Local manufacturing is one avenue for lowering CGT costs but it’s not the only one Caring Cross is pursuing. The nonprofit also accomplishes this goal through transferring technology. They currently have a collaboration with Fiocruz, sponsored by the Brazilian Ministry of Health that involves transferring the technology for making vectors. They’ll also provide a pipeline of candidates and products that can be manufactured at a price point of $35,000 per dose and provided to patients in the Brazilian public health system at no cost.
If all goes well, the plan is to duplicate this model in various contexts including remote, underserved parts of the world. And Germfree is designing the unit that will be installed in Brazil with that goal in mind. The company is also looking at implementing its modular units near hospitals, clinical centers, and research centers in the United States as well. “I don’t think we’ll be limited to just CAR T there,” Houts said, noting that Germfree also hopes to build cleanrooms for manufacturing other kinds of therapies for cancer and other conditions. “We’re exploring other cell types, and the need in regenerative medicine is strong so I think we’ll be tackling a number of these things as we move forward.”
Meanwhile, the regulatory guidance around decentralized manufacturing is still evolving and there are still conversations to be had around topics such as licensing and managing regulatory compliance in a decentralized manufacturing model, Houts said. However, regulators are open to those discussions and fully engaged in the dialogue. “I’ve worked in the industry a long time. I’m seeing them lean in more than I ever have,” she said.
For its part, Caring Cross is working on partnerships with groups in countries like South Africa, Uganda, and Tanzania as well as collaborations with countries in Asia all with an eye toward improving accessibility to needed cell and gene therapies. The nonprofit is involved in various projects including a clinical trial for a CAR T therapy for HIV as well as a treatment for sickle cell disease and beta-thalassemia. It has also spun out a for-profit contract and development manufacturing company called Vector BioMed to produce high-quality GMP lentiviral vectors at a reduced cost for low- and middle-income countries.
