Making cell- or virus-based therapies for use in humans requires a rigid set of quality-control standards outlined by the Food and Drug Administration. A new Stanford facility will allow promising new therapies to be tested in the clinic.
September 6, 2016 - By Krista Conger, Christopher Vaughan
Set back from the street, the building on California Avenue, in Palo Alto, looks like what you might see on Stanford’s main quad — with pale, beige stucco walls, a series of arched windows framed by columns and a red tile roof. In a former life it was the Stanford Genome Technology Center; now it’s found a new purpose as Stanford’s Laboratory for Cell and Gene Medicine.
With clean rooms and all the regulatory clearances necessary to safely make cell-based therapies for use in human patients, the lab will create new opportunities for research and to facilitate advances in patient care.
The lab will formally mark its opening today with an open house.
The laboratory is Stanford’s first dedicated facility to comply with the Food and Drug Administration’s current good manufacturing practices. These are standards the agency uses to ensure safety and consistency in medical therapies intended for use in humans.
The lab is devoted to making biological materials for use in phase-1 and phase-2 clinical trials. Until now, Stanford researchers wishing to conduct clinical trials of cells or viruses had to arrange to have them manufactured at other sites around the country.
‘A vast pipeline’
“Stanford has a vast pipeline of potential cell and gene therapies that can now be realized without having to go off-site to make materials for testing,” said laboratory director David DiGiusto, PhD. “Our hospital and clinics are world-renowned, and we’ve seen an explosion in cell therapy. We’ve built a biologics manufacturing facility to support the translation of cell and gene therapy from the research lab to the clinic. The LCGM expands our capacity more than twofold and will help researchers and clinicians test potential therapies safely and more rapidly.”
These therapies include, among many others, purified blood stem cells to treat genetic diseases, immune cells engineered to attack cancers, and viruses equipped to replace faulty genes with healthy, functional copies in an attempt to treat conditions as diverse as severe combined immune deficiency, sickle cell anemia and a blistering skin disorder known as epidermolysis bullosa.
“The Laboratory for Cell and Gene Medicine is going to be a major force in our precision health revolution,” said Lloyd Minor, MD, dean of the School of Medicine. “Our hope is that stem cell and gene-based therapeutics will enable Stanford Medicine to not just manage illness but cure it decisively and keep people healthy over a lifetime.”
Maria Grazia Roncarolo, MD, a professor of pediatrics and of medicine and co-director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine, helps to lead the school’s efforts to translate basic scientific discoveries in the field of regenerative medicine into stem-cell and gene therapies. She said the new lab is an essential component of that effort.
“The LCGM will manufacture cell- and gene-based cures but also develop innovative technologies to make these therapies more accessible and available to all patients in need,” she said.
The roughly 25,000-square-foot building has been completely remodeled to include clean rooms with airlocks, poured floors that don’t have cracks that can harbor bacteria, and easily sanitized surfaces. It includes separate areas for cell processing and for the development of viral vectors designed to infiltrate human cells.
“Most of our rooms undergo 40 to 60 full changes of filtered air per hour, which is like turning over the whole volume of a room every minute,” said DiGiusto. “We use special, breathable culture bags rather than tissue culture flasks to grow cells, and we transfer liquids with pharmacy pumps rather than pipettes. Everything we do is conducted according to strict, written procedures.”
Current good manufacturing practices require a high degree of sterility, strict chain-of-custody protocol and practices to ensure consistency in products. One focus of the facility will be the generation of banks of induced pluripotent stem cells and other specialized tissues such as heart muscle cells, that are derived from stem cells. These cells can be used to test the effects of drugs in a “clinical trial in a dish” or potentially even used to repair tissues injured by disease or trauma.
“We test every product before it goes out the door,” said DiGiusto, who is also the director of stem cells and therapeutic operations at the laboratory. Other directors will oversee quality assurance, regulatory affairs and other aspects of the laboratory’s operations. “We have a high degree of control over all stages of manufacture, and every stage is documented according to federal law.”
In addition to manufacturing biological products, the laboratory will also serve as a kind of pharmacy to dispense cellular therapies that were made in other facilities compliant with current good manufacturing practices.
These therapies will be for Stanford patients, as well as for patients at collaborating institutions. “Unlike a typical pharmacy, we will wash, store and distribute cells, rather than drugs,” said DiGiusto. “This will ensure each patient receives the right product at the right dose and at the right time.”
Plans are also in place to support collaborations among researchers from Stanford and elsewhere. DiGiusto and his colleagues are working to be licensed by the state of California as a biological manufacturer so that materials made in the laboratory can be shipped across state lines. They will also file a facility master file with the FDA so that non-Stanford collaborators can receive approval to use the laboratory.
In the end, the lab’s activities will be driven by the needs of the Stanford community, DiGiusto said.
“This is very much a partnership with the faculty of the medical school,” he said. “We will have a formal process for project management and budgeting, and we are here to help them develop clinical trials. But the ideas of what to produce will come from them.”
About Stanford Medicine
Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu.