The New State-of-the-Art Stem Cell Research Facility at UC Davis: an Interview with Austrian Lab Director Gerhard Bauer

bridges vol. 11, September 2006 / News from the Network
by Caroline Adenberger

 

UC Davis is currently in the process of renovating approximately 100,000 square feet of space in a building on Stockton Boulevard, part of the UC Davis Health System campus in Sacramento. The complex will be the home of the new state-of-the-art stem cell research facility of UC Davis.

After completion, the facility will include custom-designed testing and manufacturing laboratories that meet the strict US Food and Drug Administration requirements and are certified for Good Manufacturing Practice (GMP).

Since very few universities have their own GMP labs, this new facility might become an irresistible incentive for scientists as well as students and research partners to participate in the new stem cell research programs at UC Davis.


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bauer_gerhardProf. Gerhard Bauer, a native Austrian who studied medicine at the Vienna University Medical School, has been recruited to head the program's specialized cell and gene therapy laboratory. He hails from Washington University's Siteman Cancer Center, in St. Louis, MO, where he has been since 2002. There, his main focus was working on clinical applications of cellular therapies, particularly gene therapies, which can be used to improve medical outcomes for cancer and other disorders.

bridges spoke with Gerhard Bauer on his new appointment and the challenges of UC Davis' new stem cell research program:


bridges: As of September 1, you will be heading the UC Davis' newly established stem cell laboratory as lab director, and you will also be a member of the faculty as professor of medicine and cell biology. How do you plan to juggle these two appointments?

Gerhard Bauer: In my past position as the GMP director at Washington University, I also juggled several positions in one; not only did I design the GMP laboratory and made it operational, I wrote, for other investigators, Investigational New Drug Protocols (IND) for products to be manufactured in the GMP facility, and taught courses for nurses and nurse coordinators and lay people about Good Manufacturing Practice. I also was a member of the Institutional Review Board (IRB) and the Institutional Biosafety Committee (IBC) with many protocols to review on an ongoing basis. Based on my previous experience, I am confident that I will be able to help establish an excellent educational program, which is part of my faculty appointment at UC Davis; and I will again design, help construct, and make operational a state-of-the-art GMP facility, improved over my previous one.

bridges: Would you please describe, in layman's terms, the nature and goals of a typical "current Good Manufacturing Practice" (cGMP) facility at a university?

Gerhard Bauer: A Good Manufacturing Practice (GMP) facility is an ultra-clean, controlled environment where potent biological, cellular, or other pharmaceutical products for administration into humans can be manufactured safely and reliably. "Current" means that the most recent standards are being applied. In the past, GMP laboratories were mainly used in large pharmaceutical companies for the production of intravenous preparations. With the onset of cellular therapies which use blood and other body cells and highly manipulate them, typically carried out in academic centers, these manipulations have to be undertaken in GMP labs. Such laboratories have controlled, hepa-filtered airflow with as few contaminating particles as possible per cubic foot of air; high numbers of air changes per hour; and constant temperature and humidity. They also separate manufacturing areas from entry and exit areas by air-pressure gradients, so that no contaminants can enter via air turbulence. Regular cleaning cycles of the lab have to be established, and a stringent Quality Control and Quality Assurance Program needs to be present. All environmental parameters and equipment in the facility have to be constantly monitored, and logs must be kept. Of course, the cleanliness of the room and absence of bacteria and other contaminating microorganisms have to be controlled as well. This is done by the use of indicator plates, which are petri dishes that favor the growth of microorganisms, if present. The indicator plates are exposed to room air, and also pressed against surfaces like tables and walls. In my facility at Washington University, over the last three years, we never saw growth of microorganisms in our indicator plates. This certified the perfect working condition of the GMP facility.

bridges: From 2002 to present, you've been the laboratory director of the GMP lab - a 2,615-square-foot facility in the Division of Oncology - at the Washington University School of Medicine. The new facility at UC Davis is about 100,000 square feet, with a GMP lab of about 5,000 square feet. What kinds of changes - and challenges - do you expect in managing a lab of this size?

Gerhard Bauer: The total space of the stem cell center will be 100,000 square feet. We are planning several phases of expansion. The initial GMP laboratory within the stem cell center will be about 5,000 square feet, something quite manageable within an academic center and in the start-up phase of the program. The challenges will be similar to those that I have already experienced at Washington University. In the future, with increased funding and hopefully several successful human stem cell applications, we will add to the existing expansion.

bridges: What is the operating budget of the lab, and where do the funds come from? How many people will be working there, and what are the main foci in research?

Gerhard Bauer: Currently, the university provides the funding for the expansion. We have already submitted grants for state funding, and several other grant applications are in the works currently. We are expecting to have a GMP lab with five or six staff members, and we are also hoping to attract students, postdocs, and fellows who will be part of the new graduate program in Stem Cell Biology that the University of California at Davis is currently developing.

bridges: You're also in charge of overseeing the whole lab design of the new Stockton Boulevard Laboratory. Based on your experience, what are the "dos and don'ts" in designing a cGMP lab? Is sustainable design, like the Labs21 initiative, an integral part of the designing process?

Gerhard Bauer: A GMP laboratory in an academic center has to be extremely versatile, that means several different products will be manufactured, most likely, at the same time. For instance, new skin for burn victims can be grown in one part of the laboratory, while genetically modified bone marrow stem cells to correct an innate disease in children will be generated in another part of the facility. Also, one would not want to bring the finished products out where the starting products are delivered. The facility should therefore be divided into several completely separated manufacturing laboratories, and should facilitate "one way product and personnel flow" - which means the starting product enters at one part of the facility, gets manipulated in a dedicated manufacturing area, and then is brought out at the other end of the facility to be taken to the clinic. I have found that six manufacturing labs within such a facility are excellent for an academic center.

In addition, to avoid contamination, no maintenance of the facility should be performed from the inside of the lab. Therefore, in my design, all mechanical and electrical equipment (air-handlers, monitoring equipment, and even lights) are being serviced from a walkable ceiling above the laboratory. In the last three years, this design has really paid off in the lab at Washington University. Unfortunately, the Labs21 initiative cannot be easily accomplished in a GMP lab. Although air-handlers, heating and cooling systems, with high efficiency can be used to reduce the overall power consumption, the lab airflow has to be on 24 hours a day, as does the monitoring system. You can easily imagine that safety and reproducibility is paramount for a product manufactured in such a facility and administered to often gravely ill patients.

bridges: "Taking research from the laboratory bench to the patient's bedside" is the acclaimed motto of UC Davis. By your count, how long might it take before the first results of human (embryonic) stem cell research can be applied successfully in patient treatment and care?

Gerhard Bauer: We sincerely hope that within two years, the GMP facility will be completed and made operational, using adult stem cells in trials that have been in the process of development for the past several years. During these two years, Dr. Jan Nolta, the program director, will continue to drive translational research in her own laboratory and in those of other members of the stem cell program, comparing adult to embryonic stem cell technologies. This will give us an opportunity to develop applications with adult stem cells that could be used in Phase I and II clinical trials upon completion of the GMP construction phase; and if the comparative research using the embryonic stem cells is successful, hopefully these could be applied within several years after that. Dr. Nolta and I have a good amount of experience in translating basic research into the clinic. In the laboratory of Dr. Donald Kohn at Children's Hospital Los Angeles our group pioneered clinical trials of gene therapy into bone marrow stem cells of children and adults.

bridges: California, with its "Proposition 71," is one of the most progressive states in the US when it comes to embryonic stem cell research. In your opinion, will California be one of the pioneering or rather one of the exceptional states in the coming years when it comes to stem cell regulation? How do you feel about the US federal stem cell research legislation?

Gerhard Bauer: I strongly believe that California will be a pioneer in embryonic stem cell research. Working in California, we will have a unique opportunity to demonstrate that such stem cells do hold the true potential to regenerate tissue and to cure diseases that cannot be cured using any other means.

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Caroline Adenberger is assistant editor for 'bridges' at the Office of Science & Technology at the Embassy of Austria in Washington, DC.

 

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