Department of Gene and Cell Medicine
Department Shared FacilitiesVector Core and GMP Production FacilityDirected by Marcia Meseck, J.D., M.Sc., the Vector Core and GMP (Good Manufacturing Practices) Production Facility was designed for multi-use purpose use and plays a central role at the Department of Gene and Cell Medicine. Since completion of the facility in April 2000, the Vector Core has provided research grade and clinical grade recombinant viral vectors to support the investigative efforts of the Department of Gene and Cell Medicine, as well as its collaborators and other investigators at the Mount Sinai School of Medicine. Vector production services are also available to outside clients, on a fee-for-service basis. The Vector Core maximizes quality and cost effectiveness by concentrating vector rescue and production efforts in a Core Facility with an expert technical staff, which performs these procedures on a routine basis. Centralization of these functions also allows for methodologies to be optimized while consistently producing high quality recombinant vectors for all investigators. Individual investigators will no longer need to import recombinant plasmids and cells, or master techniques and procedures necessary for rescuing and producing recombinant viral vectors. This will enable investigators to focus their efforts on doing actual research in their areas of expertise rather than producing recombinant viral vectors for their research. To date, the Vector Core has primarily served the faculty of the Institute for Gene Therapy and Molecular Medicine and their collaborators. It is anticipated that Core usage by other interested Mount Sinai faculty will dramatically increase enabling the Vector Core to provide its services to all investigators at a substantially reduced cost, thus encouraging the broader application of gene transfer vectors in the study of cancer and other areas of research. The facility is comprised of a Class 100,000 area with a Class 10,000 clean-room area immediately adjoining it. The Class 100,000 area, which is primarily used for the production and quality control testing of research grade viral vectors, has two tissue culture rooms, storage areas, and a general laboratory for performing preclinical production and quality control functions, such as, testing, receipt, and storage of raw materials and final product. The Class 10,000 GMP production area has five self-contained tissue culture suites that allow for the concurrent production of up to five different vectors. Two additional self-contained production suites under temperature control are suitable for adaptation to scale-up procedures. Many features have been incorporated into the design of this facility to minimize the risk of cross-contamination between products, including unidirectional traffic flow, individual airlocks to each production suite, single-pass HEPA filtered supply air, 100 percent exhaust from the biological safety cabinets through dedicated ducts, to name a few. Large-scale production of recombinant viral vectors for use in clinical trials is performed using the current good manufacturing practice (cGMP) for methods and facilities that are set forth in the U.S. Code of Federal Regulations. These practices are necessary to assure that such vectors meet the safety requirements of the Federal Food, Drug, and Cosmetics Act. LocationThe GMP Production Facility is entered through Room 17-290, on the 17th floor of the Annenberg building, in close proximity to many of the laboratories performing basic, translational, and clinical research. Vector Core Production Facility ServicesThe Vector Core staff provides scientific advice to investigators regarding the advantages and limitations of the individual vector system that best suits their investigative needs. This will enable investigators to select the most appropriate vector systems for their respective studies based on scientific information and technical expertise. Specific Functions of the Vector Core Facility
All vectors produced for preclinical studies will be tested for mycoplasma and endotoxin contamination, as well as viral particle, and infectious unit titer. Vector preparations to be used for Phase I and II clinical trials will be certified by an independent, FDA-certified, testing facility. The Director of the GMP Production Facility will also act as the liaison with the FDA for regulatory release of all clinical grade vectors produced by the Core in support of clinical trials.
Facility SpecificationsThe facility is designed for unidirectional traffic flow with a Class 100,000 area leading directly to a Class 10,000 clean-room area. The floor to the entry airlock is surfaced with Dycem flooring to minimize contamination from outside particulate material. The walls, ceilings, and floors throughout the remainder of the clean-room facility are coated with a chemically resistant epoxy resin. The junctions of the floor and ceiling to the walls are covered in such a way that 90° angles are eliminated, minimizing areas where environmental contaminants may become trapped. The walls, floors, and ceilings of the entire clean-room facility are cleaned weekly with alternating virucidal and microbicidal cleaning agents. The Class 100,000 area of the Facility has two individual tissue culture rooms for the simultaneous maintenance of clean cells and production of a variety of vectors, primarily adenoviral- and lentiviral-based. Each tissue culture room contains a biological safety cabinet, CO2 incubators, and a microscope. There is a general wet lab area for large-scale plasmid preps and quality control assays not requiring containment within a biological safety cabinet. The general equipment area contains an ultracentrifuge, a high-speed centrifuge, a fume hood, and a shaker incubator. There is also a locked, limited access liquid nitrogen freezer, for the storage of cryopreserved cell lines. The Class 10,000 area of the Facility has five production suites that are independently air-controlled and accessed through individual air locks. All of the doors within the facility are magnetically interlocked so that both doors to an airlock cannot be opened simultaneously. Environmental cold and warm rooms that are independently airlocked are available for future adaptation to production using bioreactors and large-scale purification processes. Each suite contains a six-foot biological safety cabinet, a microscope, and two stacking incubators. A separate tissue culture suite within the facility is set up for pancreatic islet isolation. It contains two biological safety cabinets, CO2 incubators, a high-speed centrifuge, a COBE cell processor, microscope, and water bath. Depending on availability, investigators in the New York metropolitan area can rent this suite for pancreatic islet isolations. Additional suites can be rented for clinical trials utilizing cell-based therapies that require cGMP clean-room facilities. A building management system, installed and maintained by Johnson Controls, monitors the alarm status of all equipment within the facility at all times. There are two monitoring stations, one in the Vector Core Production Facility and the other in the engineering department. An alarm triggers a warning signal that beeps at the monitoring station until the alarm is addressed. The monitoring station in the engineering department is manned 24 hours a day and the engineer on duty has a list of emergency after-hours contact numbers. Request FormsVector Core Service Request |