The objectives of the Core are to enable large-scale production of helper-dependent adenoviral (HD-Ad) vectors for testing in small animals and nonhuman primates, and to provide expert technical support related to virus production. The Core will function as a shared resource among the projects of this program project, and is necessary due to the high cost of infrastructure, and to provide the expertise necessary to produce a large quantity of HD-Ad vectors. The physical characteristics of the facility will help assure the production of high quality vectors. These include the design of cell culture rooms, biosafety hoods, and physical separation of high titer virus from low titer virus during production phase. All equipment and supplies used at the facility will be approved for the production of biologicals used in pre-clinical studies. This includes certification by suppliers, quality assurance by the facility, and standard operating procedures (SOPs) for the receipt, inventory, expiration, and disposal of all material. All operations and procedures in the laboratory will be governed by SOPs. The Core will be responsible for the production of Master Cell Banks, Working Cell Banks, Master Helper-Virus Stocks, Working Helper-Virus Stocks, Master Vector Seeds, and Working Vector Seeds necessary for the production of the vectors under controlled conditions to allow for their use in laboratory animals and in pre-clinical studies. One of the major problems of HD-Ad vectors for clinical use is that of vector production capacity. The Core will be responsible to the development of methods for production of high quality HD-Ad vectors (<0.5% helper virus contamination) with high yield. The Core will exercise tight quality control to ensure the safety of end product materials, and to ensure the safety of the personnel involved in the production of the vectors. This will involve detailed record keeping, in-house quality assurance and the oversight of quality control tests. The operational director of the laboratory will be responsible for personnel training and compliance with all requirements for adenovirus production.
