State the application's broad,TffTt|-term objectives and specific aims, making reference^Fthe health relatedness of the project. Describe concisely the research design and methods for achieving these goals. Avoid summaries of past accomplishments and the use of the first person. This description is meant to serve as a succinct and accurate description of the proposed work when separated from the application. If the application is funded, this description, as is, will become public information. Therefore, do not include proprietary/confidential information. DO NOT EXCEED THE SPACE PROVIDED. This application proposes the establishment of a dual-purpose NGVL """"""""vector production facility"""""""" at the Beckman Research Instituteof the City of Hope (COH). The facility will serve as the primary site for production of plasmid DNA- based vectors and, without additionalNGVL resources, provide back-up production capacity and capability for adenovirus based-vectors. The facility has produced FDA-reviewed plasmid material that has been used in human clinical studies and currently has three additionalplasmid products in production. The staff has significant experience and expertise in the production of cGMP-compliant biologies for human clinical use. The Director, Associate Director and QA Officer have backgrounds in the biotechnology industry with expertise in regulatory affairs, product and process development, manufacturing, quality systems and molecular biology, virology, hematology, cell biology and flow cytometry. Scale-up of current processes is under way with funding from the COH. The facility is operated in accordance with cGMP for production of phase I/I1 biologies and the various facility systems are subject to an implemented and ongoing Master Validation Plan. The COH's Center for Biomedicine and Genetics (CBG), where the proposed NGVL will be located, currently produces recombinant monoclonal antibodies, plasmid DNA, viral vectors and ex-vivo manipulated cell products. The CBG is a purpose-built, two-story 20,000 sq. ft. building on the COH campus with approximately 9,000 sq. ft. of classified manufacturing space. The remaining space includes the departmental offices. QC labs and facility systems. The CBG staff completely manages and operates this $12-milHon facility. The NGVL support requested here will provide the resources to produce up to 15 clinical grade plasmid products and associated master cell banks per year plus a capacity of up to 3-4 adenoviral vector products per year. The COH is currently funding the establishment of 293 master and working cell banks that will be made available for NGVL production activities. All activitieswithin the CBG are monitored and documented through a thorough Quality System according to cGMP. The CBG supports the translation of academic-based technologies into the clinical setting and has made a significant commitment to the facility to support the development and production of recombinant proteins, viral and non-viral vectors, vaccines and ex-vivo manipulated cell products for phase I/II clinical studies. PERFORMANCE SITE(S) (organization, city, state) Beckman Research Institute of the City of Hope 1450 East Duarte Road Duarte, CA 91010-3000 KEY PERSONNEL. See instructions on Page 11. Use continuation pages as neededto provide the required information in the format shown below. Name Organization Role on Project Larry A. Couture, Ph.D. Beckman Research Institute of COH Director - PI David L. DiGiusto, Ph.D. Beckman Research Institute of COH Associate Director - Co-Pi PHS 398 (Rev. 4/98) Page 2 BB Number pages consecutively at the botton throughout the application. Do not use suffixes such as 3a, 3b. CC Principal I^fcjgator/Program Director (Last, first, middle): Type the name of the principal investigator/program director at the top of each printed page and each^Pitinuation page. (For type specifications, see instructions on page 6.) RESEARCH GRANT
