ESTABLISHMENT OF A NATIONAL GENE VECTOR LABORATORY

Beckman Research Institute/City Of Hope, Duarte CA

Investigators

Abstract

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.