Description of Research Program

The goal of the Vaccine Production Program (VPP) Laboratory is to efficiently translate candidate research vaccines into materials for proof of concept clinical trials and enable advanced development and licensure by partners. The VPP is responsible for the manufacture, pre-clinical safety testing, and regulatory strategy for VRC vaccines. This program utilizes laboratory facilities at the VRC, collaborations with industry, and a cGMP Vaccine Pilot Plant to accomplish this goal. Since its inception in 2001, the VPP has overseen the manufacture of over 29 bulk pharmaceutical compounds formulated into 14 different vaccine products. These products include candidate vaccine for HIV, Ebola, SARS, and West Nile Virus (WNV).

The Vaccine Production Laboratory, located in Bethesda, MD, includes fermentation, cell culture, purification, and analytical development facilities. The laboratory focuses on process research, including development of novel viral vectors, viral vector formulation, DNA vaccine delivery, and manufacturing process research. The analytical development group focuses on development of potency assays for candidate vaccines. These have included assays for candidate HIV, Ebola, SARS, and WNV vaccines.

The Vaccine Clinical Materials Program (VCMP) is responsible for cGMP manufacturing. The VCMP (operated by SAIC-Frederick) manufactures candidate vaccines utilizing contracts with the biopharmaceutical industry as well as the Vaccine Pilot Plant. The Vaccine Pilot Plant is a SAIC-F leased and operated cGMP pilot plant that will be completed in 2005, and is located in Frederick, MD.

The overall size of the Vaccine Pilot Plant is 126,900 square feet. There are four independent production trains whose scale of operation is defined by the largest reactor in the train. Two trains operate at 100 Liter scale, one train at 400 Liter scale, and one train at 2,000 Liter scale. There is a central inoculum preparation suite. A media/buffer preparation suite provides for internal manufacture of all solutions for the operation. The fill suite is easily accessible from the production trains and will have the capability of performing smaller scale lots up to 5,000 units and larger scale work up to 30,000 units. The warehouse is sized to handle raw materials and supplies sufficient to maintain all four production trains operating simultaneously with coordination and control through the adjacent dispensary. The quality control laboratories are designed to provide all necessary testing activities including raw materials, environmental monitoring, bioburden, water for injection and pure steam analysis, bulk and final product sterility, and in-process and final product release. The Quality Assurance department of the VCMP is responsible for oversight of cGMP manufacture including validation, compliance, lot release, and document control.

The regulatory science group within the Vaccine Production Program is responsible for the pre-clinical safety testing of candidate vaccines. The group works proactively with VRC investigators to develop regulatory strategies that safely and efficiently move products into clinical trials. The group has completed multiple repeat-dose toxicity protocols as well as the necessary biodistribution and integration analysis for candidate DNA and recombinant adenovirus based vaccines. The results of these studies, along with the animal efficacy/immunogencity results, manufacturing information, and clinical protocols are compiled into Investigatory New Drug applications (INDs). The regulatory group has assembled more than ten INDs since 2001.

The Vaccine Production Program currently has Collaborative Research and Development Agreements (CRADAs) with multiple partners for the further development of VRC vaccines against HIV, Ebola, West Nile Virus, and SARS. CRADA partners include Vical, GenVec, Chiron, and Crucell.

The divisions of the Vaccine Production Program are staffed with personnel with extensive industry experience, giving the operation many of the attributes of a classic drug development organization well suited to supporting the mission of the Vaccine Research Center