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.