The Raymond G. Perelman Center for Cellular and Molecular Therapeuticsat The Children's Hospital of Philadelphia has established a state-of-the-art cGMP clinical vector manufacturing suit for both adenoassociated and lentiviral vectors. The facility is under the direction of Han van der Loo, a leading expert in clinical vector production and characterization. Our goal is to help to realize the enormous promise of gene transfer therapy to address unmet medical needs.
The Clinical Vector Core provides manufacturing of clinical and pre-clinical Adeno-Associated Virus (AAV) vectors of serotypes 1, 2, 5, 6, 8, 9, and Lentivirus (LV) vectors. Novel or modified serotypes will require development prior to scale-up. Products for clinical use are manufactured in compliance with Current Good Manufacturing Practices (cGMP) for Phase 1 and 2 clinical trials. To support pre-clinical work, including pharmacology and toxicology studies, we offer products manufactured using a GMP-comparable process. Research-grade products for proof-of- principle and bridging studies are also offered.
The Core Facility uses a patented vector production technology and a highly efficient purification process that uses combined column and gradient centrifugation-based process steps. This system has manufactured clinical-grade AAV vectors that have demonstrated excellent safety in several clinical studies. We are also in the process of implementing GMP Lenti vector production.
Our production efficiency is achieved along with exceptionally high vector product quality. Our final product is highly purified, containing negligible amounts of impurities such as empty capsid. Prior to the final release of the clinical vectors, the vector product is subjected to numerous tests to ensure quality. We also provide federal regulatory documentation and necessary certifications.
Recently, the Clinical Vector Core has also installed Lenti viral vector production capacity. Drawing from both in-house and newly acquired expertise, our Lenti group has quickly implemented an efficient production process that can meet our collaborators' clinical protocol needs.
Our proven track record, consistency, high vector production capacity and world-class expertise have enabled us to achieve national recognition. We were awarded a prestigious five-year NHLBI contract to assist in vector design, cGMP manufacture, and certification of AAV vectors.
SDS-PAGE/Silver Stain and Cesium-chloride gradient centrifugation of Clinical Grade AAV-8
The Clinical Vector Core includes three dedicated ISO Class 7 manufacturing facilities for the production of AAV (GMP), AAV (GMP-comparable), and LV (GMP). Facility systems, manufacturing equipment, and aseptic fill & finish operations are validated.
Specialized manufacturing equipment includes units for Large and small-scale Tangential Flow Filtration (TFF), Microfluidizers, Chromatography units, Centrifuges and Ultracentrifuges, Biosafety Cabinets, Freezers and Refrigerators. Quality Control Laboratory includes equipment for incubation of Environmental Monitoring plates, Optical Density, pH, Conductivity, ELISA, Western Blot, Quantitative PCR, Digital PCR.
George LA, Sullivan SK, Giermasz A, Ducore J, Samuelson-Jones BJ, Cuker A, Sullivan LM, Majumdar S, Teitel J, McGuinn CE, Ragni MV, Luk AY, Hui D, Wright JF, Chen Y, Wachtel K, Galvao AM, Winters A, Galas T, van der Loo JCM, Zelenaia O, Takefman D, Carr ME, Couto LB, Anguela XM, High KA: Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant. New Engl J Med 377(23): 2215-2227, Dec 2017.