AKTA ready liquid chromatography system

Cincinnati Childrens Hosp Med Ctr, Cincinnati OH

Investigators

Abstract

DESCRIPTION (provided by applicant): Successful development and testing of novel therapies requires a translational "pipeline", and availability of facilities to process and manufacture clinical grade products in compliance with current Good Manufacturing Practices (cGMP). Cincinnati Children's Hospital Medical Center (CCHMC), a clinical and research institution of excellence, has developed a translational core laboratory that includes a pharmaceutical cleanroom facility for the manufacturing of viral vectors for phase I/II clinical trials in compliance with cGMP. Since its inception in 2006, the CCHMC Vector production Facility (VPF) has manufactured fourteen (14) cGMP products including master cell banks, a master viral bank, six (6) retroviral vector products in support of the FDA's National Toxicology Program (NTP), a retroviral vector for an international phase I trial for the treatment of X- linked Severe Combined Immune Deficiency (SCID), and three (3) Adeno-Associated Virus (AAV) vectors for the treatment of brain disorders for phase I and II clinical trials as well as a placebo control. In addition, the core has serviced 106 principal investigators with over 2,800 research-grade viral vector preps and has prepared over 1,000 vector preps in support of development of novel viral vector systems, including lentiviral vectors and foamy viral vectors. Finally, our group has established a track record of providing high quality "clinical-scale" molecular and cell processing services to investigators at various stages of Phase I/II clinical trial development. Recent work has shown that to be able to bring such new viral vector systems to clinic, more stringent closed-system purification methods are needed to be able to purify and highly concentrate viral vectors without increasing vector toxicity. This is particularly important for vector systems that require a high level of concentration due to low titer, such as lentiviral vectors encoding globin genes for the treatment of Sickle Cell Disease and 1-Thalassemia or foamy viral vectors for the treatment Leukocyte Adhesion Deficiency (LAD) as well as vectors that have traditionally been purified using liquid chromatography when prepared large-scale including AAV and oncolytic Herpes Simplex Virus (HSV). While a variety of chromatography systems is available that allow purification of viral vectors using anion-exchange and gel- filtration to separate viral vectors from contaminating bio-molecules such as plasmid DNA, cellular DNA, cellular proteins and to separate functional from empty viral particles, only very few systems have a closed system sanitary flow path that can be used for manufacturing of viral vectors in compliance with cGMP guidelines. The AKTAready was specifically designed for this application and is unique as compared to other systems on the market in that it eliminates the risk for cross-contamination through the use of a disposable flow path. This instrument will provide several NIH-funded investigators at CCHMC and elsewhere with highly purified viral vectors for clinical application. The award of this shared instrument grant will help bring unique and novel gene therapy approaches from bench to bedside for NIH funded academic researchers.