MADISON, Wis.--(BUSINESS WIRE)--The Waisman Clinical Biomanufacturing Facility (WCBF) at the University of Wisconsin-Madison, and Nature Technology Corporation (NTC) of Lincoln, Nebraska, today announced the implementation, at WCBF, of a high-yielding process for clinical manufacturing DNA vaccines and gene-based therapeutics. The process is scalable, from the laboratory bench to clinical trials and final product manufacturing.
“The combination of the highest-yielding fermentation process with a tested clinical-grade downstream purification process is a great starting point for the development of gene-based biologics,” said Jim Williams, NTC’s VP for R&D. The program is designed to give biomanufacturing clients a cost-effective way to make pharmaceutical grade DNA, which will carry through from animal studies to licensed product, without significant process changes.
The WCBF is a non-profit facility designed to assist clients in clinical trial biomanufacturing projects. NTC is a gene-based technology process and product developer.
In addition to continuity of process, highest yield results in improved economy, reduced waste, and higher purity due to the reduced cell mass, according to Aaron Carnes, NTC’s director of process development. Whereas a typical process yield is about 50-200mg of DNA/L, NTC’s process supports yields greater than 2g/L (1), antibiotic free fermentation, and the production of unstable or toxic DNA molecules.
“Switching either upstream (fermentation) or downstream (purification) processes, during the transition from preclinical to clinical to licensed product, would raise some thorny regulatory issues regarding bio-equivalence,” said John Keach, business development officer for Waisman. In a worst case scenario, Keach said it might be necessary to redo costly clinical trials, if major changes were introduced to the manufacturing process after human trials were successfully undertaken. Hence, it is important to maintain continuity during development.
“Unlike small molecule pharmaceutical manufacturing processes, biologics are subject to more subtle processing changes that could affect their activity and immunogenicity,” said Keach. Examples of such changes include modifications to DNA, such as methylation, mutations, and the degree of supercoiling, or twisting, which is imparted to the DNA molecules. In addition, biologics for use in humans are made at Waisman using animal product free procedures and reagents, to assure their purity and freedom from adventitious agents.
Despite potential vagaries, significant improvements in DNA manufacturing have helped to bring gene-based drugs to the forefront of clinical biopharmaceutical product development. “The potential to correct genetic defects, or to impart immunity via DNA vaccination, are tremendously promising advances that will require equally advanced manufacturing processes,” said Williams.
Although the first human DNA therapeutics and vaccines are still in clinical trials, several animal DNA vaccines have already been approved, and are in use, including a fish vaccine, an equine vaccination against west Nile virus, and a cancer vaccine against canine melanoma, according to Williams.
1) Carnes, AE, and Williams, JA, (2009) Low Metabolic Burden Plasmid Production. Gen. Eng. News 29:56-57.
2) Williams, J.A., Luke, J., Langtry, S., Anderson, S., Hodgson, C.P., and Carnes, A.E. (2009) Generic plasmid DNA production platform Incorporating low metabolic burden seed-stock and fed-batch fermentation processes. Biotechnol. Bioeng. (in press: DOI 10.1002/bit.22347).
3) Williams, J.A., Carnes, A.E., and Hodgson, C.P. (2009) Plasmid DNA vaccine vector design: Impact on efficacy, safety and upstream production, Biotechnol. Adv. (in press, doi:101016/j.biotechadv.2009.02.003).