Adjunct Professor (In Memoriam)
Department of Chemical Engineering
- B.S. (Chemical Engineering) Massachusetts Institute of Technology, 1994
- B.S. (Humanities/Music) Massachusetts Institute of Technology, 1994
- M.S. (Chemical Engineering) Georgia Institute of Technology, 1996
- Certificate (Management of Technology) Ivan Allen College of Management Georgia Institute of Technology, 1996
- Ph.D. (Chemical Engineering) Georgia Institute of Technology, 1999
- Mammalian cell culture process development
- Media development
- Recombinant protein production
Today’s biopharmaceutical market requires manufacturing processes that are flexible, robust, cost-efficient, and deliver consistent product quality. A process that is capable of producing large amounts of the product quickly is valuable not only for preclinical and early-phase clinical material generation it also has great advantages in late-clinical and commercial manufacturing arena.
PER.C6® cells is a human cell line that has been used for years for production of vaccines. In the past few years, however, this cell line has become a popular platform for the production of recombinant proteins and monoclonal antibodies as well.
Our research areas are focused on improving the yields of recombinant proteins by combination of PER.C6® cell line genetics and cell culture medium optimization, development of best practices to produce recombinant proteins in cell culture as well as state-of-the-art recovery and purification procedures that minimize production costs. All of this work is supported by a vast array of analytical tools to ensure proper quality of the proteins being developed.
One of the key advantages of the PER.C6® technology is the high performance of its platform production process. An ongoing area of development is in the continuing improvement of this baseline batch and fed-batch processes for material generation in support of pre-clinical and clinical research.
Some of the key features of the platform batch and fed-batch production processes include:
- High performance – PER.C6® cells may be cultured to very high concentrations in batch and fed-batch cultures. Viable cell concentration (Xv) > 12 X 106 cells/mL in batch and > 25 X 106 cells/mL in fed-batch are typically achieved (Figure 1). With these high cell concentrations, integral viable cell (IVC) of over 100 billion cell days per liter (bcdl) in batch and over 300 bcdl in fed-batch systems are routinely achieved. This translates to productivities of ~ 2 g/L in batch and ~ 8 g/L in fed-batch with clones whose productivities average less than 30 picograms/cell/day (pcd)
- Safety – all the media and supplements used in batch and fed-batch processes are animal-derived component free and chemically defined.
- Easy implementation – the processes are designed to be easy to implement in most mammalian cell culture labs and manufacturing plants. The processes are simplified to require minimal operator intervention and should be easily recognizable to scientists and operators familiar with standard mammalian cell culture techniques and practices
XDTM Production Process
The XDTM process takes advantage of the PER.C6® cell’s inherent ability to withstand high shear and grow to very high concentrations. This process uses Refine’s Alternating Tangential Flow (ATF) system to perfuse fresh medium through the bioreactor and remove metabolic by-products while retaining the cells. The result is a process in which PER.C6® cells may be cultured to extreme densities and very high product concentration.
The features of the XDTM process include the following:
- Extreme cell concentrations – by continuously perfusing in fresh nutrients and removing metabolic by-products, PER.C6® cells are kept growing exponentially throughout the process. Typically viable cell concentration of 100 – 150 X 106 cells/mL is normally achieved in ~ 2 weeks
- Extreme productivity – Typical process IVC is ~ 500 bcdl in two weeks. This means, with a cell line of typical productivity (30 pcd), product concentration of 10 – 15 g/L may be routinely achieved. With a typical high-producing PER.C6® clone (40 – 50 pcd), reproducibly productivity of over 27 g/L have been reported.
- Consistency – continuous perfusion of fresh medium and removal of metabolic byproducts means the cells are kept in a relatively constant environment throughout the process. This results in more consistent product quality profile and culture performance may be easily predicted using a relatively straight-forward simulation model
Dr. John Chon was the Director of Upstream Process Development with PERCIVIA, PER.C6® Development Center. Prior to joining PERCIVIA, he was a Process Engineering Manager for BioEngineering and Gene Therapy Development groups at Genzyme, where he has led numerous cell culture projects for the development of processes for the production of recombinant enzymes, antibodies, and viruses. He was also the Manager of Cell Culture, Technology group at Genzyme Flanders in Geel, Belgium, where he established a new Cell Culture Technology Group responsible for process development, tech transfer and technical support of the 10,000L manufacturing plant.