Im attending annual IBC Cell Therapy Bioprocessing meeting. It is probably the best meeting for cell product manufacturers and developers. You can follow the real time updates via hashtag #IBC_CTB13. This year, iPS cell manufacturing session was added to the program for the first time. And it has been very interesting and informative. Scott Lipnick from the New York Stem Cell Foundation Research Institute (NYSCF) and Wen Bo Wang from Cellular Dynamics International, share their experience in iPS cell manufacturing approaches and automation of the process.

Are iPS cells ready for prime time? Yes, as research tools and disease models. Not quite yet for human therapies. NYSCF is non-profit organization with ~ 45 researchers, which focused on high-risk high-reward experiments in iPS cell field. NYSCF builds infrastructure to industrialize SC research. This is one of the first organizations, which applied automation in iPS cell manufacturing. Bringing automation in iPSC cell derivation and differentiation would allow to tackle standardization and scalability issues. NYSCF approaches this problem by high-throughput platform Global Stem Cell Array.

Lipnick told that they were able to create automated assembly line with only 2 manual steps left skin biopsy and seeding in the dish. The production rate is 200 lines / per month. The whole process is traceable and recorded as a batch record. Besides iPS cell lines generation, NYSCF is also working on automation of differentiation process. For example, beta-cells production and DOPA+ neurons. They are also looking into GMP manufacturing.

Wang of CDI gave an example of their current commercial production capacity per day: 2B (billions) of iPS cells, 1B icardiomyocytes, 1B ineurons, 0.5B iendothelial, 0.4B ihepatocytes. Two more products will be launched next year. She described how CDI changed research process to make it automated and clinical-grade.

Potential challenges in scaling out of autologous iPS line production that she has mentioned: choice of starting material, footprint-free (no transgene) lines, undefined components, spontaneous differentiation, abnormal karyotype, asynchronous growth, batch record/ information review. They decided to use blood as source material, because less risk of contamination and possibility of closed system. Optimization of source material allowed them to move from 0.5L of blood to few ml. of fresh blood. They expand mononuclear cells and freeze them down for scheduled manufacturing. CDI manufactures iPS cell lines by batches. Episomal vector used to generate footprint-free lines. In order to pick right colonies, they dilute 1 clone/ well in 96-well plate. Only 2 steps left non-automated in CDI process: transfection and colony picking.

Characterization of the line includes: morphology, markers, SNP (genotype), ID match, loss of reprogramming plasmid, karyotype, mycoplasma. They used robotic streamline of qPCR 39 genes for quality control. For creation of GMP lines, they changed a process: use of GMP-grade plasmid, reprogramming by small molecules, recombinant feeder-mimetic (ECM), antibiotic-free, xeno-free medium. Finally, CDI has started a HLA-matched iPS cell line banking project. Phase 2 of the project will utilize 200 donors and can cover 90% of US and EU population.

One question from the audience was very interesting: Dont you think, HLA iPS cell banking is racing ahead of science and realization of its usefulness? Wang said: Well, we dont know how useful they will be, we just want to show we can do it!

Tagged as: automation, cell line, conference, IBC, iPS, manufacturing

See the article here:
IBC Cell Therapy Bioprocessing 2013 moving to iPS cell ...

Comments are closed.