Today’s afternoon session on iPS Cell Industrialisation kicked off with a talk by Dr Thomas Fellner, Head of Business Development, Cell Therapy Development Services at Lonza, about the generation of clinical-grade iPSCs. Since the discovery of iPSCs by Yamanaka and co-workers, there has been much excitement about their potential, and several groups have been working on translating iPSCs to the clinic. In his talk, Dr Fellner focussed on manufacturing and turning iPSC generation into an economically and technically viable process.
The cost of generating a cGMP compliant iPSC line is significantly higher compared to the cost of a research grade iPSC line. The entire manufacturing process consists of five key steps: tissue acquisition, cell isolation, reprogramming, expansion and banking, and characterisation and testing. This is a lengthy process, taking 3 to 4 months per iPSC line generated, from tissue acquisition to a banked cell line. Further essential steps include ensuring informed consent and assessing donor eligibility. For Phase I/II clinical trials, iPSC production can still be a small-scale, manual and open process, but it must be robust, reproducible and cGMP compliant. When moving on to Phase III, however, processes must additionally be closed, scalable and ideally semi-automated.
The cGMP process for generating iPSC lines developed by Lonza uses the L7 Episomal Reprogramming kit. Though reprogramming efficiency is approximately 10-fold lower under defined conditions, the episomal reprogramming method was found to improve efficiency. Lonza also developed iPSC culture media which negates the need for daily media changes, leading to a reduction in labour costs.
Dr Fellner highlighted that with autologous therapies, cost of production will be allocated to one patient, whereas in the case of allogeneic therapies the cost can be split. Though Dr Fellner suggested that autologous iPSC therapies may not be economically viable at the moment, there is hope for automation to be used to address this issue.
Currently, Lonza has a contract with the National Institutes of Health (NIH) to produce clinical grade iPSC lines, and are looking to start cGMP manufacturing of master cell banks in June 2014.
Nathalie Moens for Total BioPharma at the World Stem Cell and Regenerative Medicine Congress