br Results The Hot Start experience and outcomes were embodi

Results The Hot Start experience and outcomes were embodied in established and conceived infrastructure provided by its membership. This was both as originally proposed and subsequently informed and amended in the course of operational experience as follows.
Discussion The EBiSC Hot Start yielded a distributable resource of 27 pre-existing hiPSC lines constituting lines for which depositors had the greatest available data and working experience. As compared with EU registered lines, hiPSC in the Hot Start Collection also predominantly originated by reprogramming of fibroblasts by the canonical OKSM combination of neuronal nitric oxide synthase factors. However, the proportion of lines reflecting use of more modern technology and methods for hiPSC line derivation was greater in the collection than for lines on the registry across the spectrum of other modifiable parameters (i.e. media, matrices, passaging method, reprogramming vectors). Key lessons arising from the Hot Start experience included the following: Recently, guidelines prepared by the International Society for Stem Cell Research (ISSCR) for global standards for stem cell research and clinical translation in 2006 and updated in 2008 were updated further (see Commentary, Daley et al., 2016). Review of these to confirm complicity and alignment of hiPSC lines banked as part of EBiSC Hot Start launch verified that for the guidelines which were applicable (eg. procurement, processing and banking) EBiSC hiPSC lines either complied or enable compliance by third party users (Supplementary Fig. 12). This makes the EBiSC Hot Start collection and ongoing advances in infrastructure of broader global benefit to other small and large scale hiPSC derivation and banking initiatives.
Experimental Procedures
Contributions of authors PDS wrote paper, led work package establishing Hot Start hiPSC collection and operational Central Facility. RS, EW, KB, JK, MH, SK, GM, JH undertook operational execution of Hot Start, notably collation and review of donor informed consent (KB, SK, MH), liason with supplying centres (JK), labelling (KB, EW), cell line receipt, processing and testing (RS, EW), team management (KB, GM, JH). AK, SS lead management of Hot Start hiPSC line data. JD, SR analysed Hot Start hiPSC data. BH, MB, JD, RP Development of EBiSC Information management system and the cells.ebisc.org web catalogue. GS lead on specification of hiPSC Quality Control measures and development of partner training for Hot Start laboratory staff. OO\'S, CC, LH provision of QC testing (sterility & pluripotency assays), flow cytometry and delivering practical training for Hot Start laboratory staff. BB leads on work package for hiPSC storage and distribution and management of incorporation into existing ECACC business model. TR – IT delivery and manager of integration of EBiSC Hot Start collection and information management system with ECACC. IA – ECACC\'s website and marketing manager responsible for website scientific content as well as end user experience. IS, LC, HP, PWH, AF, LC, TB – Data management at EBiSC Central Facility. HZ leads on hiPSC mirror banking. AV, MS, BK, CT, TS, JH. OB, MP, NG, BH, CC, MLP, CL, ML, LA lead and delivery of hiPSC supply centre contributions. TA, SG, AK, RH, AJ, GB, AE, AC-S, PF, MG, TCS: specification of EFPIA requirements, validation of distributed hiPSC pipeline and quality control. OP, OK, PG, CC validation of ECACC distributed EBiSC Hot Start hiPSC using high content imaging. CG, SH, hiPSC legal governance. AR, BK, supported consortium building, recruitment of hiPSC centres, funding application, daily project management, design and provisions of communication and collaboration infrastructure and materials. PDS, GS, RS, EW, JK, AK, JD, SR contributed figures and associated text. All authors contributed review and revisions.
Acknowledgements EBiSC is supported as a multinational public-private Innovative Medicines Initiative (www.imi.europa.eu) funded by the European Commission and in kind contributions from Pfizer Ltd., H. Lundbeck A/S, Janssen Pharmaceutica NV, Novo Nordisk A/S, AstraZeneca A/B, UCB Pharma SA, and Bayer and Lilly (joining after the Hot Start). Mirror bank equipment and bioreactors for automated expansion were funded by Fraunhofer Society (Munich, Germany). UK Stem Cell Bank support was provided under phase IV funding from the Medical Research Council and the Biotechnology and Biological Sciences Research Council (United Kingdom).