Following from our prior research to

Following from our prior research to derive new hESC lines under increasingly defined culture conditions (Fletcher et al., 2006) we sought to establish a facility within which our experience and evolving practice and reagents could be implemented to a GMP and professionally accredited standard. Here we describe the concurrent CT-99021 and specification of the resulting facility established in the form of a not-for-profit company Roslin Cells Ltd, whose operation from January 2006 to November 2011, yielded seventeen new hESC lines. These were established in the course of developing and implementing QA and GMP standards in a UK authority licensed and ISO:9001 accredited facility. In so doing we believe that we have generated 8 hESC lines which comply with the current EU and US guidance and regulation governing their suitability to be considered as source material for human application. Information provided herein complements further details of resource methodology and hESC line characterisation published in Stem Cell ResearchLab Resource format (De Sousa et al., 2009; De Sousa et al., 2016a, 2016b, 2016c, 2016d, 2016e, 2016f, 2016g, 2016h, 2016i, 2016j, 2016k, 2016l, 2016m, 2016n, 2016o, 2016p, 2016q). Cell line history files with associated protocols and records are available for auditing by prospective licensors and regulatory authorities under confidentiality agreement.
Methods
Results The overarching goals of the Roslin Cells programme were the development and implementation of quality assured operational management and construction of a GMP grade cell manufacturing facility centred on establishment of GMP compliant hESC derivation, expansion, cryopreservation and banking. In order to demonstrate compliance with appropriate standards, the facility was operated under ISO9001:2008 standards and licensure from the UK HFEA and HTA. In order to comply with these standards, it was necessary to compile a systematic and traceable documentation of all elements of operation from receipt of embryos until deposition of cell lines. In accordance with the concurrent development of governance and facility infrastructure, licensure, and methodology we consider that of the 17 hESC lines derived in the programme (Table 3), RC-9, 11–17 were derived to a quality assurance standard appropriate for their use as source material for clinical application. The essential attributes of these lines includes:
Discussion We describe here the development and implementation of an operation and facility in the form of a not-for-profit company, Roslin Cells Ltd, for the specific purpose of manufacturing clinical grade hESC lines for use in regenerative medicine. This yielded 17 hESC lines of which 8 lines (RC9, 11–17; De Sousa et al., 2016e, 2016f, 2016g, 2016h, 2016i, 2016j, 2016k, 2016d) are compliant with European Union (EU) directives and United Kingdom (UK) licensure for procurement, processing and storage of quality assured human cells as source material for clinical application. The production of these lines was targeted to comply with EU GMP specifications as can be confirmed through inspection of associated cell line history files and QMS controlled documentation. Our efforts were targeted to comply with an EU GMP grade specification. However, at the time of establishing seed banks, a site license from the UK MHRA for the manufacture of biologics for human application had not yet been obtained. Thus, the extent to which the lines satisfy EU GMP specifications requires retrospective inspection of cell line history files and archived QMS controlled records. Based on our understanding of EU (Table 1) directives, guidance and regulations associated with procurement, processing, non-clinical studies, and manufacture, we believe that the lines exceed specifications to serve as source material in the EU. A second generation facility established at the University of Edinburgh Scottish Centre for Regenerative Medicine has subsequently been licensed by the MHRA and the lines continue to be stored in an MHRA licensed facility. It is known that clinical trial authorisations have been granted for the manufacture of clinical products derived from cell lines which were prepared in facilities which were not operating to GMP standards. Although our first facility, in which hESC lines were derived, was not licensed by the MHRA at the time that the cell lines were manufactured, we believe that the data available would support future clinical trials and subsequent licensure of products derived from these cell lines.