A proposal to fund an activity to coordinate the stem cell banks distributing human embryonic stem cell lines to researchers was approved by the ISCF in January 2007 who awarded a maximum of $50,000 for a series of meetings which, as a major theme for the activity, would develop consensus on the requirements for banking and distribution of human stem cell lines for research purposes and those additional considerations for development of clinical grade cell banks. This initiative, called the ‘International Stem Cell Banking Initiative’ (ISCBI), held its first meeting in Bar Harbor in October 2007 to identify the key elements of a consensus document on best practice for the banking, characterisation and testing of human embryonic stem cells (hESCs) for research purposes. A set of web pages were developed for this initiative on the ISCF website ISCBI (www.stemcellforum.org) which included details of the ISCBI meetings and a registry of national stem cell banks. In addition, the draft consensus document on hESC banking which was put up on the website for consultation in February 2008. Subsequent meetings of the ISCBI have further developed this document for publication and have moved to evaluate the challenging considerations for the establishment of banks of human stem cell lines for clinical use. This report outlines the progress since the last ISCF meeting report from ISCBI in February 2008.
ISCBI Coordination Meetings in 2008
Since the 2008 ISCF meeting in California, two formal meetings of the ISCBI were held and there have been numerous teleconference calls and meetings of working groups. These meetings have attracted contributors from more than 17 countries and additional organisations such as the ISCF Ethics Working Party, the International Society for Stem Cell Research, the Stem cell Network Asia Pacific and the International Society for Cell Therapy (see list of delegates in appendix 1).
The first of these meetings was held in Beijing in collaboration with Professors Qi Zhou (Chinese Academy of Sciences, Beijing) and Fanyi Zeng (Shanghai Institute for medical Genetics). This meeting coordinated progress on the development of the international consensus guidance on banking testing and supply of stem cell lines for research purposes, but also started the process of addressing the additional requirements for the establishment of banks of stem cell lines intended for use in humans. The meeting schedule (appendix 2) incorporated discussions on donor selection and traceability, risk mitigation for media and other critical reagents, microbiological testing, tumorigencity, quality assurance, and international distribution. Dr Tim Dyke of NHMRC recorded the meeting and detailed notes are given in appendix 3. The activity of the meeting included discussions with representatives of the US FDA and WHO. At the Beijing meeting seven working groups, with associated lead contributors, were identified to take forward a number of the aspects requiring more detailed discussion and development. These working groups are as follows:
1. Quality Assurance definitions. Contributors P Carter, J Crook, K Rajala (Lead),
2. Review of current lists for adventitious agents testing in use. Contributors D Hei, J Crook
3. Requirements for stem cells as manufacturing cell substrates. Contributors A Choo, S Oh (lead), G Stacey
4. Points to consider in the cryopreservation of clinical grade cells. Contributors J Crook, C Hunt (Lead), R Strehl
5. Release criteria additional to those currently in used for research grade banks. Contributors D Hei, J Crook, G Stacey
6. Standardised testing methods: M Firpo, C Glover, S Oh, G Stacey
7. Points to consider for donor consent for cell lines in clinical grade banks: T Dyke, R Isasi (lead), R Skinner
Formal reports from each of these groups were discussed at the second of the 2008 ISCBI meetings held at the Jackson laboratories, Bar Harbor in October 2008 (see appendix 4). At this meeting, where again 17 countries were represented, development of the working group reports and their consolidation into a consensus document were discussed. The report from working group 4 on requirements for stem cells as manufacturing cell substrates was proposed to be taken forward with the WHO Cell Substrates Study Group to be included as a new section of the WHO recommendations on cell substrates for manufacture of biological (currently under revision). Also at this meeting the final corrections to the guidance on best practice for banking and supply of hESCs for research use were agreed and updates to the ISCBI stem cell bank registry were obtained. A forward plan was established for publication of the guidance document in a stem cell journal, and for completion and publication of the working group reports on requirements for establishment of stem cell banks for clinical use. Furthermore, appropriate ongoing issues for a consortium of banks of human stem cell lines were discussed, as was establishment of a membership through a formal process of self evaluation against the ISCBI guidance document.
The guidance document on the banking and supply of hESCs for research purposes has been accepted by SCRR for publication in summer 2009 and an independent PDF of the document has also been prepared for release in agreement with JSCR (contents given in appendix 5).
Coordination between the International Stem Cell Banking Initiative (ISCBI) meetings has been maintained through telephone conference calls and email communications and the next ISCBI meeting will be held in June 2009 in Barcelona at the Centre for Regenerative Medicine at Barcelona (CRMB) with the kind support of Professor Anna Veiga of CRMB. At this meeting the final compilation and publication of the ISCBI document on requirements for clinical grade stem cell banks will be discussed and the group will consider proposals for the ongoing stem cell bank coordination.
The ISCBI project is currently within the original budget of $50,000 (see appendix 6) and would like to activate the unspent funds to complete current business and start up an independent international stem cell bank consortium.
Conclusions and Issues for Consideration by the ISCF
The ISCBI has delivered on all its primary commitments to:
- produce an international consensus guidance document on the banking, characterisation and distribution of human stem cell lines for research purposes,
- establish a registry of national stem cell banks incorporating details of the relevant national regulation,
- evaluate the specific requirements for establishing banks of human stem cell lines for clinical application.
In addition ISCBI has initiated new and very positive contacts between stem cell scientists, national banking groups, commercial suppliers of reagents and regulators; which has promoted international coordination on regulatory issues and the quality of stem cell research tools and reagents.
The effectiveness of the International Stem Cell Banking Initiative (ISCBI) and the quality of its output is also demonstrated by the active engagement welcomed by regulatory bodies such as WHO, US FDA and MHRA. It has provided a valuable framework for countries where regulation is still at an early stage of development and as a reference point for discussion with regulators on current issues for cell therapy. Furthermore, the WHO are currently incorporating ISCBI input on stem cells, into the latest revision of their international recommendations on the establishment of cell substrates for the manufacture of vaccines and biotherapeutics.
The current guidance document on cell banking for supply to stem cell researchers has received a very positive response, However, simply publishing such guidance is not enough to have full and effective impact. It is important now to get real “buy in” from suppliers of stem cell lines to evaluate exactly how they comply with the guidance to establish a real international ‘bench mark’ of the quality of material required for stem cell research. The “quality” requirements for different research applications of stem cells (e.g. toxicology, drug discovery, neurobiology) will be different to basic stem cell research, and the considerations for clinical application are clearly developing. The effective lead taken by the ISCBI partners has shown that this group can have an ongoing important role to play in the stem cell field.
The ISCF is therefore invited to endorse the formation of a consortium of stem cell banks from ISCBI membership to implement and develop best practice for supply of stem cell lines for both research and clinical use. As proposed in the original application for funding in 2007; it is envisaged this will be self financing from its members but in order to enable completion of current business it is requested that ISCBI retains use of the ISCF website and also access to the approved funding for two years in order to complete current business on clinical grade stem cell banks and start up the stem cell bank consortium. The ongoing ISCBI activity would also consider further benefits from their coordination, such as exchange of cell lines, training activities, and international advisory services.
Glyn Stacey Ph.D., ISCBI coordinator and rapporteur, April 2009