ISCBI Report to ISCF, 2011

1. Introduction

This report covers the period from the last ISCBI project report submitted  April 2010. In the intervening period the ISCBI met formally twice with ongoing tele-conference calls and email groups to sustain the work of the working groups established in 2009 in Beijing.

2. Outputs and Impact

 2.1 Guidance on Banking Research Grade hESC Lines

A comprehensive guidance document for the governance, banking characterisation and distribution of hESC lines for research purposes was published in 2009 (Stem Cell Rev and Rep (2009) 5:301–314, see attached PDF).  Since then ISCBI members have prepared translations of the guidance document in Japanese and Chinese and progress has now been made to publish the Japanese version in the Japanese Journal of Cell Therapy.

UK and Chinese representatives also began drafting guidance for UK and Chinese scientists to help them engage appropriately with respective regulation applicable to laboratory work in collaborations between Chinese and UK Universities.  This document includes a comparison of Chinese, European and US regulations on stem cell research and development.

2.2 Coordination Events 2010-2011

Event

Activity

Number of Delegates

Number of countries

Represented

ISCBI coordination meeting(CIRM offices June 2010) Working group progressreports 24 11
Organisation andContribution to ISSCRsatellite meeting (June 2010) Clinical grade facilitiesISCBI reportNaming conventions for iPSC and hESC lines c50 Unknown
ISCBI workshop ManchesterUK (back to back with ISCI) Working group updatesOpen discussion on bank governance, adventitious agents new issues: Tumorigenicity,Genetic stability, Requirements for stem cell used in toxicology. 47 21
ISCBI workshop (June 2011) Discussion on workinggroup reports and plansfor iPSC meeting 24 10

 2.3 Publications and dissemination activities

J.M. Crook, Hei,D. And Stacey, G. The International Stem Cell Banking Initiative (ISCBI): raising standards to bank on. In Vitro Cell.Dev.Biol.—Animal (2010) 46:169–172.

Stacey and Healy (2010) Banking stem cell lines; an international perspective. World Stem

Cell Report. Genetics Policy Institute, USA, October 2010.

Luong MX, Auerbach J, Crook JM, Daheron LHei D, Lomax G, Loring JFLudwig T, Schlaeger TM, Smith KP, Stacey G, Xu RH, Zeng F.(2011) A call for standardized naming and reporting of human ESC and iPSC lines. Cell Stem Cell. 8(4):357-359.

Presentations by ISCBI coordinator at >20 international scientific meetings (including ISSCR) and industry meetings on stem cell research, toxicological applications of stem cells and bio-banking

2.4 Update on clinical grade cell bank guidance

1.   Banking governance and donor selection. These documents have been developed significantly since the 2010 meetings and revisions agreed at June 2011 meeting are now being implemented for recirculation and comment.

2.   Standards working group. Established in China in May 2009 with Dr. Meri Firpo (USA) as the lead. This group has considered a range of standardisation and reagent issues and has now focused on progressing collation of standards from international pharmacopeia and other sources for testing cells for manufacturing purposes. It has also constructed a supplier audit policy and a questionnaire for lower risk supplied materials.  Establishment of a bank self evaluation process was raised again.

3.     Cryo-working group. Guidance document completed – may be published as separate text or rationalised into a single document on clinical grade cell banking

4.   Adventitious agents working group. This has proved a controversial area regarding the extent of safety testing performed on the seed stock banks as opposed to manufacturers’ cell banks and product. The working group is aiming to resolve an approach to minimum and desired levels of testing. Both EU and US standards to be represented.

5.   QA. Sections on adverse event reporting and facility and equipment validation have been circulated amongst the group and is now being prepared for incorporation in the final document.

6.   Release criteria working group. This is working closely with the adventitious agent working group and QA working group to develop the final criteria.

7.   Stem Cells in the manufacture of biological products. A number of companies are considering the use of stem cells for manufacture of vaccines and other biological medicines. Commercial cell sub group paper drafted in 2010 with input from GSK and Vivalis. Ongoing input to drafting of new WHO guidance on evaluation of cell substrates for manufacturing purposes approved at the WHO Expert Committee for Biological Standardisation October 2010 and now released on the WHO website: http://www.who.int/biologicals/Cell_Substrates_clean_version_18_April.pdf

8.   Other initiated working group activities of ISCBI:

  • Establishment of a stem cell bank self evaluation process
  • Tumorigenicity: questionnaires to be compiled for publication
  • Genetic stability: current document now being added to by expert karyologist

A current list of working group leads and contributors is given in Appendix 1

Note new website for ISCF =  http://stem-cell-forum.net/

Under current approved funding it is proposed to hold one further meeting for working group leads to put together the final guidance on clinical grade stem cell banking. This will fall within the budget already agreed by ISCF (see 3).

3.   New Activities Planned for ISCBI

3.1 iPSC Banking

Large national programmes are developing to produce thousands of iPSC lines for research and a number of initiatives are interested in developing iPSC lines for clinical applications. Funding has been secured from UKTI to run a ISCBI meeting in London in early 2012 and includes some funding for travel bursaries for ISCBI members. This will be run as a workshop to develop ideas on necessary approaches to delivering high quality iPSC lines. Issues to be addressed will include the selection of iPSC lines for banking and distribution (including reprogramming methods and minimum donor information),appropriate patient cohorts, panels of representative cells and numbers of replicate clones. In addition the meeting will address the quality control and characterisation required for research-grade iPSC line banking and distribution. A draft programme is given in Appendix 2. The need for a further guidance document will be considered that will build on the basis of the 2009

ISCBI guidance for hESC lines (attached) which contains significant generic guidance applicable to iPSC lines.

 3.2 Develop formal recognition for ISCBI activity as a standards setting organisation.

Coordination of each ISCBI member with their national standards institutes (e.g. BSI, ANSI), ICH or WHO. An additional possibility would be for the group to contribute to a new cell therapy international coordination activity being set up by NIBSC with WHO endorsement Q1 2012. ISCBI could also develop and run independent evaluation and registration schemes for pluripotent stem cell line banking for research and supporting the development of PSCs for human application. This could be self funding as part of a programme to give the ISCBI group financial independence .

 3.3 Manufacture and testing of stem cell products.

This would be a natural extension of ISCBI’s current work, applying and building on the significant expertise and knowledge within group, While undoubtedly valuable to the field, again, it could provide a source of revenue to facilitate the group’s future financial independence.

4. Project Spend

4.1  Spend since last report and planned future spend on current budget

ISCBI workshop June 2010 CIRM host, no cost to ISCF
ISCBI Manchester meeting £6465.90 (c $11,639)
ISCBI workshop June 2011 £612.20 (c$857)
Q1 2012 WG leads meeting for clinical grade banks $15,000 maximum

4.2 Proposal for supplementary funding

iPSC meeting: Funds already secured $15000 (from 5KTI)
Support requested from ISCF $5000 maximum
Establish ISCBI as a formal standards setting organisation $25,000
Total requested from ISCF $30,000

Appendices

Appendix 1: List of Working Group Leads

QA: Kevin Bruce Roslin cells, Scotland, UK

Cell banking governance and donor selection: Rosario Isasi (Canada) and Geoff Lomax (CIRM)

Standards: Meri Firpo, University of Minnesota and Teneille Ludwig, Wicell Research Institute

Adventitious agents: Derek Hei, Waisman Institute

Release criteria: Jeremy Crook, University of Melbourne

Tumorigenicity: Steve Oh, AStar, Singapore and Lyn Healy, UKSCB

Cell substrates for manufacturing: Steve Oh AStar, Singapore

Appendix 2: ISCBI Workshop on the delivery of high quality iPSC resources sponsored by UKTI

This workshop will focus on the strategy and quality control required for the delivery of iPSC resources via stem cell banks to the research community and the requirements for routine ‘Good iPSC Culture Practice’ for research laboratories. It will build on the past developments which have been achieved under the International Stem Cell Banking Initiative (ISCBI) funded by the International Stem Cell Forum. The workshop sessions will include expertise in key disease areas to identify strategies that might be used in selecting representative panels of tissue from patients for delivery as freely available cell lines for researchers. In addition experts in iPSC derivation will be invited to discuss the key issues in derivation and selection of scientifically optimal clones of iPSC cultures. A major objective of the workshop will be to engage expert members of ISCBI representing more than 20 countries worldwide, who established consensus guidance for the banking testing and distribution of hESCs for research use in 2009 (attached). This guidance will be reviewed and developed for application to iPSC line resources and to identify elements of good cell culture practice required for maintenance and use of iPSCs in research laboratories. A key output from the meeting will be a report forming the basis for consensus guidance for the international stem cell banking community on best practice in the banking and use of iPSC lines for research. This will also be an opportunity to welcome the UMass Stem Cell Bank and other potential banking centres to the ISCBI community and consider further consolidation of the ISCBI activity in support of stem cell research and the development of cell therapies.

Draft programme for discussion:

Day 1

AM/PM

Welcome and tour of local bank by UKSCB/UMASS/UKTI staff

PM

Discussions between UKSCB and UMass staff Dinner for UKSCB/UMass/visiting speakers/UKTI

Day 2

Derivation of iPSCs: critical stages and points to consider in the derivation of iPSC cultures

Evaluation of reprogramming and epigenetics in iPSC lines

Studying the nature of disease – selecting genotypes for developmental and degenerative diseases

Disease modelling and in vitro toxicology – genotypes for hepatocyte and cardiomyocyte models

ISCBI guidance for hESC culture – generic elements

Lunch

Workshop questions:

Strategy for securing representative panels of iPSCs

Banking: genetic and phenotypic stability, critical aspects of cell culture, in process monitoring

Information required from depositors of cell lines: cell line history, patient information, testing/characterisation

Summary and close

Informal reception and networking

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