The UK Stem Cell Bank:

Developments & Challenges

for International Banking

Professor Andrew Webster

Director, SATSU, University of York

Member UKSCB Steering Committee

Background

Report recommended the setting up of a non-statutory

Steering Committee to:

– monitor and approve the deposit and use of hESC lines

within the UK including the import and export of stem

cell lines

– establish a Code of Practice for the use of human ESC

– act as the principal oversight committee for the UK Stem

Cell Bank

The UKSCB was established in 2003 following a House of

Lord‟s Select Committee Report into the science and ethics

of hESC research:

Role of the UK Stem Cell Bank

• To establish, test and release well-characterised stocks of ethically-sourced adult, foetal and embryonic stem cell lines within a stringent quality framework

• To promote basic research in the UK and abroad through the provision of“Research Grade” cell banks

• To establish “Clinical Grade” cell banks under EU GMP conditions as startingmaterial for therapeutic uses

• To work with the scientific and clinical communities, commercial organisationsand regulatory agencies to assure the quality of human stem cell lines used inresearch and clinical therapy

• To develop and disseminate best practice in the culture, testing, characterisation and preservation of stem cell lines: permitted only to undertake research relating to curation.

Current Activity

Australia4%(3)

India3%(2)

Sweden6%(4)

UK60%(42)

USA27%(19)

Cell Lines Approved (by Country)

72 Cell lines approved by the SC

30 Cell lines Banked for distribution

15 Cell lines released for use

No clinical grade lines yet available

(2 awaiting approval from the HTA)

No iPS lines (unlike WiCell)

year deposit access import export total

2010 2 10 2 7 21

(YTD)

2009 5 21 14 8 48

2008 8 28 3 11 50

2007 8 33 8 8 57

2006 9 20 7 17 53

UK stem cell bank• Institutional: UKSCB seen as strong public

institution; no research also reinforces

service role/independence

• Public engagement/support: see Stem Cell

Dialogue report

• Legal background: HFEA – permissive

regime

• Bureaucratic regulation: complex –

multiple sites of regulatory authority and

influence

Q3. Will the cells be

Genetically Modified?

HSE Notification may be needed

Submissions to:

(i) HFEA,(ii) REC, &

(iii) NHS R&D Office

YESNO

YESNO

NO YES

YESNO

In vitro Stem Cell Research

In vitro Stem Cell Research

Stem Cell

Research

In Animals

NO

NO

Submissions to:

(i) HFEA,(ii) REC, &

(iii) NHS R&D Office

Generation of Stem Cell Line

Q3. Will the cells be

Genetically Modified?

In vitro Stem Cell Research

YESNO

In vitro Stem Cell Research

YESNOSubmissions to

NHS R&D Office & REC

(Non-statutory good practice

for studies outside the NHS)

Q2. Will the stem cells be

derived from Human Embryo?

Clinical Stem Cell Research

Q1. Are the stem cells intended for Human Application?

Discuss with HTA

Apply for HTA

License

Deposition in UK Stem Cell Bank via Steering Committee

YES

Regulatory

Question

Statutory

Regulatory

Process

Research or

Manufacturing

Activity

Key:

Non-Statutory

Good Practice

Start

Here

Serious Adverse Event & Reactions Reporting to HTA

Q2. Will the stem cells be

derived from Human Embryo?

Possible application

for HTA License

Discuss with HTA

Q3. Will the cells be

Genetically Modified?

Home Office

Approval

Create MCB/WCB

Stem Cell Research

in Animals

Home Office approval &

safety study under GLP

Submissions to:

(I) MHRA Clinical Trials Unit, (ii) GTAC, & (iii) NHS R&D Office

Post-marketing Surveillance of Stem Cell ATMP

Preparation of Clinical Trial documentation & obtain EudraCT number

GMP licence

from MHRA

Preparation of Regulatory Dossier for EMEA

Manufacture unlicensed

product

Manufacture Clinical Trial

product

Submission to EMEA

Q6. Is animal in vivo work required?

HSE Notification may be needed

HSE Notification may be needed

NO

Q6. Is animal in vivo work required?

YES

Home Office Approval

Stem Cell

Research

in Animals

NO

Q5. Is the product to be licensed? Dialogue with MHRA

Q6. Is animal in vivo workrequired? Discuss with MHRA/HO

NO (this route likely to berare)

YES

Q7. Will the clinical research involve gene therapy?

Stem Cell Clinical Trial

YES

HSE Notification may be neededNO

Safety reporting to Regulatory Agencies

Quality, Safety & Efficacy Data Generated

Positive Opinion of EMEA: Marketing Authorisation Granted

YES

YESNO

Stem Cell

Research in

Animals

Home Office

Approval

Q6. Is animal in vivo work required?

In vitro Stem Cell Research

Interim UK Regulatory Route Map for Stem Cell Research & ManufactureVersion: 12.03.10

Q4. Will the stem cells be

manufactured into a Medicinal

Product or Investigational

Medicinal Product? If yes, they

will be regulated as an ATMP.

Discuss with MHRA/EMEA

YES

Deposition in UK Stem Cell Bank via Steering Committee

Generation of

Stem Cell Line

Generation of

Stem Cell Line

In vitro Stem Cell Research

• Standardising stabilises discovery-led

science; need for common criteria under

which data gathered across different labs

can be classified and retrieved

• ISCI re hESC – UKSCB plays pivotal role

International collaboration (1):

Collaboration requires standardisation

across labs

Partici

pating

labs

RN, DNA

antibodies

UKSCBSpecialist reference

labs (e,g Gene

Services for RNA/DNA

fingerprinting

ISCI collaboratory

Private firm: culture

Legal and resource base to the project: data sharing and IPR

In order to identify agreed characteristics for

differentiation the collaboratory must reduce the

differentiated and heterogeneous ways in which

lines are identified and cultured across discrete labs.

It must try to overcome the local contingencies that

are defining of lines, to avoid a situation where:

„A conclusion about a line might be a conclusion

about a lab‟ (respondent at ISCI Forum 2007)

Standardisation: in banksFull characterisation of cells

Standardisation of protocols

GMP/GLP: but what counts as a „clinical grade‟ line?

Quality and safety of lines deposited in bank

To avoid…’A conclusion about a line might be a

conclusion about a bank’

Need for flexibility in characterisation?: classification of cell

lines/quality measures needs to be dynamic enough to

support ongoing and changing understanding of cells by

biologists

SO: need to engage with researchers on iterative basis

Long–term regulatory issues

Scale-up via automation is a key

regulatory issue and this in turn relates

to quality of lines in banks:

•consistency in bio-processing and in

therapeutic results (GMP as basis for stable

product)

•securing repeatable cultures

•standardising and optimising cell cultures is repetitive work but this will add value to the regulatory (GMP) process inasmuch as would be producing feed-stocks for both public and private R&D and reduce development costs.

The Review and Refresh of Bioscience 2015

report (industrial body)

Recommendation 17: Translational scale-up

centres for Regenerative medicine

Create two cell scale-up centres at

research institutions to build capacity and

capabilities (skills training and technology)

in this specialist area of bioprocessing.

Centres should work at the interface

between the researcher, the manufacturer

and the physician.

Source: Bioscience Innovation and Growth Team, 2009

Exchanging lines: lines carry the context of their production

Duplicative/alternative sources of lines: cannot claim to be distributing the

same material until they can demonstrate they are using the

same practices

Banks as curators: how do quality assurance systems record

information about stem cell lines – does this vary?

Bilateral and/or multilateral exchange: which bank acts as source

of authorisation for ethical use of material deposited/donated in

one country?

Common Materials Deposition/Use/Access Agreements? – IP

issues here – e.g. UKSCB does not allow restrictions on 3rd party

use when deposit

International collaboration (2):

Standardisation across banks

Trans-national banking

• ISCB Initiative 2008 – research grade lines only

• Harmonisation or standardisation?

- common understanding of goals but expressed differently in different countries

• Harmonisation not an end-point but process

• Ethics interoperability to complement bank interoperability – discrete codes of ethics possible

• Arrival and exchange of clinical grade lines will require subscription to other forms of „soft governance (such as ISSCR Dec 2009 guidance on CTs)

• Role of bank re iPS??

Lack of an internationally unified

regulatory framework for stem cell and

tissue transplantation (eg problem of

cross-jurisdictional transfer of hESC lines).

Problems with inconsistent tissue banking

procedures, inconsistent donor consent,

uncertain efficacy and discordant

regulatory standards.

Solutions will be socio-technical

Conclusion: Regulatory challenges for

banking at national and international levels