HSE - Scientific Advisory Committee on Genetically Modified Organisms (SACGM)

Minutes of the 7th meeting of the Scientific Advisory Committee on Genetic Modification (Contained Use) held on Thursday, 26 January 2006, in the Globe Room at Rose Court, Southwark Bridge, London

Chair

Prof Janet Bainbridge

Members

Dr Gary Burns
Dr Martin Carrier
Dr Peter Coyle
Prof Martin Gore
Prof Ernie Gould
Dr Penny Hirsch
Dr David Lewis
Dr Sue Mayer
Dr Phil Minor
Mr Bob Osborne
Dr Brian Robertson
Dr Peter Searle
Dr Michael Skinner
Prof Peter Williams

Secretariat

Mrs Diane Fox-Purday
Dr Jon Gawn
Dr Paul Logan
Mrs Diane Tsavalos

Departmental Assessors

Dr Androulla Gilliland (DEFRA)
Mr Paul Manser (DEFRA)
Mrs Susan Shearman (DEFRA)
Ms Delyth Dyne (HSE)

Apologies

Prof David Baulcombe
Dr John Carr
Dr Keith Howard

Welcome and Introductions

1. The Chair welcomed everyone, particularly Mrs Diane Fox-Purday to the seventh meeting of the SACGM. The Chair then went on to thank members for their services to the Committee during the past two years and gave specific thanks to those members who had chosen to renew their membership.

Minutes of the Sixth Meeting - SACGM/01/06/P1

2. The minutes were accepted as a true record of proceedings.

3. The meeting was asked to consider the addendum of further information on Rinderpest. Some discussion took place and the Chair concluded that the situation is far from clear and that the laboratory context is not comparable to that of the virus in the wild, but still does not substantively affect the Committee's decision. The Secretariat had further discussed the work with the group concerned and they are still of the same mind but have nevertheless agreed to comply with the recommendations of the Committee. One member commented that the overriding concern should be that the organism is zoonotic.

Matters Arising & Secretariat Report

4. The Chair and Secretariat thanked everyone for their involvement in the Compendium Working Groups.

5. Members were informed that ACRE had recently considered the first application for marketing a gene therapy product in Europe. Spain was lead reporter, and ACRE had co-opted expertise in adenoviruses from the SACGM.

6. Some discussion took place about documenting animal work in minutes that will then be placed in the public domain. The Committee agreed that it is sufficient to remove references to workers' names and locations.

Safety of lentiviral vectors and vectors containing WPRE - SACGM/01/06/P3

7. The Secretariat outlined the importance of the issue in that workers are pressing HSE for an update, as they need to press ahead with work. Members were reminded of one such project using lentiviral vectors, which had been the subject of a previous meeting and on which the Committee was about to receive an update.

8. A guest speaker, who reminded members that his group were working with an in utero method of delivery, then gave a presentation, reminding members that high levels of tumours had been detected in a number of experiments with different vectors.

9. The work is now focusing on the possible mechanism for tumour formation and a number of postulates are being considered, the most plausible being vector mediated insertional mutagenesis.

10. Plans of future international collaborative work were outlined but these are wholly dependent on funding.

11. The meeting was then opened for questions to the guest speaker.

12. The Committee agreed that its interim advice would remain. Members noted that the in utero test appeared to be an exquisitely sensitive model, and despite this, from the data presented it is apparent that the HIV vector system does not appear to induce tumour formation even though the FIV system does. It was agreed that more data is required before a definitive view can be given on the safety of the lentiviral vector systems.

13. It was further noted that the recommendation that work should be carried out at containment level 2, which is not unduly onerous but the cost implication is what is at issue here.

Action: The Secretariat should seek further data on the safety of lentiviral vectors.

Draft guidance on the safe use of viral replicon systems - SACGM/01/06/P2

14. The Chair welcomed the speaker and invited Dr Gawn to present his draft guidance on the use of viral replicons. The Secretariat reminded the committee of previous SACGM discussions on such work, notably the use of a Foot and Mouth Disease Virus replicon system, and its conclusion and recommendation that such work is carried out at a minimum of CL2. The Secretariat stated that the presence of the guest today presented an ideal opportunity to discuss the two issues in parallel.

15. A presentation was given describing work undertaken involving replicon systems and the pros and cons of using such systems in each project. The properties of the Flaviviridae and Coronaviridae were also outlined and it was explained that as replicons are not viruses, it is imperative to be cautious when extrapolating results.

16. The eventual aim of this particular group is to use a SARS replicon system for screening antiviral agents, which may theoretically be applied to high throughput processing.

17. The meeting was then opened for questions to the guest speaker.

18. The Chair asked if there were any specific views on the draft guidance. A wide-ranging discussion followed, and several minor amendments to the replicon guidance were recommended.

19. One member pointed out that there is a possible risk of recombination and asked why the guidance focuses on positive strand rather than negative strand retroviruses. All agreed that the guidance should be specifically worded to exclude viruses of bacteria and fungi.

Action: JG to do corrections & DT to distribute

Draft guidance on the use of GMMs in clinical studies - SACGM/01/06/P4

20. The Secretariat summarised the approach taken and the problems associated with a diverse NHS culture. In its current state, the guidance doesn't sit well with the clinical environment and has not considered the practicalities of using pharmacies; a sub-group has been trying to address this. The guidance strives to take a pragmatic approach while still complying with the regulations. A common, central sign-off facility for all NHS Trusts will be useful.

21. The Secretariat is aware that the sector eagerly anticipates this guidance, not least because there are several Phase 3 trials in the pipeline, but it would be pointless to publish until the multi-centre trial issue has been bottomed out with DEFRA and HSE lawyers. The view is that the regulatory burden is going to impede gene therapy research and development in Europe.

22. The Chair also pointed out that training of transient clinical staff is of concern and parallels may be drawn with some commonly occurring diseases. The precautionary approach of the guidance may cause alarm to some and although agents may be safe, they will seem dangerous. It was suggested that guidance in an animated format, rather than its current didactic approach may be beneficial.

23. The Chair commented that infection control will act as the link to management, but as they may not have a grounding in GM, to administer at a central unit level would be ideal. The Secretariat pointed out that this is precisely what the working group is working on.

24. A meeting has been arranged with HSE solicitors to explore the creation of exemption certificates.

Any Other Business

25. Dr Burns raised an issue on the existence of the CU Regulations Annexe for Safe Organism Exemption. This may be in place, but in reality to obtain one is extremely expensive, onerous and bureaucratic. Dr Burns therefore proposes that SACGM should put a case to the EU to simplify the process.

Action: PL and GB to put together a position paper

Next Meeting Date

Wednesday, 7 June 2006

Close

The Chair thanked everyone for their attendance and drew the meeting to a close.