Draft minutes of the 17th meeting of the Scientific Advisory Committee on Genetic Modification (Contained Use)

Held on Friday 20th November 2009 in BIS Conference Centre, 1 Victoria Street, London

Welcome

1. The Chair welcomed everyone to the 17th meeting of the Committee and extended a warm welcome to the new Secretariat, Dr David Brown and Mr Lee Wilson and new attendees Dr Joanne Nettleton and Mrs Sandra Fletcher from HSE, Dr Andrew Patterson (Defra assessor) and Dr Colin Cartwright (Atkins and Defra GM notification assessor).

Minutes of the previous meeting

2. The minutes were accepted as a true and accurate recording of the proceedings of the 16th meeting.

Matters arising and Secretariat report - SACGM/11/09/P2

3. The Institute for Animal Health (IAH) were unhappy with the decision made at the 16th meeting with regard to the classification of their project 'Consideration of Eimeria tenella as a heterologous vaccine vehicle'. Their initial concerns were that containment level 3 (CL3) was disproportionate to the risk presented by E. tenella and that fumigation was only being used to avoid cross-contamination. Through further dialogue with HSE these issues were resolved, although HSE were of the opinion that fumigation is being used as a control measure, which necessitated a class 3 notification with derogations.

4. HSE received a new class 3 notification from IAH with 27 requests for derogation. The Competent Authority considered the notification and associated documentation before issuing consent for the work to proceed, but granted only 10 derogations. The Chair highlighted that this notification (large number of derogation requests) could be a likely indicator of the types of notifications that may be submitted under the new contained use 2010 regulations particularly for work with non-zoonotic pathogens. However, by granting only some of the derogation requests, the Competent Authority has demonstrated that there must be risk based justification for each derogation request. The Secretariat also pointed out that declining the derogation requests would not change how IAH handle the GM parasite compared to how they would handle the wild-type.

Reports from other relevant Scientific Advisory Committees

Advisory Committee for Releases into the Environment (ACRE)

5. Dr Martin Cannell from Defra provided feedback on the recently established subgroup to consider new techniques in parallel with the EU Commission working group. The general feeling was that greater clarity was needed from the EU to establish what was required from appointed experts.

6. Dr Colin Cartright provided an overview of a Defra funded research report, which detailed the environmental risks from marketing GM veterinary and human medicines. Members indicated that they would like to see a copy of the report so this may be an agenda item for a forthcoming meeting.

Action: Defra to provide a copy of the report to the Secretariat for inclusion in the papers for the next meeting.

Gene Therapy Advisory Committee (GTAC)

7. The Secretariat provided feedback from GTAC which included:

1. An update on the progress with the development of stem cell regulatory route map toolkit which, although in a testing phase, looked very promising and should go live before the end of the year.
2. A report relating to a severe adverse event in a clinical trial involving live attenuated intranasal vaccine against respiratory syncytial virus and paraininfluenza virus in an infant in the USA. Initially suspended, this trial has recommenced and GTAC have advised that changes be made to the patient information leaflet to reflect the issue.

Advisory Committee for Dangerous Pathogens (ACDP)

8. The Secretariat invited Mr John Newbold from HSE (ACDP Secretariat) to provide feedback from a recent meeting of ACDP, which included:

1. An update on the revision of ACDP guidance for work with strains of influenza with pandemic potential and the appropriate level of containment. Work is ongoing with input from the committee's virology experts and a draft will be submitted to the next ACDP meeting in February 2010.
2. Classification of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus (HP-PRRSv). Defra are carrying out a consultation exercise to add PRRSv to Part 1 of Schedule 1 of the Specified Animal Pathogens Order (SAPO) 2008 by means of an Amendment. The effect of this amendment would be to prohibit any person from possessing this pathogen, or carriers containing it, without having a license authorising them to do so under SAPO.
3. Information relating to confirmed cases of A/H1N1 pandemic Influenza currently circulating in the human population found in three pig herds in Northern Ireland. Discussions at ACDP included whether the finding warranted any epidemiological investigation and worker protection through inoculation and additional advice. One Member asked whether it was known how the pigs had acquired the infection e.g. potential human-pig transmission. Mr Newbold responded that the route of transmission was unknown.

Other matters of interest to Members

9. The Secretariat informed Members of two potential working parties resulting from a forward look seminar held by Nuffield Council on Bioethics in April 2009; 'new approaches to biofuels', and the exploration of issues raised by 'emerging technologies'. The Secretariat will attend the 'emerging technologies' workshop in November, with particular interest in synthetic biology and its comparisons to GM. The Chair added that there was much interest in the GM approach to biofuels, citing work currently being carried out at Plymouth Marine Laboratory.

Action: The Secretariat to provide Members with relevant feedback from the 'emerging technologies' workshop at the next meeting.

10. The Secretariat invited Prof David Lewis to provide feedback on an issue relating to environmental risk assessments required for clinical trails carried out under current GM (Deliberate Release) Regulations and the need to provide specific locations/ grid references for the site of release. Prof Lewis informed Members that this could have implications for phase III clinical trials, as individuals are likely to shed live material beyond the grid reference for administration of the treatment e.g. a volunteer's house. In addition, this would necessitate a new application every time a new volunteer was recruited. The Secretariat for ACRE is trying to progress this matter with Competent Authorities from other Member States. The Secretariat asked how other Member States currently deal with this matter. Prof Lewis replied that there were different approaches across Europe dependent on the structures for reviewing these types of applications resulting in variation in implementation of the Directive. Members commented that this may have an impact on how trials are notified i.e. Contained Use instead of Deliberate Release.

Action: The Secretariat to keep Members updated on any developments on this matter.

11. The Secretariat informed Members of a recent incident that involved the accidental discarding of genetically modified Arabidopsis seeds into domestic refuge, subsequently sent to landfill. Members were informed that the modification involved deletion mutagenesis, which presented a low risk as the mutations are not believed to confer any novel properties on the plant and are more likely to decrease the fitness of the GM Arabidopsis compared to wild-type. One member stated that the seeds were unlikely to remain viable for any longer than 2 years in those conditions. Members were informed that an investigation had been carried out by HSE and a number of recommendations made to minimise the chances of such an incident reoccurring.

12. The Secretariat provided Members with an update on the foot and mouth disease replicon work, following a paper presented to Members in 2004, for the use of a sub-genomic replicon for foot and mouth disease virus at the University of St Andrews. Funding for this work is now in place and, as required by conditions recommended by the committee, HSE has carried out a pre-commencement inspection and has no objection to the work commencing. In addition, HSE has received notification for work with the same replicon from the University of Leeds for which the Competent Authority has imposed the same conditions as for St Andrews.

13. The Secretariat informed Members that the 2008 SACGM(CU) Annual Report had now been published on the website and thanked the contribution from all those involved.

14. The Secretariat informed Members that the committee would be looking to recruit three new Members in time for the next meeting.

Progress update on the Single Regulatory Framework (SRF) for contained use with wild-type animal and human pathogens and genetically modified microorganisms (GMMs) - SACGM/11/09/P3

15. The Chair invited Mr John Newbold and Mrs Lorraine Medcalf from HSE to provide Members with feedback on the progress of the SRF. There will be a 12-week formal public consultation scheduled for February 2010. In anticipation of this, great efforts have been made to consider and complete key strands of work, including:

• Stakeholder Engagement - HSE has carried out a number of focus groups across key stakeholders including academia, animal pathogen experts and NHS representatives. The meetings have been very positive and subsequent feedback very useful. Further meetings are scheduled throughout November and early December.
• Integrated Notification System - Work is ongoing with the development of an integrated notification system that will be easy to use, administer and supportive of Directive and Regulatory requirements. To facilitate a smooth changeover to the new regulatory requirements, there will be a 6-month transitional period for notifications beginning October 2010.
• Cost Recovery - The cost recovery element of the SRF is being progressed in consultation with HSE's Financial Advisors, taking into account Government and HSE policy.
• Devolved Administrations - HSE now has formal arrangements in place with Defra and devolved administrations to undertake inspection functions on behalf of Ministers. They are currently working with the Devolved Administrations to consider constitutional issues and address legal and policy implications for full implementation of the SRF.
• Biosafety Guidance - The Biosafety Guidance, drafted by HSE and the ACDP/ SACGM Containment Working Group, was included in the papers. It will be available to dutyholders who wish to work with GM and wild-type human or animal pathogens, and explains the risk based approach to be taken when deciding on containment measures.
• Common Set of Containment Measures - Appropriate containment will be determined both by the Hazard Group of the pathogen and the Activity Class of the planned work on the pathogen. Combined containment tables have been prepared which bring together measures from COSHH, SAPO and GMO(CU) regulations, and clearly outlines the requirements for each containment level.

16. Members raised a number of queries with regard to the SRF including issues relating to cost recovery, exemptions for diagnostic activities/ cell cultures, clarification on the notification requirements for plants/ GM plants infected with GMMs and derogation for wild-type human pathogens. Mr Newbold and Mrs Medcalf responded to the questions and indicated that these questions were asked previously at stakeholder events and they would endeavour to clarify all issues in the guidance before public consultation. Members were thanked for their input.

The determinants of replication of avian influenza viruses in avian and mammalian cells - SACGM/11/09/P5

This item was brought forward by the Chair to allow Members discussion time prior to the introduction of the invited speaker and as a precursor to the other influenza agenda item, which was similar in nature.

17. The Secretariat introduced a paper on the proposed submission of a new GM class 4 notification, the aim of which is to elucidate the determinants of influenza host-range restriction in mammals and birds by using reverse genetics to identify which mutations or combination of mutations increase viral replication in mammalian cells compared to avian cells.

18. The principal investigator involved in the work gave a short presentation outlining the scientific goals, the proposed genetic modifications and the risk assessment and associated containment measures.

19. Following a presentation, the Chair led a question session in which the PI responded on a number of topics associated with the scope and management of the project. These included whether they intended to cover all of the work described in the risk matrix and a number of questions related to the management of samples such as storage, item tracking, identity of stock material, transport of samples and numbers of viruses manipulated at any one time. Further discussions focussed on the risk matrix and the rationale behind the final assignment of risk levels.

20. Members concluded that the notifier needed to carefully consider and implement rigid management systems to identify, catalogue and track viruses.

Action: The Secretariat will ensure that the queries/ recommendations made by the Committee be addressed prior to issuing consent for the activity.

Pathogenesis of avian influenza virus (AIV) infections in avians and investigation of AIV adaptation to mammalian swine cells - SACGM/11/09/P4

21. The Secretariat introduced this paper following a recent class 4 notification to the Competent Authority to undertake in vivo studies in swine with genetically modified influenza viruses. The work is a significant change to an existing influenza class 4 project.

22. Members agreed that the additional information requested by the Competent Authority would be critical to assess adequately the risks posed by the work. In addition, similar issues raised during discussions on the previous influenza paper (SACGM/11/09/P5) regarding management procedures e.g. sample tracking, transport etc. were also relevant to this work.

Action: The Secretariat to provide Members with an update at the next meeting following receipt of additional information from the dutyholder.

Feedback from the European Commission new techniques working group draft report - SACGM/11/09/P6

21. The Secretariat updated Members on progress with the EC technical working group looking at new techniques. The Secretariat explained that there is an additional meeting of the working group planned for early 2010 to help devise a finalised document for presentation to the European Competent Authorities meeting. The most up-to-date draft of the report was included for Members' interest.

Any Other Business

22. The Secretariat informed Members of a recent invite to all Scientific Advisory Committee (SAC) Chairs' to a meeting with the Government's Chief Scientific Advisor (Professor Beddington). The purpose of the meeting was to discuss the recent events resulting in the dismissal of a SAC Chair and the links between SACs and policy makers.

Close

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

Date of next meeting

24. The 25th March 2010 (subsequently changed to the 24th March).