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

Minutes of the Eighth Meeting of the Scientific Advisory Committee on Genetic Modification held on Wednesday, 7 June 2006, in the Globe Room at Rose Court, Southwark Bridge, London

Chair

Prof Janet Bainbridge

Members

Prof David Baulcombe
Dr Gary Burns
Dr John Carr
Dr Martin Carrier
Dr Peter Coyle
Prof Martin Gore
Dr Penny Hirsch
Dr Keith Howard
Dr David Lewis
Dr Sue Mayer
Mr Bob Osborne
Dr Brian Robertson
Dr Peter Searle
Dr Michael Skinner

Secretariat

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

Departmental Assessors

Dr Androulla Gilliland (DEFRA)
Mr Paul Manser (DEFRA)
Ms Sarah Senior (HSE)
Dr Maggie Lacey (HSENI)

Apologies

Prof Ernie Gould
Dr Philip Minor
Mrs Susan Shearman
Prof Peter Williams

Welcome and Introductions

1.  The Chair welcomed everyone, particularly Miss Caroline Walls and Ms Sarah Senior to the eighth meeting of the SACGM.  The Chair then went on to describe the forthcoming agenda items and to name the three guest speakers.

Minutes of the Seventh Meeting – SACGM/06/06/P1

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

Matters Arising

3.  The Secretariat informed members that discussions had commenced on the issue of exemption of safe GMMs from the provisions of the contained use regulations, and the legal positions were being explored.

Secretariat Report

4.  The Competent Authority (CA) had received a notification of work on a gene therapy protocol for an ill dog.  Information had been received on similar work done in the US, copies of which were distributed to members.  The case and the potential for media interest and precedent setting were outlined.  Advice is being sought from the Veterinary Medicines Directorate, which is taking into consideration data provided by the US, which shows no shedding and a potential positive outcome.  In this case however, shedding is the primary concern because of the animal’s domestic situation.  The CA will be seeking advice from GTAC on the system used (HIV) and the Veterinary Medicines Directorate will be considering the welfare/ethical aspects of the case.

Risk Assessment Classification Query – Gene Therapy Trial – AdHIF for Treatment of Atherosclerosis /SACGM/06/06/P2

5.  Drs Coyle and Searle declared and outlined the interests that they have in the work.  They also pointed out that they had both previously raised queries with the company and with HSE.

6.  There was a general discussion about the nature of the work and the current classification.  The Secretariat outlined the background to the query.  A number of centres had been approached to participate in a clinical trial using AdHIF to stimulate angiogenesis in patients with artherosclerosis and peripheral artery disease.  The work had been classified as Class 1; however, a number of participating centres had queried the classification.  The Competent Authority (CA) had met with the sponsoring company and discussed classification and risk assessment.  The company was now seeking the CA’s advice on the classification of the products, and the CA was seeking the advice of SACGM.

7.  One member noted the timely nature of this agenda item, as the discussions and outcome of this meeting would serve to inform similar concerns raised at GTAC.  If such discussions resulted in a set of standard operating procedures, this would be of benefit to the work.

8.  The 0.3% adverse effect rate is good, given the patient profile and this information needs to be factored into the risk assessment, which is considered to be far too technical in nature.  Corneal neovascularisation in the worker caused by accidentally splashing the product into the eye seemed to be the most likely scenario, but there are no data available to address this concern.

9.  The Chair reminded members of the remit of the Committee and went on to welcome the guest speakers, who gave a short presentation which described the nature and mode of action of the product, the trial structure, its organization and plans for the future.  They also raised the issue of classification, noting that if the trial were classified as Class 2, then it would make access to pharmacy facilities difficult as current guidelines indicated that separate facilities would be required for such products.

10.  The meeting was then opened up for questions to the guest speakers.  The Chair thanked the guest speakers for a thoroughly informative presentation and discussion.

11.  The Secretariat pointed out that it was the company’s own risk assessment that was pushing the work into class 2, noting that it was not the intention of HSE to impede progress; rather HSE prefers to find a pragmatic way forward. 

12.  The speakers asked the Committee to provide clear direction so that all of the sites may receive the same classification, noting that it would be unlikely that hospitals would go against the advice of SACGM.  They further requested that any advice should state clearly the reasons for arriving at that decision.  The Secretariat reminded the meeting that legally it is the responsibility of the applicant to carry out the risk assessment and assign the classification to the activity.  SACGM could provide advice, which the CA could forward to the sponsoring company.

13.  The Secretariat informed members that the work is classified as requiring BSL2 in the United States, and members noted that this was consistent with their own views.

14.  Concern was raised that a reclassification would mean that additional controls would need to be put into place, and that this might impede the trial from progressing.  The Secretariat informed members that the containment and control methods outlined in the notification were considered fully adequate, and no additional controls would be needed.

15.  Members and the guest speakers were reminded that new SACGM/ACRE guidance on clinical trials would allow multi-centre trials to be conducted under a single notification, thus reducing the regulatory burden on organisations wanting to conduct such clinical trials with genetically modified viruses.  The committee was informed that HSE would liaise with the company to ensure that the bureaucracy was reduced to a minimum.

Action: The Secretariat to draft letter of recommendation in consultation with SACGM members.

Class 3 Project – Genetic manipulation of Dengue Fever Virus - SACGM/06/06/P3

16.  The Chair welcomed the next guest speaker and drew the meeting’s attention to the fact that Dengue is included on the draft Schedule 5 to the Anti-Terrorism, Crime and Security Act, and therefore the papers were restricted.

17.  The Secretariat outlined the history and development of the work and that although it involved animal studies, these would not take place in the UK.  The meeting agreed that as an agenda item it would serve to inform the ongoing work on the Compendium of Guidance.

18.  The guest speaker gave a presentation including an overview of the Flaviviridae, in particular the Dengue fever family and Modoc virus.  The characteristics, genomic structure and modes of transmission of the viruses were described together with the rationale of the programme of work being undertaken, i.e. there is no suitable animal model for Dengue fever studies.

19.  Reverse genetics will be used to manipulate and transfer Modoc virus genes into the Dengue virus genome at CL2 to produce cDNA clones which will be sent abroad for use in animal work.  Since none of the disease’s associated vectors will be present in the laboratory, the only foreseeable means of transmission to workers would be via a needlestick-type event.  No hypodermics will be used in the laboratory therefore the risk is low.

20.  The Chair thanked the guest speaker and opened the meeting for questions.

21.  The committee agreed that it was satisfied with the way the work is classified at present and it considered CL3 for animal work to be sufficient and welcomed the speaker’s offer to keep it informed of progress, given the hazardous nature of the work.

Action: The secretariat would ensure that the issues raised by the work were adequately addressed in the draft Compendium, and that the researchers would update the CA on progress of the work.

Compendium Update - SACGM/06/06/P4

22.  The Chair and Secretariat thanked all those involved in the compendium working groups.  Permission was sought and agreement obtained from the committee to use the next open meeting as a platform to launch the new guidance.  Mid autumn 2006 was seen as the most suitable time, with a meeting of the Committee during early to mid September to finalise the guidance.

23.  Members suggested the following features could be included in the launch:

• An introduction by the Chair
• A summary of how the structure has changed to ensure that the guidance will be more accessible and easier to read.
• A presentation from a representative of each of the working groups on each section.
• Inclusion of an explanation as to how the guidance dovetails with the regulations.

24.  A discussion took place about identifying key stakeholders to be present at the launch and the Secretariat informed the meeting that HSE holds a database of such contacts.

25.  The forthcoming launch of the Clinical Trials Guidance was also discussed, and suggestions of key stakeholders to invite included: MHRA and NHS Trust Managers who would serve as a means of communication into for example, the Royal College of Pharmacy and the National Research and Development Office.

Action: Mrs Fox-Purday to obtain availabilities and determine the dates of next committee meeting and for the open meeting

Any Other Business

26.  In addition to the launch of the new compendium, all agreed that it would be proper to also conduct some normal business during the open meeting.

27.  The canine gene therapy work is to be tabled by ACRE and SACGM members are invited to attend.

Close

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