1 Regulation 13 of the Genetically Modified Organisms (Contained Use) Regulations 2000, GMO(CU), allows users to notify more than one activity in a single notification, that is to notify connected programmes of work. This guidance aims to give advice on what is acceptable as a connected programme of work and what to include in such a notification.
2 For the purposes of GMO(CU) an activity can be considered to be the construction and/or use of one or more GMOs for a specific experimental or commercial purpose. The normal expectation is that individual activities will be individually notified. This must be done before any work with GMOs in classes 2, 3 or 4, or notifiable GM animals or plants, is undertaken.
3 However, under Regulation 13(2) it is also acceptable to make a single notification in which a number of activities involving genetic modification are presented together as a connected programme. To be treated in this way, the work covered by the notification should form a coherent and integrated programme in which all the activities can be seen as contributing to a common scientific/research goal.
4 The main advantage of notifying as a connected programme is that only a single notification fee is paid. On the other hand, setting up such a connected programme is likely to involve co-ordinating submissions from several scientists whose work may be at different stages of development. Moreover, once a connected programme is established, care will be needed to ensure that all of the scientists whose work is covered co-operate to update the connected programme, as and when this becomes necessary. Thus, centrally organised co-ordination may be necessary.
5 One specific situation where there may be a significant benefit in setting up a connected programme is when an institution or company has two or more separate departments or premises that collaborate on either a single activity or a connected programme of activities. Provided that the same body has notified in respect of each department or premises (i.e. the same employer notified in each case), a single connected programme notification can cover the work. It should be noted, however, that a single activity (or connected programme) that involves the collaboration of centres notified separately by different employers cannot be notified under a single connected programme. In this situation, each employer would have to notify their involvement in the activity/activities separately.
6 The Regulations require that connected programmes 'form a coherent and integrated programme'. The Competent Authority's interpretation of this is that the range of work under a connected programme should not:
7 In other words, it would probably be possible to draw up a connected programme to cover the work of a research team consisting of, for example, a professor and three or four post doctoral scientists. However, it is unlikely that a single notification covering all the GM work taking place in a large university department containing people with distinct research interests would be acceptable. Such a submission would almost certainly lack any scientific coherence.
8 Whilst the notification of a connected programme should contain all of the information necessary to identify all of the different types of GMOs that will be used/ constructed, it is permissible to provide varying levels of detail on the risk assessment of these GMOs. Commonly used types of construct, such as those described in the ACGM Compendium of Guidance, that are known to raise few if any additional hazards over and above the inherent hazard of the recipient strain, need much less detailed consideration than novel constructs, especially where in the latter, there is reason to believe that the insertion of the foreign DNA may bring about a significant alteration in the pathogenic properties of the recipient such as alteration of host range, tissue tropism, immune response etc. This point can be illustrated in the following connected programme.
A connected programme aimed at studying the molecular basis of the pathogenicity of human influenza virus may involve construction of three types of notifiable GMMs:
9 The notification of the GMMs covered under point (i) would require only minimal description of the vaccinia strain and the inserted genes. The notification of the GMMs covered by point (ii) would require slightly more information, but not down to the detail of individual sequence changes. The notification of the GMMs covered by point (iii) would require specific information on the exact sequence changes that would be made and a detailed discussion of likely properties that would be associated with each of these sequence changes.
10 A connected programme of work may involve any combination of class 2, class 3 and class 4 activities as well as notifiable GM plant or GM animal work. This point can be illustrated using the above example. The activities in (i) and (ii) are likely to be class 2 and the work in (iii) is probably either class 3 or 4 depending on the exact modifications undertaken. Where a range of classes of activity are covered under a single connected programme the relevant notification requirements (eg. the waiting times until it is possible to start work and the need to obtain a formal consent for classes 3 and 4) must be complied with for each activity within the programme. (The only exception to this is that a single fee corresponding to the highest class of activity involved is payable.) Thus, in the example presented above, assuming that previous activities had been undertaken at class 2, it would be possible to start the vaccinia work (i) and the gene disruption work (ii) as soon as an acknowledgement of the receipt of the connected programme notification was received from HSE. The remainder of the work could only be started once the relevant consents had been obtained from the Competent Authority.
11 There are essentially two ways to structure a connected programme notification:
12 One advantage of the second approach is that the connected programme will be easier to update when new activities are added. Moreover, if the umbrella document is structured carefully, it may be easier to justify making some minor modifications to the research programme (that do not change the hazardous nature or increase the risk of the activity), on the basis of review at local level, without any need to make a further notification to the Competent Authority.
13 To minimise the additional administrative work associated with updating risk assessments and making notifications (and paying fees!) the details provided in a connected programme notification need to be considered very carefully. For instance, if there is a possibility that alternative hosts, vectors and types of gene insert could be used as well as the 'first choice' ones, it would be wise to include them in the connected programme notification to avoid having to submit additional information to the Competent Authority at a later date.
