Amended under s67A on 23 August 2007
Application code
Application type
Applicant
Purpose
Date received
Consideration period
Considered by
21 June 2001
GMC01006
To import into containment genetically modified organisms under section
40(1)(a) of the Hazardous Substances and New Organisms (HSNO) Act.
Malaghan Institute of Medical Research
To import into containment genetically modified mice to study the pathogenesis of allergic disorders and possible therapeutic strategies
1 May 2001
31 May 2001 – 21 June 2001
A Committee of the GMO New Organisms Standing Committee of the
Environmental Risk Management Authority (the Authority).
In accordance with the relevant provisions of the Hazardous Substances and New Organisms
(HSNO) Act 1996 and of the HSNO (Methodology) Order 1998, the application to develop the following organisms was approved with controls :

Mus musculus C57B6J IL4-GFP knock in

Mus musculus Balb/c IL4-GFP knock in

Mus musculus B10.A IL4-GFP knock in
The application was lodged pursuant to section 40(1)(a) of the HSNO Act. The decision was determined in accordance with section 45, taking into account additional matters to be considered under section 44, and matters relevant to the purpose of the Act, as specified under
Part II of the HSNO Act
Consideration of the application followed the relevant provisions of the Hazardous
Substances and New Organisms (Methodology) Order 1998 (the Methodology).
This application was formally received on 01 May 2001 and verified on 03 May 2001.

The Act gives the Authority discretion as to whether to notify an application to Import into
Containment a New Organism . The Authority may notify such an application where it considers there is likely to be significant public interest in the application. The Committee agreed that the application not be notified, noting that the genetic modifications fell within the low risk criteria
1
, and thus if the mice were to be developed in New Zealand rather than being imported, the application to develop a GMO would be able to be processed by rapid assessment. The Authority has to date considered and approved some twelve applications covering the importation into containment of approximately 700 genetically modified mice and cell lines.
The documents available for the Committee’s consideration were: the application; the
Evaluation and Review of the application by ERMA New Zealand; and comments received from the Department of Conservation which were sought pursuant to section 58(c) and clauses 2(e) and 5 of the Methodology. MAF opted to not provide comment on the application.
The application was considered by a sub-Committee of the Genetically Modified Organisms
Standing Committee of the Authority appointed in accordance with section 19(2)(b) of the
HSNO Act. The Committee comprised the following members: Mrs Helen Hughes (Chair),
Ms Jill White and Dr Oliver Sutherland.
The Malaghan Institute of Medical Research in their application seeks approval to import into containment three strains of genetically modified in-bred mice. The mice will be used to study the pathogenesis of allergic disorders such as asthma and possible therapeutic strategies.
In accordance with clause 24 of the Methodology, the approach adopted by the Committee was to look sequentially at identification, assessment and evaluation of risk, costs and benefits. Management techniques were considered in relation to the potential risks (clauses
24 and 12). As no risks were identified as significant, none were assessed under clause 12.
Costs and benefits were evaluated in accordance with clause 13 of the Methodology.
Finally, the combined impact of risks, costs and benefits was evaluated in accordance with clause 34.
No significant risks or costs were identified for assessment and evaluation in terms of clauses
9 and 10 of the Methodology, which incorporate sections 5,6,and 8 of the Act. In reaching this conclusion, the Committee gave particular regard to:
1 As defined in the Hazardous Substances and New Organisms (Low risk Genetic Modification) Regulations
1998
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
Risks to the environment and to public health (clauses 9(a), 9(c)(i) – (iii), and 10(a) – (d)).
The modifications involve introduction of the green fluorescent protein (GFP) gene at a specific site by joining it to a mouse gene (IL4). The modifications will not result in the production of vertebrate toxins, or pathogens, and are unlikely to have any significant effects on the environment or on public health in the event of the mice escaping. All three genetic modifications fall within the low risk criteria
2
which, if developed in New
Zealand, could be considered by rapid assessment.

Risks from the import of inseparable organisms (section 45). The Committee considered the effects of any inseparable organisms, in accordance with section 45(a)(ii) of the
HSNO Act and noted that while organisms may carry microflora such as gut-inhabiting bacteria, it was satisfied that any such organisms are unlikely to be harmful to organisms in New Zealand, should any genetically modified mice escape from containment. The
Committee also noted that the genetically modified mice have been bred and maintained in Specific Pathogen Free animal facilities. In addition, the Committee noted that all mice imported would be quarantined for 30 days in order to identify any potential illness that may have developed in transit. Thus the probability of occurrence of inseparable organisms of any significance is very low
The types of modifications proposed in these applications are of a similar nature to those approved in previous applications to import genetically modified mice into containment. The
Committee considers that the risks associated with these applications are no different than those associated with the previous applications which have been approved.
The Committee identified as benefits (clause 9(c)(v)) the social and community benefits arising from the acquisition of scientific knowledge and the participation in international research.
In carrying out its consideration the Authority considered the adequacy of containment in accordance with section 45(i)(a)(iii) of the Act, and the magnitude and probability of the risks, costs and benefits together. This is because the former interact with the latter and this is recognised in clause 12(d) of the Methodology and in section 45(i)(a)(ii) of the Act. For convenience in setting out the decision the adequacy of containment is discussed first.
The Committee’s consideration of the adequacy of the proposed containment also included the ability of the organism to escape from containment (section 44(b)). Other matters relating to controls, but not containment were also considered.
The organisms are required to be contained in facilities that are approved containment facilities (under the Biosecurity Act 1993) in compliance with the Ministry of Agriculture and
Forestry (MAF) Regulatory Authority (Animal Health and Welfare) Standard 154.03.03:
Containment Facilities for Vertebrate Laboratory Animals.
This standard is employed to meet the requirements of the Hazardous Substances and New Organisms Act 1996 (HSNO).
2 As defined by the Hazardous Substances and New Organisms (Low Risk Genetic Modification) Regulations
1998
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Facilities into which mice under this approval may be imported, are required to comply with the Australian/New Zealand Standard AS/NZS 2243.3: 1995 Safety in Laboratories . Part 3:
Microbiology (Animal House Containment Level PC2), and the AS/NZS Standard 9002
(1994): Quality Systems – Model for quality assurance in production, installation and servicing (in accordance with the IATA Dangerous Goods Regulations) .
These standards are incorporated into the controls attached to this decision.
In addition, a requirement of the standard 154.03.03 is that the operators of the containment facilities have in place a quality assurance programme and procedures (standard operating procedures), that address the requirements of the standard and the controls imposed in this decision. These procedures are required to be documented in a containment manual , or an alternative quality system.
Taking into account the proposed containment regime, the Committee is satisfied that genetically modified mice can be adequately contained in the facilities described in the application, or any other equivalent facility registered as a Containment Facility under the
Biosecurity Act 1993 in accordance with the MAF/ERMA New Zealand Standard 154.03.03, and the Australian/New Zealand Standard AS/NZS 2243.3: 1995 Safety in Laboratories . Part
3: Microbiology (Animal House Containment Level PC2) which complies with all of the controls attached to this decision..
Other containment issues
The Committee noted that the Authority has previously approved a large number (over 700)
GM mice comparable to those which are the subject of this application. It considered the cumulative risks associated with multiple approvals, and noted that the cumulative risk of escape was a function of the number of mice in a facility, not of the number of strains approved, and that these risks were effectively managed by the containment regime and controls imposed .
In accordance with sections 44 and 37 of the HSNO Act the Authority considered the ability of the organism to establish an undesirable self-sustaining population, should it escape from containment, and the ease with which such a population could be eradicated. In evaluating these matters the Authority took into account the nature of the organisms.
Should any of the mice strains breach containment the Committee considers it is unlikely to establish a self-sustaining population. All strains identified under this approval are derived from inbred laboratory strains, and are therefore less well adapted for survival than wild type mice.
Should any of the mice that are the subject of this approval breed with mice in the wild population, the result would be the appearance of mice in the wild carrying the bound GFP gene. All mice carrying such genetic modifications would be expected to be less well adapted for survival than wild type mice, and would not be expected to have a selective advantage over wild type mice.
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The Committee noted that the applicants are required, as part of the facility approval, to implement a contingency plan and a programme of eradication and monitoring should any escape from containment of genetically modified mice occur.
The Committee concludes that the genetically modified mice are very unlikely to escape containment, taking into account the laboratory procedures proposed by the applicants and the containment controls imposed in this decision.
Having concluded that there are no significant risks and costs (see above section on identification of the significant risks, costs and benefits of the organism on page 3), the
Committee had no significant risks and costs to assess in terms of clauses 12 and 13 of the methodology. It does however record that given the low magnitude of any adverse effect, and given that the nature of the containment regime means that the probability of any adverse effect occurring is also very low, it concludes that the overall risk is negligible, with a high degree of certainty.
A “cost” is defined in clause 2 of the Methodology Order as “the value of a particular adverse effect expressed in monetary or non-monetary terms”. Given the above conclusions that risks are negligible, no further consideration of costs is considered necessary. Neither the applicant, nor the Committee identified any significant costs to third parties.
A “benefit” is defined in clause 2 of the Methodology Order as “the value of a particular positive effect expressed in monetary or non-monetary terms”. Benefits which may arise from any of the matters set out in clauses 9 and 10 of the Methodology were considered in terms of clause 13.
The Committee considered the benefits of the importation into containment of the mice strains, and identified the primary benefits as acquiring new scientific knowledge and raising the international profile of New Zealand’s scientific capabilities.
In addition, the ability to import genetically modified mice is important for organisations to be able to conduct specific research projects, and for New Zealand researchers to remain competitive and attract research funding from national and international funding bodies. The
Committee also identified that this research is very likely to add to acquisition of knowledge and understanding of the disease processes concerned.
Thus, while the benefits are likely to be both monetary and non-monetary (clause 13(a)), they are highly uncertain as to magnitude and expected value (clause 13(b)), and in the way they will be distributed over time, space, and groups in the community (clause 13(c)).
The overall evaluation of risks, costs and benefits was carried out having regard to Clauses 22 and 34 of the Methodology and in accordance with the tests in clause 26 of the Methodology and section 45 of the Act. Clause 34 of the Methodology sets out the approaches available to
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the Authority in evaluating the combined impact of risks costs and benefits i.e. weighing up risks, costs and benefits.
Based on the consideration of adverse effects to the environment, and to public health, and taking into account the containment regime, the Committee concluded that the risks associated with the importation into containment of the strains of genetically modified mice detailed in section 1.1 are negligible. The Committee has therefore considered this application in terms of clause 26 of the Methodology.
The risks were not amenable to being combined using common units of measurement because they are of different characters (clause 34(a)). The Committee concluded that the risks and associated costs were cumulatively negligible and, while it was also not able to quantify the benefits associated with the application in any numeric way, it was clearly evident to the
Committee that the benefits associated with the organisms outweighed the costs (clause 26).
Given that the risks are managed by the containment regime and controls, the Committee was satisfied uncertainties over the benefits would not affect this overall evaluation.
1.
Pursuant to section 45(1)(a)(i) of the Act, the Committee is satisfied that this application is for one of the purposes specified in section 39(1) of the Act, being section 39(1)(h):
[Such other purposes as the Authority thinks fit].
2.
Having considered all the possible effects of the organism in accordance with sections
45(1)(a)(ii) and (iii) of the Act and pursuant to clause 26 of the Methodology, and based on consideration and analysis of the information provided and taking into account the application of risk management controls specified in this decision, the view of the
Committee is that the adverse effects associated with the importation into containment of the organisms are outweighed by the benefits of conducting the research.
3.
The Committee is satisfied that the proposed containment regime together with the controls imposed will adequately contain the organism as required by section 45(1)(a)(iii) of the Act
4.
In accordance with clause 36(2)(b) of the Methodology the Committee records that, in reaching this conclusion, it has applied the balancing tests in s.45 of the Act and clause
26 of the Methodology.
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5.
It has also applied the following criteria in the Methodology:
 clause 9 - equivalent of sections 5, 6 and 8;
 clause 10 - equivalent of sections 36 and 37;
 clause 12 – evaluation of assessment of risks;
 clause 13 – evaluation of assessment of costs and benefits;
 clause 21 – the decision accords with the requirements of the Act and regulations;
 clause 22 – the evaluation of risks, costs and benefits – relevant considerations;
 clause 24 – the use of recognised risk identification, assessment, evaluation and management techniques;
 clause 25 – the evaluation of risks;
 clause 26 - risks are negligible and costs are outweighed by benefits
 clause 34 – the aggregation and comparison of risks, costs and benefits.

The application for importation into containment of the organism the three strains of genetically modified mice detailed in section 1.1 is thus approved , with controls, as follows.
In order to provide for the matters detailed in the Third Schedule Part I Containment Controls for Importing, Developing or Field Testing of Genetically Modified Organisms
3 the Authority’s approval of these applications is subject to the following below.
of the Act,
The Authority does not consider that any additional controls are required to account for matters outside of those matters specified in the Third Schedule.
3 Bold headings refer to Matters to be Addressed by Containment Controls for Development and Field Testing of
Genetically Modified Organisms, specified in the Third Schedule of the HSNO Act 1996.
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1. To limit the likelihood of any accidental release of any organism or any viable genetic material 4 :
1.1.
The person responsible for a particular research area and/or the person responsible for the operation of the containment facilities shall inform all personnel involved in the handling of the organisms of the Authority’s controls.
1.2.
The containment facilities shall be approved by Ministry of Agriculture and Forestry
(MAF) in accordance with the MAF Biosecurity Authority/ERMA New Zealand
Standards 154.03.03
5
and the controls of the Authority
1.3.
The construction and operation of the containment facilities (‘the facility’) in which the organisms are maintained, shall be in accordance with the:
 the Ministry of Agriculture and Forestry (MAF) Regulatory Authority/ERMA
New Zealand Standard 154.03.03
5
: Containment Facilities for Vertebrate
Laboratory Animals; and

Australian New Zealand Standard AS/NZS 2243.3:1995 5 Safety in Laboratories:
Part 3: (Microbiology), at Animal House Physical Containment Level 2 (PC2).
1.4 The maximum number of genetically modified mice in the containment facilities shall not exceed the capacity of the facilities, and/or any requirements of the relevant
Animal Ethics Committee.
2. To exclude unauthorised people from the facility:
2.1 The identification of entrances, numbers of and access to entrances, and security requirements for the entrances and the facility shall be in compliance with the requirements of the standards listed in control 1.3.
3. To exclude other organisms from the facility and to control undesirable and unwanted organisms within the facility:
3.1 The exclusion of other organisms from the facility and the control of undesirable and unwanted organisms within the facility shall be in compliance with the standards listed in control 1.3
4. To prevent unintended release of the organism by experimenters working with the organism:
4.1
The prevention of unintended release of the organisms by experimenters working with the organisms shall be in compliance with the standards listed in control 1.3.
4 Viable genetic material is biological material that can be resuscitated to grow into tissues or organisms. It can be defined to mean biological material capable of growth even though resuscitation procedures may be required, eg when organisms or parts thereof are sublethally damaged by being frozen, dried, heated, or affected by chemical.
5 Any reference to this standard in these controls refers to any subsequent version approved or endorsed by ERMA
New Zealand
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5. To control the effects of any accidental release or escape of an organism:
5.1 Control of the effects of any accidental release or escape of the organisms shall be in compliance with the standards listed in control 1.3.
5.2 In the event of any breach of containment the contingency plan for the attempted retrieval or destruction of any viable material of the organisms that have escaped shall be implemented immediately. The contingency plan shall be included in the containment manual in accordance with the Standard (154.03.03
5
).
5.3 If a breach of containment occurs, the facility operator must ensure that the MAF
Inspector responsible for supervision of the facility has received notification of the breach within 24 hours.
5.4 The applicants shall comply with the requirements of the standards listed in control
1.3 relating to the maintenance of records demonstrating compliance with the
Standard (154.03.03
5
), as required by the quality assurance programme, and documented in the containment manual.
6. Inspection and monitoring requirements for containment facilities:
6.1
The inspection and monitoring requirements for containment facilities shall be in compliance with the standards listed in control 1.3
6.2
The containment manuals shall be updated, as necessary, to address the implementation of the controls imposed by this approval, in accordance with the
MAF/ERMA New Zealand Standard 154.03.03
5
.
7. Qualifications required of the persons responsible for implementing those controls:
7.1
The training of personnel working in the facility shall be in compliance with the standards listed in control 1.3.
_____________________________
Helen Hughes, Chair
GMO Committee of the Authority
Date: 21 June 2001
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Amendment: November 2006
Changes to controls:

Addition of footnotes to the containment facility references and the Australian/New
Zealand containment facility references to “future proof” the decision

Standardise the wording of the breach of containment control

Removal of the control regarding inspection of facilities by the Authority, its agent or enforcement officers
____________________________
Dr Kieran Elborough
Chair, GMO Standing Committee
Date:
23 August 2007
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