Amended under s67A on 23 August 2007
Application Number NOC99008
Consideration Date 29-31 August 2000
Considered by Genetically Modified Organism (GMO)
Standing Committee of the Authority
Date 5 September 2000
Applicant
Category
University of Otago
Import into Containment any New Organism (section 40(1)(a))
Purpose To import into containment genetically modified mouse cell lines for use in research into the biochemical and cellular events underlying mammalian physiological processes. Results of this research may be applied to improving human/animal health.
Application Received 1 April 2000, resubmitted 24 July 2000.
The application is Approved with Controls.
The organisms approved are the mouse (Mus musculus) cell lines as described in Annex 1, attached.
This application was formally received on 1 April 1999. The application was stalled on 16 April
1999 whilst additional information was sought from the applicant and the organism description was developed. The final version of the application was submitted on 24 July 2000 and verified on 25 July 2000.
The application was not required under the Act to be publicly notified.
The documents available for the evaluation and review of the application by ERMA -New
Zealand included: the application, appendices and comments from other government agencies
(Department of Conservation).
The Committee comprised members of the Authority: Mrs Helen Hughes (Chair), Dr Oliver
Sutherland and Professor Colin Mantell.

The matters considered in making this decision comprise those set out in sections 37, 44 and 45 of the Hazardous Substances and New Organisms Act 1996 (the Act), and those relevant matters in
Part II of the Act.
Consideration of the application followed the relevant provisions of the Hazardous Substances and New Organisms (Methodology) Order 1998, but with particular regard to clauses 8 (dealing with the scale and significance of the risks, costs and benefits) and 26 (dealing with applications where the risks are negligible).
Purpose
In accordance with section 45(1)(a)(i) of the Act, the Committee was satisfied that the application was for one of the purposes specified in section 39(1) of the Act. The Committee concluded that importation into containment to model biochemical events constitutes an appropriate purpose under section 39(1)(h) of the Act: section 39(1)(f) Maintaining a new organism in containment to produce
antigens, biopesticides, biopharmaceuticals, enzymes, hormone, or vaccines for release and (h); such other purposes as the Authority thinks fit.
It was noted that the cell lines, derived from mouse (Mus musculus) meet the statutory definition of an “organism” under the section 2(1) of the Act.
Ability to Escape Containment
In accordance with section 44(b) the Committee considered the ability of the organisms, mouse cell lines, to escape from containment.
The applicant proposes to contain the cell lines in physical containment laboratories level 1
(PC1) in accordance with the Australian/New Zealand Standard AS/NZS 2243.3: 1995 Safety in
Laboratories. Part 3: Microbiology and registered under the MAF/ERMA New Zealand Standard
154.03.02: Containment Facilities for Microorganisms. The facility is also operated in accordance with an internal manual, University of Otago (Dunedin Campus) Containment and Quarantine Manual
(updated in August 2000), as required by the MAF/ERMA standard.
Taking into account the proposed containment regime the Committee was satisfied that the organism could be adequately contained in the facility described, or an equivalent facility registered as a Containment Facility under the Biosecurity Act 1993 in accordance with the
MAF/ERMA New Zealand Standard 154.03.02, and the Australian/New Zealand Standard
AS/NZS 2243.3: 1995 Safety in Laboratories. Part 3: Microbiology (physical containment laboratory level PC1).
Self-sustaining populations, eradication and adverse effects
In reaching its decision the Committee considered the ability of the organism to establish undesirable self-sustaining populations and the ease with which any such populations could be eradicated [section 37(a) and (b)], in the event of any escape from containment.
The Committee noted that the cell lines could not survive unassisted in the uncontrolled environment. The Committee took into account that the cell lines can only survive (i) in a
Environmental Risk Management Authority Decision: Application NOC99008 Page 2 of 7

laboratory cell culture system which provides a complex and accurately balanced mixture of highly purified nutrients and a stable temperature, or (ii) after being placed by surgery or injection inside an immune-weakened laboratory animal.
The Committee noted that there has been no recorded instance of cultured cell lines acquiring an ability to naturally infect an animal or plant. It also noted the decision prevents the use of viral vectors able to produce infective particles or able to infect human cells.
The Committee thus concluded that the probability of occurrence of any adverse effects on the
New Zealand environment is negligible.
Inseparable Organisms
In accordance with section 45(a)(ii) the Committee considered the effects of any inseparable organisms.
The Committee notes that the cell lines for importation shall only be those that are certified free of infectious diseases.
Negligible Risk
Based on the consideration and analysis of adverse effects to the environment, and to public health, and taking into account the containment proposals, in accordance with Clause 26 of the
Hazardous Substance and New Organisms (Methodology) Order 1998 the Committee considered that the risks associated with the importation into containment of the described mouse cell lines, are negligible
Benefits
The Committee considered the benefits of the importation into containment of mouse cell lines.
The Committee identified the benefit of the availability of the cell lines to reduce the use of laboratory animals for research purposes. Also identified was the importance of cell lines for medical research with potential to aid in the diagnosis of human and animal disease.
In addition, the Committee identified that the ability to import genetically modified cell lines in order to carry out research, would help New Zealand medical practices and industries keep pace with the rest of the developed world.
Conclusion
The Committee concluded that, taking account of the ability of the organism - genetically modified mouse cell lines - to escape from containment as in section 44(b) of the Act, the beneficial effects of having the organism in containment outweigh the likely adverse effects of the organism and any inseparable organisms, should the organism escape.
Having considered the possible effects of the organism in accordance with sections 45(1)(a)(ii) and
(iii) of the Act, the Committee was satisfied that the proposed containment regime and additional controls could adequately contain the organism.
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In order to satisfactorily address the matters detailed in the Third Schedule Part I Containment
Controls for Development and Field Testing of Genetically Modified Organisms approval of this application is subject to the following controls:
1 of the Act, the Authority’s
1. To limit the likelihood of any accidental release of any organism or any viable genetic material 2 :
1.1
The operation and management of the containment facilities shall be in accordance with the: a) MAF/ERMA New Zealand Standard 154.03.02
3 : Containment Facilities for Micro-
organisms. b) Australian/New Zealand Standard AS/NZS 2243.3:1995 3
(Microbiology), at Physical Containment Level 1 (PC1).
Safety in Laboratories: Part 3:
1.2 The containment facilities shall be approved by MAF as in accordance with the
MAF/ERMA New Zealand Standard 154.03.02
3 , and the controls of the Authority.
2. To exclude unauthorised people from the facility:
2.1 Any person exercising this approval shall comply with the requirements contained in the standards listed in control 1.1 relating to identification of entrances, numbers of and access to entrances and security requirements for the entrances and the facilities.
3. To exclude other organisms from the facility and to control undesirable and unwanted organisms within the facility:
3.1 Any person exercising this approval shall comply with the requirements contained in the standards listed in control 1.1 relating to exclusion of other organisms from the facility and the control of undesirable and unwanted organisms within the facility.
4. To prevent unintended release of the organism by experimenters working with the organism:
4.1 Any person exercising this approval shall comply with the requirements contained in the standards listed in control 1.1 relating to the prevention of unintended release of the organisms by experimenters working with the organisms.
1 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.
2 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.
3 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 Any person exercising this approval shall comply with the requirements contained in the standards listed in control 1.1 relating to controlling the effects of any accidental release or escape of an organism.
5.2 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.
6. Inspection and monitoring requirements for containment facilities:
6.1
Any person exercising this approval shall comply with the requirements contained in the standards listed in control 1.1 relating to the inspection and monitoring requirements for containment facilities.
6.2
Any person exercising this approval shall prepare and use a containment manual to implement the controls imposed by this approval, in accordance with MAF/ERMA New
Zealand Standard 154.03.02
3 : Containment Facilities for Micro-organisms.
7. Qualifications required of the persons responsible for implementing those controls:
7.1
Any person exercising this approval shall comply with the requirements of the standards listed in control 1.1 relating to the training of personnel working in the facility.
Signed on behalf of the Authority
Mrs Helen Hughes Date: 5 September 2000
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
 To correct original consideration date from August 1999 to August 2000
____________________________
Dr Kieran Elborough
Chair, GMO Standing Committee
Date: 23 August 2007
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Cell lines derived from any strain of laboratory mouse (Mus musculus) that are certified free of infectious diseases and modified by plasmid vectors or disabled viral vectors 1 into mouse chromosomes.
that are integrated
These vectors shall only contain one or more of the following elements, and involve genetic modifications that meet Category A or Category B experiments in the Hazardous Substances and
New Organisms (Low-Risk Genetic Modifications) Regulations 1998:
1. Promoters
1.1 Promoter, operator, and enhancer sequences derived from bacterial, yeast or mammalian genes, or from bacterial or mammalian viruses.
2. Reporter genes
2.1 Gene products that can be assayed by one or more of the following techniques:
2.1.1.
Visual colour or fluorescence, e.g., green fluorescent protein
2.1.2.
Spectrophotometrically
2.1.3.
Histochemically
2.1.4.
Enzyme-linked immunosorbent assays (ELISA)
2.1.5.
Thin layer chromatography
2.1.6.
Liquid scintillation counting
2.1.7.
Affinity purification, e.g., biotinylation, histidine affinity tags
2.1.8.
Immunological detection, e.g., epitope tags
And do not produce proteins that are pathogenic or toxic (have an LD
μg/kg) to vertebrates or are involved in cellular differentiation.
50
less than 100
3. Selectable marker genes
Well characterised genes that confer the ability to tolerate or deactivate:
3.1.1.
Antibiotics, e.g., against hygromycin, neomycin
3.1.2.
Metabolic inhibitors, e.g., against methotrexate, histidinol
3.1.3.
Vertebrate toxins
Well characterised genes that confer the ability to synthesise essential metabolites, e.g., His3,
Trp1, Ura3
And do not produce proteins that are pathogenic or toxic (have an LD
μg/kg) to vertebrates or are involved in cellular differentiation.
50
less than 100
4. Origins of replication
4.1
ColE1 or the pUC origins of replication derived from Escherichia coli plasmids.
4.2
Phage f1 origin of replication.
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5. Other features
5.1.
Multiple cloning site
5.2.
Polyadenylation signals
5.3.
Transcriptional activators
5.4.
Transcriptional responsive elements
5.5.
Transcriptional terminator sequences
5.6.
Secretory signals
5.7.
Intron sequences that function to increase gene expression
5.8.
Ribosomal binding sites and/or Kozak sequences
5.9.
Viral packaging signals, e.g., Ψ +
5.10.
Viral long terminal repeat sequences
5.11.
Viral genes required for replication
5.12.
Cre/Lox recombinase system
6. Donor DNA
6.1 These vectors may contain DNA sourced from prokaryotes or eukaryotes provided that the donor DNA shall not come from:
6.1.1
New Zealand native or endemic macroflora and macrofauna, or species valued by Mäori, that are sourced from New Zealand
6.1.2
Mäori people
6.1.3
Species from Appendix 1 of CITES
(http://www.wcmc.org.uk/CITES/eng/index.shtml), unless accompanied by written approvals from the importing and exporting countries.
6.2 And that the donor DNA shall not include:
6.2.1
Genes encoding vertebrate toxins that have an LD
50
6.2.2
More than two thirds of a complete viral genome
of less than 100 μg/kg
1 Integrated viral vectors shall not be able to produce infective particles or infect human cells
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