ENVIRONMENTAL RISK MANAGEMENT AUTHORITY
DECISION
Amended under s67A on 23 August 2007
29 June 2001
Application code
GMC01002
Application category
To import into containment a genetically modified organism under
section 40(1)(a) of the Hazardous Substances and New Organisms
(HSNO) Act
Applicant
University of Otago
Purpose
To import into containment genetically modified Chinese hamster
(Cricetulus griseus) cell lines for use in research into the
biochemical and cellular events underlying mammalian
physiological processes
Date application received
05 February 2001
Consideration date
19 March 2001
Considered by
The GMO New Organisms Standing Committee of the
Environmental Risk Management Authority (the Authority)
Decision
The application is approved subject to controls in accordance with sections 45(1)(a) and
45(2) of the of the HSNO Act 1996. The approved organisms are cell lines derived from
laboratory strains of Chinese hamster (Cricetulus griseus Milne-Edwards, 1867) genetically
modified using promoters, reporter genes and selectable marker genes (as described in Annex
1 of this decision).
Relevant Legislative Criteria
The application was lodged pursuant to section 40(1)(b) of the HSNO Act. The decision was
determined in accordance with section 45, taking into account additional matters to be
considered under sections 43, and matters relevant to the purpose of the Act, as specified
under Part II of the Act.
Consideration of the application followed the relevant provisions of the Hazardous
Substances and New Organisms (Methodology) Order 1998 (the Methodology), as specified
in more detail below.
Purpose of Application
The purpose of the application is to seek approval to import Chinese hamster cell lines into
containment at the University of Otago’s Medical Schools (Christchurch, Otago and
Wellington) and at the University of Canterbury. The application falls under section 40(1)(a)
of the HSNO Act: To import into containment any new organism.
The organisms will be used to conduct research into several areas of experimental biology
and disease treatment. Mammalian cell lines are used to model the biochemical and
molecular events that occur inside normal cells, as an alternative to using actual animals. The
applicant expects that results of this research may be applied to improving human and animal
health through the development of diagnostic tests and therapies against disease.
In accordance with section 45(1)(a)(i) of the HSNO Act, the Committee determined that this
was an appropriate purpose under the following sections of the HSNO Act: 39(1)(f)
maintaining a new organism in containment to produce antigens, biopeptides,
biopharmaceuticals, enzymes, hormones, or vaccines for release and 39(1)(h) such other
purposes as the Authority thinks fit.
Background information on cell lines
A cell line is defined as an 'organism' under the HSNO Act, ie ‘a genetic structure,
…capable of replicating itself, whether that structure comprises all or only part of an entity,
and whether it comprises all or only part of the genetic structure of an entity’.
Mammalian cells are approved Schedule 2 hosts in the HSNO (Low-Risk Genetic
Modification) Regulations 1998, as long as non-viral vectors or defective viral vectors that
cannot infect human cells are used. Such approved Schedule 2 hosts can be held under
physical containment level 1 (PC1) containment conditions.
The Committee notes that any further genetic modification of the approved cell lines,
including infection of the cell lines with other genetically modified organisms, would require
additional development approval under the HSNO Act.
The importation of the cell lines is also subject to the Biosecurity Act 1993 and would thus
require a MAF Import Permit.
This application is considered to be very similar to an application to import mouse cell lines
(application NOC99008) that was approved by the Authority on 05 September 2000.
Application Process
Application receipt
The application was formally received and verified to contain sufficient information to be
processed 05 February 2001. There were two adjustments to the organism description after
the date of formal receipt. The first adjustment (19 February 2001) was to specify that
integrated viral vectors should not be able to produce infective particles or be able to infect
human cells. The second adjustment (05 March 2001) was to include the ability to use
“genetic material sourced from prohibited or unwanted organisms”, since genetic material
from such organisms is not prohibited.
Notification of receipt
The receipt of an application to import into containment new organisms is not required to be
publicly notified unless the Authority considers there is likely to be significant public interest
(in accordance with section 53(2) of the HSNO Act). In accordance with internal guidelines
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(section 3.2.23 of the ERMA New Zealand Corporate Manual: Notification of applications to
import or develop a new organism in containment) this application did not meet criteria that
required public notification, as the genetic modifications meet Category A or Category B
experiments in the Hazardous Substances and New Organisms (Low-Risk Genetic
Modifications) Regulations 1998.
Information available for consideration
The staff of ERMA New Zealand prepared an Evaluation and Review (E&R) Report to assist
and support decision-making by the Committee, by consolidating and evaluating the relevant
information in a format and sequence which is consistent with the decision-making
requirements of the HSNO Act and of the HSNO (Methodology) Order 1998. The documents
available for the evaluation and review of the application by ERMA New Zealand included
the application (including supporting documentation), written comments from the
Department of Conservation (DoC) and verbal advice regarding importation of cell lines,
received from the MAF Biosecurity Authority.
Recognised techniques were used in identifying, assessing, and evaluating the relevant
information, as required under clause 24 of the Methodology. Techniques for identifying and
preparing information on risks, costs and benefits were based on internal procedures as
specified in the ERMA New Zealand Technical Guide publications. Potential effects were
identified by staff through a process of brainstorming, reviewing the application, as well as
comparison with other applications to import genetically modified cell lines into containment.
The Committee considered the information provided by the applicant was relevant and
appropriate to the scale and significance of the risks, costs, and benefits associated with the
application (as required by clause 8 of the Methodology).
Decision-Making Committee
The application was considered by the Genetically Modified Organisms Standing Committee
(the Committee) of the Authority appointed in accordance with section 19(2)(b) of the HSNO
Act. The Committee comprised the following members: Ms Jill White and Mrs Helen
Hughes.
Consideration of the application (approach & sequence)
In accordance with clause 24 of the Methodology, the approach adopted by the Committee in
considering this application was to look sequentially at identification, assessment and
evaluation of risks, costs and benefits. Those risks identified as significant were assessed in
accordance with clause 12. Costs and benefits were assessed in accordance with clause 13.
In assessing risks, the ability of the organisms to escape containment, establish undesirable
self-sustaining populations, and ease of eradication of any such populations (sections 37 and
44 of the Act), were considered.
The Committee's approach to risk was established in light of the risk characteristics of the
organisms (clause 33 of the Methodology). Taking account of the risk characteristics of the
organisms, the combined impact of risks, costs and benefits was evaluated in accordance with
clause 34.
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The identification of significant risks, costs & benefits
Risks and associated costs
Two significant potential risks 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 HSNO
Act:

Risks from the importation of inseparable organisms (section 45).

Risks to human health (clauses 9(c)(iii), 10(c), 10(g) and 12 of the Methodology).
The Committee records that risks to the environment, economy, society, communities and
Māori culture were considered, in accordance with clauses 9(a)-9(c) and 10 of the
Methodology. The Committee accepts the conclusions reached in the application and E&R
Report that the importation and use of the cell lines in containment is very unlikely to pose
significant risks related to these areas of effect. Therefore no further consideration of these
aspects was warranted.
Benefits
The Committee identified potential economic, human health, social and community benefits
associated with the application arising from the acquisition of scientific knowledge, ability to
attract research funding and potential for use of scientific knowledge to contribute to new
medical therapies (in accordance with clause 9(b) and (c)(v) of the Methodology).
Adequacy of the proposed containment regime
In carrying out its consideration the Committee considered the adequacy of containment in
accordance with section 45(i)(a)(iii) of the HSNO Act. The Committee’s consideration of the
adequacy of the proposed containment regime focused on the ability of the organisms to
escape from containment (section 44(b)), the ability of the organisms to establish undesirable
self-sustaining populations should they escape from containment (section 37(a)), and the ease
with which such populations could be eradicated (section 37(b)).
Ability to escape containment
In accordance with section 44(b) of the HSNO Act, the Committee considered the ability of
the cell lines to escape from containment.
Containment controls to which the approval of this application is subject (refer to the
Containment Controls section, pages 9-11 below) are considered to satisfactorily address the
matters detailed in the Third Schedule Part I: Containment controls for importing, developing
or field testing of genetically modified organisms of the HSNO Act.
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) Biosecurity Authority/ERMA New Zealand Standard 154.03.02:
Containment Facilities for Microorganisms.
Facilities into which the cell lines may be imported are required to comply with the
Australian/New Zealand Standard AS/NZS 2243.3: 1995 Safety in Laboratories. Part 3:
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Microbiology, at Physical Containment Level 2 (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 the basis of the containment controls specified in this decision. Four
additional containment controls (numbers 1.5 to 1.8), ie above and beyond the standard
requirements of PC1, are discussed below under assessment of adverse human health effects
(page 7).
The applicant states that the cell lines will be maintained at the University of Otago’s
Medical Schools (Otago, Christchurch and Wellington) and at the University of Canterbury
in facilities that are registered by MAF in accordance with MAF/ERMA New Zealand
Standard 154.03.02 and meet PC1 containment requirements.
The Committee is satisfied that it is very unlikely that the cell lines could escape
containment, taking into account the nature of cell lines, laboratory procedures proposed by
the applicant and the containment controls imposed in this decision.
The Committee notes that the applicant is required to implement procedures for the retrieval
or destruction of any viable material of the organism that has breached containment, as part
of the facility approval, and as detailed in the Universities of Otago and Canterbury
containment manuals.
Ability to form an undesirable self-sustaining population and ease of
eradication
In accordance with section 44 of the HSNO Act, the Committee considered the ability of the
organisms to establish an undesirable self-sustaining population, should they escape from
containment (section 37(a)), and the ease with which such populations could be eradicated
(section 37(a)). In evaluating these matters the Authority took into account the nature of the
organisms.
Should the cell lines breach containment the Committee considers they could not survive
unassisted in the uncontrolled environment and therefore could not establish a self-sustaining
population. In reaching this conclusion, the Committee notes that the cell lines represent
“immortalised clones” (ie are able to grow and divide indefinitely) that can only be grown
under specific culture conditions, typically in a defined culture medium at a constant
temperature with regulated CO2 levels.
Assessment of adverse effects (risks & costs)
Adverse effects are defined as including risks and costs. The adverse effects assessed were
those identified above (page 4) as being potentially significant, ie:
(i) Presence of associated organisms
(ii) Human health effects related to presence of associated organisms
Risks were considered in terms of the requirements of clause 12 of the Methodology,
including especially the assessment of consequences and probabilities, the impact of
uncertainty and the impact of risk management. Costs were considered in terms of clause 13
of the Methodology.
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In considering potential adverse effects, the Committee has taken into account the nature and
characteristics of the organisms, the applicant's assessments, written comments provided by
DoC, the E&R Report prepared by staff, and verbal advice provided by MAF (clauses 2(c)
and 22 of the Methodology). The evidence available was largely scientific in nature and was
considered in terms of clause 25(1) of the Methodology.
Presence of inseparable organisms
The Committee considered potential adverse effects associated with inseparable organisms,
in accordance with section 45(a)(ii) of the HSNO Act. The Committee has taken particular
note of the assessment of potential adverse effects associated with inseparable organisms
provided by staff in the E&R Report.
In considering the likelihood that inseparable organisms would be associated with the cell
lines (clause 12(c) of the Methodology) the Committee notes that the introduction of infective
viral agents into the cell lines is not permissible under the organism description (refer to
Annex 1 of this decision). To gain an import permit, MAF requires a statement from the
exporting organisation certifying that cell lines are free of disease or contamination.
However, the Committee notes that there is a degree of uncertainty relating to the quality of
assurance procedures in place in all organisations producing cell lines, so that some cell lines
may contain potentially infective viruses. Additionally, there may be a degree of uncertainty
associated with detecting the presence of viral agents, since some animals harbouring viruses
may be asymptomatic (clause 12(e) of the Methodology). The Committee notes that
uncertainty about the presence of viral agents also exists for non-modified cell lines, which
are not defined as new organisms under the HSNO Act.
The Committee considers that it is very unlikely that cultures that are known to be diseased
would be knowingly exported, as cultures producing infectious agents are likely to be
destroyed if detected. The Committee notes that cell lines derived from recognised
commercial suppliers are unlikely to have inseparable organisms associated with them, due to
the quality assurance standards such companies normally employ. However, there is a degree
of uncertainty related to the disease-free status of cell lines developed by non-commercial
suppliers (clause 12(e) of the Methodology), as quality assurance may be of a lower standard
and appropriate testing procedures may not be available in such laboratories.
The Committee considered whether or not a declaration from the supplier to attest that, to the
best of their knowledge, the cell lines are disease-free, would sufficiently minimise the risk of
importation of inseparable organisms. However, it was considered that to be meaningful, the
declaration would need to be very prescriptive, including details about the testing and
certification processes used. Ultimately a judgement call would still need to be made by MAF
staff whether or not the declaration adequately gave assurance as to the disease-free status of
cell lines. The Committee concluded that without extensive detail being available, any such
declaration would not give a meaningful level of assurance that the cell lines were diseasefree. The Committee, therefore, considered that risks would be better managed by assuming
that all the cell lines may potentially carry inseparable organisms, such as viral agents, and
handled as such. Controls for managing adverse human health effects associated with the
presence of viral agents in cell lines are discussed below, under assessment of adverse human
health effects (clause 12(d) of the Methodology).
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Adverse human health effects
Clauses 9(c)(iii), 10(c), 10(g) and 12 of the Methodology are considered to be particularly
relevant to the assessment of human health effects, including effects on public health and
safety.
The Committee considers a worst-case scenario related to contamination of cell lines with
other organisms is that the health of staff handling the cell lines could be adversely affected
(clause 12(a) of the Methodology). In considering human health effects, the Committee has
taken note of the assessment provided by staff in the E&R Report, including that:

the use of non-defective viral vectors or viral vectors able to infect humans are not
permissible under the organism description.

dangerous toxins or virulent microorganisms are very unlikely to be produced by the
approved cell lines since modifications are restricted to Category A or B
experiments as defined in the HSNO (Low-Risk Genetic Modification) Regulations
1998.

some rodent viruses can be transmitted to humans.
As discussed above, there is uncertainty about the potential presence of viral agents in the cell
lines. Therefore, the Committee requires that the cell lines be considered to contain
inseparable organisms, such as viral agents, and handled as such. The Committee has
instigated the following four additional controls (ie over and above standard PC1
requirements) to minimise any direct contact that facility staff may have with the cells, the
culture medium, and aerosols from the cultures:

Disposable laboratory gloves shall be worn when handling the cells and culture
medium (Control 1.5).

Any work that may result in the production of aerosols shall be carried out in a Class
II Biological Safety Cabinet (Control 1.6).

Microbiological waste shall be incinerated, or autoclaved before disposal. However, all
waste involving genetically manipulated organisms shall be steam sterilised before
disposal (Control 1.7).

Where imported cell lines are subsequently found to contain infectious agents these
cell lines shall be destroyed since they do not meet the conditions of the approval
given in this decision (Control 1.8).
The Committee notes that costs (monetary and non-monetary) associated with treating any
adverse health effects could accrue to parties other than the applicant (clauses 13(a) and
13(c)). While the magnitude of costs is uncertain, the Committee is satisfied that adverse
human health effects would be very unlikely to eventuate, based on the containment controls
specified in this decision (clause 13(b) of the Methodology).
In considering the extent to which risk characteristics exist (under clause 33 of the
Methodology) the Committee notes that adverse human health effects would primarily be
voluntary and may be treatable. However, adverse health effects could also persist over time,
could be subject to spread and could be irreversible. The Committee considers that staff
handling the organisms would have a good understanding of potential adverse health effects.
The Committee is willing to tolerate these risk characteristics because potential human health
effects are considered to be very unlikely to eventuate, taking into account the containment
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controls (in accordance with the need for caution where scientific uncertainty exists - clause
30).
Assessment of beneficial effects
A “benefit” is defined in clause 2 as “the value of a particular positive effect expressed in
monetary or non-monetary terms”. Benefits that may arise from any of the matters set out in
clauses 9 and 10 were considered in terms of clause 13.
The evidence available to assess beneficial effects included scientific information and
reference to other values and matters relevant to Part II of the HSNO Act and was considered
in terms of clause 25(2) of the Methodology. This evidence comprised that provided by the
applicant and the assessment of information in the E&R Report prepared by staff.
The Committee considered the primary potential benefit associated with the importation and
use of the cell lines in containment to be increased scientific knowledge, gained by
understanding the range of biomedical and cellular events involved with mammalian
physiological processes. Additionally, the ability to attract research funding and potential for
use of scientific knowledge to contribute to new medical therapies were identified as longerterm benefits.
In considering the nature of benefits under clause 13 of the Methodology, the Committee
concludes that both monetary and non-monetary are possible (clause 13(a)). While the
magnitude and expected value of benefits (clause 13(b)) is uncertain, immediate benefits
related to increased scientific knowledge are likely to accrue directly to the applicant (clause
13(c)). Longer-term benefits to parties other than the applicant are uncertain (clause 13(c)).
Overall evaluation of risks, costs & benefits
In accordance with clause 36(2)(b) of the Methodology the Committee records that this
decision was reached after assessment and evaluation of the information provided against
relevant criteria in the HSNO Act and the Methodology, in particular:

Pursuant to section 45(1)(a)(i) of the HSNO Act, the Committee is satisfied that this
application is for one of the purposes specified in section 39(1) of the Act (ie
sections 39(1)(f) and (h));

After consideration of the possible effects of the organisms and any inseparable
organisms, the beneficial effects of having the organisms in containment outweigh
the adverse effects of the organisms and any inseparable organisms, should the
organisms escape (sections 45(1)(a)(ii) of the HSNO Act);

The Committee is satisfied that the organisms can be adequately contained (section
45(1)(a)(iii) of the HSNO Act

Taking into account the application of containment controls (as specified below) to
manage the potential risks identified, the Committee formed the view that risks
associated with the importation into containment of the genetically modified hamster
cell lines are negligible and that benefits outweigh the costs. Therefore the
Committee has considered this application in terms of clause 26 of the Methodology;
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
Information used in considering the application was relevant and appropriate
(Methodology clause 9 - equivalent of sections 5, 6 and 8 of the Act and clause 10 equivalent of sections 36 and 37 of the Act);

Evaluation of risks, costs and benefits took into account relevant criteria
(Methodology clauses 12 and 13);

The decision accords with the specific requirements of the Act and regulations
(Methodology clause 21);

The overall evaluation of risks, costs and benefits was carried out having regard to
clauses 22 and 34 of the Methodology. The risks, costs and benefits were not
amenable to being combined using common units of measurement because they are
of different characters (clause 34(a) of the Methodology).

Recognised risk identification, assessment, evaluation and management techniques
were used (Methodology clause 24);

Scientific evidence and the degree of uncertainty attached to that evidence, was
taken into account (Methodology clause 25).
Decision
The application for importation into containment of the new organisms, Chinese hamster
(Cricetulus griseus) cell lines (as detailed in Annex 1), is approved in accordance with
section 45(1)(a) of the HSNO Act. As required under section 45(2) the approval is subject to
containment controls, as specified below.
Containment controls
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 Organisms1 of
the Act, the Authority’s approval of this application is subject to the containment controls
listed below.
The Committee notes that four additional containment controls (ie additional to requirements
of the formal standards listed under control number 1.3) are included as control numbers 1.51.8. These controls are included to help manage risks associated with undetected inseparable
organisms.
The Committee does not consider that any additional controls are required to account for
matters outside of those matters specified in the Third Schedule.
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.
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1
To limit the likelihood of any accidental release of any organism or any viable
genetic material2:
1.1
The person responsible for a particular research area and/or the person responsible for
the operation of the containment facilities ('the facility') 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
Standard 154.03.023 and the controls of the Authority.
1.3
The construction and operation of the facility in which genetically modified hamster
cell lines are maintained, shall be in accordance with the:
a)
MAF Biosecurity Authority/ERMA New Zealand Standard 154.03.023: Containment
Facilities for Microorganisms, and
b)
Australian New Zealand Standard AS/NZS 2243.3:19953 Safety in Laboratories: Part
3: (Microbiology), at Physical Containment Level 1 (PC1).
1.4
The minimum requirement for packaging for transportation of the microorganisms by
all modes (ie air, land and sea) from overseas and for transfers between facilities the
organism shall be packaged according to Packing Instruction No. 650 of the
International Air Transport Association (IATA) Dangerous Goods Regulations (refer to
MAF Biosecurity Authority/ERMA New Zealand Standard 154.03.023). All containers
must be clearly labelled with the name, address and phone number of both the sender
and the recipient.
1.5
Additional control: Disposable laboratory gloves shall be worn when handling the
cells and culture medium.
1.6
Additional control: Any work that may result in the production of aerosols shall be
carried out in a Class II Biological Safety Cabinet.
1.7
Additional control: Microbiological waste shall be incinerated, or autoclaved before
disposal. However, all waste involving genetically manipulated organisms shall be
steam sterilised before disposal.
1.8
Additional control: Cell lines found to contain infectious agents shall be destroyed.
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:
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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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 organism by experimenters working with
the organism shall be in compliance with the standards listed in control 1.3.
5.
To control the effects of any accidental release or escape of an organism:
Control of the effects of any accidental release or escape of an organism shall be in
compliance with the standards listed in control 1.3.
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.
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 MAF Biosecurity
Authority/ERMA New Zealand Standard 154.03.023: Containment Facilities for
Microorganisms.
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.
Date: 29 June 2001
Mrs Jill White Chair,
Genetically Modified Organisms Standing Committee of the Authority
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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Annex 1: Organism descriptions (Application GMC01002)
Cell lines derived from any strain of laboratory Chinese hamster (Cricetulus griseus MilneEdwards, 1867) that are free of known infectious agents and modified by plasmid vectors or
disabled viral vectors4 that are integrated into Chinese hamster chromosomes. 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
2
Promoter, operator, and enhancer sequences derived from bacterial, yeast or
mammalian genes, or from bacterial or mammalian viruses.
Reporter genes
2.1
Gene products that can be assayed by one or more of the following
techniques:
2.1.1
2.1.2
2.1.3
2.1.4
2.1.5
2.1.6
2.1.7
2.1.8
2.2
3.
And do not produce proteins that are pathogenic or toxic (have an LD505 less
than 100 μg/kg) to vertebrates or are involved in cellular differentiation.
Selectable marker genes
3.1
3.2
4
Visual colour or fluorescence, eg green fluorescent protein
Spectrophotometrically
Histochemically
Enzyme-linked immunosorbent assays (ELISA)
Thin layer chromatography
Liquid scintillation counting
Affinity purification, eg biotinylation, histidine affinity tags
Immunological detection, eg epitope tags
Fully characterised6 genes that confer the ability to tolerate or deactivate:
3.1.1
Antibiotics, eg against hygromycin, neomycin
3.1.2
Metabolic inhibitors, eg against methotrexate, histidinol
3.1.3
Vertebrate toxins
Fully characterised genes that confer the ability to synthesise essential
metabolites, eg His3, Trp1, Ura3
Integrated viral vectors shall not be able to produce infective particles or infect human cells
5
LD50 is defined as Lethal Dose, 50%. The basic idea (and practice) of the test is to take healthy animals (usually mice or rats but sometimes
dogs, monkeys or other animals) and force feed them enough toxin to kill (usually slowly) 50% of them. (Variations include starving the
individual before testing, injecting the tested substance, or coating the animal's skin with the tested chemical.)
6
Fully characterised means that the sequence and function of the gene is known
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3.3
4.
5.
7
And do not produce proteins that are pathogenic or toxic (have an LD50 less
than 100 μg/kg) to vertebrates or are involved in cellular differentiation.
Origins of replication7
4.1
Origins of replication derived from Escherichia coli plasmids
4.2
Origin of replication from Saccharomyces cerevisiae plasmids
4.3
Origins of replication from bacteriophage or mammalian viruses.
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, eg Ψ+
5.10
Viral long terminal repeat sequences
5.11
Cre/Lox recombinase system
Origins of replication are the nucleotide sequences at which DNA synthesis is initiated.
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6.
Donor DNA
6.1
6.2
6.3
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 Māori, that are sourced from New Zealand
6.1.2
Māori 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.
And that the donor DNA shall not include:
6.2.1
Genes encoding vertebrate toxins that have an LD50 of less than
100 μg/kg
6.2.2
More than two thirds of a complete viral genome
Genetic material sourced from humans shall require the informed consent of
the donor or be obtained from a recognised and reputable commercial
supplier.
Environmental Risk Management Authority Decision: Application GMC01002
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