ENVIRONMENTAL RISK MANAGEMENT AUTHORITY
DECISION
20 June 2005
Application Code
HSC05010
Application Type
To import or manufacture a hazardous substance in
containment under Section 31 of the Hazardous
Substances and New Organisms (HSNO) Act 1996
Applicant
Industrial Research Ltd
PO Box 31310
Gracefield
Lower Hutt
Purpose of the Application
To manufacture in containment a developmental
pharmaceutical product with low mammalian toxicology
but no available ecotoxicology data, to be transferred to
research facilities in NZ and overseas for research and
development
Date Application Received
17 May 2005
Consideration Date
17 June 2005
Considered by
Bas Walker, Chief Executive of ERMA New Zealand
1
Summary of Decision
1.1
The application to manufacture in containment the hazardous substance IRL
Glycotherapeutic 0005 is approved with controls in accordance with the relevant
provisions of the Hazardous Substances and New Organisms Act 1996 (the HSNO Act)
and the HSNO (Methodology) Order 1998 (the Methodology).
1.2
The substance has been given the following unique identifier for the ERMA New
Zealand Hazardous Substances Register:
IRL Glycotherapeutic 0005
2
Legislative Criteria for Application
2.1
The application was lodged pursuant to section 31 of the HSNO Act. The decision was
determined in accordance with section 32, taking into account additional matters to be
considered in that section and matters relevant to the purpose of the Act, as specified
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under Part II of the HSNO Act and the provisions of Part III of the Third Schedule of
the HSNO Act. Unless otherwise stated, references to section numbers in this decision
refer to sections of the HSNO Act.
2.2
Consideration of the application followed the relevant provisions of the Methodology.
Unless otherwise stated, references to clauses in this decision refer to clauses of the
Methodology.
3
Application Process
3.1
The application was formally received on 17 May 2005 and assessed as having
sufficient information on 18 May 2005.
3.2
Project Team:
Beth Dye
Applications Advisor (Hazardous Substances)
Tania van Maanen
Science Advisor (Hazardous Substances)
Report review and sign-out by:
Noel McCardle
Applications Team Leader (Hazardous
Substances)
3.3
The applicant supplied the following documents:
 The application, including confidential appendices containing commercially
sensitive information.
3.4
The following Government departments were advised of the receipt of the application
(in accordance with clause 2(2)(e)) and given the opportunity to comment:
 The Ministry of Health
 The Department of Labour (Occupational Safety and Health)
 The New Zealand Food Safety Authority (Agricultural Compounds and Veterinary
Medicines Group (ACVM Group)).
3.5
The Ministry of Health responded that, “with appropriate HSNO controls, The Ministry
has no issues to raise at this time relating to the acceptance of this application based on
non-confidential information provided from a public health perspective (nonoccupational)”.
3.6
The applicant was provided with a copy of the proposed controls for IRL
Glycotherapeutic 0005 and given the opportunity to comment on them. The applicant
raised no issues with the proposed controls.
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4
Consideration
Sequence of the Consideration
4.1
This application was considered by the Chief Executive of ERMA New Zealand under
delegated powers from the Authority (section 19(2)(e) of the HSNO Act).
4.2
In accordance with section 32 of the Act, the approach adopted when considering this
application was to confirm whether the application was for one of the purposes
specified in section 30, to identify and assess the risks and to determine whether the
substance could be adequately contained by controls to provide for each of the matters
specified in Part III of the Third Schedule of the Act.
Purpose of the Application
4.3
The purpose of the application is to manufacture in containment a developmental
pharmaceutical product with low mammalian toxicology but no available ecotoxicology
data, to be transferred to research facilities in NZ and overseas for research and
development.
4.4
The applicant has previously applied for and received a containment approval for this
substance (Application number HSC04006, decision notified 12 July 2004, approval
number HSC000096). This second application is required because the applicant wishes
to increase the quantity produced to 400kg (a total of 17.5kg was the maximum amount
of the substance covered by the first approval), and because the applicant wishes to
include transport to a containment facility in Palmerston North for lyophilisation, a step
which was not covered in the first approval.
4.5
As the purpose amounts to “research and development on any hazardous substance”, I
consider that the application qualifies for consideration under section 30(ba) of the Act.
Description and Use of the Substance
4.6
IRL Glycotherapeutic 0005 is comprised of an organic active ingredient in a complex
with beta-cyclodextrin as a carrier, for use in pharmaceutical research. It is being
developed as a treatment for Freidreich’s ataxia and Huntingdon’s Disease.
Hazardous Properties
4.7
I note that a containment application only requires sufficient understanding of the
hazardous properties to ensure that any risks can be managed by the containment
controls.
4.8
The applicant states that IRL Glycotherapeutic 0005 is a complex formed between the
active chemical and the carrier. The toxicity and ecotoxicity of the substance are
largely unknown, but the applicant considers that by comparison with similar
substances, any toxicity or ecotoxicity is expected to be low. It is not expected to have
any explosive, flammable or oxidising hazardous properties.
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4.9
The active chemical is a new substance and there is no published information on its
toxicity or ecotoxicity. The portion of the molecule responsible for its anti-oxidant
properties is nevertheless closely related to the nutritional supplement ingredient
idebenone, which is consumed widely by humans in the USA.
4.10
The carrier, beta-cyclodextrin, is a low toxicity, naturally occurring compound used as
a food additive.
4.11
I have reviewed the applicant’s hazard information. This is insufficient to fully
describe the hazards of the substance but provides a workable basis for setting the
containment controls to ensure that any risks can be adequately managed.
Life Cycle
4.12
IRL Glycotherapeutic 0005 will be synthesised at Industrial Research Limited,
Gracefield Research Centre, Lower Hutt, within purpose-built facilities. In total, 20
batches of approximately 20kg will be produced. Once synthesised, the substance will
be transported as a 5% w/w aqueous solution in secondary, secure containment to a
containment facility in Palmerston North, where it will be lyophilised. A maximum of
400 litres will be transported at any one time. The lyophilised substance (as a dry
powder) will be returned to IRL GlycoSyn for packaging and despatch to:
 Huntington Research Labs, UK, for toxicology studies in animals;
 Douglas Pharmaceuticals Ltd, Auckland, for formulation into tablets;
 ESR, Porirua, small samples for analysis; and
 School of Pharmacy, University of Otago, small samples for analysis.
The tablets produced by Douglas Pharmaceuticals Ltd will be shipped to clinical trial
facilities in Christchurch, Australia and the USA for use in phase 2 studies in patients.
Identification and Evaluation of the Significant Risks of the Substance in
Containment
4.13
In accordance with sections 5, 6, and 8 and clauses 9 and 11, I considered the potential
risks of escape from containment under the headings of environmental, human health
and welfare and Māori issues and concerns.
4.14
In the application, the applicant identified and assessed potential risks, and detailed
proposals for, and impacts of risk management. I have reviewed the applicant’s
assessment of risks and agree that it is suitable for the consideration below.
Risks to the Environment
4.15
No ecotoxicological data are available on the substance, but the applicant considers that
by comparison with similar substances, any ecotoxicity is expected to be low.
4.16
On the basis of the lifecycle of the substance outlined in paragraph 4.12, adverse effects
could arise from:
 An accident during manufacture or transportation, resulting in release of the
substance.
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4.17
I note that the synthesis facilities have primary, secondary and tertiary containment, and
that the lyophilisation facility is a contained processing area with its own waste
collection system. I note also that both transport of the substance to the lyophilisation
facility and subsequent transport of the dry powder will be in a container within a
container, with the secondary container sufficient to control any release should the
primary container be damaged and leak.
4.18
I consider that, taking into account the likely properties of the substance, the
containment controls in Appendix 1 and controls in place under other legislation, there
are no significant risks to the environment.
Risks to Human Health and Welfare
4.19
Limited toxicological data are available on the substance, but the applicant considers
that by comparison with similar substances, any toxicity is expected to be low.
4.20
On the basis of the lifecycle of the substance outlined in paragraph 4.12, adverse effects
on human health and welfare could arise from:
 An accident, resulting in exposure during manufacture or transportation.
4.21
I note that the synthesis facility has been designed with a focus on operator safety, and
that all transport of the substance will be in a container within a container, with the
secondary container sufficient to control any release should the primary container be
damaged and leak. I note that the applicant states that normal access to the
lyophilisation facility is controlled by an electronic security system (swipecard) with
only trained authorised personnel having access to the facility.
4.22
I consider that, taking into account the likely properties of the substance, the
containment controls in Appendix 1 and controls in place under other legislation, there
are no significant risks to human health and welfare.
Māori issues and concerns
4.23
I have considered the potential Māori cultural effects of this application in accordance
with sections 6(d) and 8 of the HSNO Act, and the assessment framework contained in
the ERMA New Zealand User Guide “Working with Māori under the HSNO Act
1996”.
4.24
I consider that the substance is unlikely to have an impact on the relationship of Māori
and their culture and traditions with their ancestral lands, water, sites, waahi tapu,
valued flora and fauna and other taonga. This is on the condition that the substance is
used in accordance with the controls in Appendix 1, and in accordance with any other
relevant controls applied under other legislation.
5
Containment and Controls
5.1
I have evaluated the adequacy of the containment arrangements proposed by the
applicant and the controls listed in Appendix 1, and note that these cover the matters set
out in Part III of the Third Schedule of the Act, being:
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




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To limit the likelihood of escape of any contained hazardous substances or
contamination by hazardous substances
To exclude organisms from a facility
To exclude unauthorized people from the facility
To prevent unintended release of the substances by experimenters working with the
substances
To control the effects of any accidental release of the substances
Inspection and monitoring requirements.
5.2
I am satisfied that with adherence to the controls listed in Appendix 1 and those
controls in place under other legislation, the substance can be adequately contained.
6
Decision
6.1
I have considered this application under section 31 to manufacture in containment a
hazardous substance, and pursuant to section 32, I am satisfied that this application is
for the purpose specified in section 30(ba).
6.2
Having considered the risks associated with the lifecycle of IRL Glycotherapeutic
0005, I am satisfied that the controls imposed, including those in place under other
legislation, will result in the substance being adequately contained.
6.3
In accordance with clause 36(2)(b) of the Methodology I record that, in reaching this
conclusion, I have applied the criteria specified in section 32 of the Act.
6.4
I have also applied the following criteria in the Methodology:
 clause 9 – equivalent of sections 5, 6 and 8;
 clause 11 – characteristics of substances;
 clause 21 – the decision accords with the requirements of the Act and regulations;
 clause 22 – the evaluation of risks – relevant considerations;
 clause 24 – the use of recognised risk identification, assessment, evaluation and
management techniques.
6.5
The application to manufacture in containment the hazardous substance IRL
Glycotherapeutic 0005 is thus approved pursuant to section 32 of the Act, with controls
as set out in Appendix 1.
Bas Walker
Date 20 June 2005
Chief Executive of ERMA New Zealand
ERMA New Zealand Approval Code:
IRL Glycotherapeutic 0005:
HSC000156
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Appendix 1: List of controls that apply to the
hazardous substance IRL Glycotherapeutic 0005
1. The facilities where the substance will be synthesised and lyophilised shall comply with
the Hazardous Substances (Exempt Laboratories) Regulations 2001. Compliance with
these regulations will cover the matters to be addressed by the containment controls for
hazardous substances contained in Schedule 3, Part III, of the HSNO Act.
2. The substance shall be shipped only to the facilities which have been identified in the
application.
3. A maximum of 400 kilograms of the substance shall be manufactured.
4. Synthesis shall take place within the facilities at Industrial Research Limited (IRL) as
identified in the application. Lyophilisation shall take place at the Palmerston North
facility as identified in the confidential appendix to the application.
5. All personnel carrying out the synthesis, lyophilisation and packaging of the substance
shall wear appropriate personal protective equipment.
6. Handling of the substance shall be in accordance with good laboratory practice. Any
spillage of the substance shall be cleaned up with appropriate absorbent material. The
used absorbent material shall be securely packaged and retained in the relevant facility
until it has been rendered non-hazardous prior to disposal.
7. The substance shall be stored in the IRL facility initially following manufacture. Only
authorised personnel shall be allowed into the IRL facility, which has access controlled
by electronic security systems and is itself located within a controlled access site.
8. The substance shall be packaged for transportation in a container within a container
(secondary containment) and that secondary container shall be sufficient to control any
release if the primary container should leak. The containers shall comply with the
Hazardous Substances (Packaging) Regulations 2001, and shall be labelled in accordance
with Regulation 11 of the Hazardous Substances (Exempt Laboratories) Regulations
2001. A Safety Data Sheet shall accompany each shipment.
9. The substance shall be transported in accordance with good practice. This may require
compliance with the Land Transport Rule: Dangerous Goods 1999.
10. If for any reason a breach of containment occurs, the Manager: GSF Facility shall notify
OSH (HSNO Project Manager) and ERMA New Zealand (Beth Dye) within 24 hours of
the breach being detected. It is suggested that if a breach in containment results in
contamination of a waterway, the relevant iwi authorities be advised of the contamination
and the measures taken in response.
11. The Authority, or its authorised agent or properly authorised enforcement officers, may
inspect the facility at any reasonable time.
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