NBTNBTNBTNBTSSSS ANDANDANDAND AAAAUSTRALIANUSTRALIANUSTRALIANUSTRALIAN GGGGENEENEENEENE TTTTECHNOLOGYECHNOLOGYECHNOLOGYECHNOLOGY

LLLLEGISLATIONEGISLATIONEGISLATIONEGISLATION

Dr. Michael DornbuschOffice of the Gene Technology Regulator

Australia

Integrated Regulation of GMOs & GM ProductsIntegrated Regulation of GMOs & GM ProductsIntegrated Regulation of GMOs & GM ProductsIntegrated Regulation of GMOs & GM Products

� OGTR regulates GMOs. Some overlap with other agencies

� Avoid duplicating regulation where another agency has oversight

� Align decision making as far as possible

� Herbicide tolerant GM crops – human food safety is assessed by FSANZ & herbicide use is regulated by the APVMA

FSANZFood Standards

Australia New Zealand

Food standardsand labelling

TGATherapeutic

GoodsAdministration

Human medicines & medical devices

NICNASNational

IndustrialChemicals

Notification & Assessment

SchemeAuthority

OGTR

Office of the Gene Technology Regulator

Live & viablemodified

organisms

www.foodstandards.gov.au www. nicnas.gov.au

www.tga.gov.au www.apvma.gov.au

APVMAAustralian

Pesticides& Veterinary

MedicinesAuthority

1st DNAtransfer 1946

Discussion of new breeding technologies 2010

Voluntary oversight begins in Australia

Bt cotton in Australia 1996

100th DIR licence 2013

AsilomarConference1975

Flavr Savrtomato in USA 1995

Gene Technology Act and Regulations 2001

GM tobacco plant produced 1983

Genetic Manipulation Advisory Committee (GMAC) 1987

GM cotton comprises 95% of crop 2009

Technology and regulation

Review of GT Act 2005

Review of GT Act 2011

Gene technology in late 1990’s

10

35S gene nos

Explanatory Memorandum for GT Act“Gene technology involves the modification of organisms by the direct incorporation or deletion of one or more genes to introduce or alter a specific characteristic or characteristics”

‘To protect the health and safety of people, To protect the health and safety of people, To protect the health and safety of people, To protect the health and safety of people,

and to protect the environment, and to protect the environment, and to protect the environment, and to protect the environment,

by identifying risks posed by by identifying risks posed by by identifying risks posed by by identifying risks posed by

or as a result of or as a result of or as a result of or as a result of gene technologygene technologygene technologygene technology, , , ,

and by managing those risks through regulating and by managing those risks through regulating and by managing those risks through regulating and by managing those risks through regulating

certain dealingscertain dealingscertain dealingscertain dealings withwithwithwith GMOGMOGMOGMOs’s’s’s’

Gene Technology Act 2000Gene Technology Act 2000Gene Technology Act 2000Gene Technology Act 2000

DEFINITIONS

The Gene Technology Act 2000

genetically modified organism means:

a) an organism that has been modified by gene technology; or

b) an organism that has inherited particular traits … that occurred in the initial organism because of gene technology; or

c) anything declared by the regulations to be a GMO;

but does not include:

d) a human being, if the human being is covered by paragraph (a) only because [of] somatic cell gene therapy; or

e) an organism declared by the regulations not to be a GMO

DEFINITIONS

The Gene Technology Act 2000

gene technology means any technique for the modification of

genes or other genetic material, but does not include:

a) sexual reproduction; or

b) homologous recombination; or

c) any other technique specified in the regulations

DEFINITIONS

The Gene Technology Regulations 2001

Schedule 1A Techniques that are not gene technology

1. Somatic cell nuclear transfer (not involving GM material)

2. Electromagnetic radiation-induced mutagenesis

3. Particle radiation-induced mutagenesis

4. Chemical-induced mutagenesis

5. Fusion of animal or human cells, if unable to form a viable whole animal or human

6. Protoplast fusion, including fusion of plant protoplasts

7. Embryo rescue

8. In vitro fertilisation

9. Zygote implantation

10. A natural process (not involving GM material)

Examples of natural processes include conjugation, transduction, transformation and transposon mutagenesis.

DEFINITIONS

The Gene Technology Regulations 2001

Schedule 1 Organisms that are not GMOs

1. A mutant organism in which the mutational event did not involve the introduction of any foreign nucleic acid (that is, non-homologous DNA, usually from another species)

....

6. An organism that results from an exchange of DNA if:

(a) the donor species is also the host species; and

(b) the vector DNA does not contain any heterologous DNA

IIIINTENTIONNTENTIONNTENTIONNTENTION OFOFOFOF GT AGT AGT AGT ACTCTCTCT DEFINITIONSDEFINITIONSDEFINITIONSDEFINITIONS

• Gene technology/GMO definition designed to have a broad capture

• Regulations intended to provide criteria to exclude organisms and/or techniques which:

• Give rise to organisms that occur in nature so have no unique biosafety risks

• Commonly used in biological research

• Long history of safe use

Year 2014+ ‘genome editing’

Cisgenesis and intragenesis

Transient expression

Targeted mutagenesisOligo-directed mutagenesis

RANGE OF TECHNIQUES

� Oligonucleotide direct mutagenesis

� RNAi

� Cisgenesis

� Grafting

� Zinc Finger Nucleases

� TALENs

� Meganucleases

� CRISPRs

� Negative segregants

REGULATOR’S APPROACH

� Range of possible applications and outcomes of technologies-general advice difficult

� Provide advice on case-by-case basis

� Careful examination of the technical details, processes used and final organism produced in relation to the relevant provisions of the Act and the Regulations.

� Work with other regulatory agencies to harmonise approaches wherever possible within legislative restrictions

CONSIDERATIONS

� Did it involve gene technology?

� Look in detail at process making the organisms

� Definition in the Act and

� Schedule 1A regulations- techniques excluded

� Is it a GMO?

� Did it inherit traits from a GMO?

� Schedule 1- Is it excluded?

eg did the mutational event involve the introduction of foreign nucleic acid?

SOME EXAMPLES - SDNS

SOME EXAMPLES RNAi

� Introduced silencing constructs eg hairpin

� Not so “new” technology

� Approved 19 field trials since 2002

� Poppies, wheat and barley, papaya, ryegrass, cotton

� Special risk assessment method required?

8 Experiments in laboratory or glasshouse (‘contained’)

8 Field trials (with limits & controls)

8 Commercial release (with minimal controls)

TYPICAL DEVELOPMENTAL PATHWAY

Risk assessment approaches

� Same risk assessment methodology applies

� Specific information in application may differ

� Look at each case-by-case

What is the level of risk ?

Risk estimation

How likely is harm to occur ?

Likelihood assessment

How serious could the harm be ?

Consequence assessment

EVIDENCE

UNCERTAINTY

What could go wrong ?

How could harm occur ?

Risk identification/scenario

(causal pathway to harm)

Risk AssessmentRisk AssessmentRisk AssessmentRisk Assessment–––– simple questionssimple questionssimple questionssimple questionsRISK ASSESSMENT CONTEXTRISK ASSESSMENT CONTEXTRISK ASSESSMENT CONTEXTRISK ASSESSMENT CONTEXT

RNAi risk assessment

� Same risk assessment methodology

� Product of introduced genetic material =RNA

� No new protein produced

� Don’t look at toxicity/ allergenicity of protein product

Risk AssessmentRisk AssessmentRisk AssessmentRisk Assessment–––– broad broad broad broad considerationsconsiderationsconsiderationsconsiderations

� A GM plant is a plant

� Plants developed using NPBTs are still plants

� Phenotype is important for risk assessment

� Able to identify weediness/invasiveness traits

� Weediness/invasiveness traits encompass all undesirable effects

BIOLOGY

GMO

All harms

Harms from weeds Potential

harmsfrom GM plants

FUTURE WORK ON NBTS

� Independent review of the Act in 2011 considered the coverage of new technologies.

� Government response to the review now finalised.

� The review recommended and all governments supported :

Investigate regulatory scope to reduce ambiguity and ensure that it keeps up with technology

Copyright

© Office of the Gene Technology Regulator 2014.

This work is copyright. You may download, display, print and

reproduce this material in unaltered form only (retaining this notice)

for your personal, non-commercial use or use within your

organisation. Apart from any other use as permitted under the

Copyright Act 1968, all other rights are reserved.

Requests for further authorisation should be directed to

ogtr@health.gov.au