Safety Requirements for Work involving Genetic Modification Covering risk assessment and the...

Safety Requirements for Work involving Genetic Modification

Covering risk assessment and the regulatory and notification requirements for genetic modification work

Dr Joanna MarshallUniversity Biological Safety AdviserHealth & Safety Department

Reference documents and information source

Health and Safety Department website:

http://www.safety.ed.ac.uk/resources/Bio/

Guidance/Index.html

Various sections

General, Containment Laboratories, Pathogens,

Genetic modification, Work with other materials,

Risk assessment forms, Transport

In particular read:

• Good microbiological practice and containment• Hazard grouping and containment requirements• Preventing injuries from glass and sharps• Requirements under the GMO (Contained Use)

Regulations for work with biological agents

Select others depending on nature of your work

egs - Safety cabinets, Work with blood and tissues, Work with naked DNA, Work with animals

Individual workers responsibilities That means YOU!

Individual workers responsibilities

• familiarise yourself with University and School Health and Safety Policies

• carry out your work safely and in accordance with these policies using all control measures specified

• exercise care in relation to yourself and others who may be affected by your actions (or inactions)

• report any safety concerns

The legislation

• The Genetically Modified Organisms (Contained Use) Regulations 2000

Depending on the nature of the work otherlegislation may ALSO apply • for work with plant or animal pathogens

- the Plant Health (Great Britain) Order 1993 (as amended) or the Specified Animal Pathogens Order 1998

• for deliberate release experiments such as field trials and some clinical trials– the Genetically Modified Organisms (Deliberate

Release) Regulations 2002

The Contained Use Regulations

• made under the Health and Safety at Work etc

Act 1974 and the European Communities Act 1972

• replaces earlier legislation – Health and Safety (Genetic Manipulation) Regulations 1978

– Genetic Manipulation Regulations 1989

– Genetically Modified Organisms (Contained Use) Regulations 1992 and subsequent amending regulations

• the 2000 Contained Use Regulations are currently in force

• implement various European Directives

for the protection of

• human health and safety and the environment from contained use activities involving genetically modified micro-organisms (including animal and plant cultures), and

• human health and safety from GM animals and plants

in parallel (and so included in the requirements set out in the remainder of this presentation)

Genetically Modified Organisms (Risk Assessment) (Records and Exemptions) Regulations 1996, as amended in 1997

• made under the Environmental Protection Act 1990

• for the protection of the environment from GM animals and plants

Supporting guidance

• A Guide to the Genetically Modified Organisms (Contained Use) Regulations 2000

• ACGM Compendium of Guidance

• ACGM Newsletters

Also useful is

• categorisations of biological agents in Hazard Groups 2, 3 and 4 - contained in the Approved List of biological agents

Terminology

contained use is defined as

“an activity in which organisms are genetically modified or in which genetically modified organisms are cultured, stored, transported, destroyed or disposed of or used in any other way and for which physical, chemical or biological barriers, or any combination of such barriers, are used to limit contact with, and to provide a high level of protection for humans and the environment”

Key point to remember

Having (on the premises) a GMM or a GMO that has been genetically modified constitutes “use” under these regulations and so you must comply fully with all the provisions of the Contained Use Regulations

more terminology

the term biological agent is not used and instead the definition of micro-organism is extended to include cell cultures as follows

“micro-organism means a microbiological entity, cellular or non-cellular, capable of replication or of transferring genetic material, and includes a virus, viroid, and an animal or plant cell in culture”

more terminology

organism is defined as

“a biological entity capable of replication or of transferring genetic material and includes a micro-organism, but does not include a human or a human embryo”

more terminology

genetic modification is defined as

“… the altering of the genetic material in an organism in a way that does not occur naturally by mating or natural recombination or both …”

the Contained Use Regulations include examples of techniques that do and do not result in genetic modification

Examples of techniques constituting genetic modification• recombinant nucleic acid techniques

involving the formation of new combinations of genetic material by the insertion of nucleic acid molecules, produced by whatever means outside an organism, into any virus, bacterial plasmid or other vector and their incorporation into a host organism in which they do not occur naturally but in which they are capable of continued propagation

another example of GM …..

• techniques involving the direct introduction into an organism of heritable genetic material prepared outside the organism, including micro-injection, macro-injection and micro-encapsulation

another example of GM …..

• cell fusion (including protoplast fusion) or hybridization techniques where live cells with new combinations of heritable genetic material are formed through the fusion of two or more cells by means of methods that do not occur naturally

Key point in defining GM

any technique which alters the genetic material of an organism using a method that would not occur by natural mating or recombination

gene deletions or insertion of multiple copies of a gene are GM if brought about by listed techniques or artificial means

as always though there are exceptions to the rule ………

Techniques which are not considered to result in genetic modification• in vitro fertilisation

• natural processes including conjugation, transduction or transformation

• polyploidy induction

providing they do not involve the use of recombinant nucleic acid molecules or genetically modified organisms

Techniques to which these regulations do not apply• mutagenesis • cell fusion of prokaryotic species which can

exchange genetic material through homologous recombination

• cell fusion of cells of any eukaryotic species, including production of hybridomas and plant cell fusions

providing they do not involve the use of recombinant nucleic acid molecules or genetically modified organisms as recipient or parental organisms

Duties under the Contained Use RegulationsBefore any work is started

• notify premises to HSE– become a registered GM Centre– all individual buildings used must be detailed– information goes on public register

• establish a Genetic Modification Safety Committee (GMSC)– to review and approve risk assessments

and ….before each project is started

• assess risks to human health and safety and the environment– must be suitable and sufficient– take into account matters in Schedule 3 or 4

and include the steps specified– select appropriate containment and control

measures

for GMMs: Containment Levels 1-4

for GMOs: Containment A or B

and ….

• classify the activity– for GMMs: Class 1-4– for GMOs: non-notifiable or notifiable

(notifiable have greater potential to cause harm to humans than the unmodified equivalent)

• submit to GMSC for approval– once approved

• Class 1 GMM and non-notifiable GMO work can proceed

• remainder need activity notification to HSE

and ….various general requirements including• review risk assessments

– regularly– if may no longer be valid– if work changes

• keep records– risk assessment must be recorded and be kept for at

least 10 years after work has finished

• maintain appropriate standards of occupational and environmental safety (GMP and GOSH) – in addition to the control and containment measures

• draw up emergency plans (if necessary)• notify accidents

Individual activity notifications

• required for– Class 2 and above GMMs– notifiable GMOs

• must submit full risk assessment and notification form

• fee payable

• waiting period before work can start

• written consent required before Class 3 and 4 work can start

and ….further notification required• if there is any significant change to the

work• new information becomes available that

effects the risk assessment • any changes are made to the containment

and control measures

Again – must first be approved by local GMSC– fee payable

Notifications and disclosure of information• Public register contains

– premises details– an outline of any notified activity

• All information submitted to HSE is disclosable UNLESS a claim for confidentiality has been made and agreed by HSE - but limited grounds– international relations, national defence or public

security– if affects matters where legal proceedings involved– commercial or industrial confidentiality including

intellectual property rights– confidentiality of a person

and a final point on the regulations….

Meaning of “work” extended

to cover all contained use activities by any persons in any place

Health and Safety at Work etc Act 1974 modified

to treat students as if they are employees of the University

So we now know what we’ve got to do under the Contained Use Regulations

do we feel ready to think about our own work and have a go at a risk assessment?

The bad news

Under the COSHH Regulations• the number of the Hazard Group indicates

the level of containment under which the work must be carried out

• identify whether any additional control measures needed depending on nature of work and route of infection

Unfortunately not so simple under Contained Use Regulations

The good news

• Schedules 3 and 4 specify the matters to be taken into account and steps to be included

• the containment and control measures are very similar

Schedule 3 for GMMs - matters to consider

• potentially harmful effects of– the recipient– the inserted genetic material– the vector– the resulting GMM

• characteristics of activity

• severity and likelihood of harm being realised

Schedule 3 for GMMs - potentially harmful effects

• disease to humans • disease to animals or plants• resulting from inability to treat disease or

offer effective prophylaxis• resulting from establishment or

dissemination of GMMs in environment• resulting from natural transfer of genetic

material from or to GMMs• resulting from interactions of GMMs with

other organisms at premises

Schedule 3 for GMMs - order of steps

• Overview and summary• RA for human health and safety• Assign provisional containment level• Nature of work• RA for environmental harm• Assign any additional control measures• Classify• Assign corresponding level of

containment

Schedule 4 for GMOs - matters to consider

• potentially harmful effects of– the recipient– the inserted genetic material– the vector– the resulting GMO

• characteristics of activity

• severity and likelihood of being realised

Schedule 4 for GMOs - potentially harmful effects

• disease to humans

• acting as a human disease vector or reservoir

• to humans arising from changes in behaviour

• arising from inability to treat human disease or offer effective prophylaxis

Schedule 4 for GMOs - order of steps

• Overview and summary

• RA for human health and safety

• Select containment and protective measures

• Nature of work

• Review and reconsider control measures

• Decide if notifiable

In parallel

consider risks to environment under the

Genetically Modified Organisms (Risk Assessment) (Records and Exemptions) Regulations 1996, as amended in 1997

and assign appropriate control measures

Where to start?

Use the forms available on H&S Dept website

Form GMMO:

Form GMAni:

It’s simple when its spelt out in black and white!

http://www.safety.ed.ac.uk/click on Resources window

click on Biosafety Guidance on left panel

click on Guidance and Information in index

click on selected items for further choices

Health and Safety Department website:

http://www.safety.ed.ac.uk/resources/Bio/

Guidance/Index.html

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