GM ASSESSMENT MASTERCLASS

Giving Expert Advice on GM Risk

Assessments

Jonathan Gawn University Biological Safety Officer

University of Manchester

David Brown Biosciences Technical Lead (Contained Use),

HSE Microbiology and Biotechnology Unit

Your morning…

Part 1: Reviewing risk assessments What to look for, good questions to ask, how to deal with uncertainties, and ways of

tackling tricky classifications (e.g. lentiviruses; CRISPR/Cas9)

Comfort break

Part 2: Notifying HSEWhat to include, and what not to say to avoid requests for additional information

Lunch

GM ASSESSMENT MASTERCLASS

Overall objective…

Get an appreciation of the things to consider

when reviewing risk assessments as a

competent individual (class 1) or as part of a

genetic modification safety committee (class 2

and above).

Regulation 8 - Advice from a genetic modification safety committee

A person responsible for contained use must obtain advice on a risk assessment from either—

(a) a person; or [class 1 only](b) a genetic modification safety committee [class 2 – 4]

with expertise in risk assessment relating to contained use.

GM Safety Committee

GM Safety Committee• Review proposals involving Genetic Modification and consider whether

the proposed activity class and control measures are appropriate

• Review proposals involving work with biological agents and consider whether the containment and control measures are appropriate

• Consider whether the competence of those involved in each proposal are sufficient to carry out the work safely

• Consider queries received from the Health & Safety Executive concerning proposals

• Develop an inspection program and monitor progress and findings

• Consider accidents and incidents related to GMOs and biological agents

• Advise on general laboratory practice with regards to safety

• Consider whether arrangements for health surveillance and workplace monitoring are adequate

• To advise on the drawing up of local rules to cover work involving GMOs and biological agents

The core mission…

Assurance that:

1. All reasonable hazards have been identified

2. Control measures are appropriate

3. The GM activity classification is correct

4. Information clear and appropriate enough to send to HSE (class 2+)

…through challenging the risk assessment and it’s assumptions

An important point

GM risk assessments are predictive

Not knowing is not a reason for not

assessing

Need to consider potential for harm

• To people

• To the environment

…as a function of what is being donewith the GMO – ACTIVITY BASED

• One-word answers or poor justification

• Not describing mechanism of

disablement/attenuation or possibility of reversion

• Limited prediction of the final properties of a GMM

• In vivo activities - probably involves the greatest risk

of worker exposure

– Mentioned and not assessed

– Poorly assessed

• Environmental hazards overlooked

– Survivability, dissemination and transfer of genes

• Containment and control measures not linked to

identified hazards

Shortcomings in risk assessments

• Identify the most hazardous GMO

• E.g. Transduced cells are unlikely to be the most hazardous

part – the vector is!

• Don’t forget the environment• Don’t get unduly caught up in the technical

• E.g. What might it do… not how is it made…?• Watch for:

• Non-standard control measures

• Use of ‘central’ facilities and equipment• Vague references to animal work, needles and scalpels

• ‘Unnecessary’ use of cabinets and gloves• Using ‘no evidence that…’ to dismiss a hazard

Top tips

Classification

• Determined by the control measures specifically required to

mitigate risks to human health and the environment

– Activity, not just the GMM!

• For class 1, it must also be justified that it is of no or negligible risk to human health/environment

• Not determined by standard good practice in the labs

– Labs built to CL2 standard

– Cabinets used to protect the product

– Gloves/PPE always worn

– Training records kept

What makes it class 2?

If the risk assessment identifies the following controls as being

required to control risks then it is class 2:

– Safety cabinet or other measures to minimise aerosol risks (to

protect human health/environment, not the work)

– Restricted access (activity specific, not routine)

– Gloves (to protect human health, not the work)

– Records of training (specific to the activity)

Or

The nature of the organism or the activity make it more likely that it

could cause harm to human health/environment

Or

You cant justify that it is of no or negligible risk to human

health/environment

Playtime!

• You are, the UK’s biggest GMSC, and I am its Chair!

• A researcher is going to present a project regarding

the use of Lentiviral vectors

• What questions are you going to ask?

• What comments are you going to make?

• What will you ask the researcher to change or do

next?

• Ask them!

Classifying Lentiviral Vectors

The problem…?

Risks from inserted material

LV vector

Oncogene

Reporter

Cytokine

Not just transgene that needs to be considered…

Toxin

CRISPR Cas9gRNAsiRNA

gRNA

CRISPR/Cas9

Unknown

Restricted

tropism

Broad tropism Increased likelihood of

harm

Increased likelihood of

harm

Required control

measure

RESTRICTED ACCESS