University Arrangements for Working with Genetically Modified ...

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University Arrangements for Working with Genetically
Modified Organisms



Policy
.


It is the policy of the University that all work involving genetically modified
organisms is carried out in such a way as to prevent undue risk either to those carrying
out
the work, to those who may otherwise be affected by the work, or to the
environment. The University will seek to ensure that all relevant statutory
requirements are complied with.


In particular, work will only be carried out after prior assessment of the
hazards
associated with it and providing that suitable facilities, local procedures and
organisational arrangements are in place. Work may only be carried out by trained
competent workers and will be adequately supervised.


The arrangements described in th
is document form a part of the University’s Health
and Safety Policy.



Definition of Work with Genetically Modified Organisms.


Genetic Modification is defined as the altering of the genetic material of an organism
by a way that does not occur naturally
by mating and/or natural recombination. The
following are examples of techniques that are considered to comprise genetic
modification:
-




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




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




Cell fusion or hybridisation techniques where live

cells with new combinations of
heritable genetic material are formed through fusion of two or more cells by
means or methods that do not occur naturally.


The following techniques are not considered to result in genetic modification:
-




In
-
vitro fertilisa
tion;



Natural processes including conjugation, transduction or transformation;



Polyploidy induction.


Furthermore the Regulations (other than Regulation 17


Principles of Occupational
and Environmental Safety) do not apply to the following techniques:
-




Mutagenesis (
using agents other than GM constructs
);



Cell fusion (including protoplast fusion) of prokaryotic species which can
exchange genetic material through homologous recombination;



Cell fusion (including protoplast fusion) of cells of any eukaryotic

species,
including production of hybridomas and plant cell fusions;



Self
-
cloning, where the resulting organism is unlikely to cause disease to humans,
animals or plants.



Self
-
cloning in this instance means the removal of nucleic acid sequences
from a cel
l of an organism which may or may not be followed by reinsertion
of all or part of that nucleic acid (or a synthetic equivalent), whether or not
altered by enzymic or mechanical processes, into cells of the same species or
into cells of phylogenetically cl
osely related species which can exchange
genetic material by homologous recombination.



Self
-
cloning may include the use of recombinant vectors with an extended
history of safe use in the particular organism, to manipulate and reinsert the
nucleic acid sequ
ences, but the vectors shall not consist of any genetic
elements other than those designed for vector structure, vector replication,
vector maintenance or marker genes.


Commentary Note

HSE have confirmed that knockout mice can be considered as being self
-
cloned.
However such work
is

subject to Home Office Regulation


see following section.


Summary of Relevant Legislation


The principal legislation is the Genetically Modified Organisms (Contained Use)
Regulations 2000. This covers human health and enviro
nmental aspects of work
involving genetically modified micro
-
organisms (GMMs) and human health aspects
of work with animals and plants. Contained use relates to laboratory
-
type work in
which the organisms are contained inside suitable facilities, e.g. a la
boratory designed
to a certain containment level. These regulations require:
-




Establishment of a Genetic Modification Safety Committee to authorise and
supervise GM work;




Submission of a GM Risk Assessment for each project to the GMSC before work
is sta
rted


the purpose being to categorise its hazard and confirm that relevant
containment facilities and procedures are in place;




Prior notification to the Health and Safety Executive of premises to be used for
GM activities and of work with GMMs falling in
to Class 2 and above. HSE
consent is required for Class 3 and 4. Work with plants and animals only requires
prior notification if the product of the genetic modification presents an increased
risk to human health and safety over the unmodified parental org
anism, however
the premises need to be notified if not previously notified for other GM work. The
premises notification must be accompanied by a copy of the risk assessment.
Appendix G summarises the requirements, including fees, relating to notifications
of activities and premises.




Adherence to general principles of good microbiological practice and of good
occupational safety and hygiene (see Appendix A).




Prepare an emergency plan to protect health, safety and the environment.
Appendix B describes the c
ircumstances under which such a plan is required.


Environmental protection aspects of work with GM plants and animals are regulated
under the Environmental Protection Act 1990 and associated regulations. These
regulations include a requirement to carry ou
t risk assessments for environmental
harm, which must be recorded and kept for 10 years after the work has been
completed. Guidance on environmental risk assessments is contained in the HSE
“Compendium of Guidance”. The deliberate release of GMOs into the
environment is
also subject to these controls.


The Control of Substances Hazardous to Health Regulations apply to work with
biological agents, which includes micro
-
organisms, cell cultures and human
endoparasites that may cause infection, allergy toxicity

or other ill
-
health effect.
Biological agents are covered by COSHH in both unmodified and genetically
modified form. The requirement under COSHH to prevent or minimise exposure to a
biological agent means that for GM activities disabled or attenuated deri
vatives of
pathogenic host and vector organisms must be used wherever possible. These
regulations also define the criteria for health surveillance.


Work with animals is also subject to regulation by the Home Office and must be
carried out in accordance wi
th the Animals (Scientific Procedures) Act 1986 and
within the guidelines outlined by the University.


Organisation
.


The Safety Office oversees and advises on compliance with the relevant legislation
and reports to the University Safety Committee on matte
rs relating to activities
involving Genetic Manipulation. In particular:




Any proposal to establish or modify a GM Centre must be approved by the Safety
Office, and




Any proposal to carry out GM work in locations that are not at that time under the
superv
ision of a GMSC must be notified to the Safety Office in order that
appropriate arrangements for local supervision may be established.




Copies of notifications to the HSE, for example activities at class 2 and above, and
of any consents received from HSE,
must be sent to the Safety Office.


Each GM Centre must be notified to the Health and Safety Executive, for which there
is a notification fee payable by the GM Centre. The Safety Office will advise on
notification procedures. The terms of reference and con
stitution of a GMSC are
described in Appendix C. There must be locally held copies of relevant HSE
documents.


The Head of School in any School that carries our genetic modification must ensure
that appropriate arrangements have been made for the work to b
e overseen by a
Genetic Modification Safety Committee and that a suitable Biological Safety Officer
has been appointed. The role of the BSO is described in Appendix D.


The GMSC will report to the School Safety Committee via either the Chair of the
GMSC or

the Biological Safety Officer. Where a GMSC supervises work in more
than one School, a suitable representative from each School on the GMSC will report
to the School Safety Committee on matters relating to that School’s activities
involving genetic manipu
lation.



Project Approval


All work involving genetic manipulation must be initially approved by a GMSC. A
GM risk assessment for the project must be submitted to the GMSC on the standard
university GM risk assessment form (Appendix E).


Proposal submiss
ions will typically follow the following steps:




A new project should be discussed with an appropriate member of the relevant
GMSC. This person should be identifiable from the constitution of the GMSC and
may be a divisional GMSC representative and/or the
Biological Safety Officer. It
may be necessary to consider whether the work actually involves genetic
manipulation as defined. Other chemical and biological hazards should not be
overlooked.



If the project is within the remit of the GMSC, a GM Risk Assess
ment Form
should be completed.



The first draft of the form may be discussed with an appropriate member of the
GMSC. The form will then be presented to all members of the GMSC, usually by
electronic circulation. A paper copy will need to be submitted to th
e Chair for
final formal approval.



When considering a project for approval, the Committee will consider whether the
hazard classification for the work, the environment and the skills etc of the
researchers involved in the project are appropriate. Following

approval
Notification will be given to the Principal Investigator to the effect that:
-



Work may commence, or



That it is of a category that requires notification to the Health and Safety
Executive in which case this will be made by the GMSC. Subsequent
No
tification will be given to the Principal Investigator of when work may
commence. The project will receive final, formal approval at this time.


Additional Considerations




It is permissible to “fast
-
track” proposals clearly falling within the definition o
f a
Class 1 activity. However such work must have received interim approval by at
least three appropriate members of the GMSC, which must include the Chair of
the GMSC, the BSO and one independent committee member. This must be
submitted to the next full G
MSC for full approval. In the event that significant
concerns are identified the GMSC may, according to circumstances, require that
work be suspended.



With the exception of Class 1 activities as described above, work cannot begin on
any project until the C
ommittee’s final, formal approval has been obtained. It is
the role of the Principal Investigator to ensure that everyone working on the
project is aware of the potential risks.



If new staff join a project it need not be classed as a new proposal if the P
rincipal
Investigators, procedures and location remain the same.



If the Principal Investigator changes but the nature of the project, procedures and
location remain the same, the project need not be classed as a new proposal. The
change must however be no
tified to the GMSC, which will then update the project
record.



Records of risk assessments, and any reviews of them, must be kept for at least 10
years following the cessation of the activities to which they relate.



Health Surveillance


Much work involv
ing genetic modification has no identifiable health risk. However,
some types of GM work may involve a risk of ill health resulting from work exposure
to the GM activity in which case
health surveillance may be required.


Examples of GM work that may invo
lve a risk of ill health as a result of exposure are:




Genetically modified micro
-
organisms derived from biological agents classified in
ACDP hazard groups 2
-

4, particularly for example, where modified viruses may
exhibit different tissue tropism, or whe
re the agent is less susceptible to
therapeutic agents, or where immunised workers may not be fully protected;



Cloning of oncogenic or tumorigenic sequences, mutant tumor suppresser genes
or anti
-
sense constructs for tumor suppresser genes;



Work with modif
ied prion protein genes;



Organisms expressing biologically active molecules such as enzymes, hormones,
toxins which may pose risks to health;



Work with a potential for exposure to cloned human genes which may lead to an
immune response and subsequent auto
-
immune type disease;



Work that may cause respiratory sensitisation, especially at large scale and with
the possibility that fusion proteins or inclusion bodies may enhance sensitisation.
The University policy concerning health surveillance for respiratory
sensitisers
would apply under these circumstances.


Health surveillance will only be appropriate where an identifiable health effect may
be related to exposure;
and

there is a reasonable likelihood that the health effect may
occur under the conditions of w
ork;
and

there are means for detecting indications of
the health effect. If a project risk assessment indicates that health surveillance may
need consideration in the light of the above criteria then further advice should be
obtained from Occupational Heal
th.

Records of exposure


Certain types of work require exposure records to be maintained. Exposure records do
not include medical information and are a record of the agents with which an
individual has worked over time. These are as follows:
-




Hazard Gr
oup 3 and 4 biological agents


10 years after work ceases.



Agents that can cause delayed onset illness, examples listed below


40 years after
work ceases:
-

Hepatitis B, C, D and unclassified hepatitis viruses,

Human papillomaviruses,

Human retroviruses a
nd

Prion agents.



Oncogenes and related sequences


40 years after work ceases.


In the case of work with oncogenes and related sequences a copy of the exposure
record to this type of agent should be given to the worker on termination of a contract
so the
information can be passed to the next employer. Appendix F contains a report
that should be issued on termination.


Each GM centre should have in place a mechanism for associating GM projects with
all those that have worked on them. This record should be k
ept with the risk
assessment for a minimum of 10 years after the work ceased, or 40 years if it falls into
either the second or third category above.
Appendix A
-

General Principles of Good Microbiological Practice

and of Good Occupational Safety and Hygie
ne


The general principles of good microbiological practice and of good occupational
safety and hygiene are as follows:
-


a.

Keeping workplace and environmental exposure to any genetically modified
micro
-
organism to the lowest reasonably practicable level;

b.

Exercising engineering control measures at source and supplementing these
with appropriate personal protective clothing and equipment where necessary;

c.

Testing adequately and maintaining control measures and equipment;

d.

Testing, where necessary,

for the presence of viable process organisms outside
the primary physical containment;

e.

Providing appropriate training of personnel;

f.

Formulating and implementing local codes of practice for the safety of
personnel, as required;

g.

Displaying bioha
zard signs where appropriate;

h.

Providing washing and decontamination facilities for personnel;

i.

Keeping adequate records

j.

Prohibiting in the work area eating, drinking, smoking, applying cosmetics or
the storing of food for human consumption;

k.

Prohibiting mouth pipetting;

l.

Providing written standard operating procedures where appropriate to ensure
safety;

m.

Having effective disinfectants and specified disinfection procedures available in
case of spillage of genetically modified organisms; a
nd

n.

Providing safe storage for contaminated laboratory equipment and materials
where appropriate.


Appendix B


Emergency Plans


There are limited circumstances that require an emergency plan. One is required if the
nature of the activity is such tha
t in the event of an accident there could be a serious
off
-
site impact to the health and safety of the public or to the environment.


The requirements for an emergency plan may be summarised as follows:
-




Class 1


safe, none needed.




Class2


Unlikely to
be serious off
-
site risks. Not needed for small
-
scale
operations, large
-
scale operations need to be assessed on a case by case basis but
it is very unlikely that one would be needed in most cases.




Class 3


Required for large
-
scale activities. Small
-
scale

activities must be
individually assessed. One may be needed if the GMMs have novel pathogenic
traits, likely dispersion routes, susceptible populations or environments.




Class 4


Required for all activities.


Incidents to consider include fire; vehicle c
ollision from adjacent road; failure of
fermentation vessel, pipes, seals; and human error.


Should the GMSC consider that an emergency plan might be required then the Safety
Office must be consulted as it may be necessary to liase with external agencies.
Appendix C


Genetic Manipulation Safety Committee



The Genetic Modification Safety Committee has the following functions:




To advise on risk assessment;



To monitor and review GM activities carried out in the GM Centre;



To develop Local Rules for work in
volving genetic modification;



To consider accidents or incidents involving genetic modification;



To consider the findings from safety inspections where these relate to activities
involving genetic modification.


The Advisory Committee on Genetic Manipulati
on recommends the following
constitution:




A chair (elected by the committee)



Representatives of Management (Head of School/senior member of staff
appointed by Head of School)



Biological Safety Officer (appointed by the Head of School)



Deputy BSO where o
ne has been appointed



A representative who sits on the GM committee and the main safety committee



Co
-
opted members to supplement internal expertise as needed to assess particular
proposals


In practice within the University a Genetic Modification Safety

Committee should
typically comprise the following so far as it is applicable to the local circumstances:




Chair



Secretary



Head of School or representative (may be Chair of committee)



Biological Safety Officer (and/or deputy BSO)



Technical Staff Repre
sentative



Research Staff Representative


The BSO should not be the Chair of the Committee.

There should be a mechanism for consulting and informing a representative of the
Estate Office staff (cleaning and maintenance etc).

The Occupational Health Physicia
n should be invited to attend in connection with
issues relating to the management of health risks.


The Committee should report to the School Safety Committee.


The Committee should have a formally specified regularity for meetings determined
by the typi
cal workload for it. Typically two or three meetings a year should be
sufficient and could be shortly before the School Safety Committee meeting. Other

meetings are arranged on an ad hoc basis as necessary.


Sources of Reference


It is essential that the
GMSC can refer to the principal HSE documents relating to GM
activities. The following should be locally available:




The HSE guidance document that supports the Genetically Modified Organisms
(Contained Use) Regulations;




ACGM Compendium of Guidance
-

Guid
ance from the Health and Safety
Commission's Advisory Committee on Genetic Modification;




ACGM Newsletters.




Categorisation of Biological Agents according to Hazard and Categories of
Containment, Fourth Edition, Advisory Committee on Dangerous Pathogens, H
SE
Books 1995, ISBN 0
-
7176
-
1038
-
1




University guidance.


Appendix D
-

The Role of the Biological Safety Officer


The Biological Safety Officer (BSO) fulfils an important role in the local control of
genetic modification activities. The BSO is appointed b
y the Head of School and
should have sufficient seniority and authority coupled with extensive knowledge and
experience of

working within a containment laboratory or with similar practices
.
Deputising arrangements will also need to be made.


Examples of ma
tters upon which the BSO may advise or assist the employer to enable
them to meet the statutory requirements for work with GMOs, include:




ensuring that local rules are drawn up and followed for the safety of personnel;



advising on training of personnel in

appropriate microbiological practice (the level
of training will depend on the level of work being undertaken);



investigating accidents, spillage etc. in the laboratory (or other containment
facility) and taking what action they consider necessary. Approp
riate records and
reports should be made;




the safe storage of modified organisms/harmful or potentially harmful material
and ensuring that records of these are kept;



the appropriate transport of all modified organisms;



ensuring that appropriate disinfecti
on procedures for the laboratories are in place
and followed;



participating in locally organised inspections;



methods for testing, when necessary, for the presence of viable process organisms
outside the primary containment;



ensuring that control measures

and equipment are tested and maintained at
appropriate intervals, for example, by using outside contractors to test and
maintain microbiological safety cabinets;



ensuring appropriate waste disposal procedures are used;



providing technical support to the G
MSC on risk assessment and classification;



ensuring all statutory notifications are made to HSE with copies to the Safety
Office;



adequacy of arrangements for the physical security of the laboratories.



Appendix E
-

University of Nottingham

Genetic Man
ipulation Risk Assessment Form

GM Centre



Project title



Project leader


Intended

start date

Location


Anticipated

duration

Overview


(Brief and simple
project outline, include
purpose and intended
outcome)




Hazard

Identification


in respect of
human
health and
environmental safety.
(Consider host, vector,
insert and final
GMM).




Estimation of the
severity or
consequence of the
harmful effect were it
to occur.





Provisional
Class/
Containment
Level


(in particular taking
account of the
biol
ogical agents
hazard group and other
classification scheme
for pathogens).


This step will often
involve considering
the containment level
necessary to control
the risk of the host and
making a judgement
about whether the
modification will
result in a GMM
which is more
hazardous, less
hazardous or about the

same. Sometimes it
might help to compare
the GMM with the
relative hazard
presented by other
organisms.

Environment
and Activity
Considerations


This includes an
estimation of the
likelihood that haza
rds
will be realised.
Given that the
provisional Class (and
hence containment
level) has already been
decided it helps to
bear this in mind when
deciding how likely a
harmful event is.


Use these
considerations of
likelihood to revise the
provisional
cont
ainment so that all
risks are controlled to
low of effectively
zero.


Double check that all
hazards are properly
controlled by the
proposed containment.



Assign Final
Class of
Activity.


This is done by
comparing the
containment and
control measures
iden
tified as necessary
to control the risk

with
the tables of
containment in
Schedule 8 to the
Regulations.


Notes

or additional
comments





Assessment Submitted by


Date Submitted

Approved by
(on behalf of GM Cttee)

Date Approved


Appendix F


Terminat
ion record for individual exposure.



Control of Substances Hazardous to Health Regulations 1999

Genetically Modified Organisms (Contained Use) Regulations 2000


Record of Work Involving Oncogenes or other Hazardous Sequences


at the University of Nottingh
am


Name:


University Location:



Project
Ref No.

Oncogenes Studied

Start
date

Stop
Date





































Note to leaving worker.


The above record summarises your work with oncogenic or other hazardous sequences during your period

of
work at The University of Nottingham. Employers are required to maintain such records for 40 years after
the work has been completed. You should give this to your new employer to maintain continuity.
Appendix G


Summary of Notification Requirements




Notification of Micro
-
organisms


Notification of Plants and Animals