1. Safety Requirements for Work involving Genetic Modification Covering risk assessment and the regulatory and notification requirements for genetic modification work Dr Joanna Marshall University Biological Safety Adviser Health & Safety Department

2. 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

3. 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

4. Individual workers responsibilities That means YOU!

5. 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

6. The legislation The Genetically Modified Organisms (Contained Use) Regulations 2000 Depending on the nature of the work other legislation 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

7. 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

8. f or 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

9. 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

10. 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

11. 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”

12. 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

13. 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 ”

14. 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”

15. 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

16. 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

17. 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

18. 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

19. 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 ………

20. 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

21. 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

22. Duties under the Contained Use Regulations Before 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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?

31. 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

32. 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

33. 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

34. 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

35. 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

36. 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

37. 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

38. 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

39. 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

40. Where to start?

41. Use the forms available on H&S Dept website

42. Form GMMO:

56. Form GMAni:

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

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

65. click on Biosafety Guidance on left panel

66. click on Guidance and Information in index

67. click on selected items for further choices

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