Dr Tom McLoughlin Senior Inspector Office of Climate Change, Licensing & Resource Use EPA

1. Regulation of GMOs in Contained Use facilities in Ireland by the EPA Regulations • S.I. No 73 of 2001 (Contained Use of GMOs) transposes Directive 98/81/EC amending Directive 90/219/EEC-Contained use of GMM. • S.I. No 54 of 2004 (Transboundary Movement)-Reg. 1946/03 Dr Tom McLoughlin Senior Inspector Office of Climate Change, Licensing  & Resource Use  EPA

2. Aims and Objectives • Government Policy • Definitions • Interpretations • Legislation • Obligations on the GMO user • Classification of GMM • Risk Assessment • Requirements for GMM/GMO Notifications • Biological Safety Committee/BSO • Cartegena Protocol • Enforcement by the EPA • Duties and Power of the Agency • Future Trends

3. Definitions Micro-organismmeans ‘any microbiological entity, cellular or non cellular, capable of replication or of transferring genetic material, including viruses, viroids, animal and plant cells in culture’ Genetically Modified Micro-organisms-GMM • bacteria, • viruses, • fungi, • plant & animal cells, capable of replication or of transferring genetic material in which the genetic material has been altered in a way that does not occur naturally by mating or natural recombination.

4. Definitions • Genetically Modified Organisms means any organism in which the genetic material has been altered in a way that does not occur naturally by mating or natural recombination or by a combination of both e.g. plants & animals GMOs inclusive of Genetically Modified Micro-organisms (GMMs).

5. Definitions Contained use ‘any activity in which organisms are genetically modified or in which such organisms are cultured, stored, transported, destroyed, disposed of or used in any other way and for which specific containment and other protective measures are used to limit their contact with the general public and the environment'. Containment measures/barrierscan be physical, biological or chemical or a combination of these.

6. Contained Use (CU) Directive 98/81/EC amending 90/219/ECC Objectives of Directive: Preventive action be taken - protect the environment & human health CU of GMMs - classified in relation to the risks - present for human health & environment Classification - based on RA Containment and other protective measures – correspond - classification of CU Adopt appropriate measures for the disposal of waste - from CU of GMM

7. GMO (Contained Use) Regulations, 2001-S.I. No. 73 of 2001(60 Articles + 8 Schedules) Part I - General Part II - Contained use of GMMs Part III - Contained use of GMOs Part IV - Fees & charges Part V - Enforcement & regulation Part VI - Advisory Committee on GMOs, Monitoring & Reporting etc.

8. Obligations Article 5- A user or any other person carrying out an activity involving a contained use shall ensure that all appropriate measures are taken to avoid adverse effects on human health and the environment. Article 13-Before commencing a Contained Use- RA must be carried out –human health and the environment-which may be associated with such use.

9. What we don’t want…

10. What is Regulated/Not Regulated? Techniques of Genetic Modification - cloning vectors -plasmids & viruses-direct introduction - micro-injection, macro-injection and micro-encapsulation-cell fusion Techniques which are not considered to be GMO - In vitro fertilisation-conjugation, transduction, transformation, mutagenesis, cell fusion, self cloning Oct 2007 - Working Group to be set at EU level up to look at ‘newer’ techniques of GE to ascertain if they should be included or excluded from the remitt of EU Directives-CU/DR? Exemption of safe organisms - Annex II, Part B?

11. Classification of GMM based on Risk Assessment • Activities classified into 1 of 4 classes (Class 1, 2, 3, or 4) Class 1- activities of no or negligible risk, Containment Level 1 (CL1) is appropriate Class 2 - activities of low risk, CL2 Class 3 - activities of moderate risk, CL3 Class 4 - activities of high risk, CL4 • Classification is based on Risk Assessment (Art. 13) • Appropriate level of containment required to control risk to human health and the environment.

12. Register of GMO users in Ireland – October 2007 • 261 registered users • 78% contained use consents (Class 1 & 2) 58% 20%

13. Elements of Risk Assessment • Provisional allocation to Class 1, 2, 3 or 4 as per DIRECTIVE 2000/54/EC –Biological agents at work • Identification of potentially harmful effects associated with: • Recipient Micro-organism • Genetic insert • Vector • Donor micro-organism • Resulting GMM • Assessment of potentially harmful effects occurring • Assign appropriate containment level (CL 1, 2, 3 or 4) and other protective measures to control risk • Review and confirm classification in light of completed assessment

14. Containment Levels and Measures (4th Sched) Table 1A – minimum requirement for contained use of a GMM in a laboratory Table 1B – in addition to Table 1A contained use of a GMM in plant growth facilities Table 1C – in addition to Table 1A contained use of a GMM in animal units Table II – minimum requirements for GMM in facilities other than those covered by tables 1A, 1B or 1C

17. Containment Measures GMP (Good Microbiological Practices) GOSH (Good Occupational Safety and Hygiene) Training, Containment equipment& Special Installation Design. Advice - Biological Safety Committees, BSO

18. GMP & GOSH Keep workplace & environmental exposure - GMM - lowest practicable level; Exercise engineering control measures - source & supplement - protective clothing & equipment; Test & maintain control measures/equipment; Test for presence of GMM outside-primary physical containment; Provide training of personnel; Establish biological safety committees/subcomm. Formulate & implement local codes of practice- safety of personnel, display biohazard signs;

19. GMP & GOSH-cont. Provide washing & decontamination facilities - personnel; Adequate records; written SOP’s to ensure safety; Effective disinfectants - disinfection procedures - spillage of GMMs; Safe storage - contaminated laboratory equipment & materials Prohibit eating, drinking, smoking, application of cosmetics or storage of food for human consumption -work area; prohibit mouth pipetting.

20. GMM Notification Requirements • Art. 16 states that a premises shall not be used for the first time unless • a notification has been submitted by user to EPA • a consent for such use has been granted by EPA • compliance with consent conditions

21. GMM Notification Requirements GMM notification Class 1, 2, 3 & 4. First time use of a premises + Subsequent contained use Class 2, 3 & 4.

22. GMM Notification requirements

23. GMM Notification Requirements Timeframe for decisions First time use of a premises • Class 1/2 - 45 days • Class 3/4 - 90 days Subsequent use of a premises • Class 2 – 10 days • Class 3/4 - Notifier may not proceed without the EPA’s prior approval and the EPA must revert within 45 days. Clock Stoppage

24. GMM Notification Requirements Consents (Article 26) EPA will • issue consent with or without conditions, or, • refuse consent Fees (8th Schedule) • Receipt of fees validates notification • Refund/waiver of up to 50% of fees payable (Article 48)

25. GMM Notification Requirements Annual Reporting User is required to carry out and maintain Risk Assessments (RAs) and to submit to EPA with annual report.

26. INFORMATION REQUIRED -NOTIFICATION FOR FIRST TIME USE OF PREMISES FOR CONTAINED USE - ARTICLE 16 Name of user, persons responsible for supervision & safety Training & qualifications of persons - supervision & safety Details - biological committees/subcommittees Address & general description of premises Description of the nature of the work Class of the contained use Class 1 GMM - a summary of RA - Article 13 Information on waste management Relevant fee - 8th Schedule

27. Information required for a Class 2 contained use - Article 18 Date of submission of the notification - Article 16 Names of persons-supervision & safety & information - training & qualifications Recipient, donor &/or parental micro-organism(s) used & the host -vector Source(s) & intended function(s) of the genetic material - used in modification Identity & characteristics of the GMM Purpose of contained use - expected results Approximate culture volumes - used Description of containment measures, information about waste Management - wastes generated – treatment, final form & destination A summary of the RA - Article 13 Information - CA to evaluate any emergency response plans - Article 30. Relevant fee - 8th Schedule

28. GMO Notification Requirements Notification of Contained Use for a GMO (GM plants/animals) must contain • Risk Assessment (Article 36(2), Part II of 7th Schedule) • Information set out in Part I of 7th Schedule • Fees – no requirement • Activity may commence 45 days after submission of notification • The EPA is not required to issue consent • Annual reporting applies • Guidelines

29. Enforcement • Under Article 26 of the CU Regulations the EPA can issue a consent with or without conditions or refuse consent. • Enforcement - Article 56 –‘The Agency shall carry out, cause to be carried out or arrange for such monitoring, inspections ….’ • To ensure - users comply – conditions - licence • To ensure - risks to human health & environment - managed properly - promote high standard of biological safety • Allay public concerns • Regulator of GM technology - 3rd level; biopharma industry

30. Site Inspection What we look for (use a checklist that was agreed at the European Enforcement Project CU) • General Information re the premises • Containment measures in place • Restricted access • Biohazard signs • Procedures / RA • Training / training records • Class of MSC /date of last validation • Personal protective measures • GMP / GOSH • Handwashing facilities • Segregation of write up area • General observations

31. Site Inspection continued • GMM Storage • Location /in lab?/ elsewhere? / inventory • Waste Inactivation • Location of autoclave relative to lab • Last date of validation • Procedure for decontamination of • Solid waste • Liquid waste • Sharps • Procedure for treatment of spillages • Decontaminating agents • Procedure for reporting of accidents / incidents • Are GMOs/GMMs used for teaching purposes?

32. Enforcement actions Site inspection is followed up with • Site inspection report • Letter of non-compliance to registered user, where applicable, for example, • Annual reporting • Where user has relocated activity and has not informed the Agency • SOPs • Non-notified activity • BSC-management structure • Prosecution of Offences • HC injunction • Notice to Take Measures

33. Duties & Power of the EPA • Review of contained use activities • Enforce Regulations - site inspections, compliance with consent conditions • EPA - require modification, suspension or termination • Report - Minister-performance of functions • Inform the EU Commission of accidents • Notice to take measures • Prosecution of offences • High Court Injunction

34. Cartegena Protocol UN legislation to protect biodiversity – EU Regulation Covers all LMO’s transboundary movement outside the EU Reguirements for Contained Use: Exporters need to provide documentation: Labelling-that it contains or consists of a GMO Unique code, if available RA relating to the safe handling, storage and transport Contacts for further information

35. Help and Guidance www.epa.ie - under ‘What we do/Licensing and Permitting/GMOs’ Licensing process explained Contained Use of GMMs and GMOs, Risk assessment - examples Who should apply - procedures Annual reporting guidance Legislation

36. Future Trends Move to use replicating viral vectors with altered tropism/tissue specificity/ immune evasion Increasing development of viral chimeras Reverse genetics of multi-segmented ds RNA viruses (e.g., Blue-tongue, Rotavirus) Biopharming-to produce human medicines? Drivers for change - e.g., SARs, Influenza H5N1, Climate Change - Blue tongue

37. Concluding remarks The overriding concern of the EPA in the implementation of the GMO Contained Use Regulations is to ensure that their use does not have an adverse effect on human health or the environment.