Dir 116 Risk Assessment and Risk Management Plan

Conclusions of the consultation RARMP

The risk assessment concludes that this proposed limited and controlled release of GM virus to take place in hospitals in ACT, NSW, QLD, SA, VIC and WA, involving up to 1200 trial participants and expected to run for up to five years, poses negligible risks to the health and safety of people or the environment as a result of gene technology.

The risk management plan concludes that these negligible risks do not require specific risk treatment measures. If a licence were to be issued, conditions are proposed to limit the release to the size, locations and duration requested by the applicant, and to require controls in line with those proposed by the applicant, as these were important considerations in establishing the context for assessing the risks.

Call for comment

The Regulator invites comments on the RARMP for application DIR 116, including the licence conditions proposed if a licence were to be issued to the Pharmaceutical Product Development Australia Pty Ltd (PPD) for this release. The closing date for written submissions is 3 September 2012.

The Regulator would particularly value comments relating to risks to the health and safety of people or the environment posed by the proposed release.

All comments relating to the protection of people or the environment that are received by the closing date will be considered by the Regulator in finalising the RARMP, which will then form the basis of his decision whether or not to issue a licence.

Please note that issues such as patient safety and the quality and efficacy of a therapeutic product do NOT fall within the scope of the evaluations that the Regulator is required to conduct under the Gene Technology Act 2000 and corresponding State and Territory legislation as these are the responsibilities of other agencies and authorities.

The consultation RARMP can be accessed on the OGTR website under 'What's New' or you can request a copy of the RARMP or the application from the OGTR. Please quote application number DIR 116.

The Regulator's Risk Analysis Framework and a plain English Questions and Answers on this application can also be accessed on the OGTR website or obtained from the OGTR.

If you have any questions about the RARMP or the evaluation process, please contact:

The Office of the Gene Technology Regulator

MDP 54 GPO Box 9848 Canberra ACT 2601

Tel: [phone]

Fax: [phone]

Email: [e-mail]

Website: http://www.ogtr.gov.au

Table of Contents

Executive Summary I

Introduction I

The application I

Confidential Commercial Information I

Risk management plan II

Conclusions of the consultation RARMP II

Call for comment III

Table of Contents IV

Abbreviations VI

Technical Summary 1

Introduction 1

The application 1

Confidential Commercial Information 1

Risk assessment 1

Risk management plan 2

Proposed licence conditions 2

Other regulatory considerations 3

Identification of issues to be addressed for future releases 3

Conclusions of the consultation RARMP 3

Risk context 4

Section 1 Background 4

Section 2 The legislative requirements 4

Section 3 Scope and boundaries 5

Section 4 The proposed dealings 5

4.1 The proposed activities 6

4.2 The proposed limits of the dealings (size, location and duration) 7

4.3 The proposed controls to restrict the spread and persistence of the GMOs and their genetic material in the environment 7

Section 5 The parent organisms 8

5.1 Vaccinia virus and Fowlpox virus taxonomy 8

5.2 Distribution and transmission 9

5.3 Vaccinia virus and Fowlpox virus genomic organisation 11

5.4 Poxvirus life cycle 11

5.5 Pathology of viral infection 13

5.6 Poxvirus environmental stability 14

5.7 Vaccinia virus vaccine strain NYCBH 15

5.8 Fowlpox virus vaccine strain POXVAC-TC 15

Section 6 The GMOs, nature and effect of the genetic modification 15

6.1 Introduction to the GMOs 16

6.2 The introduced genes, their encoded proteins and their associated effects 17

6.3 The regulatory sequences 18

6.4 Method of genetic modification 18

6.5 Characterisation of the GMOs 19

6.6 Results of previous clinical trials with the GM vaccines 19

Section 7 The receiving environment 20

7.1 Relevant environmental factors 20

7.2 Presence of related viruses in the receiving environment 21

7.3 Presence of the introduced genes, similar genes and encoded proteins in the environment 21

Section 8 Australian and international approvals 21

8.1 Australian approvals of GM vaccinia and fowlpox vaccines 21

8.2 International approvals of GM poxvirus vaccines against prostate cancer 22

Risk assessment 24

Section 9 Introduction 24

Section 10 Risk identification 25

10.1 Production of a substance toxic/allergenic to people or toxic to other organisms 27

10.2 Increased disease burden from the GM virus 28

10.3 Unintended changes in viral characteristics 32

10.4 Horizontal transfer of genes or genetic elements to other organisms 33

10.5 Unauthorised activities 34

Section 11 Risk estimate process and assessment of significant risk 35

Section 12 Uncertainty 35

Risk management plan 37

Section 13 Background 37

Section 14 Responsibilities of other Australian regulators 37

Section 15 Risk treatment measures for identified risks 37

Section 16 General risk management 38

16.1 Proposed licence conditions to limit and control the release 38

16.2 Other risk management considerations 39

Section 17 Issues to be addressed for future releases 41

Section 18 Conclusions of the RARMP 41

Proposed licence conditions 42

Section 19 Interpretations and Definitions 42

Section 20 General conditions 43

Section 21 Limits and control measures 46

Section 22 Transport and Disposal 48

Section 23 Samples containing the GMO 48

Section 24 Reporting and Documentation Requirements 48

References 50