Topic 2: Part A, sections 4 to 6
Mr. Stephane Bilodeau,
Secretariat of the Convention on Biological Diversity#11767
Secretariat of the Convention on Biological Diversity#11767
منذ ٣ أعواممنذ ٣ أعوام
Part A: Risk assessment of living modified organisms containing engineered gene drives (EGD-LMOs)
4. Planning phase of the risk assessment of EGD-LMOs
5. Conducting the risk assessment
6. Related issues
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4. Planning phase of the risk assessment of EGD-LMOs
5. Conducting the risk assessment
6. Related issues
Participants are requested to follow the forum guidelines:
1. Briefly introduce themselves when posting their first message, including their name, country and institutional affiliation.
2. Keep their messages short, concise and focused.
3. Ensure that the messages are relevant to the topic/question being discussed.
4. Make sure that the text or files attached do not contain viruses, corrupted files or any other similar file deficiencies.
5. Be respectful of others’ points of views.
Dear All
My name is Marvis Esther Suárez Romero, I am Veterinary Doctor and Master degree in Virology, currently working in the Biodiversity and Biosafety Department (Office of Regulation and Environmental Safety) in Cuba, as Senior Specialist in Regulation, Control and Safety.
I am also Technical assistant in the GEF - UNEP International Project on “Creation of additional biosafety capacities that lead to a full implementation of the Cartagena Protocol on Biosafety in Cuba” and the other hand technical expert on Biosafety in the international project "Support for early action of the Global Biodiversity Framework" in our country.
For me is a pleasure to participate in this discussions for second time, the first time was in 2019.
In relation to the planning phase of the risk assessment of EGD-LMOs, it is very important to take into account national legislation. The cuban biosafety legislation regulates all activities with genetically modified organisms, including EGD-LMOs. Currently this issue in Cuba is only in the laboratory phase, under investigation.
Another important aspect is that the risk assessment should be conducted by a multidisciplinary group that can provide information about the technology, the identified protection goal, and its receiving environment in order to identify possible damages.
Kind regards,
My name is Marvis Esther Suárez Romero, I am Veterinary Doctor and Master degree in Virology, currently working in the Biodiversity and Biosafety Department (Office of Regulation and Environmental Safety) in Cuba, as Senior Specialist in Regulation, Control and Safety.
I am also Technical assistant in the GEF - UNEP International Project on “Creation of additional biosafety capacities that lead to a full implementation of the Cartagena Protocol on Biosafety in Cuba” and the other hand technical expert on Biosafety in the international project "Support for early action of the Global Biodiversity Framework" in our country.
For me is a pleasure to participate in this discussions for second time, the first time was in 2019.
In relation to the planning phase of the risk assessment of EGD-LMOs, it is very important to take into account national legislation. The cuban biosafety legislation regulates all activities with genetically modified organisms, including EGD-LMOs. Currently this issue in Cuba is only in the laboratory phase, under investigation.
Another important aspect is that the risk assessment should be conducted by a multidisciplinary group that can provide information about the technology, the identified protection goal, and its receiving environment in order to identify possible damages.
Kind regards,
Dear all,
My name is Raja CHALGHOUMI. I am an Associate Professor in Animal Nutrition at the College of Agriculture of Mateur – University of Carthage – Tunisia. I am also IFBA certified professional in both Biorisk Management and Biosecurity and I serve as Biosafety officer in my institution. I am very pleased to participate to this forum and exchange information and views with experts worldwide.
I agree with the second point of view of Dr. Suárez Romero. Indeed, risk assessment is a science-based process. It should be performed case by case basis, iterative and comparative. It should take into account the nature of the introduced sequences, the traits of the organism and the receiving environment and of course interactions between all of these elements. Thus, it should be a conducted by multidisciplinary scientific experts’ group to provide appropriate expertise for a particular risk assessment. However, I think that stakeholders such as those with stake in the safe transfer, handling and use of LMOs should also participate.
Best reagards
My name is Raja CHALGHOUMI. I am an Associate Professor in Animal Nutrition at the College of Agriculture of Mateur – University of Carthage – Tunisia. I am also IFBA certified professional in both Biorisk Management and Biosecurity and I serve as Biosafety officer in my institution. I am very pleased to participate to this forum and exchange information and views with experts worldwide.
I agree with the second point of view of Dr. Suárez Romero. Indeed, risk assessment is a science-based process. It should be performed case by case basis, iterative and comparative. It should take into account the nature of the introduced sequences, the traits of the organism and the receiving environment and of course interactions between all of these elements. Thus, it should be a conducted by multidisciplinary scientific experts’ group to provide appropriate expertise for a particular risk assessment. However, I think that stakeholders such as those with stake in the safe transfer, handling and use of LMOs should also participate.
Best reagards
My name is Christoph Then, I am working for Testbiotech, a science based CSO in Germany (http://www.testbiotech.org).
Under 4 and 5, the issues of uncertainties should be mentioned as a separate topic being relevant throughout the whole process of planning and conducting risk assessment.
The potentially very high level of uncertainty caused by potential next (or multi-) generation effects of EGD-LMOs, the complexity of the affected ecologial networks and the potential lack of spatio-temporal control have to be considered and discussed in detail. Under point 6, measures have to be foreseen in case no reliable conclusion can be drawn because there are too many ‚unknowns‘ and uncertainties. In this context cut-off criteria will be needed that allow the authority to decline the release of the EGD-LMO.
Under 4 and 5, the issues of uncertainties should be mentioned as a separate topic being relevant throughout the whole process of planning and conducting risk assessment.
The potentially very high level of uncertainty caused by potential next (or multi-) generation effects of EGD-LMOs, the complexity of the affected ecologial networks and the potential lack of spatio-temporal control have to be considered and discussed in detail. Under point 6, measures have to be foreseen in case no reliable conclusion can be drawn because there are too many ‚unknowns‘ and uncertainties. In this context cut-off criteria will be needed that allow the authority to decline the release of the EGD-LMO.
My name is Piet van der Meer. I am trained in environmental microbiology and environmental law, and I have for over 35 years been involved in risk assessments in the context of biosafety regulations. I have participated in the CBD COPs and CPB MOPs since COP1 in 1992, and I have served on a former AHTEG on risk assessment.
My thanks to the Secretariat for preparing the materials for this on line forum and to Luciana for having volunteered again to moderate this debate.
Hereby my observations on Part A, sections 4 to 6.
Line 25: very good to start the planning phase with the context and scope. I agree with Marvis Esther Suárez Romero that it should emphasis the importance of starting with the applicable laws and regulations.
Line 29 - 31: the section that is now ‘problem formulation’ is best brought to the section ‘conducting the risk assessment’, under Step 1, whereby the term ‘pathway to harm’ should read ‘scientifically plausible pathways to harm’.
Line 32: this section should clarify that in different steps of the risk assessment different comparisons are made with different comparators (e.g. ranging from near isogenic lines to the variability of certain characteristics in a certain crop).
Line 37: as said in my general observations, I was surprised to see reference to “Application of the Roadmap for risk assessment of living modified organisms” (line 37 with footnote 1), because the draft guidance that contained that roadmap was, after long and extensive debate, not endorsed by COPMOP2016, not even ‘welcomed’, but being ‘taken note of’. I believe that these draft guidance materials are not the appropriate place to renegotiate the conclusions of COPMOP2016
Line 41: before the bullet on “Identification of plausible risk hypotheses and clear pathways to harm” we need a bullet on what to look at for the part “Identification of any novel genotypic and phenotypic”. See also my above comment on comparators.
Line 58: focus this bullet on likelihood and exposure, and leave ‘risk’ for Step 4.
Line 66: take out ‘hazard identification’ – that belongs in Step 1.
Lines 93 – 97: the second and fourth bullets are important aspects, but are part of decision making.
Line 98: this can be brought under section 3.3. on uncertainty.
My thanks to the Secretariat for preparing the materials for this on line forum and to Luciana for having volunteered again to moderate this debate.
Hereby my observations on Part A, sections 4 to 6.
Line 25: very good to start the planning phase with the context and scope. I agree with Marvis Esther Suárez Romero that it should emphasis the importance of starting with the applicable laws and regulations.
Line 29 - 31: the section that is now ‘problem formulation’ is best brought to the section ‘conducting the risk assessment’, under Step 1, whereby the term ‘pathway to harm’ should read ‘scientifically plausible pathways to harm’.
Line 32: this section should clarify that in different steps of the risk assessment different comparisons are made with different comparators (e.g. ranging from near isogenic lines to the variability of certain characteristics in a certain crop).
Line 37: as said in my general observations, I was surprised to see reference to “Application of the Roadmap for risk assessment of living modified organisms” (line 37 with footnote 1), because the draft guidance that contained that roadmap was, after long and extensive debate, not endorsed by COPMOP2016, not even ‘welcomed’, but being ‘taken note of’. I believe that these draft guidance materials are not the appropriate place to renegotiate the conclusions of COPMOP2016
Line 41: before the bullet on “Identification of plausible risk hypotheses and clear pathways to harm” we need a bullet on what to look at for the part “Identification of any novel genotypic and phenotypic”. See also my above comment on comparators.
Line 58: focus this bullet on likelihood and exposure, and leave ‘risk’ for Step 4.
Line 66: take out ‘hazard identification’ – that belongs in Step 1.
Lines 93 – 97: the second and fourth bullets are important aspects, but are part of decision making.
Line 98: this can be brought under section 3.3. on uncertainty.
My name is Anastasia Matthies, I have more than 10 years of experience in Biosafety and Risk Assessment of LMOs as scientific officer at the German Federal Office of Consumer Protection and Food Safety. Firstly, I wish to thank for the opportunity to contribute to the discussions in this online forum. Further I would like to thank Ms. Luciana Pimenta Ambrozevicius for moderating this forum, and all colleagues contributing to the discussion.
Before commenting on individual sections, allow me to make a general remark on the structure of the draft outline. Part A of the outline duplicates on chapters from the Guidance on risk assessment for living modified organisms (UNEP/CBD/BS/COP-MOP/8/8/Add.1). In my view, similar or identical content in the new additional voluntary guidance material on LMO containing engineered gene-drives should be avoided to prevent duplication. The new additional guidance materials should focus on novelties and updates and on specific aspects for risk assessment regarding engineered gene drive organisms. As already stated by parties (see submissions to ntf-2023-007. Therefore, I suggest to reconsider the structure of the whole draft outline and to incorporate/elaborate aspects suggested in previously reported documents e. g. by EFSA (doi: 10.2903/j.efsa.2020.6297).
Further comments on Topics 4 to 6:
- Topic 4.1; lines 25 to 28: The objective of this chapter is not clear –aspects listed in the brackets are content-wise not connected to each other. Furthermore, to my understanding they should be better addressed in other parts of the outline. E.g. “Protection goals”, “experience” and “available information” are aspects that belong to problem formulation.
- Topic 4.2; lines 29 to 31: As problem formulation is the crucial step for the whole risk assessment, this chapter must be especially thoroughly elaborated focusing on available information on the biology and ecology of the insect species under consideration, the gene drive design and strategy, the introduced traits, the intended uses of the gene drive, the scale and frequency of the deliberate release, the receiving environments and the interactions among these variables. All elements of problem formulation must be considered: hazard identification, identifying protection operational goals, devising plausible pathways to harm that describe how the deliberate release could be harmful, formulating risk hypotheses about the likelihood and severity of such events; identifying the information that would be useful to test the risk hypotheses; and developing a plan to acquire new data for hypothesis if existing information is insufficient for decision-making.
- Topic 4.3, lines 32 to 34.: the choice of comparators is a methodological issue and should be considered among other methodological recommendations. Unfortunately, such section is not present in the current outline and should be considered.
- Topic 5, line 35 to 91: the whole section is a short copy of a Guidance on risk assessment for living modified organisms (UNEP/CBD/BS/COP-MOP/8/8/Add.1) and does not address specific issues of engineered gene drive organisms.
- Topic 6, lines 92 to 98: Socioeconomic consideration should not be a part of a technical risk assessment. These aspects may be considered at other steps of the decision making process.
Before commenting on individual sections, allow me to make a general remark on the structure of the draft outline. Part A of the outline duplicates on chapters from the Guidance on risk assessment for living modified organisms (UNEP/CBD/BS/COP-MOP/8/8/Add.1). In my view, similar or identical content in the new additional voluntary guidance material on LMO containing engineered gene-drives should be avoided to prevent duplication. The new additional guidance materials should focus on novelties and updates and on specific aspects for risk assessment regarding engineered gene drive organisms. As already stated by parties (see submissions to ntf-2023-007. Therefore, I suggest to reconsider the structure of the whole draft outline and to incorporate/elaborate aspects suggested in previously reported documents e. g. by EFSA (doi: 10.2903/j.efsa.2020.6297).
Further comments on Topics 4 to 6:
- Topic 4.1; lines 25 to 28: The objective of this chapter is not clear –aspects listed in the brackets are content-wise not connected to each other. Furthermore, to my understanding they should be better addressed in other parts of the outline. E.g. “Protection goals”, “experience” and “available information” are aspects that belong to problem formulation.
- Topic 4.2; lines 29 to 31: As problem formulation is the crucial step for the whole risk assessment, this chapter must be especially thoroughly elaborated focusing on available information on the biology and ecology of the insect species under consideration, the gene drive design and strategy, the introduced traits, the intended uses of the gene drive, the scale and frequency of the deliberate release, the receiving environments and the interactions among these variables. All elements of problem formulation must be considered: hazard identification, identifying protection operational goals, devising plausible pathways to harm that describe how the deliberate release could be harmful, formulating risk hypotheses about the likelihood and severity of such events; identifying the information that would be useful to test the risk hypotheses; and developing a plan to acquire new data for hypothesis if existing information is insufficient for decision-making.
- Topic 4.3, lines 32 to 34.: the choice of comparators is a methodological issue and should be considered among other methodological recommendations. Unfortunately, such section is not present in the current outline and should be considered.
- Topic 5, line 35 to 91: the whole section is a short copy of a Guidance on risk assessment for living modified organisms (UNEP/CBD/BS/COP-MOP/8/8/Add.1) and does not address specific issues of engineered gene drive organisms.
- Topic 6, lines 92 to 98: Socioeconomic consideration should not be a part of a technical risk assessment. These aspects may be considered at other steps of the decision making process.
In relation to section 5.1, there is no specific assessment point raised to address potential adverse impacts on human health. This is particularly pertinent for gene drive applications designed to address health issues, and by design will mediate pathogens. There are numerous plausible risk pathways that may result, for example, pathogen evolution in response to the gene drive (e.g. with altered pathogenicity, evasion of vaccine-induced immunity etc), alterations in human immunity, niche replacement. It is vital that any RA will specifically address how gene drives may interfere with disease burden with regard to target and non-target vector controlled disease), in addition to the current human health risk pathways assessed for LMOs e.g. generation of novel toxins/allergens.
Coming back to the issue of uncertainty raised in my post for sections 1-3, section 5 appears to not move sufficiently beyond current RA guidance. For example, genomic instability is a key aspect already noted in the outline, and I support it's inclusion. This is highly relevant considering that the doublesex Anopheles mosquito has been recently noted by the WHO to now be in the process of re-development due to issues of transgene instability (link here: https://www.who.int/publications/i/item/9789240066021). Due to the continued activity of genetic engineering machinery following release in GDOs, with drive activity/behaviour mediated by both background host genetics and ecological factors, uncertainties around genomic stability are increased, with genomic changes potentially occurring also post-release. However, next-generation effects are not taken into consideration in this outline as a specific challenge of gene drive assessment. Once again, it is vital that addressing uncertainty and the inability to gain sufficient information prior to release is well incorporated into the outline, e.g. via the inclusion of cut-off criteria. Next-generation effects e.g. via introgression into sibling species via gene flow, may alter the behaviour of a gene drive with both biodiversity and health implications and this needs to be explicitly acknowledged. In my view, it is vital that current guidance is not lost to focus in novel risks of gene drives, but is instead extended to incorporate any additional or heightened risks and uncertainties.
In relation to sections 4 and 5, relevant considerations that were raised during the online discussion could be included here, for example, consideration of alternative solutions during problem formulation or acceptability of risk steps. In the case of vector control for example, alternative solutions also include addressing social determinants of health, and consideration of any opportunity costs that may arise from neglecting investment in known solutions e.g. access to medicine needs to taken into account instead of narrowing the discussion to biomedical vector control interventions.
For section 5 and 6, ensuring liability for unintended effects is of particular relevance to gene drives that are designed to spread with the potential for transboundary movement, and the lack of ability to control spread or recall or revert gene drive organisms post release. In the case of ecological or health impacts, some may take time to become visible and such issues thus need to be carefully accounted for. The inability to recall gene drive organisms, including mosquitoes needs to be further emphasised.
Coming back to the issue of uncertainty raised in my post for sections 1-3, section 5 appears to not move sufficiently beyond current RA guidance. For example, genomic instability is a key aspect already noted in the outline, and I support it's inclusion. This is highly relevant considering that the doublesex Anopheles mosquito has been recently noted by the WHO to now be in the process of re-development due to issues of transgene instability (link here: https://www.who.int/publications/i/item/9789240066021). Due to the continued activity of genetic engineering machinery following release in GDOs, with drive activity/behaviour mediated by both background host genetics and ecological factors, uncertainties around genomic stability are increased, with genomic changes potentially occurring also post-release. However, next-generation effects are not taken into consideration in this outline as a specific challenge of gene drive assessment. Once again, it is vital that addressing uncertainty and the inability to gain sufficient information prior to release is well incorporated into the outline, e.g. via the inclusion of cut-off criteria. Next-generation effects e.g. via introgression into sibling species via gene flow, may alter the behaviour of a gene drive with both biodiversity and health implications and this needs to be explicitly acknowledged. In my view, it is vital that current guidance is not lost to focus in novel risks of gene drives, but is instead extended to incorporate any additional or heightened risks and uncertainties.
In relation to sections 4 and 5, relevant considerations that were raised during the online discussion could be included here, for example, consideration of alternative solutions during problem formulation or acceptability of risk steps. In the case of vector control for example, alternative solutions also include addressing social determinants of health, and consideration of any opportunity costs that may arise from neglecting investment in known solutions e.g. access to medicine needs to taken into account instead of narrowing the discussion to biomedical vector control interventions.
For section 5 and 6, ensuring liability for unintended effects is of particular relevance to gene drives that are designed to spread with the potential for transboundary movement, and the lack of ability to control spread or recall or revert gene drive organisms post release. In the case of ecological or health impacts, some may take time to become visible and such issues thus need to be carefully accounted for. The inability to recall gene drive organisms, including mosquitoes needs to be further emphasised.
I am John Connolly, working for Target Malaria at Imperial College London.
Uncertainty is not a concept unique to gene drive, and as for other LMOs, the quality of data will correlate with the level of confidence and reduce uncertainty (Connolly et al 2022). It is important to recognize that the existence of uncertainties does not preclude taking a decision. This view is compatible with a precautionary approach.
Modeling, as noted by EFSA (2020) and others, can play a useful role in reducing uncertainty as sensitivity analysis can help identify which components have an effect on outcomes.
Risk assessments for gene drive need to draw from a variety of sources and are likely to combine both probabilistic (quantitative) and qualitative information, elicited through a variety of methods, from interviews with stakeholders to literature review and laboratory studies.(Connolly et al 2022).
Probabilistic risk assessments use quantitative modeling approaches to represent a probability distribution for a range of potential outcomes for a particular event. Qualitative risk assessments categorize, in a structured and systematic way, the likelihoods and consequences of outcomes into a limited number of ordered classes to give a categorical indication of relative risk, such as 'high', 'moderate', 'low', or 'negligible'. Where feasible, such qualitative terms should preferably be defined as precisely as possible in a quantitative way (Connolly et al 2022). Both types of assessments involve seeking expert opinion to determine the likelihood and possible outcomes of certain events.
In addition, there are methodologies that support assessing and weighing different information that is relevant to risk assessment (“weight of evidence”) (EFSA 2017). For example, WHO and other institutions use the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. This is a widely endorsed and used approach to assess evidence and develop recommendations.
There is also experience of discussions of these issues with biological control agents, where the same topics have been considered. Although these are not LMOs, the spatial and temporal dimensions are similar to gene drive and could offer useful points of comparison (WHO 2021).
References:
Connolly, J.B., Mumford, J.D., Glandorf, D.C.M. et al. (2022) Recommendations for environmental risk assessment of gene drive applications for malaria vector control. Malar J 21, 152. https://doi.org/10.1186/s12936-022-04183-w
EFSA (2017). EFSA Scientific Committee, Hardy A, Benford D, Halldorsson T, Jeger MJ,Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Silano V,Solecki R, Turck D, Benfenati E, Chaudhry QM, Craig P, Frampton G, Greiner M, Hart A, Hogstrand C,Lambre C, Luttik R, Makowski D, Siani A, Wahlstroem H, Aguilera J, Dorne J-L, Fernandez Dumont A,Hempen M, Valtue~na Martınez S, Martino L, Smeraldi C, Terron A, Georgiadis N and Younes M, 2017.Scientific Opinion on the guidance on the use of the weight of evidence approach in scientificassessments. EFSA Journal 2017;15(8):4971. https://doi.org/10.2903/j.efsa.2017.4971
EFSA (2020). Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post‐market environmental monitoring of genetically modified insects containing engineered gene drives. EFSA Panel on Genetically Modified Organisms (GMO), Naegeli H, Bresson J, et al (2020) https://doi.org/10.2903/j.efsa.2020.6297. Page 53
GRADE working group - https://www.gradeworkinggroup.org/
What is GRADE? BMJ Best Practices – available online: https://bestpractice.bmj.com/info/toolkit/learn-ebm/what-is-grade/
WHO. (2021) Guidance framework for testing genetically modified mosquitoes, second edition. Geneva:
World Health Organization. https://www.who.int/publications/i/item/9789240025233
Mr. John Connolly, Imperial College London #11793
4 minutes ago
I am John Connolly, working with Target Malaria and am based at Imperial College London. Thank you very much to the Moderator and Secretariat for providing us with an opportunity to comment on the draft outline.
The guidance should complement existing guidance & focus on items that are novel for gene drive organisms (compared to other LMOs), noting where it is not necessary to reiterate existing guidance.
The guidance should be science-based and based on the principle of case-by-case assessments. The new guidance should remain in alignment with paragraph 11 of CBD decision 14/19 on the necessary conditions for the experimental release of organisms containing engineered gene drives.
A wealth of experience with LMOs is available to draw upon, as well as from other fields (biocontrol, etc). It is important to reflect these existing resources where possible.
Relevant guidance from WHO and from national authorities should also be taken into account to ensure coherence and compatibility with guidance from the CBD. Examples are included in the references below.
References:
EFSA (2020). Panel on Genetically Modified Organisms (GMO); Naegeli H, Bresson JL, Dalmay T, Dewhurst IC, Epstein MM, Guerche P, Hejatko J, Moreno FJ, Mullins E, Nogué F, Rostoks N, Sánchez Serrano JJ, Savoini G, Veromann E, Veronesi F, Bonsall MB, Mumford J, Wimmer EA, Devos Y, Paraskevopoulos K, Firbank LG. Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post-market environmental monitoring of genetically modified insects containing engineered gene drives. EFSA J. 2020 Nov 12;18(11):e06297. doi: 10.2903/j.efsa.2020.6297.
National Institute for Public Health and the Environment. Technical evaluation of a potential release of OX513A Aedes aegypti mosquitoes on the island of Saba. https://www.rivm.nl/bibliotheek/rapporten/2017-0087.pdf
Government of Australia. Office of the Gene Technology Regulator (2019). Regulatory requirements for contained research with GMOs containing engineered gene drives. https://www.ogtr.gov.au/sites/default/files/files/2021-06/guidance_on_gene_drives.pdf
James SL, Quemada H, Benedict MQ, Dass B. Requirements for market entry of gene drive-modified mosquitoes for control of vector-borne diseases: analogies to other biologic and biotechnology products. Front Bioeng Biotechnol. 2023 Jun 8;11:1205865. doi: 10.3389/fbioe.2023.1205865.
Murray JV, Jansen CC, De Barro P. Risk Associated with the Release of Wolbachia-Infected Aedes aegypti Mosquitoes into the Environment in an Effort to Control Dengue. Front Public Health. 2016 Mar 22;4:43. doi: 10.3389/fpubh.2016.00043.
WHO (2021). Guidance framework for testing genetically modified mosquitoes, second edition. Geneva:
World Health Organization. https://www.who.int/publications/i/item/9789240025233
Uncertainty is not a concept unique to gene drive, and as for other LMOs, the quality of data will correlate with the level of confidence and reduce uncertainty (Connolly et al 2022). It is important to recognize that the existence of uncertainties does not preclude taking a decision. This view is compatible with a precautionary approach.
Modeling, as noted by EFSA (2020) and others, can play a useful role in reducing uncertainty as sensitivity analysis can help identify which components have an effect on outcomes.
Risk assessments for gene drive need to draw from a variety of sources and are likely to combine both probabilistic (quantitative) and qualitative information, elicited through a variety of methods, from interviews with stakeholders to literature review and laboratory studies.(Connolly et al 2022).
Probabilistic risk assessments use quantitative modeling approaches to represent a probability distribution for a range of potential outcomes for a particular event. Qualitative risk assessments categorize, in a structured and systematic way, the likelihoods and consequences of outcomes into a limited number of ordered classes to give a categorical indication of relative risk, such as 'high', 'moderate', 'low', or 'negligible'. Where feasible, such qualitative terms should preferably be defined as precisely as possible in a quantitative way (Connolly et al 2022). Both types of assessments involve seeking expert opinion to determine the likelihood and possible outcomes of certain events.
In addition, there are methodologies that support assessing and weighing different information that is relevant to risk assessment (“weight of evidence”) (EFSA 2017). For example, WHO and other institutions use the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. This is a widely endorsed and used approach to assess evidence and develop recommendations.
There is also experience of discussions of these issues with biological control agents, where the same topics have been considered. Although these are not LMOs, the spatial and temporal dimensions are similar to gene drive and could offer useful points of comparison (WHO 2021).
References:
Connolly, J.B., Mumford, J.D., Glandorf, D.C.M. et al. (2022) Recommendations for environmental risk assessment of gene drive applications for malaria vector control. Malar J 21, 152. https://doi.org/10.1186/s12936-022-04183-w
EFSA (2017). EFSA Scientific Committee, Hardy A, Benford D, Halldorsson T, Jeger MJ,Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Silano V,Solecki R, Turck D, Benfenati E, Chaudhry QM, Craig P, Frampton G, Greiner M, Hart A, Hogstrand C,Lambre C, Luttik R, Makowski D, Siani A, Wahlstroem H, Aguilera J, Dorne J-L, Fernandez Dumont A,Hempen M, Valtue~na Martınez S, Martino L, Smeraldi C, Terron A, Georgiadis N and Younes M, 2017.Scientific Opinion on the guidance on the use of the weight of evidence approach in scientificassessments. EFSA Journal 2017;15(8):4971. https://doi.org/10.2903/j.efsa.2017.4971
EFSA (2020). Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post‐market environmental monitoring of genetically modified insects containing engineered gene drives. EFSA Panel on Genetically Modified Organisms (GMO), Naegeli H, Bresson J, et al (2020) https://doi.org/10.2903/j.efsa.2020.6297. Page 53
GRADE working group - https://www.gradeworkinggroup.org/
What is GRADE? BMJ Best Practices – available online: https://bestpractice.bmj.com/info/toolkit/learn-ebm/what-is-grade/
WHO. (2021) Guidance framework for testing genetically modified mosquitoes, second edition. Geneva:
World Health Organization. https://www.who.int/publications/i/item/9789240025233
Mr. John Connolly, Imperial College London #11793
4 minutes ago
I am John Connolly, working with Target Malaria and am based at Imperial College London. Thank you very much to the Moderator and Secretariat for providing us with an opportunity to comment on the draft outline.
The guidance should complement existing guidance & focus on items that are novel for gene drive organisms (compared to other LMOs), noting where it is not necessary to reiterate existing guidance.
The guidance should be science-based and based on the principle of case-by-case assessments. The new guidance should remain in alignment with paragraph 11 of CBD decision 14/19 on the necessary conditions for the experimental release of organisms containing engineered gene drives.
A wealth of experience with LMOs is available to draw upon, as well as from other fields (biocontrol, etc). It is important to reflect these existing resources where possible.
Relevant guidance from WHO and from national authorities should also be taken into account to ensure coherence and compatibility with guidance from the CBD. Examples are included in the references below.
References:
EFSA (2020). Panel on Genetically Modified Organisms (GMO); Naegeli H, Bresson JL, Dalmay T, Dewhurst IC, Epstein MM, Guerche P, Hejatko J, Moreno FJ, Mullins E, Nogué F, Rostoks N, Sánchez Serrano JJ, Savoini G, Veromann E, Veronesi F, Bonsall MB, Mumford J, Wimmer EA, Devos Y, Paraskevopoulos K, Firbank LG. Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post-market environmental monitoring of genetically modified insects containing engineered gene drives. EFSA J. 2020 Nov 12;18(11):e06297. doi: 10.2903/j.efsa.2020.6297.
National Institute for Public Health and the Environment. Technical evaluation of a potential release of OX513A Aedes aegypti mosquitoes on the island of Saba. https://www.rivm.nl/bibliotheek/rapporten/2017-0087.pdf
Government of Australia. Office of the Gene Technology Regulator (2019). Regulatory requirements for contained research with GMOs containing engineered gene drives. https://www.ogtr.gov.au/sites/default/files/files/2021-06/guidance_on_gene_drives.pdf
James SL, Quemada H, Benedict MQ, Dass B. Requirements for market entry of gene drive-modified mosquitoes for control of vector-borne diseases: analogies to other biologic and biotechnology products. Front Bioeng Biotechnol. 2023 Jun 8;11:1205865. doi: 10.3389/fbioe.2023.1205865.
Murray JV, Jansen CC, De Barro P. Risk Associated with the Release of Wolbachia-Infected Aedes aegypti Mosquitoes into the Environment in an Effort to Control Dengue. Front Public Health. 2016 Mar 22;4:43. doi: 10.3389/fpubh.2016.00043.
WHO (2021). Guidance framework for testing genetically modified mosquitoes, second edition. Geneva:
World Health Organization. https://www.who.int/publications/i/item/9789240025233
My name is Samson Simon, I work for the German Federal Agency for Nature Conservation (BfN) as a biosafety expert.
Line 32: 4.3. “The choice of comparators”
The novelty of EGD-LMOs when compared to other LMOs is widely recognized. The comparative approach tends to come to its limits when the intrinsic properties of the LMO go beyond the known traits for that given organisms. For EGD-LMOs that is the case for mechanisms like forced dispersal or change in sex ratio. This section should thoroughly analyze shortcomings of the comparative approach. I suggest to change the heading to: “comparative approach for EGD-LMOs” and to add a subheading (bullet point): “Challenges to the comparative approach by EGD-LMOs”. “The choice of comparators” could be a subheading (bullet point) under the suggested new heading.
Line 97: “Risks vs. benefits”
Drafting a guidance on EGD-LMOs in the context of the Cartagena protocol will be a challenging task. Many aspects recognized in the Cartagena protocol will have to be considered. To my humble understanding of the processes the topic of “risks vs. benefits” is not to be considered under the Cartagena protocol.
Line 32: 4.3. “The choice of comparators”
The novelty of EGD-LMOs when compared to other LMOs is widely recognized. The comparative approach tends to come to its limits when the intrinsic properties of the LMO go beyond the known traits for that given organisms. For EGD-LMOs that is the case for mechanisms like forced dispersal or change in sex ratio. This section should thoroughly analyze shortcomings of the comparative approach. I suggest to change the heading to: “comparative approach for EGD-LMOs” and to add a subheading (bullet point): “Challenges to the comparative approach by EGD-LMOs”. “The choice of comparators” could be a subheading (bullet point) under the suggested new heading.
Line 97: “Risks vs. benefits”
Drafting a guidance on EGD-LMOs in the context of the Cartagena protocol will be a challenging task. Many aspects recognized in the Cartagena protocol will have to be considered. To my humble understanding of the processes the topic of “risks vs. benefits” is not to be considered under the Cartagena protocol.
To address the suggestion that problem formulation should focus on intended gene drive design, strategy and intended uses, I would like to recall the discussions in the previous online forum and captured in the synthesis of inputs from submissions (para 16 and 18) that gene drives may not behave as intended, with for example, population reduction drives potentially resulting in mixed populations with unpredictable chaser dynamics e.g.
https://doi.org/10.1111/mec.15788
Numerous studies further suggest that, rather than the drive operating via the expected CRISPR-based homing process of copying and pasting, inheritance bias was being achieved at least in part, and in some studies, exclusively, via decreasing the inheritance of the non-drive recipient chromosome i.e. a meiotic drive mechanism (https://doi.org/10.1101/645440; https://doi.org/10.1038/s41467-021-21771-7; https://doi.org/10.1101/2020.12.15.421271; https://doi.org/10.1016/j.molcel.2020.09.003). The intended molecular design has not behaved as predicted and thus cannot form sufficient basis for a risk assessment.
There are also concerns that under real life ecological conditions, self-limiting drives could instead behave like self-sustaining drives. As stated by Rode et al., (2020) “real life” ecological conditions are likely to alter the genetic parameters of any gene drive, in particular its fitness cost https://doi.org/10.1534/g3.120.401484. Fitness costs are difficult to estimate in the field and can vary either across genomic backgrounds, spatially or temporally (Marshall and Hay 2012; Backus and Delborne 2019). Hence, depending on ecological conditions, the threshold value for the invasion of a threshold-dependent homing drive could change, or even decrease to 0. Thus, a homing drive that is threshold-dependent in the laboratory might turn into a threshold-independent drive in the wild.”
Restriction any RA to intended design/use would not sufficiently address above unintended impacts if they do indeed arise.
Thanks
Eva
https://doi.org/10.1111/mec.15788
Numerous studies further suggest that, rather than the drive operating via the expected CRISPR-based homing process of copying and pasting, inheritance bias was being achieved at least in part, and in some studies, exclusively, via decreasing the inheritance of the non-drive recipient chromosome i.e. a meiotic drive mechanism (https://doi.org/10.1101/645440; https://doi.org/10.1038/s41467-021-21771-7; https://doi.org/10.1101/2020.12.15.421271; https://doi.org/10.1016/j.molcel.2020.09.003). The intended molecular design has not behaved as predicted and thus cannot form sufficient basis for a risk assessment.
There are also concerns that under real life ecological conditions, self-limiting drives could instead behave like self-sustaining drives. As stated by Rode et al., (2020) “real life” ecological conditions are likely to alter the genetic parameters of any gene drive, in particular its fitness cost https://doi.org/10.1534/g3.120.401484. Fitness costs are difficult to estimate in the field and can vary either across genomic backgrounds, spatially or temporally (Marshall and Hay 2012; Backus and Delborne 2019). Hence, depending on ecological conditions, the threshold value for the invasion of a threshold-dependent homing drive could change, or even decrease to 0. Thus, a homing drive that is threshold-dependent in the laboratory might turn into a threshold-independent drive in the wild.”
Restriction any RA to intended design/use would not sufficiently address above unintended impacts if they do indeed arise.
Thanks
Eva
My name is Marco Gielkens. I have a scientific background as a molecular geneticist and I have over 20 years of experience in biosafety and risk assessment of LMOs. I am a senior risk assessor and policy advisor at the Dutch National Institute for Public Health and the Environment (RIVM) within the department of Biological Safety and Gene Technology. I would like to thank the moderator and the Secretariat for the opportunity to contribute to this discussion.
I agree with the points raised by Mr. Piet van der Meer (#11785).
In addition I would like to draw your attention to a recent, and within the context of this discussion, important document developed by the OECD Working Party on the Harmonisation of Regulatory Oversight in Biotechnology on the “Environmental Considerations for Risk/Safety Assessment for the Release of Transgenic Plants” (https://read.oecd.org/10.1787/62ed0e04-en?format=pdf). Although the document contains general information on points that risk/safety assessors could focus on when planning assessments for the release of transgenic plants into the environment, the general principles outlined in the document can be applied more widely. In my view the document describes well an approach for planning and structuring an environmental risk/safety assessment in general and thus can also be applied in case of EGD-LMOs.
Furthermore I observe that some of the contributions do not seem to focus on the process of risk assessment or how to decide which considerations or information elements could be of relevance for risk assessments of EGD-LMOs. I think it would not be appropriate if the guidance would prescribe what and how to consider when conducting a risk assessment of EGD-LMOs. This holds in particular to the discussion regarding uncertainties and setting tresholds for uncertainties. I consider acceptance of potential risks and possible surrounding uncertainties to be the responsibility of risk managers and I therefore doubt whether such considerations would be in scope for the additional voluntary guidance material.
I agree with the points raised by Mr. Piet van der Meer (#11785).
In addition I would like to draw your attention to a recent, and within the context of this discussion, important document developed by the OECD Working Party on the Harmonisation of Regulatory Oversight in Biotechnology on the “Environmental Considerations for Risk/Safety Assessment for the Release of Transgenic Plants” (https://read.oecd.org/10.1787/62ed0e04-en?format=pdf). Although the document contains general information on points that risk/safety assessors could focus on when planning assessments for the release of transgenic plants into the environment, the general principles outlined in the document can be applied more widely. In my view the document describes well an approach for planning and structuring an environmental risk/safety assessment in general and thus can also be applied in case of EGD-LMOs.
Furthermore I observe that some of the contributions do not seem to focus on the process of risk assessment or how to decide which considerations or information elements could be of relevance for risk assessments of EGD-LMOs. I think it would not be appropriate if the guidance would prescribe what and how to consider when conducting a risk assessment of EGD-LMOs. This holds in particular to the discussion regarding uncertainties and setting tresholds for uncertainties. I consider acceptance of potential risks and possible surrounding uncertainties to be the responsibility of risk managers and I therefore doubt whether such considerations would be in scope for the additional voluntary guidance material.
Dear Participants of the online forum on risk assessment,
My name is Mrs Blessing Aligwekwe, an Assistant Director working for the National Biosafety Management Management Agency of Nigeria. My background is Botany, with an M.Sc in Managing the Environment (Pathway: GM Crop Risk Assessment) and 14 years of biosafety experience. For the document “Draft outline of the Additional voluntary guidance materials”, the following suggestions may be important:
1. In 5.1, bullet number 3: Elements for Consideration for the intended use and in the receiving environment, “field trials” should be included after containment.
2. In 5.2, line 59: Elements for consideration, we need to make some clarifications. In the sentence “relevant characteristics in the receiving environment”, are we referring to the characteristics of the EGD-LMO in the receiving environment or the characteristics of the receiving environment?
3. In 5.5, there should be a clause for ‘Risk level” before ‘Acceptability of Risks” in line 82
4. In 5.5, line 85: Elements for consideration related to risk management, “sustainability of proposed risk management strategies” should be included and that can come after “methods for evaluating proposed risk management and monitoring strategies”
5. In 5.5 lines 85 to 88 should be completely expunged and written as PART C: RISK MANAGEMENT OF LIVING MODIFIED ORGANISMS CONTAINING ENGINEERED GENE DRIVES. Risk management is an important aspect of risk analysis.
Based on suggestion number 5,
6. “Risk management” in 5.4, line 79; “ability to manage adverse effects” in 5.5 line 91 should be expunged and put under PART C proposed here
My name is Mrs Blessing Aligwekwe, an Assistant Director working for the National Biosafety Management Management Agency of Nigeria. My background is Botany, with an M.Sc in Managing the Environment (Pathway: GM Crop Risk Assessment) and 14 years of biosafety experience. For the document “Draft outline of the Additional voluntary guidance materials”, the following suggestions may be important:
1. In 5.1, bullet number 3: Elements for Consideration for the intended use and in the receiving environment, “field trials” should be included after containment.
2. In 5.2, line 59: Elements for consideration, we need to make some clarifications. In the sentence “relevant characteristics in the receiving environment”, are we referring to the characteristics of the EGD-LMO in the receiving environment or the characteristics of the receiving environment?
3. In 5.5, there should be a clause for ‘Risk level” before ‘Acceptability of Risks” in line 82
4. In 5.5, line 85: Elements for consideration related to risk management, “sustainability of proposed risk management strategies” should be included and that can come after “methods for evaluating proposed risk management and monitoring strategies”
5. In 5.5 lines 85 to 88 should be completely expunged and written as PART C: RISK MANAGEMENT OF LIVING MODIFIED ORGANISMS CONTAINING ENGINEERED GENE DRIVES. Risk management is an important aspect of risk analysis.
Based on suggestion number 5,
6. “Risk management” in 5.4, line 79; “ability to manage adverse effects” in 5.5 line 91 should be expunged and put under PART C proposed here
Dear all, I am Barbara Pilz from Save Our Seeds, member of the current multidisciplinary AHTEG on synthetic biology. Thank you, once again, for opening this crucial discussion.
My suggestions for Part A 4-6 are the following:
Section 4.1, Line 26: In line with Article 26 of the Cartagena Protocol and in order to ensure a more holistic and responsible approach to risk assessment while upholding the precautionary principle, socioeconomic (as well as cultural and ethical considerations) should be mainstreamed throughout the assessment. Therefore, the examples under relevant considerations in Line 26 should include “socioeconomic, cultural and ethical considerations”
Section 4.1, Line 28: Stakeholder engagement is a vague term that does determine who or how stakeholders will be engaged. Instead, and in line with the Free, Prior, and Informed Consent (FPIC) Line 28 should involve “Stakeholder mapping, Free, Prior, and Informed Consent (FPIC), and participation in decision-making”.
Section 4.2, Line 30: “Pathways to harm” should not be the only consideration in problem formulation as it lacks context. The type of change should also be addressed as pathways can vary depending on the type of change introduced. (e.g., fertility, resistance to disease). So, the line would read “Types of change and pathways to harm”
Section 4.2, Line 34: It is not clear whether ‘alternative approaches’ refers to, clarification here would be helpful.
Section 5, Line 36: As previously mentioned, it is important to note that an eventual release of gene drive organisms into the environment would be the first time that LMOs are intended to modify/eradicate wild species and their various present and potential future ecosystems. Annex III of the Cartagena Protocol was not developed with such circumstances in mind. Therefore it is important to account the aspects to which are not accounted for in Annex III of the Protocol that are particular to EGD-LMOs. Therefore, this line should include “Annex III of Cartagena Protocol on Biosafety and the particular circumstances of EGD-LMOs”.
Section 5.1., Line 40: Reference is made to ‘receiving environment’ as per Annex III 9 (c) of the Cartagena Protocol. However, no mention is made on how to identify and narrow down such receiving environment in the case of EGD-LMOs that spread independently. I would suggest the AHTEG discussing and considering this point in their next meeting and adapting the outline accordingly.
Same comment is valid for the other mentions of the term throughout the outline.
Section 5.1, Line 41: Reference is made to ‘identification of plausible risk hypotheses and clear pathways to harm’. Due to the hypothetical nature of the effect of the release of EGD-LMOs there are potential risks that cannot yet be accounted for and in line with the precautionary principle all risks shall be considered. Therefore a more appropriate title for this section would be “identification of known risks and clear pathways to harm”.
Section 5.3, Line 68: Elements for consideration should also include “effects on human health and socioeconomic, cultural and ethical considerations”. Here of note is that in line with Annex III of the Cartagena Protocol risk assessment should also take into account risks to human health. As per the Constitution of the Word Health Organisation “Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity” (https://apps.who.int/gb/bd/PDF/bd47/EN/constitution-en.pdf?ua=1).
Section 5.4, Line 78: Same as above and should also include reversibility of effects as an element for consideration.
Section 5.5, Line 80: Reference is made to ‘Recommendation as to whether or not the risks are acceptable, manageable’. In the case of EGD-LMOs ability to independently modify entire ecosystems, reference should also be made to ‘reversibility’.
Accordingly, the title could read “Step 5. Recommendation as to whether or not the risks are acceptable, manageable or reversible, including, identification of strategies to manage and reverse these risks”
Section 5.5, Line 82: In line with that was said in intervention [#11781], should make clear reference to cut off criteria. “Acceptability of risks in light of cut-off criteria”
Section 5.5, Line 89: Elements for consideration should include cut-off criteria and alternatives (in line with comments made in [#11790]).
Section 6.: The title does not provide any specification of the relevance of the listed issues for risk assessment. Issues listed under this item should be taken into account when providing recommendations. The title could read: “6. Further considerations”.
Section 6., Line 93: Firstly, as suggested above, socioeconomic considerations should be mainstreamed into the risk assessment exercise. Therefore, this item should bring a summary of those, instead of being the only mention to it. The line could read “Summary of socioeconomic considerations”
Section 6., Line 96: Should provide more detail about the issues it is referring to. A clearer title could be: “Participation of Indigenous Peoples and Local Communities and Free, Prior and Informed Consent”
Section 6., Line 97: Line could be deleted as related issues already addressed under acceptability of risks and in line with what said in submission [#11797]
Additional line to be considered: Line 99 – Overview of suitable alternatives (in addition to what was proposed regarding alternatives on submission [#11790])
My suggestions for Part A 4-6 are the following:
Section 4.1, Line 26: In line with Article 26 of the Cartagena Protocol and in order to ensure a more holistic and responsible approach to risk assessment while upholding the precautionary principle, socioeconomic (as well as cultural and ethical considerations) should be mainstreamed throughout the assessment. Therefore, the examples under relevant considerations in Line 26 should include “socioeconomic, cultural and ethical considerations”
Section 4.1, Line 28: Stakeholder engagement is a vague term that does determine who or how stakeholders will be engaged. Instead, and in line with the Free, Prior, and Informed Consent (FPIC) Line 28 should involve “Stakeholder mapping, Free, Prior, and Informed Consent (FPIC), and participation in decision-making”.
Section 4.2, Line 30: “Pathways to harm” should not be the only consideration in problem formulation as it lacks context. The type of change should also be addressed as pathways can vary depending on the type of change introduced. (e.g., fertility, resistance to disease). So, the line would read “Types of change and pathways to harm”
Section 4.2, Line 34: It is not clear whether ‘alternative approaches’ refers to, clarification here would be helpful.
Section 5, Line 36: As previously mentioned, it is important to note that an eventual release of gene drive organisms into the environment would be the first time that LMOs are intended to modify/eradicate wild species and their various present and potential future ecosystems. Annex III of the Cartagena Protocol was not developed with such circumstances in mind. Therefore it is important to account the aspects to which are not accounted for in Annex III of the Protocol that are particular to EGD-LMOs. Therefore, this line should include “Annex III of Cartagena Protocol on Biosafety and the particular circumstances of EGD-LMOs”.
Section 5.1., Line 40: Reference is made to ‘receiving environment’ as per Annex III 9 (c) of the Cartagena Protocol. However, no mention is made on how to identify and narrow down such receiving environment in the case of EGD-LMOs that spread independently. I would suggest the AHTEG discussing and considering this point in their next meeting and adapting the outline accordingly.
Same comment is valid for the other mentions of the term throughout the outline.
Section 5.1, Line 41: Reference is made to ‘identification of plausible risk hypotheses and clear pathways to harm’. Due to the hypothetical nature of the effect of the release of EGD-LMOs there are potential risks that cannot yet be accounted for and in line with the precautionary principle all risks shall be considered. Therefore a more appropriate title for this section would be “identification of known risks and clear pathways to harm”.
Section 5.3, Line 68: Elements for consideration should also include “effects on human health and socioeconomic, cultural and ethical considerations”. Here of note is that in line with Annex III of the Cartagena Protocol risk assessment should also take into account risks to human health. As per the Constitution of the Word Health Organisation “Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity” (https://apps.who.int/gb/bd/PDF/bd47/EN/constitution-en.pdf?ua=1).
Section 5.4, Line 78: Same as above and should also include reversibility of effects as an element for consideration.
Section 5.5, Line 80: Reference is made to ‘Recommendation as to whether or not the risks are acceptable, manageable’. In the case of EGD-LMOs ability to independently modify entire ecosystems, reference should also be made to ‘reversibility’.
Accordingly, the title could read “Step 5. Recommendation as to whether or not the risks are acceptable, manageable or reversible, including, identification of strategies to manage and reverse these risks”
Section 5.5, Line 82: In line with that was said in intervention [#11781], should make clear reference to cut off criteria. “Acceptability of risks in light of cut-off criteria”
Section 5.5, Line 89: Elements for consideration should include cut-off criteria and alternatives (in line with comments made in [#11790]).
Section 6.: The title does not provide any specification of the relevance of the listed issues for risk assessment. Issues listed under this item should be taken into account when providing recommendations. The title could read: “6. Further considerations”.
Section 6., Line 93: Firstly, as suggested above, socioeconomic considerations should be mainstreamed into the risk assessment exercise. Therefore, this item should bring a summary of those, instead of being the only mention to it. The line could read “Summary of socioeconomic considerations”
Section 6., Line 96: Should provide more detail about the issues it is referring to. A clearer title could be: “Participation of Indigenous Peoples and Local Communities and Free, Prior and Informed Consent”
Section 6., Line 97: Line could be deleted as related issues already addressed under acceptability of risks and in line with what said in submission [#11797]
Additional line to be considered: Line 99 – Overview of suitable alternatives (in addition to what was proposed regarding alternatives on submission [#11790])
My name is Ernst Wimmer and I am Professor for Developmental Biology at the Georg-August-University Göttingen, Germany. My research includes applied approaches in insect biotechnology to establish modern genetic pest management methods. For the Open-ended Online Forum, I was nominated by the German Federal Ministry of Education and Research.
Regarding the use of comparators, I would like to again point out the EFSA activities regarding Gene Drive Modified Insects: Potential novel aspects of EGD-LMOs can be compared to LMOs that do not contain an engineered gene drive such as RIDL and fsRIDL and other disease vector/pest control strategies that involve the release of non-LMOs such as Wolbachia-mediated pathogen interference (PI), classical Sterile Insect Technique (SIT), Wolbachia-mediated Incompatible Insect Technique (IIT), or Classical Biological Control (CBC).
Devos, Y., Mumford, J.D., Bonsall, M.B., Camargo, A.M., Firbank, L.G., Glandorf, D.C.M., Nogué, F., Paraskevopoulos, K., Wimmer, E.A. (2021). Potential use of gene drive modified insects against disease vectors, agricultural pests, and invasive species poses new challenges for risk assessment. Critical Reviews in Biotechnology, DOI: 10.1080/07388551.2021.1933891.
Devos, Y., Bonsall, M.B., Firbank, L.G., Mumford, J., Nogué, F., Wimmer, E.A. (2020). Gene Drive-Modified Organisms: Developing Practical Risk Assessment Guidance. Trends in Biotechnology: 39, 853-856.
EFSA GMO Panel (EFSA Panel on Genetically Modified Organisms), Naegeli H, Bresson J-L, Dalmay T, Dewhurst IC, Epstein MM, Guerche P, Hejatko J, Moreno FJ, Mullins E, Nogue F, Rostoks N, Sanchez Serrano JJ, Savoini G, Veromann E, Veronesi F, Bonsall MB, Mumford J, Wimmer EA, Devos Y, Paraskevopoulos K and Firbank LG (2020). Scientific Opinion on the adequacy and suffciency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post-market environmental monitoring of genetically modified insects containing engineered gene drives. EFSA Journal 2020;18:6297, 90 pp.
Regarding the use of comparators, I would like to again point out the EFSA activities regarding Gene Drive Modified Insects: Potential novel aspects of EGD-LMOs can be compared to LMOs that do not contain an engineered gene drive such as RIDL and fsRIDL and other disease vector/pest control strategies that involve the release of non-LMOs such as Wolbachia-mediated pathogen interference (PI), classical Sterile Insect Technique (SIT), Wolbachia-mediated Incompatible Insect Technique (IIT), or Classical Biological Control (CBC).
Devos, Y., Mumford, J.D., Bonsall, M.B., Camargo, A.M., Firbank, L.G., Glandorf, D.C.M., Nogué, F., Paraskevopoulos, K., Wimmer, E.A. (2021). Potential use of gene drive modified insects against disease vectors, agricultural pests, and invasive species poses new challenges for risk assessment. Critical Reviews in Biotechnology, DOI: 10.1080/07388551.2021.1933891.
Devos, Y., Bonsall, M.B., Firbank, L.G., Mumford, J., Nogué, F., Wimmer, E.A. (2020). Gene Drive-Modified Organisms: Developing Practical Risk Assessment Guidance. Trends in Biotechnology: 39, 853-856.
EFSA GMO Panel (EFSA Panel on Genetically Modified Organisms), Naegeli H, Bresson J-L, Dalmay T, Dewhurst IC, Epstein MM, Guerche P, Hejatko J, Moreno FJ, Mullins E, Nogue F, Rostoks N, Sanchez Serrano JJ, Savoini G, Veromann E, Veronesi F, Bonsall MB, Mumford J, Wimmer EA, Devos Y, Paraskevopoulos K and Firbank LG (2020). Scientific Opinion on the adequacy and suffciency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post-market environmental monitoring of genetically modified insects containing engineered gene drives. EFSA Journal 2020;18:6297, 90 pp.
Good morning from Cuba to all the colleagues in our group, my name is Marvis Esther Suárez Romero, currently working in the Biodiversity and Biosafety Department (Office of Regulation and Environmental Safety) in Cuba, as Senior Specialist in Regulation, Control and Safety.
I wanted to thank you for having in our hands a document that allows us to discuss the EGD-LMOs and their possible risks. I totally agree with the comments of Anastasia Matthies, Dr. Eva Sirinathsinghji and Mr. Pieter van der Meer. The Guidance on risk assessment for LMO prepared in 2016 is very useful for any LMO, in its general aspects, so in this new document we must focus on understanding this technology, especially for regulators who must authorize or not its use. Hence the importance that interested parties demonstrate with facts and over time, that technology solves a problem without high costs for biodiversity and human health and for that, scientific information is needed that can be subsequently verified.
Kind Regards,
I wanted to thank you for having in our hands a document that allows us to discuss the EGD-LMOs and their possible risks. I totally agree with the comments of Anastasia Matthies, Dr. Eva Sirinathsinghji and Mr. Pieter van der Meer. The Guidance on risk assessment for LMO prepared in 2016 is very useful for any LMO, in its general aspects, so in this new document we must focus on understanding this technology, especially for regulators who must authorize or not its use. Hence the importance that interested parties demonstrate with facts and over time, that technology solves a problem without high costs for biodiversity and human health and for that, scientific information is needed that can be subsequently verified.
Kind Regards,
I am Stephanie James from the GeneConvene Global Collaborative at the Foundation for the National Institutes of Health in North Bethesda, Maryland, USA. I would like to thank Dr. Wimmer for pointing out the utility of other genetic biocontrol agents as potential comparators for gene drive modified organisms. I would also highlight that in the case of gene drive modified mosquitoes intended for population suppression, the utility of comparison to insecticides (larvicides or adulticides), which have a similar effect of depleting the mosquito population, has been cited (https://www.who.int/publications/i/item/9789240025233, https://www.liebertpub.com/doi/10.1089/vbz.2019.2606?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed). This is exemplified by a review of potential for release of vector species from competition following insecticide-based population suppression of Anopheles species in Africa (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425169/).
Hi Evrybody. My name is Angela Lozan, I am a PhD, associate professor and project manager at the National Office for Environmental Projects at the Ministry of Environment. I am with the Biosafety issues since 2007.
Section 5, line 48-53, I would like to extend the Elements for consideration regarding potential adverse effects resulting from the interaction between EGD-LMO and the receiving environment, considering in-depth effects to inter-specific competition affecting the trophic chains, that may provoke a dis-balance of prey/predators, host/parasite, symbioses life forms etc., would influence negatively ecosystems and their resilience capability and sustainability.
Line 58-63, along with geographic and bio geographic information that would describe the receiving environment, I would suggest to additionally provide with climatic, hydro-meteorologic information, inclusive possible hazardous, short-terms and long-terms climatic events, which may determine some unexpected effects and consequences of EGD-LMO over biodiversity and ecosystem in a long term perspective.
Section 5, line 48-53, I would like to extend the Elements for consideration regarding potential adverse effects resulting from the interaction between EGD-LMO and the receiving environment, considering in-depth effects to inter-specific competition affecting the trophic chains, that may provoke a dis-balance of prey/predators, host/parasite, symbioses life forms etc., would influence negatively ecosystems and their resilience capability and sustainability.
Line 58-63, along with geographic and bio geographic information that would describe the receiving environment, I would suggest to additionally provide with climatic, hydro-meteorologic information, inclusive possible hazardous, short-terms and long-terms climatic events, which may determine some unexpected effects and consequences of EGD-LMO over biodiversity and ecosystem in a long term perspective.
I am Stephanie James from the GeneConvene Global Collaborative at the Foundation for the National Institutes of Health. The GeneConvene Global Collaborative supports efforts to advance best practices and informed decision making for developing genetic biocontrol technologies for public health.
I would like to thank the organizers for this discussion and Luciana for moderating, and add that I appreciate the comment by Dr. Eva Sirinathsinghji (#11799) citing the numerous studies examining the behavior of gene drives under various ecological conditions. I would like to highlight that those publications cited and others (e.g., https://besjournals.onlinelibrary.wiley.com/doi/full/10.1111/2041-210X.13318, https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-019-0645-5, https://www.annualreviews.org/doi/abs/10.1146/annurev-ecolsys-031120-101013) illustrate how modeling can take the ecological landscape and population structure of the target organism into account to predict outcomes such as spread and persistence of the gene drive modified organism - characteristics that are important for risk assessment. It is widely recognized that more can be done to enhance the utility of modelling for investigating ecological interactions (e.g., https://www.cell.com/trends/biotechnology/ppt/S0167-7799(20)30233-X.ppt, https://www.sciencedirect.com/science/article/abs/pii/S0168952523000902, https://www.sciencedirect.com/science/article/pii/S0304380023000133), and this work is in progress. Assumptions made in modelling can be customized to different target organisms and receiving environments to query a range of possible scenarios. This should provide outcomes that are informative in addressing the range of uncertainty for particular interactions.
I would like to thank the organizers for this discussion and Luciana for moderating, and add that I appreciate the comment by Dr. Eva Sirinathsinghji (#11799) citing the numerous studies examining the behavior of gene drives under various ecological conditions. I would like to highlight that those publications cited and others (e.g., https://besjournals.onlinelibrary.wiley.com/doi/full/10.1111/2041-210X.13318, https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-019-0645-5, https://www.annualreviews.org/doi/abs/10.1146/annurev-ecolsys-031120-101013) illustrate how modeling can take the ecological landscape and population structure of the target organism into account to predict outcomes such as spread and persistence of the gene drive modified organism - characteristics that are important for risk assessment. It is widely recognized that more can be done to enhance the utility of modelling for investigating ecological interactions (e.g., https://www.cell.com/trends/biotechnology/ppt/S0167-7799(20)30233-X.ppt, https://www.sciencedirect.com/science/article/abs/pii/S0168952523000902, https://www.sciencedirect.com/science/article/pii/S0304380023000133), and this work is in progress. Assumptions made in modelling can be customized to different target organisms and receiving environments to query a range of possible scenarios. This should provide outcomes that are informative in addressing the range of uncertainty for particular interactions.
Topic 2: Part A, sections 4-6
Hello everyone. My name is Adam Cornish and I work in the Office of Agricultural Policy at the U.S. Department of State and serve as the U.S. national focal point for the Cartagena Protocol on Biosafety. I am pleased to see the continued discussion on the forum and thank the moderators for their work and the thoughtful comments of the other participants in the forum.
The United States is encouraged by the discussion on the topic of LMOs containing engineered gene drives (EGD-LMOs) and appreciates the chance to provide information and perspective on this topic.
Section 4.1: The precautionary approach is explicitly referenced in the Cartagena Protocol on Biosafety, providing a foundation by which risk assessments for EGD organisms can be considered. In this context, it is important to note the core concept of precaution as indicated in the Convention text - “where there is a threat of significant reduction or loss of biological diversity, lack of full scientific certainty should not be used as a reason for postponing measures to avoid or minimize such a threat”. In practice, this suggests that the need for delaying or postponing additional measures is triggered only when sufficient reason exists to expect that some specific course of action will lead to “a threat of significant reduction or loss of biological diversity” (Ad van Dommelen et al. 1997). For example, should an EGD organism provide a demonstrated benefit to biodiversity, particularly when compared to existing measures (e.g., pesticide use), scientific uncertainty should not be used to delay the development, approval, and adoption of that EGD organism. Further, precaution can be applied inappropriately to impede regulatory actions, creating unnecessary burdens during an approval when clear (or even probable) evidence about its negative impacts is lacking. In short, precaution incorporates the concept of proportionality between level of risk and measures adopted, and should include some form of analysis of both the various costs and benefits involved (IUCN, Cooney et al. 2004).
Section 4.1: Regarding stakeholder engagement, the United States believes that stakeholder engagement is useful in identifying potential risk and benefits from the applications of technologies, although this engagement should remain voluntary for all Parties as they develop their own risk assessment methodologies.
Section 5.1. Step 1: During MOP10, Parties recognized that attempts to develop guidance for any or all EGD-LMOs were unlikely to be successful, hence specifying that this guidance was meant to be developed only for EGD modified mosquitoes. As the guidance is to be developed with a specific focus for EGD mosquitoes, the amount of detail currently described in Part A does not seem to match the directive of the description. We recommend that this section be appropriately scoped to enable Parties to focus on the most relevant and generalizable components of risk assessments related to EGD-LMOs. Some described components will be dependent on the application and organism identity, requiring evaluation on a case-by-case basis and we suggest that the outline be updated to reflect this. In addition, any risks resulting from the transformation method are unlikely to be relevant during release of an EGD organism or will be captured during other methods – we suggest removing this as a consideration in this section. We also note that horizontal gene transfer is not, in and of itself, a risk to biodiversity conservation – all organisms in an environment, regardless of status as an EGD organism, exchange genetic information. That said, horizontal gene transfer and expression of DNA between organisms is unlikely to occur. Although there are many opportunities for organisms to directly interact with fungi and bacteria (e.g., as commensals, symbionts, parasites, pathogens, decomposers, or in the guts of herbivores) and with other invertebrates, there are almost no evolutionary examples of horizontal gene transfer from eukaryotes to bacteria or from plants to fungi or invertebrates (Keese et al., 2008). It is important to note that, in cases where review of sequence data implied that horizontal gene transfer occurred, these events are inferred to occur on an evolutionary time scale on the order of millions of years (Brown, 2003; EFSA, 2009; Koonin et al., 2011). The related trait and its persistence/reproductive advantage is the component that must be considered on a case-by-case basis.
Sections 5.2 and 5.3. Steps 2 and 3: The United States expresses some confusion on these two sections, as the order of operation does not match the best practices in risk assessment processes. The risk characterization cannot be fully evaluated without a complete understanding of the potential adverse effects that may be presented by the release of the EGD organism. We suggest that the development of this section match the process described in Annex III of the Protocol. In addition, the choice of comparators for EGD organisms is an important topic.
Section 5.5. Step 5: Regarding the recommendation as to whether or not the risks from the release of an EGD organism are acceptable, it is worth referring back to the comparators and the associated consequences that are downstream of a lack of action and the cost of “business as usual.” Maintaining "traditional" measures (e.g., pesticide applications) may have far greater negative impacts on biodiversity conservation than the release of an EGD organism, which should also be considered in developing a recommendation. We also want to emphasize the importance of considering the use of the EGD organisms relative to other applications that are intended to achieve similar results. For example, the use of an EGD in a target organism for pest control may be far more specific and have limited to no effects on non-target organisms when compared to traditional pesticide applications.
Hello everyone. My name is Adam Cornish and I work in the Office of Agricultural Policy at the U.S. Department of State and serve as the U.S. national focal point for the Cartagena Protocol on Biosafety. I am pleased to see the continued discussion on the forum and thank the moderators for their work and the thoughtful comments of the other participants in the forum.
The United States is encouraged by the discussion on the topic of LMOs containing engineered gene drives (EGD-LMOs) and appreciates the chance to provide information and perspective on this topic.
Section 4.1: The precautionary approach is explicitly referenced in the Cartagena Protocol on Biosafety, providing a foundation by which risk assessments for EGD organisms can be considered. In this context, it is important to note the core concept of precaution as indicated in the Convention text - “where there is a threat of significant reduction or loss of biological diversity, lack of full scientific certainty should not be used as a reason for postponing measures to avoid or minimize such a threat”. In practice, this suggests that the need for delaying or postponing additional measures is triggered only when sufficient reason exists to expect that some specific course of action will lead to “a threat of significant reduction or loss of biological diversity” (Ad van Dommelen et al. 1997). For example, should an EGD organism provide a demonstrated benefit to biodiversity, particularly when compared to existing measures (e.g., pesticide use), scientific uncertainty should not be used to delay the development, approval, and adoption of that EGD organism. Further, precaution can be applied inappropriately to impede regulatory actions, creating unnecessary burdens during an approval when clear (or even probable) evidence about its negative impacts is lacking. In short, precaution incorporates the concept of proportionality between level of risk and measures adopted, and should include some form of analysis of both the various costs and benefits involved (IUCN, Cooney et al. 2004).
Section 4.1: Regarding stakeholder engagement, the United States believes that stakeholder engagement is useful in identifying potential risk and benefits from the applications of technologies, although this engagement should remain voluntary for all Parties as they develop their own risk assessment methodologies.
Section 5.1. Step 1: During MOP10, Parties recognized that attempts to develop guidance for any or all EGD-LMOs were unlikely to be successful, hence specifying that this guidance was meant to be developed only for EGD modified mosquitoes. As the guidance is to be developed with a specific focus for EGD mosquitoes, the amount of detail currently described in Part A does not seem to match the directive of the description. We recommend that this section be appropriately scoped to enable Parties to focus on the most relevant and generalizable components of risk assessments related to EGD-LMOs. Some described components will be dependent on the application and organism identity, requiring evaluation on a case-by-case basis and we suggest that the outline be updated to reflect this. In addition, any risks resulting from the transformation method are unlikely to be relevant during release of an EGD organism or will be captured during other methods – we suggest removing this as a consideration in this section. We also note that horizontal gene transfer is not, in and of itself, a risk to biodiversity conservation – all organisms in an environment, regardless of status as an EGD organism, exchange genetic information. That said, horizontal gene transfer and expression of DNA between organisms is unlikely to occur. Although there are many opportunities for organisms to directly interact with fungi and bacteria (e.g., as commensals, symbionts, parasites, pathogens, decomposers, or in the guts of herbivores) and with other invertebrates, there are almost no evolutionary examples of horizontal gene transfer from eukaryotes to bacteria or from plants to fungi or invertebrates (Keese et al., 2008). It is important to note that, in cases where review of sequence data implied that horizontal gene transfer occurred, these events are inferred to occur on an evolutionary time scale on the order of millions of years (Brown, 2003; EFSA, 2009; Koonin et al., 2011). The related trait and its persistence/reproductive advantage is the component that must be considered on a case-by-case basis.
Sections 5.2 and 5.3. Steps 2 and 3: The United States expresses some confusion on these two sections, as the order of operation does not match the best practices in risk assessment processes. The risk characterization cannot be fully evaluated without a complete understanding of the potential adverse effects that may be presented by the release of the EGD organism. We suggest that the development of this section match the process described in Annex III of the Protocol. In addition, the choice of comparators for EGD organisms is an important topic.
Section 5.5. Step 5: Regarding the recommendation as to whether or not the risks from the release of an EGD organism are acceptable, it is worth referring back to the comparators and the associated consequences that are downstream of a lack of action and the cost of “business as usual.” Maintaining "traditional" measures (e.g., pesticide applications) may have far greater negative impacts on biodiversity conservation than the release of an EGD organism, which should also be considered in developing a recommendation. We also want to emphasize the importance of considering the use of the EGD organisms relative to other applications that are intended to achieve similar results. For example, the use of an EGD in a target organism for pest control may be far more specific and have limited to no effects on non-target organisms when compared to traditional pesticide applications.
Greetings this is Brinda Dass from the Foundation for the National Institutes of Health, USA.
As mentioned in my response under Topic 1, I would suggest moving Section 3.1 (Line 15) Protection goals, assessment endpoints, and measurement endpoints under section 4, preferably as the first bullet under 4.2 prior to pathways to harm. Alternatively, it can be moved under 4.1 as the last bullet because protection goals will follow from national law as well as stakeholder engagement.
On the topic of stakeholder engagement (line 28) mention should be made that some countries have existing requirements for other assessment processes such as Strategic Environmental Assessments - SEA; and Environmental and Social Impact Assessments – ESIA, or sometimes known as Environmental, Social and Health Impact Assessments – ESHIA. These processes while independent of environmental risk assessment ERA have value in terms of engagement, information gathering, risks and benefits all of which could also benefit the risk assessment scoping process. Perhaps mention could be made for how other processes where nationally mandated could be beneficial to ERA scoping.
Environmental Impact Assessment and Strategic Environmental Assessment: Towards an Integrated Approach. UNEP 2004 https://www.unep.org/resources/report/environmental-impact-assessment-and-strategic-environmental-assessment-towards
International Principles For Social Impact Assessment (Vanclay, 2003) https://doi.org/10.3152/147154603781766491
This additional guidance should recognize the importance of engagement and encourage governments to set out clear expectations for engagement in the risk assessment process. This would allow support of Article 23 of Cartagena Protocol on public awareness and participation. Stakeholder concerns can be used in scoping and describing top level harms for pathways to harm. Stakeholder concerns also feeds back to Section 3.2 line 19 sources and relevance of information for risk assessment.
As mentioned in my response under Topic 1, I would suggest moving Section 3.1 (Line 15) Protection goals, assessment endpoints, and measurement endpoints under section 4, preferably as the first bullet under 4.2 prior to pathways to harm. Alternatively, it can be moved under 4.1 as the last bullet because protection goals will follow from national law as well as stakeholder engagement.
On the topic of stakeholder engagement (line 28) mention should be made that some countries have existing requirements for other assessment processes such as Strategic Environmental Assessments - SEA; and Environmental and Social Impact Assessments – ESIA, or sometimes known as Environmental, Social and Health Impact Assessments – ESHIA. These processes while independent of environmental risk assessment ERA have value in terms of engagement, information gathering, risks and benefits all of which could also benefit the risk assessment scoping process. Perhaps mention could be made for how other processes where nationally mandated could be beneficial to ERA scoping.
Environmental Impact Assessment and Strategic Environmental Assessment: Towards an Integrated Approach. UNEP 2004 https://www.unep.org/resources/report/environmental-impact-assessment-and-strategic-environmental-assessment-towards
International Principles For Social Impact Assessment (Vanclay, 2003) https://doi.org/10.3152/147154603781766491
This additional guidance should recognize the importance of engagement and encourage governments to set out clear expectations for engagement in the risk assessment process. This would allow support of Article 23 of Cartagena Protocol on public awareness and participation. Stakeholder concerns can be used in scoping and describing top level harms for pathways to harm. Stakeholder concerns also feeds back to Section 3.2 line 19 sources and relevance of information for risk assessment.
Dear all,
My name is Eder Toppa, I've been working for the Brazilian Ministry of Agriculture and Livestock for the past decade and I am currently the Head of Biosafety Service as well as I am member of the National Biosafety Commission. I attended the COP / MOP meetings held in Montréal last December and I am following all the discussion about gene drive.
Apologies for only writing now, however I would like to highlight some comments.
Line 97: "Part A, Section 6. Risks vs. benefits"
It is important to keep inbalance the risk vs. benefit, as we are talking about the control of a vector of an important disease that deeply affects the population of developing countries - the disease rate can even get worse with climate change. From the WHO Guidance: "A new product such as GMMs should be assessed in the regulatory review process on the basis of both the benefits and risks. The primary potential benefit of GMMs would be the improvement of human health. Therefore, efficacy data will enter into decision-making regarding benefit [...] Variations in individual judgement, as well as the context in which decisions are being made, can lead to differing opinions about risk–benefit assessment. Some might advocate for withholding regulatory approval until absence of risk can be assured, regardless of benefit. However, decision-makers may feel that other contextual factors should also be taken into account, such as the severity of the health problem addressed by the new technology, and the availability and utility of alternative disease control methods. The meaning of “safe” is not easily defined, as it is recognized that virtually all public health products (including those currently in widespread use against diseases such as malaria and dengue) have some ability to cause adverse effects under certain conditions. With regard to genetically modified organisms (GMOs), the Nuffield Council on Bioethics has recommended that “all possible paths of action must be compared, including inaction”, recognizing that “there can be dangers in inaction, or alternative courses of action, as well as in the adoption of a particular innovation”
Best regards
Eder Toppa
My name is Eder Toppa, I've been working for the Brazilian Ministry of Agriculture and Livestock for the past decade and I am currently the Head of Biosafety Service as well as I am member of the National Biosafety Commission. I attended the COP / MOP meetings held in Montréal last December and I am following all the discussion about gene drive.
Apologies for only writing now, however I would like to highlight some comments.
Line 97: "Part A, Section 6. Risks vs. benefits"
It is important to keep inbalance the risk vs. benefit, as we are talking about the control of a vector of an important disease that deeply affects the population of developing countries - the disease rate can even get worse with climate change. From the WHO Guidance: "A new product such as GMMs should be assessed in the regulatory review process on the basis of both the benefits and risks. The primary potential benefit of GMMs would be the improvement of human health. Therefore, efficacy data will enter into decision-making regarding benefit [...] Variations in individual judgement, as well as the context in which decisions are being made, can lead to differing opinions about risk–benefit assessment. Some might advocate for withholding regulatory approval until absence of risk can be assured, regardless of benefit. However, decision-makers may feel that other contextual factors should also be taken into account, such as the severity of the health problem addressed by the new technology, and the availability and utility of alternative disease control methods. The meaning of “safe” is not easily defined, as it is recognized that virtually all public health products (including those currently in widespread use against diseases such as malaria and dengue) have some ability to cause adverse effects under certain conditions. With regard to genetically modified organisms (GMOs), the Nuffield Council on Bioethics has recommended that “all possible paths of action must be compared, including inaction”, recognizing that “there can be dangers in inaction, or alternative courses of action, as well as in the adoption of a particular innovation”
Best regards
Eder Toppa
Hi my name is Eva Sirinathsinghji, I work as a Research Associate for Third World Network.
I would like to raise the limited usefulness or relevance of using existing biocontrol methods as a comparator for suppression drives. While some aspects may be relevant e.g. the impacts of population suppression, the use of such comparators deals only with the intended aims of population suppression. It however, fails to capture various unintended impacts of gene drives. For example, gene drives that are designed to suppress populations but may fail to do so. Some are predicted to potentially persist long-term despite the design aims of eliminating populations. This potential long-term persistence in the environment and thus long-term exposure to the gene drive organism, and its potential spread into non-target geographical areas, are of concern.
As an example of a potential risk with direct relevance to biodiversity, is a new study assessing gene drive suppression of invasive wasp species. The study described a likely long-term persistence of gene drive wasps as a result of chase dynamics occurring where simultaneous localised suppression as well as population abundance takes place. As stated by the authors “the predicted long-term persistence of genetically modified pests will influence the ethics and likelihood of using gene drives for pest control, especially given concerns that modified wasps would eventually be transported back to their home range.” https://doi.org/10.1002/eap.2912
There is also the added expectation of resistance development of drives, with developers predicting the need for multiple and sequential releases. This may lead to additional barriers to long-term population suppression and thus persistent exposure and spread.
Such a scenario would also raise novel risk management considerations due to the continued need to monitor unintended spread outside of the target geographical area, including across national borders and/or into indigenous territories where approvals may not have been granted.
I would like to raise the limited usefulness or relevance of using existing biocontrol methods as a comparator for suppression drives. While some aspects may be relevant e.g. the impacts of population suppression, the use of such comparators deals only with the intended aims of population suppression. It however, fails to capture various unintended impacts of gene drives. For example, gene drives that are designed to suppress populations but may fail to do so. Some are predicted to potentially persist long-term despite the design aims of eliminating populations. This potential long-term persistence in the environment and thus long-term exposure to the gene drive organism, and its potential spread into non-target geographical areas, are of concern.
As an example of a potential risk with direct relevance to biodiversity, is a new study assessing gene drive suppression of invasive wasp species. The study described a likely long-term persistence of gene drive wasps as a result of chase dynamics occurring where simultaneous localised suppression as well as population abundance takes place. As stated by the authors “the predicted long-term persistence of genetically modified pests will influence the ethics and likelihood of using gene drives for pest control, especially given concerns that modified wasps would eventually be transported back to their home range.” https://doi.org/10.1002/eap.2912
There is also the added expectation of resistance development of drives, with developers predicting the need for multiple and sequential releases. This may lead to additional barriers to long-term population suppression and thus persistent exposure and spread.
Such a scenario would also raise novel risk management considerations due to the continued need to monitor unintended spread outside of the target geographical area, including across national borders and/or into indigenous territories where approvals may not have been granted.
Hello. My name is ROUAMBA Wend-Rabo Mathurin, from Burkina Faso's National Biosafety Agency. I have about ten years' experience in the regulation of GMOs in Burkina Faso.
Based on the moderator's questions, concerning Section 4 to 6, the mobility aspect of the GD mosquito is a particular aspect of this type of GMO. It would be good to take this into account, as well as the factors that can influence spread and persistence (the latter are already considered) in the problem formulation stage.
Regarding the choice of appropriate comparators, a participant in this forum has already mentioned the existence of evaluations of other vector control methods (chemical...) against malaria. I agree with him that these methods could serve as appropriate comparators.
Based on the moderator's questions, concerning Section 4 to 6, the mobility aspect of the GD mosquito is a particular aspect of this type of GMO. It would be good to take this into account, as well as the factors that can influence spread and persistence (the latter are already considered) in the problem formulation stage.
Regarding the choice of appropriate comparators, a participant in this forum has already mentioned the existence of evaluations of other vector control methods (chemical...) against malaria. I agree with him that these methods could serve as appropriate comparators.
My name is Felicity Keiper and I am participating in this forum as a representative of the Global Industry Coalition (GIC). I have made general comments under Topic 1 on Part A (#11847, #11849) of the draft outline suggesting substantial rearrangement and editing, including merging sections 3 and 4 into one “Planning an environmental risk assessment” section. We also suggest that section 5 is deleted. We support retaining a section for “related issues” (section 6 in the draft outline).
Section 4
Line 25: we agree the important relevant considerations are applicable laws and regulations (per #11778, #11785) and suggest that relevant regional initiatives are also included here. The WHO Guidance Framework (second edition, 2021) includes an extensive list of developments relevant to risk assessment spanning 2000-2020.
Lines 32-24: we support the inclusion of the topic of comparators in this context and appreciate the relevant examples contributed by #11811, #11813, #11829, #11832, #11843.
Section 5
Lines 35-91: the steps listed are reproduced from Annex III paragraph 8 (methodology)/the previous Guidance document. We question the purpose of this section since the relevant issues/considerations should already be addressed in the preceding sections. We therefore suggest that this entire section is deleted.
We note that this section of the draft outline includes risk management (lines 85-88) and that “appropriate risk management strategies” are relevant in Annex III (para 8(e), (f)). We suggest that consideration of risk management strategies are discussed in earlier sections where relevant, such as technology types and treatment of uncertainty.
Section 6
Line 98: delete this – uncertainty is dealt with in section 3.
Section 4
Line 25: we agree the important relevant considerations are applicable laws and regulations (per #11778, #11785) and suggest that relevant regional initiatives are also included here. The WHO Guidance Framework (second edition, 2021) includes an extensive list of developments relevant to risk assessment spanning 2000-2020.
Lines 32-24: we support the inclusion of the topic of comparators in this context and appreciate the relevant examples contributed by #11811, #11813, #11829, #11832, #11843.
Section 5
Lines 35-91: the steps listed are reproduced from Annex III paragraph 8 (methodology)/the previous Guidance document. We question the purpose of this section since the relevant issues/considerations should already be addressed in the preceding sections. We therefore suggest that this entire section is deleted.
We note that this section of the draft outline includes risk management (lines 85-88) and that “appropriate risk management strategies” are relevant in Annex III (para 8(e), (f)). We suggest that consideration of risk management strategies are discussed in earlier sections where relevant, such as technology types and treatment of uncertainty.
Section 6
Line 98: delete this – uncertainty is dealt with in section 3.
My name is Anke Hein. I have several years of experience in the area of LMO risk assessment and regulation and currently work for the German Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection. This is my first participation in the open ended online forum and I would like to thank for the opportunity to contribute to the discussions.
General remark:
Line 24 f.: I agree with several comments that encourage further elaboration of the Risk Assessment and addition of a risk assessment methodology section (echoing #11787, #11796).
Line 80-82:
The risk assessment should be in line with the precautionary approach stated in the preamble of the Cartagena Protocol of biosafety. I would therefore recommend to take the precautionary approach into account accordingly when reasonable levels for the acceptance of risks are identified and assessed. The same should apply when assessing which end points of uncertainty (due to lack of knowledge or non-robust methodology) is acceptable (topic 1).
However, the decision as to whether risks are acceptable or manageable in my view cannot be taken by one organisation or country alone, since gene drive organisms will have the potential to produce large-scale environmental impacts. Therefore, the decision-making process should include discussion of protection goals of needs informed consent of stakeholders such as neighbouring countries and IPLCs.
Line 83:
Large-scale environmental monitoring before, during and after release should be established to gain insight into the potential adverse environmental effects of gene drive organisms besides gene drive function and efficiency. Risk assessment and computer modelling will not be able to predict all unforeseen, cumulative and long-term effects on the environment. Therefore, it is necessary to carry out an environmental monitoring in order to take action in respect of protecting environment, nature and human health. A monitoring plan with appropriate indicators should be implemented before release for testing or large-scale release can be considered. It will be necessary to develop and test suitable long-term monitoring concepts to identify potential adverse effects on the environment e.g. on biodiversity, food chains, species interactions prior to anticipating the release of gene drive organisms.
General remark:
Line 24 f.: I agree with several comments that encourage further elaboration of the Risk Assessment and addition of a risk assessment methodology section (echoing #11787, #11796).
Line 80-82:
The risk assessment should be in line with the precautionary approach stated in the preamble of the Cartagena Protocol of biosafety. I would therefore recommend to take the precautionary approach into account accordingly when reasonable levels for the acceptance of risks are identified and assessed. The same should apply when assessing which end points of uncertainty (due to lack of knowledge or non-robust methodology) is acceptable (topic 1).
However, the decision as to whether risks are acceptable or manageable in my view cannot be taken by one organisation or country alone, since gene drive organisms will have the potential to produce large-scale environmental impacts. Therefore, the decision-making process should include discussion of protection goals of needs informed consent of stakeholders such as neighbouring countries and IPLCs.
Line 83:
Large-scale environmental monitoring before, during and after release should be established to gain insight into the potential adverse environmental effects of gene drive organisms besides gene drive function and efficiency. Risk assessment and computer modelling will not be able to predict all unforeseen, cumulative and long-term effects on the environment. Therefore, it is necessary to carry out an environmental monitoring in order to take action in respect of protecting environment, nature and human health. A monitoring plan with appropriate indicators should be implemented before release for testing or large-scale release can be considered. It will be necessary to develop and test suitable long-term monitoring concepts to identify potential adverse effects on the environment e.g. on biodiversity, food chains, species interactions prior to anticipating the release of gene drive organisms.
My name is Marja Ruohonen-Lehto, and I have more than 25 years of experience with biosafety and LMO risk assessments. I work for the Finnish Government, and I am a previous and present member of the RARM AHTEG. Many thanks to the Secretariat and Luciana for facilitating and providing useful questions to keep us focused.
I find the comments and information on the choice of comparators very useful. Also comments and information on the biology and behaviour of mosquitoes species and the specificities of the receiving environment are important. I concur with colleagues that suggest that the newly published OECD document [OECD Working Party on the Harmonisation of Regulatory Oversight in Biotechnology on the “Environmental Considerations for Risk/Safety Assessment for the Release of Transgenic Plants” (https://read.oecd.org/10.1787/62ed0e04-en?format=pdf)] can provide useful additional information in structuring of the problem formulation approach and developing plausible pathways to harm.
Many thanks!
I find the comments and information on the choice of comparators very useful. Also comments and information on the biology and behaviour of mosquitoes species and the specificities of the receiving environment are important. I concur with colleagues that suggest that the newly published OECD document [OECD Working Party on the Harmonisation of Regulatory Oversight in Biotechnology on the “Environmental Considerations for Risk/Safety Assessment for the Release of Transgenic Plants” (https://read.oecd.org/10.1787/62ed0e04-en?format=pdf)] can provide useful additional information in structuring of the problem formulation approach and developing plausible pathways to harm.
Many thanks!
My name is Thato Mogapi from the Department of Forestry, Fisheries and the Environment in South Africa.
With regards to Section 4 to 6, the additional voluntary guidance material should look at key elements of the risk assessment at different phases as proposed in the WHO guidance document. The WHO guidance recommends a phased testing pathway stepwise approach to guide and conduct research from the laboratory to deployment. For section 4.1. Establishing the context and scope (line 25), consideration should be given to national, regional and international obligations; environmental, health, and agricultural policies and strategies, intended use of the EGD-LMO, baseline information for the likely potential receiving environment; the biology and ecology of the recipient organism, and the scale and duration of the release.
With regards to Section 4 to 6, the additional voluntary guidance material should look at key elements of the risk assessment at different phases as proposed in the WHO guidance document. The WHO guidance recommends a phased testing pathway stepwise approach to guide and conduct research from the laboratory to deployment. For section 4.1. Establishing the context and scope (line 25), consideration should be given to national, regional and international obligations; environmental, health, and agricultural policies and strategies, intended use of the EGD-LMO, baseline information for the likely potential receiving environment; the biology and ecology of the recipient organism, and the scale and duration of the release.
Considerations for Section 4 to 6:
- Considering the importance of problem formulation step, is the proposed approach focusing on items that are novel for LMOs containing gene drive?
In short yes this is voluntary and additional guidance specifically for EGD mosquitoes not a manual on how to conduct risk assessment. The starting point should be a basic agreement that risk assessment paradigm is as described in Annex III. Therefore this document should take the overall approach of Annex III and specifics should focus on items that are novel to EGD mosquitoes.
I would suggest moving 3.1 protection goals assessment endpoints and measurement endpoints (as they relate to EGD mosquitoes) to the third bullet in 4.1 following stakeholder engagement.
Unsure what “analysis plan” specifically refers to on Line 31 Section 4.2
4.3 Choice of comparators is an important consideration as these are likely to be different during the different phases of testing (Phased testing pathway describe by WHO) with initial laboratory studies using lab strains of unmodified mosquitoes of the same species and generational equivalent. Subsequent phases would likely rely on field caught mosquitoes of the local unmodified or wild type strain.
Suggest deleting line 37 under section 5- application of the Roadmap.
Line 38 or section 5.1 step 1 should be titled hazard characterization because that is what it essentially describes.
Line 41 should read “utilize detailed pathways to harm to generate risk hypotheses”
Line 42- should read “Potential Hazards related to parental/ wild type characteristics, molecular characteristics of introduced sequences and their expression products, transformation method, site of integration”
Note introduced sequence genotype and phenotype is where there could be a difference between EGDMs and other LMOs/GMMs.
Line 46- unclear what “containment characteristics of the receiving environment” means in the context of hazard characterization. Is this referring to geographical containment of the released insects?
Lines 51-52 outcrossing and HGT are processes in themselves and not hazards per se.
Line 58 should not mention risk as this appears to be more of likelihood evaluation
Step 5.3 should be exposure characterization
Step 5.4- should be consequence analysis or risk estimation
Line 66 should be deleted as this is already completed much earlier and not a consideration this late in the process.
Section 6 should be deleted here as Risk assessment typically does not consider benefits though this maybe obtained via other assessments such as EIA.
thanks
Brinda Dass, FNIH
- Considering the importance of problem formulation step, is the proposed approach focusing on items that are novel for LMOs containing gene drive?
In short yes this is voluntary and additional guidance specifically for EGD mosquitoes not a manual on how to conduct risk assessment. The starting point should be a basic agreement that risk assessment paradigm is as described in Annex III. Therefore this document should take the overall approach of Annex III and specifics should focus on items that are novel to EGD mosquitoes.
I would suggest moving 3.1 protection goals assessment endpoints and measurement endpoints (as they relate to EGD mosquitoes) to the third bullet in 4.1 following stakeholder engagement.
Unsure what “analysis plan” specifically refers to on Line 31 Section 4.2
4.3 Choice of comparators is an important consideration as these are likely to be different during the different phases of testing (Phased testing pathway describe by WHO) with initial laboratory studies using lab strains of unmodified mosquitoes of the same species and generational equivalent. Subsequent phases would likely rely on field caught mosquitoes of the local unmodified or wild type strain.
Suggest deleting line 37 under section 5- application of the Roadmap.
Line 38 or section 5.1 step 1 should be titled hazard characterization because that is what it essentially describes.
Line 41 should read “utilize detailed pathways to harm to generate risk hypotheses”
Line 42- should read “Potential Hazards related to parental/ wild type characteristics, molecular characteristics of introduced sequences and their expression products, transformation method, site of integration”
Note introduced sequence genotype and phenotype is where there could be a difference between EGDMs and other LMOs/GMMs.
Line 46- unclear what “containment characteristics of the receiving environment” means in the context of hazard characterization. Is this referring to geographical containment of the released insects?
Lines 51-52 outcrossing and HGT are processes in themselves and not hazards per se.
Line 58 should not mention risk as this appears to be more of likelihood evaluation
Step 5.3 should be exposure characterization
Step 5.4- should be consequence analysis or risk estimation
Line 66 should be deleted as this is already completed much earlier and not a consideration this late in the process.
Section 6 should be deleted here as Risk assessment typically does not consider benefits though this maybe obtained via other assessments such as EIA.
thanks
Brinda Dass, FNIH
