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Past Activities 2014-2016

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Opening of the discussion [#7197]
Dear Participants of the Open-Ended Online Forum on Synthetic Biology,

Welcome to the discussion on Topic 5: “Best practices on risk assessment and monitoring regimes currently used by Parties to the Convention and other Governments “. It is a pleasure to moderate this discussion, and I would like to thank the Secretariat for inviting me to do so. The discussion on Topic 5 opens today and continues until June 8.

As you are all aware, the purpose of the Open-Ended Online Forum on Synthetic Biology is to support the work of the Ad Hoc Technical Expert Group (AHTEG) on Synthetic Biology, as indicated in decision XII/24 of the Conference of the Parties to the Convention on Biological Diversity (https://www.cbd.int/doc/decisions/cop-12/cop-12-dec-24-en.doc). The topics selected for this round of discussion are drawn directly from the Terms of Reference for the AHTEG. As such, for this topic, the Terms of Reference state that the AHTEG will:

“Building on the work on risk assessment and risk management undertaken by the Cartagena Protocol, compile information on best practices on risk assessment and monitoring regimes currently used by Parties to the Convention and other Governments, including transboundary movement, to inform those who do not have national risk assessment or monitoring regimes, or are in the process of reviewing their current risk assessment or monitoring regimes and to help those Parties and other Governments to regulate organisms, components and products from synthetic biology techniques appropriately.”

As a starting point for this discussion, I’d like to summarize the work that has been completed to date on risk assessment and risk management undertaken by the Cartagena Protocol. First, I’d like to draw your attention to Articles 15 and 16 of the Cartagena Protocol, which address risk assessment and risk management of Living Modified Organisms (LMOs), respectively, and Annex 3, which further addresses risk assessment of LMOs (https://bch.cbd.int/protocol/text/). Additional work has been done on risk assessment in the context of the Cartagena Protocol, including the “Guidance on Risk Assessment of Living Modified Organisms” (http://www.cbd.int/doc/meetings/bs/mop-06/official/mop-06-13-add1-en.doc) and the “Training Manual on Risk Assessment of Living Modified Organisms in the context of the Cartagena Protocol on Biosafety” (http://www.cbd.int/doc/meetings/bs/mop-07/information/mop-07-inf-06-en.pdf).

Moreover, the following documents have been developed and are provided as background documents for this discussion (available for download in the discussion page at https://bch.cbd.int/synbio/open-ended/discussion.shtml#topic5):

•        Summary and Comparative Analysis of Nine National Approaches to Ecological Risk Assessment of Living Modified Organisms in the Context of the Cartagena Protocol on Biosafety, Annex III
•       CBD Technical Series 82 (pages 37-38): Adequacy of current methodologies for environmental risk assessment

Keeping in mind the work described above, I will now invite you to provide information on best practices on risk assessment and monitoring regimes that are currently used by Parties to the Convention and other Governments.

Best regards,
Jaimie Schnell
posted on 2015-05-25 01:07 UTC by Ms. Jaimie Schnell, Canada
This is a reply to 7197 RE: Opening of the discussion [#7211]
Dear Jaimie, dear all,
Thanks to Jaimie for moderating this discussion and all other participants who will react later on. My name is Boet Glandorf, and I work as a senior risk assessor in the GMO Office in the Netherlands for more than 15 years, and am involved in the risk assessment of GM plants and microorganisms. Therefore, my information on risk assessment and monitoring is based on GMOs, with a focus on the environmental risk assessment (ERA).

The question in this online forum is to provide information on best practices on risk assessment and monitoring regimes that are currently used by Parties to the Convention and other Governments.

In my opinion, at the moment all organisms obtained by synthetic biology are considered to be GMOs (or LMOs) and we consider the current GMO risk assessment framework therefore applicable also for these 'synthetic' organisms.

With respect to existing guidance on environmental risk assessment and monitoring of GMOs:
The Dutch GMO legislation is based upon European GMO legislation1. This legislation defines a risk assessment framework for GMOs  and requirements in case of transboundary movement of GMOs1. For ERA of GMOs, Directive 2001/18/EC1 as well as regulation (EC) 1829/20031 can be applicable.
Data requirements are documented in Annex III of Directive 2001/18/EC1, steps in the ERA in Annex II and monitoring in Annex VII. Further guidance on Annex II is given in 2002/623/EC2 and on Annex VII in 2002/811/EC3.  More extensive guidance is written by the European Food Safety Authority (EFSA) on ERA of GM plants4, GM microorganisms4 and on post market monitoring4 in the framework of Regulation (EC) 1829/2003.

With respect to actual cases of environmental risk assessment of GMOs as performed by the Netherlands the following information can be accessed:
- With respect to field trials with GMOs, information on risk assessment and monitoring can be found in the BCH and on the site of the GMO Office6. Scientific opinions of the Dutch Committee of Genetic Modification (COGEM) with respect to field trials with GMOs in the Netherlands can be accessed on the COGEM site5.
- For commercial release of GM plants under Directive 2001/18/EC, information on risk assessments performed by the Netherlands, including opinions from COGEM5, can be found on the site of the GMO office6.
- For commercial releases of GM plants under Regulation (EC) 1829/2003, opinions of EFSA can be found at the EFSA site7 and opinions of COGEM on the COGEM site5.
- Post market monitoring plans GM plants are found on the site of the European Commission8,  the opinions of EFSA on these monitoring reports are accessible on the EFSA site7.

Best regards,
Boet

1. http://ec.europa.eu/food/plant/gmo/new/legislation/index_en.htm
2. http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=celex:32002D0623
3. http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=celex:32002D0811
4. http://www.efsa.europa.eu/en/gmoapplicationshelpdesk/guidancedocumentsgmo.htm
5. http://www.cogem.net/index.cfm/en/publications/categorie/advice
6. http://www.ggo-vergunningverlening-zoeken.nl/
7. http://www.efsa.europa.eu/en/gmo/gmoscdocs.htm
8. http://ec.europa.eu/food/plant/gmo/new/reports_studies/index_en.htm
posted on 2015-05-29 15:00 UTC by Ms. Boet Glandorf, Netherlands
This is a reply to 7197 RE: Opening of the discussion [#7220]
Dear Participants,

We are now entering the second and final week of the discussion on Topic 5. I would like to thank those who have contributed so far to providing best practices on risk assessment and monitoring regimes. I would also like to encourage those who have not yet done so to provide their input on this topic. It would be ideal to collect a broad spectrum of risk assessment and monitoring regimes for the AHTEG to consider, and I look to the members of this forum to help in this regard.

I’m looking forward to further discussion on this topic in the coming week.

Best regards,
Jaimie Schnell
posted on 2015-06-01 12:23 UTC by Ms. Jaimie Schnell, Canada
This is a reply to 7220 RE: Opening of the discussion [#7222]
Dear All

My name is Christoph Then. I work for a German NGO called Testbiotech.

There were three questions raised under Topic 4 and a further question raised under Topic 5, and so in response to those questions I would like to introduce an “organism” into the debate that might prove helpful in further discussion and in seeking answers:

The “organism” is to some degree hypothetical, but very much based on current technology. It is an insect, a fly that in its native form causes problems in agriculture in the same way as fruit flies or olive flies. Created through synthetic genetic engineering, it carries artificial DNA that kills female offspring but enables male offspring to survive (in a similar way to the flies produced by UK company Oxitec). Further, its synthetic DNA is meant to act as a gene driver, changing the pattern of heredity in order to spread more rapidly into native populations (Gantz & Bier, 2015).

I believe that an organism such as this should come under the definition of a synbio-organism. Changes in the genome would be much more radical than in any previous transgene species, and it would be difficult to create without the means and tools of DNA synthesis. One could, however, even suppose that a whole chromosome containing the artificial genetic information had been inserted into the insects (as it was done on yeast, see Annaluru et al., 2014).  

The “organism” could now be deliberately released into the environment in large numbers.

The benefits of this scenario would be a decrease in populations of flies which are, for example, regarded as a major economic threat to agriculture in Mediterranean countries. So if everything goes to plan, the farmers might use fewer and less insecticides and have a higher income.

But the down side would be the numerous environmental risks. If the technology were successful it could lead to the extinction of the fly species. Thus, biodiversity would be lost, with various potential consequences for the environment, food web etc. If the technology were only partially successful, the artificial genes would end up permanently in the native populations, from where they might spontaneously cross boundaries and come into contact with a wide range of environmental conditions (in the whole of the Mediterranean area), be expressed in various genetic backgrounds (there are genetic differences in the regional varieties of the flies) and be exposed to environmental stressors such as climate change. No matter which specific perspective we have on the technology, we have to agree that the predictability of such a scenario is very, very low. So any risk assessment would necessarily suffer from a substantial amount of non-reducible non-knowledge (see Boeschen et al, 2006).

The negative socioeconomic impacts would be, for example, that organic farmers might not be able to avoid their products coming into contact with these flies, and therefore their food products might even contain the biotech-larvae. Markets could be lost as a consequence – and in an extreme scenario, the whole of the harvest in the Mediterranean area could be affected if consumers reject this technology.

Coming to the question of best practice in performing risk assessment, it does not make much sense to perform detailed risk assessment on such an insect, because its biological properties would be hard to compare with existing organisms, no clear hypothesis could be formulated to identify the most relevant risks. Thus, we might not be aware of any evidence that these flies pose specific risks at the time of their release. At the same time, however, we would have to admit that we are not able to assess the risks in a way that allows us to come to any conclusions upon the long-term safety of such an organism since any spatio-temporal control is missing.

As a result, under best practices on risk assessment, it would be necessary to define clear cut criteria for such organisms in order to make a distinction between an organism that can undergo risk assessment and those organisms that cannot be assessed properly, and should under no circumstances be released.


Annaluru, N. et al. (2014). Total Synthesis of a Functional Designer Eukaryotic Chromosome. http://www.sciencemag.org/content/early/2014/03/26/science.1249252.abstract

Boeschen S., Kastenhofer, K., Marschall, L., Rust,I., Soentgen, J., Wehling, P., (2006) Scientific Cultures of Non-Knowledge in the Controversy over Genetically Modified Organisms (GMO) The Cases of Molecular Biology and Ecology, GAIA 15/4: 294 – 301

Gantz, V.M., & Bier E. (2015). The mutagenic chain reaction: A method for converting heterozygous to homozygous mutations. Published Online March 19 2015, Science DOI: 10.1126/science.aaa5945
posted on 2015-06-01 20:29 UTC by Mr. Christoph Then, Testbiotech
This is a reply to 7197 RE: Opening of the discussion [#7226]
Dear Jamie, Dear fellow participants,
My name is Margret Engelhard, I work at The German Federal Agency for Nature Conservation in the area of GMO Regulation and Biosafety

In comparison to genetic engineering, organisms produced by synthetic biology are characterized by a much larger depth of intervention into the organism. With a decreasing familiarity of these novel organisms to organisms that we have long lasting experience with, the level of uncertainty in the evaluation of the impact of synthetic organisms on biodiversity is rising. (See also my posts in Online-discussion 1 [#7134] and Online-discussion 2 [#7135].)

Against the background of a low level of experience we have with organisms produced by synthetic biology, a good monitoring regime is of special importance, in the case of release. In this context I would like to draw you attention to a policy paper on monitoring that has been published as a joined publication the National Environment Agencies in Austria and Switzerland and the Federal Agency for Nature Conservation in Germany. It was developed to provide substantial input into the discussion on best practice in GMO monitoring within the EU and outlines necessary elements and requirements for an appropriate GMO monitoring, because “the implementation of GMO monitoring at the national and EU-level, specifically for the cultivation of GM plants, proved to be a challenging issue and is subject to ongoing discussions.” (Züghart, et al. 2011).

For more information please see:
Züghart, W., Raps, A., Wust-Saucy, A.-G., Dolezel, M. & Eckerstorfer, E. 2011: Monitoring of genetically modified organisms: a policy paper representing the view of the National Environment Agencies in Austria and Switzerland and the Federal Agency for Nature Conservation in Germany. Online:
http://www.bfn.de/fileadmin/MDB/documents/themen/monitoring/positionspapier_monitoring-gentechnik.pdf

This policy paper was also taken up by The Joint ENCA / EPA Interest Group on Risk Assessment and Monitoring of GMOs:
“Steps towards a comprehensive post market environmental monitoring of genetically modified organisms” 
Online:
http://www.bfn.de/fileadmin/BfN/monitoring/Dokumente/Position_paper_on_GMO_monitoring_neu_barrfrei.pdf

With best regards,
Margret
posted on 2015-06-02 12:38 UTC by Ms. Margret Engelhard, Germany
This is a reply to 7226 RE: Opening of the discussion [#7229]
My name is Genya V. Dana and I am Senior Science Policy Officer in the Office of the Science & Technology Adviser to the Secretary of State, at the U.S. Department of State. It is my pleasure to participate in this forum, and thank you to Ms. Schnell for moving the conversation along.

Our comments below try to generally target the theme of this particular forum “Best practices on risk assessment and monitoring regimes currently used by Parties to the Convention and other Governments.”  We understand that there are a lot of examples of best practices that many countries can learn from, and we hope to focus more on these in this thread. It is important to stress that we do not need to reinvent the wheel, so to speak, on risk assessment and monitoring for biological engineering.

The United States believes that transparency in decision making, and sharing publicly the decisions and methodologies of developing the decisions, is essential to the global development and any review of national risk assessment and monitoring of regimes. The United States has a robust, practical, science-based approach to enable the safe use of organisms for a variety of uses from education to research, to medical uses, as well as uses in food production, crop production and animal husbandry. The U.S. approaches embrace the spectrum of tools common to regulatory frameworks, ranging from guidance for best practices, to laws that set standards for product attributes, to regulations for specific activities and uses. The United States has in place programs to detect and monitor the health and safety of humans, plants and animals, and we encourage sharing of such best practices.

In the realm of biomedical research, the National Institutes of Health (NIH) published its first Guidelines for the creation and containment of recombinant DNA organisms in 1976. Updated guidelines, the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines), were issued in 2013 to cover research involving recombinant or synthetic nucleic acid molecules, and detail safety practices and containment procedures for basic and clinical research involving recombinant or synthetic nucleic acid molecules, including the creation and use of organisms and viruses containing recombinant or synthetic nucleic acid molecules. An entity receiving NIH funding for recombinant or synthetic nucleic acid molecule research is obligated to follow the NIH Guidelines for all research involving recombinant or synthetic nucleic acid molecules, regardless of a specific project’s funding source. Many companies not receiving NIH funding, but that are working with recombinant or synthetic nucleic acids, also voluntarily follow the NIH Guidelines as best practice.

Moreover, there are a number of international forums and arrangements that currently exist where nations can share, communicate and develop, as needed, international guidelines for regulatory frameworks and risk management recommendations that they may then implement as appropriate and consistent with their individual national statutory and governance authorities. Some, such as the Organisation for Economic Co-operation and Development’s (OECD) Environmental Risk Assessment Toolkit, offer guidance on risk assessment and provide consensus information useful in a risk assessment. The OECD has a Working Group on Harmonization of Regulatory Oversight in Biotechnology, which produces consensus documents on the biology of organisms as well as guidance documents relevant to risk assessment practices.
posted on 2015-06-02 14:09 UTC by Ms. Genya Dana, United States of America
This is a reply to 7197 RE: Opening of the discussion [#7231]
Dear colleagues,
I am not going to share specific examples but would like to invite the fellow participants to have a look on the websites of European Medicines Agency, European Chemical Agency, European Food Safety Authority and European Commission, particularly DG SANTE, where you can find many examples and guidance documents for risk assessment and monitoring and taking into account socio-economic considerations of potentially dangerous products –chemicals, pesticides, GMO, etc. I personally find the procedures of EMA very useful, especially with regards of medicinal products containing or consisting of GMO, which should undergo very stringent evaluation using the principles of Directive 2001/18/EO, in addition to all other requirements of medicines legislation.
Best Regards,
Nikolay
posted on 2015-06-02 15:16 UTC by Mr. Nikolay Tzvetkov, Bulgaria
This is a reply to 7197 RE: Opening of the discussion [#7233]
Thank you Jamie for agreeing to moderate this discussion and in particular for your excellent synopsis in the first post.  I have been actively involved in the regulation of products of biotechnology in Canada since 1994 including many environmental introductions.

In keeping with your invitation, namely to
“provide information on best practices on risk assessment and monitoring regimes that are currently used by Parties to the Convention and other Governments.”
I offer the following comments.

In Canada, in January 1993, we (the Government of Canada at the time) agreed to a set of principles for regulating the products of biotechnology (The Federal Regulatory Framework).  I suppose this could be said to be our suite of ‘best practices’; among them were statements that the Canadian Regulatory Framework would be built on existing legislation while contributing to the prosperity and well-being of Canadians, would maintain Canada’s high standards for the protection of human health and the environment and would provide for the development of clear guidelines, standards, codes of practice and monitoring capabilities for pre-release assessment of the risks associated with release to the environment and would promote development and enforcement of Canadian regulations in an open and consultative manner, in harmony with national priorities and international approaches.  There was also a statement made that risk assessment should be ‘product oriented’ (i.e. not ‘process’ oriented).  After more than 20 years, I can say that these principles still resonate.  Indeed, Canadian regulations are focussed on the characteristics of any ‘new’ or ‘novel’ organism that is put on the market, regardless of the method used to develop that organism.  This practice has served us well and will continue to do so when regulating the living products of synthetic biology.  

The second part of your invitation dealt with ‘monitoring regimes’ and that deserves an additional comment.  While it was mentioned in our 1993 Federal Framework, in practice, monitoring regimes come into play when a risk assessment results in a determination that it is necessary.  One would need the risk assessment to disclose or reveal what end-point needed to be monitored; otherwise it would be impractical or even impossible to monitor everything.   For example, in Canada, it is common to monitor for Bt insect resistance where Bt crops are deployed because there is evidence that Bt crops can select for Bt resistance in insect pests.  In many other cases, the risk assessment does not result in any concern.  Therefore, in the latter case, there would be no purpose to require monitoring nor any precision on what exactly, would be monitored?  To sum up, monitoring regimes can be used where necessary when the risk assessment determines that there is a concern that should be monitored.

Jim Louter
Environment Canada
http://www.ec.gc.ca/subsnouvelles-newsubs/default.asp?lang=En&n=E621534F-1
posted on 2015-06-02 17:40 UTC by Mr. Jim Louter, Canada
This is a reply to 7233 RE: Opening of the discussion [#7234]
Dear participants,

Dr. Boet addressed very important points and as a risk assessor I totally agree, echoing her conclusion “we therefore do not need a new risk assessment system for organisms obtained by synthetic biology and we can make use of the system that has proven to have its value in protecting biodiversity, including human health”   (# 7232).

Having said that and in response to topic 5 about “best practices” and “monitoring regimes”, in Brazil  the legal framework is  established according to the Law 11.105/2005 (http://www.ctnbio.gov.br/index.php/content/view/12847.html) and Decree 5591/2005 (http://www.ctnbio.gov.br/index.php/content/view/12848.html). Some principles for GMO risk assessment in our framework are: stepwise approach, science-driven, case-by-case, comparative assessment; transparency and a interactive process including public communication for all decisions. There is also a monitoring system in place, based on a case specific monitoring and a general surveillance according to the outcome of the risk assessment phase(http://www.ctnbio.gov.br/index.php/content/view/18000.html).

It is also important to mention the documents and guidelines developed by some international institutions / forums about risk assessment, for example: the FAO Biosafety Resource Book  (http://www.fao.org/docrep/014/i1905e/i1905e00.htm); the CPB Training Manual on RA (https://bch.cbd.int/cpb_art15/training.shtml); the CPB Guidance on RA (https://bch.cbd.int/protocol/guidance_risk_assessment); and the excellent consensus documents about biology and composition from OECD WG of Regulatory Oversight in Biotechnology, already mentioned by Dr. Genya Dana (#7229).

Taking into consideration the discussions under the topics 1-4 and all the experience with GMO risk assessment we already have it´s clear that we are not dealing with a completely new situation. Hopefully  we can understand the challenges presented by SynBio and progress towards a more sustainable environment, using all the knowledge we have since first guidelines about Recombinant DNA developed in 1975.

Best regards,
Luciana P. Ambrozevicius / Ministry of Agriculture - Brazil
posted on 2015-06-02 18:55 UTC by Ms. Luciana Ambrozevicius, Brazil
This is a reply to 7197 RE: Opening of the discussion [#7235]
Dear Jaimie, Dear Colleagues,

During my work as policy advisor I have had many years of experience in the field of chemical substances regulation from both the environmental as well as the occupational health perspective.  As already put forward by Mr. Tzvetkov (#7231) there are several bodies of EU regulations that have well-developed and tested strategies for risk assessment, risk management and safe use of e.g. chemical substances. It might be worthwhile to scrutinize and relate to these systematics developed for e.g. chemical substances (REACH – Registration, Evaluation, Authorisation, and Restriction of Chemical Substances). Detailed information on this regulation and numerous guidance documents can be found at http://echa.europa.eu/

Kind regards,

Jaco Westra
posted on 2015-06-02 20:23 UTC by Mr. Jaco Westra, Netherlands
This is a reply to 7197 RE: Opening of the discussion [#7240]
Dear Participants,

I am pleased to see discussion on Topic 5 gaining momentum. Thank you to all those who have contributed to date and will contribute over the next few remaining days of the discussion.
We have now collected quite a few best practices on risk assessment and monitoring regimes. Many of these best practices come from risk assessment of LMOs, with the assertion that most organisms derived through synthetic biology will be considered LMOs. As a summary to guide further discussion, the following best practices have been cited to date: European GMO legislation and actual cases of environmental risk assessment of GMOs from the Netherlands (#7211); a policy paper on monitoring published by the National Environment Agencies in Austria and Switzerland and the Federal Agency for Nature Conservation in Germany (#7226); the National Institutes of Health (NIG) Guidelines for the Creation and Containment of Recombinant DNA Organisms and Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules as well as the Organisation for Economic Co-operation and Development’s (OECD) Environmental Risk Assessment Toolkit and work by the OECD’s Working Group on Harmonization of Regulatory Oversight in Biotechnology (#7226); Canada’s Federal Regulatory Framework (#7233); and Brazil’s legal framework, the FAO Biosafety Resource Book, and the CPB Guidance on RA and Training Manual on RA (#7233).

Other participants have referenced best practices in risk assessment and monitoring for chemicals substances, including those found on the websites of the European Medicines Agency, European Chemical Agency, European Food Safety Authority and European Commission (#7231 and #7197).

And finally, an alternate view has also been expressed that some organisms of synthetic biology will differ significantly from existing organisms such that current risk assessment practices will be insufficient to draw any conclusions relative to their long-term safety (#7222).
We have a little under a week remaining for the current round of discussions. I would like to encourage participants to review the best practices provided to date and submit any that you feel are missing. I look forward to the continued discussion on best practices on risk assessment and monitoring regimes.

Best regards,
Jaimie
posted on 2015-06-03 12:40 UTC by Ms. Jaimie Schnell, Canada
This is a reply to 7197 RE: Opening of the discussion [#7241]
Dear participants,

First of all let me thank the moderator Jaimie Schnell for guiding this discussion.

My name is Didier Breyer. My scientific background is in molecular biology applied to micro-organisms. I work as a senior scientist in the Biosafety and Biotechnology Unit (SBB) of the Scientific Institute of Public Health (Brussels, Belgium) for more than 20 years. I am mainly involved in the risk evaluation of biosafety dossiers, including contained use applications and environmental releases. I am also appointed as national focal point for the BCH of the Cartagena Protocol.

I am pleased to contribute to the invitation to provide information on best practices on risk assessment and monitoring regimes that are currently used in Belgium and that are relevant to regulate organisms, components and products from synthetic biology techniques appropriately.

Considering the current SynBio applications, my main message is that there is no need to reivent the wheel and that we should primarily consider practices and regimes already existing for GMOs and when necessary specific products (living or non-living).
As mentioned in my previous post under the discussion on topic 4 [#7238] I consider indeed that most of current SynBio organisms, components and products can be assessed and managed on the basis of the risk assessment principles and methodology currently applied to GMOs.
In that respect, I can refer to the contribution of Boet Glandorf [#7211] since the Belgian GMO legislation is also based upon European GMO legislation.

Best practices that characterize GMO risk assessment as it is performed in Belgium include:
- science-based risk assessment
- final advices to the authorities are the synthesis of several (and sometimes divergent) scientific opinions encompassing many different scientific fields
- risk assessment is supported by many tools including webpages and guidance documents, which are regularly updated and adjusted to new scientific and technical developments. For the deliberate release and commercial use of GMOs guidance are generally developed at EU level (EFSA, EMA). For contained use activities, my Unit developed a comprehensive set of guidance documents (see http://www.biosafety.be)
- transparent process (all risk evaluations, including individual expert's opinions, are made publicly available)
- public participation is ensured
- risk assessment takes into account relevant developments at international level (e.g. Cartagena, OECD, FAO).

Whether or not these practices will be sufficient to deal with potential future SynBio developments such as organisms with a much larger depth of intervention into the organism (see post #7226 by Margret Engelhard) or organisms involving the insertion of an increased number of parts/traits, remains of course a matter of discussion.
However decreased familiarity or higher level of uncertainty is inherent to any new scientific developments or applications, and does not necessary imply per se drawing up new risk assessment methodologies and practices. Scientific knowledge (including data coming from monitoring activities) will also evolve over time and feed the risk assessment of these new developments/applications. New guidance can be developed to deal with specific scientific issues. Uncertainty can be addressed by applying appropriate and proportionate risk management strategies.

Best regards,

Didier Breyer
posted on 2015-06-03 13:47 UTC by Mr. Didier Breyer, Belgium
This is a reply to 7197 RE: Opening of the discussion [#7248]
Dear the Forum Participants,

My name is Kazuyuki SUWABE, I'm in charge of environmental risk management of LMOs in the Japan Ministry of Agriculture, Forestry and Fisheries (MAFF).
I would like to thank you to Dr. Jaimie Schnell for moderating this online discussion and also thank participants for their valuable comments from which I have learnt a lot.

As many people commented at this thread, I agree that the current methodologies of risk assessment of LMOs will be applied to organisms developed by synthetic biology since nature/characteristic of risk arising from such organisms is same as the one from LMOs. In this sense, I appreciate concrete materials or examples suggested by Dr. Genya Dana [#7229], Dr. Jim Louter [#7233], Dr. Luciana Ambrozevicius [#7234] and Dr. Didier Breyer [#7241] as best practices on RA or monitoring. I would like to join this good atmosphere by introducing a document on our standard operational procedures of RA & RM for genetically modified crops in Japan. It shows the regulatory framework by MAFF, which does not have big differences from points raised by those I support above since we make decisions on science and of course follow the CPB. http://www.maff.go.jp/j/syouan/nouan/carta/about/sop_eng.html

With regards to “uncertainty” related to synthetic biology, I do not think we can tell there will be either more or less uncertainty with synthetic biology at this moment even though it is not clear yet which techniques will fall within a definition of synthetic biology under the CBD discussion.
On one hand, some techniques maybe introduce new characteristics into an organism more precisely than genetic modification, i.e. transgenic, then there may be less uncertainty or unintended effects. On the other hand, other techniques maybe need more careful check if there is more unstable construction of DNA sequences, in such cases there may be more uncertainty.
With that, at this moment we should not prejudice whether there is either more or less uncertainty relating to organisms developed by synthetic biology. Uncertainty should be evaluated on a case-by-case basis, and should not be generalized by techniques used, as Dr. Didier Breyer said it could be addressed by applying appropriate and proportionate risk management strategies [#7241].

I will be happy if my comment can contribute to this discussion.

Best Regards,
Kazu
posted on 2015-06-04 04:19 UTC by Mr. Kazuyuki SUWABE, Japan
This is a reply to 7248 Topic 5: Best practices on risk assessment etc [#7249]
Dear participants of the Forum
I reach law at the university of Bremen specializing in environmental law.
Following the contributions it appears to me there is agreement that synthetic biology (SynBio) will generate not only new benefits but also new risks to human health and the environment. There is however no agreement whether SynBio is already adequately supervised by the existing regulatory frameworks concerning genetically modified organisms (GMOs). I have studied this question taking as a yardstick the EU GMO regime which probably is the most sophisticated in the existing plurality of regimes.
My conclusions:
(1) While the EU GMO regime is applicable to many kinds of SynBio activities, others are not covered, such as the complete replacement of the genetic material of a cell, the insertion of transgenes into an organism by other methods than those listed as qualifying as genetic engineering—or not—the construction of a protocell and minimal cell, the placing on the market of bioparts, and xenobiochemistry.
(2) To the extent SynBio is covered it must be determined if the risk assessment methodology applicable to GMOs is suited for products from SynBio. I believe this question must be denied concerning the principles of familiarity and comparison with non-GM organisms which guide present-day GMO risk assessment. These principles build on existing knowledge about parental organisms and comparable "natural" organisms. However, the more artificial SynBio operates the less valid is knowledge about parents and relatives.
(3) New and genuine methodology for SynBio must therefore be developed to identify hazards and evaluate risks. This should be done not only for those SynBio products that are covered by GMO regimes but all the more for those which escape that regime.
For more details of the said study see Gerd Winter, The Regulation of Synthetic Biology by EU Law: Current State and Prospects DOI 10.1007/978-3-319-02783-8_11
Yours sincerely
Gerd Winter
posted on 2015-06-04 08:03 UTC by Mr. Gerd Winter, University of Bremen
This is a reply to 7197 RE: Opening of the discussion [#7251]
Dear Colleagues,

In previous posts reference was made to good practices on risk assessment  which can be found in specific bodies of EU-regulation, among which the REACH chemicals regulation.

I think it is worthwhile to mention that within the REACH procedures as systematic approach is developed to address social-economic issues. Although maybe slightly besides the issue of risk assessment as it is usually interpreted, but  interesting from a somewhat broader perspective nevertheless.

In short within the REACH process, in case a specific substance is banned or strictly regulated through a EU-wide permitting,  an independent expert committee (SEAC) advices the European Commission on
- the economic impact of a specific measure (in this case the banning/permitting duty)
- the social impact of that specific measure
They advise the European Committee on the proportionality of such a measure. In their assessment, one of the procedural steps is a public consultation. The final decision is made by the European Commission.

Although this REACH/chemical substance context is of course very specific, scrutinizing this approach might be a useful learning step. It may shed some light on procedural and process aspects, as the procedures are formalized and the approaches taken are (in the process of) being formalized and are described in specific guidances.

Best regards,

Jaco Westra
National Institute of Public Health and the Environment (RIVM), the Netherlands.
posted on 2015-06-04 09:45 UTC by Mr. Jaco Westra, Netherlands
This is a reply to 7251 RE: Opening of the discussion [#7254]
Dear Colleagues,

My name is Paul Freemont and I am co-director and co-founder of the Centre for Synthetic Biology and Innovation and UK Innovation and Knowledge Centre for Synthetic Biology at Imperial College London. Firstly I would like to thank the forum for the opportunity of participating in these very important discussions.

I have followed the latest discussions (Topic 4 and 5) with great interest and as a scientist I can only offer my views from the lab bench so to speak.  From the discussions so far I think it is critical that we separate the risk assessment of synthetic biology experiments and research from the socio-economic impacts of potential synthetic biology applications as suggested by many other forum members [#7202 [#7203 [#7208].  This would allow a more focused discussion on the risk and regulatory issues surrounding synthetic biology research and synthetic biology products without confusing the debate with politically motivated opinions which in their own right are extremely valuable and helpful.

Most bench scientists are not trained in social science, economics or politics but are trained to carry out carefully thought out experiments within their local regulatory frameworks. For me this is the UK/EU regulatory framework as oversee by the HSE (for example on synbio see http://www.hse.gov.uk/research/rrhtm/rr944.htm) and currently all of our synthetic biology work fits within these frameworks.  As many forum colleagues have pointed out there are existing and extensive regulatory frameworks already in place around the world for LMO’s and in the last discussions there was agreement among many regulatory experts that such frameworks are appropriate to cover existing synthetic biology developments and LMO’s (see e.g. [#7234]).

From this discussion and previous discussions it is clear that there are some areas of research development (e.g. protocells; xenobiology; germ line editing e.g. gene drives) that will require future deliberations on risk assessment and safety regulations as these applications develop as suggested by others (e.g.  [#7250]).  It is also important to differentiate between applications that are for contained use (e.g. industrial biotechnology applications) where accidental spills/leakages would be a key issue versus deliberate release applications where interactions with the environment and natural biodiversity would be key issues (e.g. horizontal gene transfer, unexpected unbalancing of local eco-systems etc).

Such research programs need to be considered individually on a case-by-case basis in the context the two usages mentioned above. Furthermore, much more research/research funding is required to investigate the safety of such applications (e.g. developing appropriate comparator strains, exploring rates of genetic change and gene transfer etc) and in the context of this forum the effects  (if any) on local and global biodiversity. It is essential that as synthetic biology applications increase an evidence-based regulatory framework is developed based on internationally peer-reviewed research and cross-border agreements.

Finally I wanted to briefly mention that the ‘natural’ versus ‘synthetic’ product debate is perhaps missing the point. Nature has provided us with wonderful chemical substances (smells, tastes, sustenance, medicinal) many from botanical sources. By applying synthetic biology technologies it will be possible to extend the physical and functional diversity of such compounds which could have significant benefits both in developing sustainable production practises but also in discovering new chemical entities that could be used in medicine, agriculture and food. However I can also fully understand the idea of a life cycle approach applied to such new products and processes [#7218].
(edited on 2015-06-04 13:41 UTC by Ms. Manoela Miranda)
posted on 2015-06-04 11:07 UTC by Mr. Paul Freemont, Imperial College London
This is a reply to 7197 Topic 5 - best practise in risk assessment [#7255]
My name is Mike Paton. I am a policy advisor on microbiology (including LMOs and synthetic biology) in the UK’s principal workplace safety regulator (Health and Safety Executive). Thanks for the opportunity to contribute to the discussion. As summarised by the moderator, there is a plethora of good and effective guidance on risk assessment and monitoring for GMOs, as well as risk assessment guidance for chemicals, food, feed, medical and veterinary applications, that would encompass many of the organisms, components and products of synthetic biology.

In addition to those mentioned in other posts, guidance on contained use of GMOs can be found in Annex 3 of the European Commission directive (2009/41/EC) on the contained use of genetically modified microorganisms (http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32009L0041&from=EN), which  sets out the EU adopted approach to risk assessment with respect to human health and safety and environmental protection and application of containment in a proportionate manner. In the UK, this is supplemented by additional guidance on risk assessment and containment produced by the Scientific Advisory Committee for Genetic Modification (SACGM) entitled “The SACGM Compendium of Guidance” (http://www.hse.gov.uk/biosafety/gmo/acgm/acgmcomp/), which is in the process of being updated to reflect new technologies.

It is worth noting that the EU group of Scientific Committees (SCENIHIR) recently reviewed ‘Risk assessment methodologies and safety aspects’ for synthetic biology at the request of the EU Commission. The Preliminary Opinion has been published and provides some useful approaches for addressing some of the possible challenges for the assessment of risks (eg in the absence of comparators) http://ec.europa.eu/health/scientific_committees/emerging/docs/scenihr_o_048.pdf

With respect to current CBD guidance on risk assessment, the Conference of the Parties in South Korea 2014 set in motion a mechanism for revising and improving their guidance on risk assessment for LMOs, a view to having an improved version of the Guidance by the eighth meeting of the Parties in 2016.
posted on 2015-06-04 13:10 UTC by Mr. Michael Paton, United Kingdom of Great Britain and Northern Ireland
This is a reply to 7197 RE: Opening of the discussion [#7257]
My name is Dr. Todd Kuiken. I am an environmental scientist who has been researching the governance and ecological risks and benefits of synthetic biology for the past 6 years. Prior to this I was a field scientist researching the biogeochemical cycling of mercury in varying types of ecosystems.  

I have more in depth remarks in topic area 4 (#7256) but wanted to submit the following documents and suggestions to this topic area as well.

The Wilson Center has done extensive work in evaluating and suggesting how one might develop or utilize some facet of a risk assessment to evaluate the impacts of releasing a “synthetic biology” application. I point you to the following document (http://www.synbioproject.org/publications/creating-a-research-agenda-for-the-ecological-implications-of-synthetic-biology/) which lays out a research agenda around the ecological impacts of synthetic biology. As our inventory suggests (http://www.synbioproject.org/cpi/), the potential range of synthetic biology applications is large and the number of actors is global (http://www.synbioproject.org/inventories/maps-inventory/).

I would also like to point the forum to some specific models and work produced by the International Institute for Applied Systems Analysis (http://www.iiasa.ac.at/).  Their work, in particular the FELIX model (http://www.felixmodel.com/), could be utilized in a risk assessment framework developed by the CBD including the socioeconomic issues.

I look forward to continuing the discussion.

Todd Kuiken
posted on 2015-06-04 15:47 UTC by Mr. Todd Kuiken, North Carolina State University
This is a reply to 7257 RE: Opening of the discussion [#7259]
Dear participants,

My name is Maria Mercedes Roca.  I am a Visiting Professor of Biotechnology in the School of Medicine at the Tecnológico de Monterrey (University) in Mexico. I also participate in the Risk Assessment and Risk Management AHTEG and have been a member of the Honduran Biosafety Committee for 12 years.

I thank Dr. Jaimie Schnell for moderating this interesting discussion. In her opening remarks  (# 7197) she reminded us of the task of  “Building on the work on risk assessment and risk management undertaken by the Cartagena Protocol  …  …to inform those who do not have national risk assessment or monitoring regimes, or are in the process of reviewing their current risk assessment or monitoring regimes  … and to help those Parties and other Governments to regulate organisms, components, and products from synthetic biology techniques appropriately”.

I strongly support the statements by Dr. Genya Dana (# 7227), Dr. Jim  Louter (# 7233), Dr. Luciana Anbrozevicius (#7234) and  Dr. Didier Breyer (# 7241), among others, who state that  best practices for risk assessment applied to  synthetic biology should  include a stepwise and case-by case approach,  should be a transparent and interactive process  and should be  science-based.

I also question the wisdom of proposals by those participants (#7258) who suggest bringing socio-economic consideration into the risk assessment process. Conducting an environmental risk assessment of a LMO, formulating coherent risk questions and using measurable indicators for end-points is hard  and costly enough (especially for developing nations).

In the technical discipline of Risk Analysis, risk assessment is only one of three components – a highly technical component that requires specialists that understand the science (in the case of LMO risk assessment). Then comes risk management – a legitimate political process that acts upon the results of the risk assessment and introduces the important issues of socio-economic considerations.  Part of risk management is an economic assessment that attempts to put a value on the possible consequences as well as the benefits of a product, etc.  The risk assessment and the economic analysis/risk management work are done by different groups – indeed, those persons qualified to do risk assessments are rarely qualified to do economic assessments or risk management studies—and vice versa.

The decision making process which incorporates the risk assessment and risk management studies is done by ministers or other high-ranking government officials who typically attempt to understand the concerns of all stakeholders. The third element in Risk Analysis is risk communication and perception.  

Introducing socio-economic considerations into risk assessment is technically incorrect and confuses the issues when evaluating the biological risk of an LMO or a product of synthetic biology.

Best regards,

Maria Mercedes Roca
posted on 2015-06-05 02:55 UTC by Ms. Maria Mercedes Roca
This is a reply to 7197 RE: Opening of the discussion [#7261]
Many thanks again for the opportunity to provide comment. We have extracted the section of our Topic 4 response on New Zealand’s risk assessment framework, and have posted it here.

New Zealand undertakes risk assessment through the Hazardous Substances and New Organisms Act (HSNO Act), which would likely regulate organisms produced through synthetic biology. This Act: regulates both new organisms (including GMOs/LMOs) and hazardous substances (with defined intrinsic properties); considers both environmental and human effects; and decides on applications for import, development, containment or full release into the environment.

The purpose of the HSNO Act is to protect the environment and the health and safety of people and communities by preventing or managing the adverse effects of hazardous substances and new organisms. ‘Environment’ includes ecosystems and their constituent parts including people and communities, all natural and physical resources, amenity values, and the related social, economic, aesthetic and cultural conditions. ‘Effects’ include potential or probably effects; positive or adverse effects; temporary or permanent effects; past, present or future effects; acute or chronic effects; and cumulative effect which arises over time or in combination with other effects.

To achieve the purpose there are several principles: the safeguarding of the life-supporting capacity of air, water, soil, and ecosystems; and the maintenance and enhancement of the capacity of people and communities to provide for their own economic, social, and cultural well-being and for the reasonably foreseeable needs of future generations. A further principle of the Act is the precautionary approach.

Other matters relevant to achieve the purpose of the Act include: the sustainability of all native and valued introduced flora and fauna; the intrinsic value of ecosystems; public health; the relationship of Maori and their culture and traditions; the economic and related benefits and costs of using a particular hazardous substance or new organism; and New Zealand’s international obligations.

In relation to field testing, the HSNO Act states that hazardous substances and new organisms must be strictly contained within an approved field test site, and the benefits of the field testing must outweigh the risks. In regards to the effects assessment, the areas of impact looked at are the environment, human health and safety, society and community, Maori, economy and international obligations.

In relation to release, the HSNO Act states that the benefits of releasing a hazardous substance (i.e. commercial release) or new organism must outweigh the risks. Controls may be imposed on a release approval to mitigate identified risks. Again, in regards to the effects assessment, the areas of impact looked at are the environment, human health and safety, society and community, Maori, economy and international obligations. If the hazardous substance or the new organism is to be used for food, medicine etc. other legislation such as the Medicines Act will also apply.

Risk assessment under each scenario varies depending nature of the hazardous substance/new organism (e.g. likelihood of escape from containment, hazard assessment, toxicity data, etc.).

Kind regards,
Mariska Wouters
New Zealand Ministry for the Environment
posted on 2015-06-05 05:31 UTC by Ms. Mariska Wouters, New Zealand
This is a reply to 7261 RE: Opening of the discussion [#7262]
Dear all:

This is Prof. Kazuo Watanabe, Gene Research Center,  Univ. of Tsukuba, Japan

While I have introduced myself in Topics 1, 2 and 3, and it may overlap with the previous sessions, let me state.

Recalling that Synthetic biology was listed as one of potential candidate subjects for discussion at RA&RM AHTEG under COPMOP of the Cartagena Protocol on Biosafety at the beginning, but it was not included in the topics for the development of the guidance doc for RA(UNEP/CBD/BS/COP-MOP/5/INF/15 Page 41, ANNEX V. topics for the development of the guidance doc , in the list there is a sentence “the Risk assessment of living modified organisms produced through synthetic biology”). While COP-12 of CBD, made the mandates on the on-line forum, many of the present discussion could be revisit of previous discussion.

In considering the precautionary approach, any new item can be examined well, but synbio itself was once the initial subject of the discussion at the RA&RM AHTEG at COPMOP.

Now for the present session particularly, I would follow the interventions by Dr. Jaimie Schnell (# 7197), Dr. Genya Dana (# 7227), Dr. Jim  Louter (# 7233), Dr. Luciana Anbrozevicius (#7234) and  Dr. Didier Breyer (# 7241)summarized by [#7259]Maria Mercedez Roca. The base concept of RA&RM is primary the same as done in LMOs stated in CPB, and with the precautionary approaches, a stepwise and case-by case approach with hard science foundation, should be considered.


regards,

K. Watanabe
posted on 2015-06-05 08:53 UTC by Mr. Kazuo Watanabe, Japan
This is a reply to 7197 RE: Opening of the discussion [#7266]
Dear participants,
my name is Swantje Strassheim and I work for the German Federal Office of Consumer Protection and Food Safety in the department for genetic engineering and I am charged with the monitoring of Synthetic Biology on behalf of the German Central Committee for Biological Safety (ZKBS).

I think it is hard to judge something that is not clearly defined. As many have already stated before, organism produced from synthetic biology today and in the near future fall under existing GMO/LMO regulations such as the Cartagena protocol or the EU regulation. For these “synthetic biology” organisms, we do not need new risk assessment practices and can use the ones already in place. However, it is necessary to continuously monitor developments in the field to eventually amend regulations.

Synthetic biology applications or products that do not fall under LMO/GMO regulations might be covered by other regulations such as REACH, or might need new risk assessment methodologies. For these methodologies, I agree with all those who have stated that risk assessment should be separated from risk management. For me, a case-by-case approach is the only possible method to assess organisms and products from synthetic biology that will not fall under GMO or other regulations. These organisms and products will, at least in the near future, be very few and very diverse and that is why no general approach can be applied.
posted on 2015-06-05 11:26 UTC by Ms. Swantje Strassheim, Germany
This is a reply to 7197 RE: Opening of the discussion [#7275]
Dear fellow participants,
I appreciate having the opportunity to comment. I am Dr. Nancy Podevin from DuPont Pioneer (based in Europe) representing CropLife International. My educational background is in molecular biology and the past years I have been involved in the risk assessment of GMOs.

Before phrasing my response to topic 5 I would like to frame my comment. I agree with many that in case where the product, developed with the use of synthetic biology approaches, is a living organism it is and should be considered an LMO (1). Synthetic biology and the widely applied ‘genetic engineering’ are both approaches covered under modern biotechnology.

As already said a lot of knowledge has been acquired during the risk assessment of LMOs and I agree with others that the current regulatory and risk assessment frameworks for LMOs are appropriate to cover organisms developed using a synthetic biology approach (2). Risk assessment needs to be performed case-by-case in order to take into account the characteristics of the organism, its intended use and any environment which may be exposed to the organism. Risk assessment is a well-defined process starting from problem formulation to risk characterization.  In problem formulation protection goals are identified, knowledge is gathered, and areas of uncertainty are identified.  During risk characterization, data are brought together on hazard and exposure. This basic process can also be applied to products [nl. organisms] arising from synthetic biology approaches.

At this moment risk assessors and risk managers are already looking at LMOs created using synthetic biology approaches although these are currently restricted to contained use of microorganisms. It is not inconceivable that if some of these or future LMOs are put forward for release into the environment that adjustments to risk assessment methodologies (data and studies needed to support the risk assessments) might be needed. However, the need for adjustment or development of new validated risk assessment methods does not warrant the setup of new regulatory or risk assessment frameworks. For this reason, a clear distinction needs to be made between risk assessment frameworks and risk assessment methods.

However, what we have seen in the past with emerging technologies is that policy makers sometimes respond as if the technologies only represent risks, putting in place very prescriptive regulatory frameworks that limit certain developments and do not remain fit for purpose over time.

References
(1): as indicated in comments 7243, 7167, 7160, 7125, 7105, 7104, 7103, 7067, 7057, 6992, 6942, 6901, 6879, 6872, 6843, 6781, etc. & UNEP/CBD/COP/12/INF/12
(2): as indicated in comments 7137, 7123, 7115, 7093, 7087, 7066, 6998, 6941, 6929, 6878, etc., & EC 2015 [Preliminary Opinion on Synthetic Biology II: Risk assessment methodologies and safety aspects], CBD Technical Series No 82
posted on 2015-06-05 16:36 UTC by Ms. Nancy Podevin, Pioneer Overseas Corporation
This is a reply to 7197 RE: Opening of the discussion [#7277]
Dear all:
My name is Daniela Conte Grand and I work as a policy maker at the Biotechnology Directorate - Ministry of Agriculture, Livestock and Fisheries of Argentina.

I agree with previous posts voicing that until now all organisms produced from synthetic biology fall under existing GMO/LMO regulations, so, current GMO risk assessment framework is applicable for these 'synthetic' organisms.

Regarding agricultural applications, there are no practical applications for this technique yet.

Argentina’s regulatory framework is a dynamic system which evolves simultaneously with scientific developments. Argentina has a regulatory framework composed of several resolutions related to GMO. Under resolution MAGyP 763/11, Argentina regulates GMO´s  activities. A complementary resolution, MAGyP 173/15, regulates products derived from new breeding techniques, such as synthetic biology. As a consequence, if an applicant wants to develop a crop resulting from synthetic biology techniques, regulators will perform a rigorous, science-based evaluation of the potential impacts on a case-by-case approach, according to the GMO regulation in force.

Finally, I would like to remark that the establishment of an adequate, solid and updated regulatory system is a tool that can enhance the benefits, reduce possible risks and mitigate potential adverse effects of new technologies (including synthetic biology).

Best regards,
Daniela
posted on 2015-06-05 18:56 UTC by Ms. Daniela Conte Grand, Ministry of Agriculture, Livestock and Fisheries of Argentina.
This is a reply to 7197 RE: Opening of the discussion [#7279]
Dear participants,
My name is Felicity Keiper and I am from Bayer CropScience, also representing CropLife International. I have expertise in agricultural biotechnology research, LMO risk assessment and international regulatory policy in this area. My experience includes the preparation of regulatory submissions for the environmental release of LMOs (field trial and commercial) according to the risk regulation regimes of many countries throughout the world. Thank you for the opportunity to comment on this topic, I would like to use it to point out characteristics of these regimes that may be considered best practice. Notably, many of these are consistent with the general principles for risk assessment provided in Annex III of the Cartagena Protocol.

I agree with many other participants in this and other discussion topics in this forum that living organisms created by synthetic biology approaches are LMOs. Therefore, LMOs created by synthetic biology approaches are within the scope of Parties’ LMO regimes and the best practices stated below are applicable.

Best practices – risk assessment:
- Evaluation of the level of risk that includes identifying potential sources of harm (problem formulation), and assessing the likelihood of harm arising (possibility of exposure) and the potential consequences (effect of exposure).
- Risk evaluation should be based on sound scientific information. This includes, for example, a requirement for internationally harmonized scientific methodology (where this is possible), international reference materials (e.g. OECD Consensus Documents), and peer-reviewed published literature.
- Risk evaluation should also take into account the body of international experience gained in LMO risk assessment generally, and for the particular LMO under assessment.
- The risk assessors should have up-to-date scientific expertise. This may include, for example, a requirement for ongoing education and training. This is of particular importance for synthetic biology approaches that may involve new tools and technologies and LMOs of greater complexity.
- A case-by-case approach to risk assessment, this includes consideration of:
(i) The characteristics of the LMO. This means that the data required for each LMO should vary in proportion to the available knowledge. For example, there should be reduced data requirements where the LMO and/or its products are familiar and have a history of safe use, regardless of the technology used to create them.
(ii) The intended use of the LMO. This includes the particular receiving environment and any containment measures, levels of exposure, and likely impact.
- Transparent processes for risk assessment and decision making, this includes:
(i) A regulatory framework (laws, regulations, policies, guidelines, etc) that sets out a process for risk assessment and decision making which is adhered to.
(ii) Risk assessment principles that are consistent with international standards and guidelines (e.g. OECD, FAO).
(iii) The risk assessment, decision made, and reasons for the decision are publicly available, for example on a website or regulatory authority publications.
(edited on 2015-06-06 22:52 UTC by Ms. Felicity Keiper)
posted on 2015-06-06 03:29 UTC by Ms. Felicity Keiper, Bayer CropScience
This is a reply to 7220 RE: Opening of the discussion [#7281]
dear all,

So far all organisms obtained by synthetic biology are considered to be GMOs thus the same risk assessment framework could apply. The concept of a case by case is crucial and in this regards it is important for each case to be addressed separately, taking into account specific information on the organism concerned, its intended use, and its potential receiving environment.

Some of the synthetic biology products are never meant to be released in the environment and this implies a very specific risk assessment. The intended use of an organism in question or its parts can provide valuable information and context for the risk assessment process. Understanding the intended use allows a risk assessor to structure the exposure assessment by starting with the environment where the organism or its parts will be deliberately or unintentionally introduced.

Regards,
O.A.El-kawy
posted on 2015-06-06 08:10 UTC by Mr. Ossama AbdelKawy, Mauritania
This is a reply to 7197 RE: Opening of the discussion [#7285]
I thank Dr. Jaimie Schnell for moderating this session of discussion. In the opening session, it is mentioned that “…to provide information on best practices on risk assessment and monitoring regimes that are currently used by Parties to the Convention and other Governments”.
While a number of participants have introduced many guidelines from other sources, but I agree with the opinion that the best practices on risk assessment and monitoring should be science-based, case-by-case basis,  stepwise approach, transparent, public engagement and consultation, conducted within the Precautionary Principle.

Now for the present session particularly, I would follow the interventions by Dr. Jaimie Schnell (# 7197), Dr. Genya Dana (# 7229), Dr. Luciana Anbrozevicius (#7234) and  notably Dr. Didier Breyer (# 7241), Maria Mercedez Roca (#7259) and Prof Dr Kazuo Watanabe (# 7262).

As some participants have also mentioned about socioeconomic factor, which I again direct the readers to the text of the Cartagena Protocol, as per the proviso in Article 26 of the Cartagena Protocol, socioeconomic impacts should be part of the decision-making.

Thank you.

Regards,
Dr Kok Gan Chan
University of Malaya
Malaysia
posted on 2015-06-07 18:22 UTC by Dr Kok Gan Chan, Malaysia
This is a reply to 7285 RE: Opening of the discussion [#7287]
Once again, my name is Christoph Then. I work for the German NGO, Testbiotech.

I read with interest some of the critical comments made on my previous contribution in which I introduced a hypothetical genetically engineered organism, an insect, a fly that in its native form might have caused problems in agriculture. I suggested in my hypothesis that this organism would have artificial DNA that kills the female offspring but enables male offspring to survive. There would be no plan to terminate the life of these organisms once released (this is similar to an olive fly developed by the UK company, Oxitec). I further suggested that these hypothetical flies could act as “gene drivers”, changing the pattern of heredity in order to spread more rapidly into native populations (Gantz & Bier, 2015). Based on this hypothetical example, I suggested there should be agreement on clearly defined criteria that would allow the regulator to prevent the release of any such organisms. The reason I introduced this hypothesis is that there are too many gaps in our knowledge concerning long-term effects, and no possibility of ensuring adequate spatio-temporal control.

To the comment made by Bob Friedman: He wrote that he did not agree with my argument that such a hypothetical organism should never be released, because in his view genetically engineered mosquitos are needed to control malaria and other diseases. I would be happy to discuss this with Mr Friedman in regard to risks and benefits if need be. However, for the sake of argument, I have to say that the properties of the mosquitos that Mr Friedman means are very different to those of my hypothetical organism. At least the mosquitos that have been released so far ( also produced by Oxitec, but with different biological properties compared to the flies mentioned) are not meant to survive and do not act as gene drivers. So, whether someone is in favour of those mosquitos or not is irrelevant and not helpful in answering my questions.

Further, several experts suggested that there is no need to further develop the risk assessment currently used for genetically engineered organisms (LMOs). These experts should, however, be aware that even some of the scientists developing new methods, such as gene drivers, are asking for specific regulation of these new technologies and for a higher level of precaution in comparison to existing LMOs (see Gantz & Bier, 2015 or Ledford, 2015).

I agree that not all these questions are completely new. For example, there was an international call in 2014 for the CBD to take measures against spontaneous transboundary movements of genetically engineered organisms (http://www.stop-the-spread-of-transgenes.org/). This call shows that the problems of uncontrolled spread of genetically engineered organisms moving into the environment has not been solved in regard to the LMOs released over the last 20 years. But with the emergence of synthetic biology and synthetic gene engineering these questions are more pressing than ever. So in regard to the benefits and best practice for risk assessment, we have to face up to the actual developments and not seek to conceal them.

Any discussion about future applications of synthetic biology should clearly include those examples that may appear hypothetical at the moment, but which might become reality very, very soon. As mentioned in my first contribution, we can expect a high number of new organisms derived from synthetic genetic engineering to enter the environment. To quote in Ledford (2015), we need to be aware that humans have already hugely changed the biosphere of this planet. This alone should be a convincing reason to discuss the next steps thoroughly, before we put new burdens on to future generations simply because some stakeholders want to make a profit from new technologies within the period that a patent is valid.

Gantz, V.M., & Bier E. (2015). The mutagenic chain reaction: A method for converting heterozygous to homozygous mutations. Published Online March 19 2015, Science DOI: 10.1126/science.aaa5945

Ledford, H. (2015) CRISPR, the disruptor, A powerful gene-editing technology is the biggest game changer to hit biology since PCR. But with its huge potential come pressing concerns,  Nature, Vol 522, 20, 4 JUNE 2015
posted on 2015-06-07 19:09 UTC by Mr. Christoph Then, Testbiotech
This is a reply to 7197 RE: Opening of the discussion [#7288]
Dear Jaimie Schnell, Dear fellow participants,

I would like to add on the discussion on the case-to-case approach that had been suggested in many posts in this forum. Since synthetic biology is a brought filed reaching from applications that are close to what we have done before to applications that reach beyond the evolutionary realm. A case-to-case approach is a good solution to give this diversity justice. However I would like to point to some points, where the comparative risk assessment comes to its limits and where we need to further develop our current practices:

1.) As I have also stated at the online-discussion topic 3 [#7143], the more orthogonal synthetic organisms are to their natural counterparts, the more unfamiliar they are, not only for the ecosystem and its biodiversity but also for both scientists and the public. This unfamiliarity results in an enhanced uncertainty with respect of risk assessment and the assessment of the impact on biodiversity, since any predictions are normally modelled along the known properties of related organisms we are familiar with. Thus, we can stick to the case-to-case approach, but we need to find solutions for the cases, where sound risk assessment becomes limited by a lack of familiarity. In these cases the implementation of the precautional principal is of special importance.

2.) One central characteristic of synthetic biology is to optimize its ability to engineer organisms for different applications. Thus the optimization of methodology is central. This includes both the quick adaptation and incorporation of new molecular methods and their development. The discovery of a new method of genome editing called CRISPR/Cas9 (clustered regularly interspersed short palindromic repeats) for example will further boost the field. Thus the number and diversity new applications for commercial use will increase in the near future. This development might also challenge a sound risk assessment on a case-to-case basis, since the sheer number of new applications and the potential new model organisms will challenge the resources and experience of administrations. Here it will become important not to implement any generalized approval systems like the general approval of a platform organism, but to stick to a case-to-case approach for the different applications and cases.

With best regards,
Margret Engelhard,
(German Federal Agency for Nature Conservation)
posted on 2015-06-07 21:00 UTC by Ms. Margret Engelhard, Germany
This is a reply to 7240 RE: Opening of the discussion [#7292]
Dear Jamie,

Thanks for moderating this round and for a very clear summary to get this round started.

Referring to the discussion under topic 4, I offer the following in response to the question posed:

• The current applications of SynBo involve the development or use of organisms that possess novel combinations of genetic material that go beyond natural physiological reproductive or recombination barriers, which means that existing biosafety regulations such as the Cartagena Protocol apply.
• As explained by Glandorf, Tzvetkov, Louter, Tzvetkov, Westra, Breyer, and others have said, the risk assessment as outlined in Annex III of the Cartagena Protocol is at this point in time sufficient. That risk assessment takes into account the resulting organisms and, where appropriate, their products. It will be important to keep monitoring this field for points where the current risk assessment approaches need further development.

Best regards !

Piet van der Meer
posted on 2015-06-07 23:23 UTC by Mr. Piet van der Meer, Ghent University, Free University of Brussels, Belgium, PRRI
This is a reply to 7292 RE: Opening of the discussion [#7294]
Dear Jamie, dear all,

I have appreciated this discussion, and it clearly picked up momentum over this last week, bringing in the complexity of the issue one more again.

My name is Ricarda Steinbrecher,  I am a developmental biologist and molecular geneticist with the Federation of German Scientists, and have been involved in the processes of  the Cartagena Protocol on Biosafety (CPB) since their onset in 1995.

When looking at best practices, I think it is still the CPB that offers the best guidance with regards to LMOs and related risks. In fact, many on this online forum have brought up the importance of the roadmap and the guidance(s) developed under the CPB and its AHTEG on risk assessment and risk management. It has to be recalled though, no guidance has so far been developed for LMOs derived through synthetic biology, a topic which has been identified as lacking guidance and to be addressed in future.

It has been expressed (e.g. by Luciana P. Ambrozevicius) that hopefully we can utilise the knowledge we have gained from working with recombinant DNA technologies, and risk assessments, regulations and guidelines developed since.  I agree and fully support, it is important to learn from knowledge gained and experience with releases of LMOs and related risk assessments and to take these learnings forward. It has not been fully appreciated though, that we are facing a new situation with synthetic biology, one that has clear overlaps with LMOs, but does also go further and requires further thinking,  scientific discourse analysis and analysis.

Margaret Engelhard’s reminder [#7226] on the issue of familiarity – or rather lack of familiarity, is important in this context. “With a decreasing familiarity of these novel organisms to organisms that we have long lasting experience with, the level of uncertainty in the evaluation of the impact of synthetic organisms on biodiversity is rising.”

On a similar line, Christof Then [#7222] tried to develop a scenario that might help stimulate a debate about the "new" and "beyond current GMOs" organisms produced through synthetic biology. A debate still to be had.

Additionally we are facing a lack of regulations and practices that also look at compounds and products with regards to the mandate given by COP and the protection goals and obligations presented by the objectives and articles under the CBD. Jaco Westra (and Mr. Tzvetkov) has pointed to separate EU regulation regarding chemicals we might want to be looking at, which is important.  These regulations though are limited and do not cover the spectrum and complexity we are required to look at here, including the link between organisms, compounds and products. And with regards to socioeconomic considerations and impacts, the LMO regulations of Norway should considered amongst best practice regimes.

Clearly - as spelled out by many – we need to build on the various best practices, yet need to bear in mind that there is more to be done than just extrapolating from LMOs (and the regulations surrounding it) to organisms, compounds and products of synthetic biology.

Whilst a case by case risk assessment may be a helpful approach, this is not likely to be sufficient when there is a bigger complexity, depth of question, lack of comparator and a lack of familiarity. 

There seems to be a trail of thought – as for example expressed by Paul Freemont [#7254]  – to have ‘socioeconomic impacts’ and ‘politically motivated opinions’ kept separate from scientific risk assessment and the discussion on “the risks and regulatory issues surrounding synthetic biology research and synthetic biology products”. Whilst I appreciate that there are and have to be different strands to a risk assessment I think it is important to keep socioeconomics in the equation, ie have it as part of the risk assessment and decision making.  It has been recognised that socioeconomics, eg such as threats to or loss of livelihoods, or loss of small scale farming, can be directly linked to negative impacts on the conservation and sustainable use of biological diversity.  In the same line, our given mandate is for the inclusion of socioeconomic considerations in the assessment of organisms, compounds and products of synthetic biology. Clearly we are facing and are having to rise to a challenge by having to address the issue in a multi-disciplinary way - and also in line with the precautionary principle. But there is meaning in this.

Whilst taking in the various contributions on topic 5, I got the impressions that inputs often depended on the definition of what was covered under synthetic biology.  Gerd Winter [#7249] pointed out again where there was a discrepancy between SMOs and GMOs (according to EU regulation) and hence which organisms would not be covered. I would like to add dsRNA dependend DNA methylation. Winter’s next points I find equally important.

As I did not provide my thoughts on definitions under topic 3, I would like to share them now, especially as its very much related to what I consider is missing in current regulations and best practices.  Please see below for my contribution on definitions.

with kind regards,

Ricarda
Federation of German Scientists


Re topic 3 as relevant to topic 4 & 5:
As much as we may try to achieve a perfect definition of Synthetic Biology, I do not think it is possible – nor is it necessary. Rather I understand that we are required (as per COP decision) to come up with an operational definition that is broad enough to ensure that all techniques currently used or to be developed in the future, related to synthetic biology, are included in principle, and that such technologies and techniques are linked to the definition through an continuously updated list or appendix. Such technologies would include all genome editing techniques as well as any RNA related techniques, such as RNAi and dsRNA-dependent DNA methylation. I regard it as a given that there will be an overlap between the definition of LMOs under the Cartagena Protocol, and that of organisms derived through synthetic biology, as some of the technologies are shared, yet the contextualisation is different.

I see the purpose of such an operational definition to be to ensure that none of the technologies and applications (and the resulting organisms, components and products) accidentally escape an assessment just because the definition is too narrow or too quickly outdated. An operational definition will need to enable parties to fulfil their obligations under the convention, and the mandate and spirit of the last COP decision, beyond where it is not covered by the Cartagena Protocol either in definition or in scope.

Many contributors to this online forum discussion pointed out the need for a broad definition. In this I very much agree with the view and conclusion of Lázaro Regalado, who stated: “In my view we should develop a sufficiently broad definition as simple as possible with room for all possible characteristics, techniques, the scope is understood and leaves room for its expansion, collect scientific aspects and to provide a framework of ethical and social analysis. On the other hand the broad spectrum of proposal should lead to find a common ground.” [#7045]

I also found Gerd Winter’s input [#7036] very helpful. Re his point 4, which I support, I would like to add, that there were reasons why COP decided to not only refer to organisms, but also to compounds and products. There was a recognition that negative impacts could arise from all of them, especially to the conservation and sustainable use of biodiversity, and related to this to health, socio-economics (incl. livelihoods), food security, indigenous peoples and local communities, including cultural aspects  -  both within and outside party’s jurisdictions.
posted on 2015-06-08 00:53 UTC by Ms. Ricarda Steinbrecher, Federation of German Scientists (Vereinigung Deutscher Wissenschaftler)
This is a reply to 7197 RE: Opening of the discussion [#7296]
Dear Participants,

Thank you to all who contributed best practices on risk assessment and monitoring regimes over the last two weeks. This current round of online discussions has now come to a close. A summary will be prepared from the contributions and this will be made available to all participants. It has been a pleasure to moderate the discussion on Topic 5, and I look forward to the next round of discussions planned for the Open-Ended Forum on Synthetic Biology.

Best regards,
Jaimie
posted on 2015-06-08 01:03 UTC by Ms. Jaimie Schnell, Canada