Dear members of the Open-ended Group and AHTEG,

I am pleased to inform that the discussion on the "Revision of the "Guidance on Risk Assessment of LMOs" (revised on 4 July 2011)" is now open.

Please attach your file containing suggestions for revision  to a message and post it in the online forum. Please note that only suggestions marked as "track changes" to the Guidance version of 4 July 2011 (available at http://bch.cbd.int/onlineconferences/discussiongroups_ra.shtml) will be taken into consideration. If you encounter any difficulty in attaching and posting your file please do not hesitate to contact me.

This topic will be open for discussion until 30 July (1:00 a.m. GMT).

Many thanks and best regards,
Manoela

Dear Members, dear Secretariat.
Please find enclosed some initial contributions (3 remarks) to the Guide.
Best regards
Paulo Andrade

POSTED ON BEHALF OF PHIL BEREANO

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The following refer to the changes and comments proposed by Paulo Andrade in document ra_guidance_v4july2011-comments_1_p-andrade.doc:

Lines 58-59: Some assessment evaluations are not comparative; eg if eating a GMO causes stomach lining ulceration,, one need not compare it to anything—it is undesirable ipso facto.

Lines 69-71: The material proposed for deletion needs to be retained. Not only does the Protocol specifically allow use of socio-economic considerations (Art. 26), but in reality almost all current risk assessments in all fields (other than those purely for health) are conducted in the first place because of economic considerations.  And, we recall the extensive discussions during the Protocol negotiations about trade issues—which are, of course, economic considerations.  The same arguments can be made for social concerns as goals or endpoints for current assessments (eg, evaluating public policies in an attempt to reduce urban violence, etc).

Lines 186-187: Retain the material proposed to be deleted.  Why be general when you can be specific?  This document is for regulators who may not have very much experience.

Regarding lines 58-59 it is appropriate to add reference to comparative assessment. Comparison is required in the case of an LMO because the risk assessments required under the protocol are not intended identify all the risks of agriculture, eating, or use of plants in general.  The purpose is to identify any additional risks presented by the LMO.  The myriad other risks that are encountered (for example in agriculture, and everyday life) are appropriately handled elsewhere, such as in a country's phytosanitary regulations.

The following are posted in response to the comments by Phil Bereano on 2011-07-21

Re: Lines 58-59.  A comparison to the nontransgenic is always needed.  In the example cited, some raw fruits and vegetables can cause stomach ulcers depending on the amount consumed and the test species.  Thus, in the absence of a proper comparator, it would be impossible to tell if the result was diet-related or LMO-related.

Re: Lines 69-71.  Overall, this document does not make a big distinction between risk analysis (essentially step 1 in this document) and risk assessment.  Paulo's comments were to clarify that socioeconomic factors are not part of step 1.

I am attaching some comments on the current version of the Roadmap.  I remain concerned that the language is complex and convolted and that some of the concepts are not well explained for the non-technical reader.
I am having some difficulty uploading the file (not sure if it has worked or not) so will also send it to the Secretariat.

POSTED ON BEHALF OF HIROSHI YOSHIKURA

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Dear Manoela,

Again, may I ask you to post my comment to the “Online discussion on the revision of the Guidance on Risk Assessment of LMOs", as the high security of the Ministry does not allow the posting?

In the file, I made comments to the text following your guidance. Only to the main text I gave comment, as I believe that annex should be examined after we agree on the main text (though there may be different view).

My main concern is the present text is based on the original assumption that the environment does not change if no LMOs are introduced into the environment. But, environment is rapidly changing from bad to worse even without them.

Another concern is that we should have a room to consider what kind of organisms should be chosen as recipients/hosts. In my view, for foreseeable future, we should restrict the technology to the organisms to which we are familiar. 

Best regards,
Hiroshi


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Please see attached file at http://bch.cbd.int/onlineconferences/discussiongroups_ra.shtml?threadid=2485

Dear Dr. Yoshikura and members of the open-ended group and AHTEG,

Please allow me to respond to the changes proposed by Dr. Yoshikura. Dr. Yoshikura provided many valuable modifications. In particular, on line 67, I agree that it is important to consider that many effects may in fact be neutral. Also, on lines 554-560, the suggested changes to the text on monitoring help to clarify this section. I also agree that the phrasing of the paragraph at lines 554-558 could lead to endless cycles of risk assessment and management decisions. Risk management is typically only considered in cases where the risk is considered to be unacceptable. If the text in this paragraph is kept, it should be made clear that an unacceptable level of risk is the starting point for considering risk management options.

In regards to the text which was added that relates to addressing global climatic and environmental changes (lines 58-59, 71-72, 467-468), although it is recognized that such changes are occurring, and these should be considered where possible as part of the risk assessment, in practice this is difficult to do primarily because it is difficult to predict exactly what those changes will be. As a result, these considerations often do not play a predominant role in the risk assessments. In practice, lines 90-92 are considered to be more effective for addressing such concerns, because they allow for a re-assessment of the LMO whenever such changes are recognized to have occurred.

Also, in regards to the text added on lines 240-241 (“Preferably, comparators should be organisms with long history of safe use”), the use of a comparator with a long history of safe use, although it may be preferable, may not always be practical, nor is it necessary. I am concerned that the inclusion of this statement may create a barrier for LMOs that are being introduced as a new crop in the country conducting the risk assessment. In such situations, experimental data from field studies can be used to develop a case for the safety of the LMO without a need to rely on the history of safe use of the comparator. In addition, recommendations on restricting the development of LMOs such that only species with a long history of safe use are used is outside the scope of this document.

Thank you for the opportunity to comment.

Regards,
Jaimie

POSTED ON BEHALF OF HIROSHI YOSHIKURA

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I appreciate Dr. Schnell’s comments on my previous comments. The following is my response.

1. Lines 58-59, 71-72, 467-468: My point is to “take into account the ongoing climate change”. I think this is an important consideration during the risk assessment. For example, drought and stress-tolerant crop plants are actively being searched in the world. Without consideration of changing environment, developing such crop plants could be just considered as potential pest plants, and could be considered ethically unacceptable. In addition, during assessment of such crop plants, we are obliged to consider various future possibilities, not only temperature but also drought or flood, soil quality degradation, etc. I believe that risk assessment should take into account the continuously changing environment that occurs without introduction of LMOs and, if possible, consider the ongoing ecological evolution of living organisms in the changing world.

2. Lines 240-24: I understand Dr. Schnell’s comment that inclusion of the criteria of “recipients’ long history of safe use” may create a barrier for LMOs that are being introduced as a new crop. However, my intent is entirely different. The comment is rather based on the concern as regards excessively prescriptive risk assessment in the present road map, which requires formal comparative safety assessment even when the recipient organisms are very familiar to us owing to long history of use.

3. Traditionally, new varieties of food plants have not been systematically subjected to extensive environmental evaluation as mandated by the present text. New varieties of corn, soybean, potatoes and other common plants have been evaluated by breeders for agronomic and phenotypic characteristics, and, generally, such new plant varieties have not been subjected to the rigorous and extensive environmental testing. Do we know what is the ecological function of potatoes planted in your back yard ( though I know planting the potatoes prevents weeds from expanding to the neighbors’ garden)?

4. In addition, rigorous and extensive environmental studies in long range are actually difficult on account of confounding factors, such as, temperature, rain fall, human activities, global climate change and their complex interactions. Therefore, my proposal is to use the experience gained through long history of use or “familiality” (in the OECD wording) to reduce the unnecessary burden of the comparative studies, such as requesting the ecological function of the potatoes. As most living organisms currently used for genetic modification have long history of safe use, why not use such knowledge obtained through experience instead of requesting all the items which may not be easy to respond.

5. For producing LMOs from organisms that humans have no experience of use, I believe we should first investigate their biological behaviors including interaction with other organisms and environment. Once such knowledge is obtained through the risk assessment as described in the present road map, then we may be able to proceed for genetic modification of the organisms. This process is routine in the present science, I believe.

Best regards,
Hiroshi



Hiroshi Yoshikura
Adviser, Food Safety Division,
Ministry of Health Labour and Welfare
1-2-2　Kasumigaseki Chiyoda-ku, Tokyo 100-8916
FAX:+81-3-3503-7965
Tel: +81-3-3595-2142/+-81-3-5253-1111 (2408)
E-mail:yoshikura-hiroshi@mhlw.go.jp

Dear online forum members.
In the annexed revised text I send for your consideration some remarks on the risk assessment of living modified mosquitoes. My remarks start at line 1031 and end up at line 1264.
Irrespective of the specific remarks, it is my opinion that the whole text is over precautionary and raises very creative yet unrealistic issues, listed as points to be considered. If any country were to follow such guidelines, a GM mosquito release would never happen, even after many years of intense research.
Please consider again the fact that, although not mandatory, these guidelines are supposed to help beginners. As it is, the guideline for mosquitoes does not help the neophyte risk analyst, just on the opposite: raising all possible imaginative issues it creates a  large mass of problems to be considered and questions to be asked, some of them undoubtedly important but many other irrelevant.
I understand that the issue is complex. If it is wholly impossible to keep it simple and straightforward, taking into account the whole set of possible GM mosquitoes constructions, than it is better to reduce the scope of the guideline to one or two typical constructions.
Kindly
Paulo Andrade

Dear online forum members.
In the attached file  my comments on risk assessment transgenic mosquitoes.
I agree with Paulo that some points are very unrealistic, and also I would like to say that the RIDL Aedes aegypti technology as a pilot project is going on in Brazil (Bahia State, Juazeiro City).

best regards
Margareth Capurro

Dear online forum members,

Please find attached some more comments regarding LM mosquitoes:

Introduction, para 6:
I have added the following two sentences regarding self-propagating strategies that are aimed at reducing or eliminating the vector population and hence don’t fit into the categories as they are currently outlined:
“In a related approach, gene-drive systems may be used to promote the spread of a gene that confers a fitness load or a male bias in the offspring ratio. In this way, gene-drive systems may be used to suppress vector population sizes or induce a cascade of population crashes.”
An example of such a system is an X-shredding homing endonuclease gene (HEG) which can be driven into a population at the same time as biasing the offspring ratio towards males and hence potentially inducing an all-male population crash.

Planning phase of the risk assessment, para 1:
I have added the following sentence to account for the fact that, when an LM mosquito is first imported into a new country, the precise release site is often not known. This is because a contained assessment is often conducted first and it is not certain whether the LMO will be released into the environment. However, this should not be used as an excuse for the inapplicability of a risk assessment prior to importation:
“In cases where the planned release site is not known, a generic risk assessment should be conducted at the national level.”

Unintentional transboundary movement, para 1:
I changed “containment of the LM mosquitoes” to “confinement of self-propagating LM mosquitoes.” I think that “confinement” is a more appropriate term for limiting the spatial spread during an environmental release. Also, if a release of self-limiting LM mosquitoes is conducted sufficiently far away from a national border, I don’t think that transboundary movements are an issue; however, for self-propagating LM mosquitoes, this is an issue regardless of where the release is conducted.

Unintentional transboundary movement, para 3:
I added the following paragraph acknowledging that transboundary movements are essentially unavoidable for LM mosquitoes engineered with invasive gene drive systems, and therefore countries should be encouraged to enter into bi-lateral, multi-lateral or regional agreements:
“In cases where LM mosquitoes are engineered with invasive gene-drive systems, confinement may not be possible, even when efforts are made to reduce long-distance dispersal due to anthropogenic activities. Countries should therefore be encouraged to enter bi-lateral, multi-lateral or regional agreements regarding the release of self-propagating LM mosquitoes. Such agreements should acknowledge that such a release is intentionally international.”

Kind regards,

John Marshall

Dear Colleagues,
Dr. Marshall has contributed several valuable points, some of which I would like to comment on and propose expansion.

Introduction, para 6: This is a worthwhile expansion.

Planning phase of the risk assessment, para 1:

I do not understand the rationale of conducting an RA when the site of release is unknown since (1) the quality of the RA will be improved when the site is selected, (2) it will require revision when the receiving environment is specified, and (3) releases cannot begin until the site-specific RA is completed. Furthermore, a generic RA would be conducted for a mosquito which may never be released at all e.g. if it is in preliminary testing in containment. For these reasons, a generic RA seems wastefully premature.

Unintentional transboundary movement, para 1: I was remiss in not noting the language originally used which was far too strong, and I generally agree with Dr. Marshall's rewrite assuming his comments are reflected in the body text. (As an aside, the term "broad dissemination spectra" is vague to me.)

I would prefer:
"Mosquitoes, being LM or not, have very broad (dissemination spectra?) and geographical distribution. Individual mosquitoes however do not with lifetime dispersal distances commonly of less than 5 km and for some urban species, as short as 200 m. Confinement will therefore be highly dependent upon the species and specific LMM technology. Self-limiting sterile male types of technologies will be highly confined temporally and spatially. On the other extreme, ensuring the confinement of self-propagating LM mosquitoes to a particular receiving environment or to a country is thus unlikely and may result in transboundary movement."

I do not think that it is appropriate to call non-anthropogenic transboundary movement "unintentional" since the potential for this should have been anticipated and prepared for in the RA based on the technology. Calling it unintentional suggests that it was (1) unanticipated and not prepared for or (2) it was anticipated but there was no preparation e.g. agreements between countries that anticipated this. Anticipating such is described by Dr. Marshall's comments under "Unintentional transboundary movement, para 3" which are a useful addition.

The document needs to clearly distinguish between LMM that have potential for transboundary movement and those that do not and advise that the RA be prepared accordingly. If contained trials are properly conducted, this risk will be sufficiently documented that *unintentional* non-anthropogenic transboundary movement will be extremely rare. The document should anticipate the exceptions, but not focus the guidance around them.


Mark Q. Benedict

Dear Colleagues,
Please find attached my comments on the document.
Wish you all a nice week.
Moisés

Dear online forum members,

I’d like to thank Dr. Benedict for the insightful feedback on my earlier comments. I support Dr. Benedict’s proposed expansion, but would also like to explain my reasoning regarding the possibility of conducting a generic risk assessment (RA) at the national level prior to the importation of a novel LM mosquito (this reasoning may also apply to other LMOs).

My concern here is that the Advance Informed Agreement (AIA) procedure does not apply to LMOs destined for contained use. This is particularly relevant to LM mosquitoes because, in almost all cases, LM mosquitoes are first exported for careful analysis in laboratory and/or cage studies in the receiving country. The first importation is therefore considered to be for contained use and is exempt from the AIA procedure. Subsequent importations are then exempt from the Cartagena Protocol because the Protocol only applies prior to the first importation of an LMO. What this means is that the right of an importing country to request the exporting country to perform a RA at its own expense (as per the AIA procedure) is annulled under these circumstances. Technically, this means that recent imports of LM sterile mosquitoes from the United Kingdom to Malaysia, Brazil, India, Vietnam, Singapore, France and the United States were all exempt from the AIA procedure. Since the AIA procedure is a central part of the Protocol, this significantly reduces the Protocol’s relevance.

To remedy this, my suggestion is that for LM mosquitoes imported for initial contained analysis with the ultimate intent of an environmental release, the importing country be entitled to require that the exporting country conduct a generic RA at its own expense. Then, if an environmental release is to go ahead, the receiving country may use this generic RA as a starting point from which to conduct its own RA specific to the release site. This issue is particularly relevant to self-propagating LM mosquitoes, for which the risks are magnified by the ability of transgenes to spread. I understand that this is a more general comment concerning the text of the Cartagena Protocol itself, and therefore may not be appropriate to address in the AHTEG’s guidelines; however, I believe it to be worthy of consideration.

Another overarching issue that I would like to expand upon relates to the release of self-propagating LM mosquitoes with invasive gene drive systems. My suggestion here is that, in the near future, discussion be initiated on what form of agreement would be required for a release that is expected to be international. A process whereby every country within the host range of the species must first agree to the release would be very difficult to achieve. While I agree with the ideal of unanimous agreement, I think this is more likely to lead to unilateral decisions being made without considering other countries. While not genetically modified, this has been seen in the recent release of Wolbachia-infected mosquitoes in Australia (Wolbachia-infected mosquitoes are expected to spread widely, but the RA was only conducted with Australia in mind). A more achievable process is more likely to be abided by; but it must be decided what form this would take (e.g. an independent review?). Once again, this is a broader issue concerning the Protocol itself; but I’m not sure where else to address it since this is the only document that specifically concerns LM mosquitoes.

Kind regards,

John Marshall

Dr. Marshall highlights several features of the existing Protocol that he believes do not adequately address anticipated activities. However, the Protocol was deliberately written so that the AIA has specific exceptions, among which are LMOs that will be used in containment. As part of our AHTEG activities, it is not appropriate to recommend procedures that effectively extend the Protocol to compensate for its perceived shortcomings. Generic RA’s specifically are outside of the Guidance document on RA and RM which states that “ the risk assessment is performed on a case-by case basis”.

Moreover, “entitlement” to a risk assessment for exceptions to the AIA cannot be annulled since it does not exist under the Protocol. It may be however (and typically is), required under national legislation, as provided for under Article 2, paragraph 4 of the Protocol. No imports can be made without the subsequent import permit. I suspect that many of these issues are not unique to LM mosquitoes and have been addressed elsewhere.

One item which Dr. Marshall raises and which is perhaps unique to mosquitoes is spread of organisms containing a gene-drive system. If the Parties agree that the Protocol is not sufficiently expansive for this case, this issue must be dealt with at the level of the Protocol but not within these guidance documents. International harmonization is certainly desirable and has been achieved in other fields such as plant protection (IPPC).  This forms a useful model as to how such agreements could be made in the future regarding LMM with invasive gene drive mechanisms.

Mark Q. Benedict

Dear Online Forum Members

I would specifically like to address the comment from Dr John Marshall on the LMM guidelines (#2548) regarding the imports of LM sterile mosquitoes from the UK to various countries.  Dr Marshall suggests that all these imports were exempt from the AIA procedure as they were for contained use.  I’d like to point out that exports from the UK have to comply with Regulation 1946/2003 on Transboundary Movement, which implements the Cartagena Protocol in the EU.  Additionally import permits are required under national legislative frameworks, which include a risk assessment of the receiving environment.  Materials cannot be shipped without an import permit  in place. So all such imports will have been subject to prior consideration, permitting and risk assessment.

I don't think that there should be a concern that “[s]ubsequent importations are then exempt from the Cartagena Protocol because the Protocol only applies prior to the first importation of an LMO".  Article 7, paragraph 1 states that the AIA procedure applies to the “first intentional transboundary movement of living modified organisms FOR INTENTIONAL INTRODUCTION INTO THE ENVIRONMENT“ (emphasis mine; I'm not shouting, but the only way to emphasize something in plain text is to put it in caps).  Therefore, there should be no concern that a first transboundary movement into a contained facility subsequently exempts future importations for the purpose of a field release.  Since that field release would be the first transboundary movement subject to the Protocol, it would be subject to the AIA procedure.  Furthermore, the Protocol does not prohibit importing countries from imposing their own requirements for risk assessments, either for introduction into a contained facility or for introduction directly into the field.  Countries have done this for years with respect to transgenic crop plants.

Hi John,
thanks for your helpful input.
I agree mostly with your comments, and have added my comments to your version (hope you don't mind).

if still time, I'll add some more comments later.

Ricarda

Please find attached comments on intro to LMO mosquitoes.

Hi, Mark, I cant open your file, it seems it has some broken string on it. Could you post another copy for us?
Thanks.
Paulo Andrade

Dear members of the open-ended group and AHTEG, dear colleagues,

first of all I would like to thank those of you who have already contributed their comments in track-changes to the current version of the Draft Guidance on risk assessment of LMOs. These are very valuable contributions for further developing and improving this important document.

At the same time I would like to remind you that you that this round of discussion is open only for a few more days. According to the action plan it will be closed by the Secretariat by the end of this working week, in concrete terms on 30 July at 1:00 am (GMT).

I therefore would like to encourage and motivate you to provide further comments in track-changes in the remaining time available. As AHTEG Chair I will then have a good basis for the consolidation of suggested amendments and - in consultation with the AHTEG Bureau and the Secretariat - provide a revised Chair`s draft of the Guidance in the course of August/early September to be circulated online on 12 September 2011.

I thank you for your expert input and continuous support of this important piece of work. Thank you and best wishes

Helmut
AHTEG Chair

Dear all,

I tried to have a look at all the different comments and appreciate the tremendous work gone into all of these. I have commented to some of the points raised (see attached), but realised that many of the suggestions are major rewordings and rearrangements, such that I cannot see a way of how to comment. Since the draft text is the result of loooong deliberations taken place over years with the involvement of many I feel similar to Kazuo, Beatrix and David, in that I would not like us to reopen the whole text and structure, but focus on fine-tuning and making language easy to read and comprehend (I would like here to particularly thank Janet to help so skilfully with language).
Concerning a suggestion made to mostly change text to quote and directly reflect Appendix III language, I would find this not sufficient for a guidance document meant to be additional guidance to the Appendix.

Concerning LM mosquitoes, I will send my comments seperately.

With kind regards

Ricarda

This copy is a Word ".doc" file. Please let me know if you have problems with this.

Hi Mark, I have the latest version of Word, it opens all docx files except...your attachment. Could you post it as an attachment to meat andrade@ufpe.br.
Thanks in advance.[
Paulo Andrade

Thanks, mark, now it is OK

Dear Friends, Attached please find a few changes from me. Thanks! Wei

Dear Members and Secretariat,
Please find attached some suggested revisions to the Guidance document.
Best regards,
Jawahir Karihaloo

Dear colleagues,
Thanks for all the constructive contributions, the work done on the roadmap so far and the opportunity to contribute to its improvement. I believe we still have a number of details to deal with, in order to make it easier to understand and a more useful guidance.
Attached, you`ll find my suggestions for the first part (until line 386). Several are simply substitutions with text/wording used in annex III to prevent from confusion with different interpretations and challenges due to the multi-language background of the different risk assessors to use it, etc.
The introduced guidance on the choice of comparators is indeed a great idea. It is a very important step in risk assessment to identify the relevant differences of the LMO.  But the text needs to be clearer about taking into consideration the natural variation and in case of the newer more complex phenotypes that might be better if compared with other comparators than the usual near-isogenic non-GM counterpart grown under similar conditions. It is not the case of different risk assessment frameworks but finding the best choice depending on the need. While the choice of comparators needs better and appropriate explaining, the long text on uncertainties as it is now is rather confusing than useful. Uncertainty is inherently not only to Risk assessment but to Science and actually everyday life; there is no need to make it complicated detailed.
Overall, I think the improvements to the roadmap should be where it lost its focus from annex III. It should not add complexity and require more information that it`s beyond the scope and requirements of annex III. The more information and complexity than needed does not necessarily increase safety and can actually have the opposite effect. Besides, more complexity than needed is a waste of resources and opportunities to improve conservation and make a more sustainable use of biological diversity.
Best regards,
Lúcia

POSTED ON BEHALF OF WADZI MANDIVENYI

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File attached.

POSTED ON BEHALF OF DEBORA PIRES PAULA

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Dear Manoela,
I would like to ask you to post my suggestions to the "Guidance on Risk Assessment of LMOs (revised on 4 July 2011)" related to the topic "The choice of comparators".
I did not find the applicative.
Thank you in advance.
Best regards,

Debora

Attached please find the comments on the roadmap and additional guidance documents on behalf of PRRI.

Dear Hector and all:

While being in the RA AHTEG member, I shall not alter the content as it is built after intensive discussion over three years. However,  considering the purpose of the use of the guidance doc on roadmap, yet I feel that the content can be further elaborated as the baseline on simple and easy to use for a novice users without confusion.　But addition of wording to enhance clarity is another side of consideration if the elaboration further make easier comprehension.


Kind regards,

Kazuo Watanabe

Dear collegues
Please find enclosed the file with some comments and reactions to proposals from my side. In addition I like to explicitly support the proposals to the comparator section (lines 198-237) by our collegue Deborah Pires from Brazil. I find these very pertinent.
Altogether I like to emphasize that we are dealing with a document which has been discussed for quite a time as also Kazuo pointed out. I am quite content with our compromise and would caution against mayor changes in content or structure.
best regards
Beatrix

this time hopefully the attachment

POSTED ON BEHALF OF PHIL BEREANO

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Re: comments by Hector Quemada:

line 218--we should retain the original; there is ALWAYS a difference (why else would the developer of the LMO be pushing it?)

lines 223-225--this is unwarranted; it is reductionistic reasoning.

lines, 220 and 467. "direct" and "indirect" are different variables than "intended" and "unintended". One describes the causal chain and the other describes the motivation of the creator of the LMO.  Thus, BOTH pairings are necessary, since in reality there are 4 different possible relationships to be investigated. Similarly, "direct" and "indirect" need to be added to line 68.

line 282.  I would object to such a change, since it can also be indirect.

line 334--re: management measures.  this is a bit circular.  Such measures result from the assessment and, as such, are not part of performing it.

line 571--the form of the report is a risk management concern, not one of assessment.

lines 738-740.  I believe this change is unwarranted.  it is reductionistic; the genome is more fluid, not a static LEGO construction.

line 1051--add "including the receiving environment".  In the negotiations, at least one delegation attempted to ignore such a parameter, but this was rebuffed.


Re: comment of WADZI MANDIVENYI

the comment referring to line 169--I do not see that material at that line.  Anyway, the examination of benefits is presumably something the risk management process would be doing; it is inappropriate in an assessment of the risks.



Re: comments of Lúcia de Souza

line 72.  again, I object to deleting this sentence.  Annex III is about risk assessment, not risk management.  A risk management process will have set "protection goals and assessment endpoints"  These MUST be reflected in the specific assessment since they help define how that assessment shall be performed. thus, the sentence is necessary as well as proper.


Philip L. Bereano
Washington Biotechnology Action Council
49th Parallel Biotechnology Consortium

POSTED ON BEHALF OF OSSAMA ABDEL-KAWY

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File attached.

POSTED ON BEHALF OF LES PEARSON

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Dear Colleagues:

I very much appreciate the additional time provided to allow input but regret that even so I have been able only to review the Roadmap and the guidance on abiotic stress tolerance.  Please see my attached suggestions.

I also appreciate the hard work and effort by others that has been put into getting these documents to their present form (including the suggestions already submitted in the on-line forum), and recognize the desire to finalize them without making too many changes.   I think it is important to reiterate something that Hans pointed out in the beginning: to be truly of value these must be living documents and should be adapted and changed over time as we gain new knowledge.

Les

Dear colleagues,

I have gone through the various comments, and want to thank you for your efforts to help further develop this important document.
I have collated a number of my comments to the comments in the attached document.

Best wishes,

Hans

Dear All,


Thanks very much to Hans Bergmans for compiling the comments in one document and adding his observations to those comments.

Seeing his compilation, I realise the immense task it is going to be to reflect all those track changes in a new version.

I will therefore not add any further track changes, because much of what I would wanted to say has already been said by Janet Gough, Paulo Andrade, Jaimie Schnell. Lucia de Souza and some others, but I just limit myself to some general observations.

As a member of the AHTEG, I am very keen that the result of our work is of use to people who are asked by their government or organisation to conduct or verify a risk assessment, but who have limited experience with risk assessments. 

In this respect I have the same concern as Janet Gough that the text is in many parts still convoluted and difficult to read, and I share the concern of Paulo Andrade and others that the text at various parts seems to raise more questions than that it assists in answering the need to know questions.

I note Beatrix Tappeser’s observation that she “is quite content with our compromise”, and I am afraid that that is exactly where the problem lies: this is a compromise text between two very different perspectives and the result is something that leaves many important questions open.

One of the most disconcerting points is that some people seem to forget the comparative character of risk assessment, and that with any conventional crossing there are many, many changes in the resulting organisms, that not every change is significant, and that not every significant change is biologically relevant.

To verify the usefulness of our work, I hope that the AHTEG in its next face to face meeting will take the guidance documents and uses them to assess a few a real life cases.

Thanking all those who have contributed to this process, of which already at the adoption of the Protocol in 2000 we expressed hope that it would take place soon...

Kind regards

Piet van der Meer

Please find attached my comments on the Roadmap. I’ve worked primarily from Hans’ posting to reduce redundancy. With others who have said the same thing, I appreciate the great amount of interest shown in the Roadmap by this online forum. It is welcome indeed. There is a need to strike a balance between revising text that advances the Roadmap and preserving what what has already been of value to the Parties and expressed in the confidence they placed in it in MOP5. As Tom nicely put it, I think this is a time for those in the AHTEG to listen too so I’ve not made extensive comments.

With this post I would like to make a few general comments.

1. I support Beatrix’s intervention on the comparator and reinforce that in my comments in the document attached. The RA is foremost a scientific process. It must be built on the strongest scientific method which in the case of an LMO is through comparison to the near isogenic conventional parent. Later, any statistically significant effects deemed to be potentially adverse that are revealed by these comparisons can be investigated to determine if additional risk mitigation is necessary or not. To adopt procedures, such as the use of ever more distantly related controls (which are not comparators but reference lines as our colleague Deborah Pires correctly points out) in effect adds noise to the scientific process rather than increases assurance that it is reaching the correct outcome. It is therefore essential to ensure that the same and appropriate line be used as a comparator in all experiments/trials and not a mix, or an inconsistent collection, of genotypes be used that may change from experiment to experiment. Where a developer or an assessor believes that the potential adverse effect is not requiring risk mitigation then qualitatively different experiments may be warranted to establish this fact, rather than the same experiment done with less precision by increasing the genotype and genotype x environment noise in the measurements.

2. Several commentators to this thread have indicated that the Guidance, if followed, would simply prevent the adoption of presumably safe products. This argument has picked up a cohort of related statements usually associating “clarity” and a need to streamline the list of issues that an RA may consider because our target audience includes the least experienced of assessors. Assuming that I have been fair in this extremely brief summary of the points of view, my response is:
a. our audience is intelligent people who know more about the potential receiving environment than more experienced assessors who do not live in the same country;
b. the Guidance is not binding, so the assessor would not necessarily require all possible kinds of information that the Guidance indicates could be considered;
c. since our target audience is those with less experience, the Guidance should be comprehensive in its framework and advice on how to generate the kind of knowledge that would reduce “the lack of certainty” and allow the assessor to decide which of those sources of knowledge are relevant to her.

Best wishes to all

Dear collegues,

Please find enclosed the file with some comments and suggestions for the RA guidance.

Best Regards,
Luciana.

Dear All,

Please find my attached concrete suggestions and comments to the Roadmap and Terms of Use. I think the many helpful contributions that have come are quite useful, yet I echo the sentiment of Kazuo and Beatrix that large changes and deletions are perhaps difficult to revisit lengthy discussions we have had in the AHTEG deliberations on many of the points raised.

Further, Id like to draw your attention to recommendations to alterations of the Flowchart. I have included detailed comments there, and a rough sketch of how the structure might look to be consistent with the text of the Roadmap.

Kind regards,

David Q

I would like to add my voice to those who have expressed thanks to all the commenters for their constructive feedback and input of these guidance documents.  I chose to not comment on this advanced text at this time because it is my opinion that this was the time for AHTEG members to "listen" and consider the input from experts outside the immediate group who were present when the text was put forward to the online peer review. 

I also hope that commenters outside the AHTEG are not confused or discouraged by some statements implying that changes of any nature to the text put before us at this time would be difficult to consider.  The text put before us is not a consensus of experts because the process has operated otherwise.  Rather, I see it as a proposal from the Chair who had the difficult task of considering a great diversity of input from within the AHTEG and previous online fora.  It is relevant that one of the few points of consensus is that the Roadmap and other guidance will be living documents - tested and refined with time, use and feedback.  As such, constructive comments from experience experts are alway welcome and considered.  It is truly the nature of an iterative and open process.  Perhaps it is best to look at this process as a conversation that will ultimately be presented to the MOP for their decision.  Until that time, it is my opinion and hope that all comments offered in a constructive manner will be thoughtfully considered.

Thanks,
Tom

Dear members of the Open-ended Group, AHTEG and Secretariat,

I am attaching here suggestions marked as "track changes" to the Guidance version of 4 July 2011.

Best regards

Adriana

Dear members of the open-ended group and AHTEG colleagues, dear Chair of the AHTEG

First of all I would like to thank for the opportunity to send comments to the least version of the guidance document.
Here are my comments to the roadmap as track-changes. I know that some proposed changes reflect part of the discussions that we had in the AHTEG but that did not make it to this version of the document. I find that to include them here maybe informative for the rest of the open-ended group. I did not have the time to look at all the changes and comments proposed this far by everubody, but I hope that we will have the chance to do so and consider them.
Thank you
Sol

Dear friends:

Please find enclose some few comments on the guidance. I am also including some comments on the monitoring guidance. Although I am one day late I hope it can be considered

Best regards

Elizabeth Bravo

POSTED ON BEHALF OF LUCETTE FLANDROY

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Dear all,
 
I am coming late in that important forum, through overloading with other professional obligations these last times.
 
I want first to thank the participants for the interesting and professional interventions of most of them, showing the great care they want to bring in this exercise.
I obviously also thank the members of the AHTEG who have the complex charge of the integration of all these comments in a document that should become consensual.
And thanks to Manoela to have extended this session of the forum in face of the internet problems. 
 
I went through the revised roadmap beginning of July, but did not find the time to make detailed personal comments.
 
I' ll thus just make main remarks on various comments of other participants that I read these last days ( I am sorry if I do not in each place remind the name of the concerned participant ) .
 
 
General comments:
 
I agree with the majority of simplifying, clarifying comments/changes made by Janet Gough intended to facilitate the use of this roadmap.
 
Concerning the Introduction:
 
l. 65-66 : Could the meaning, the purpose, of the last sentence of this § not be better explained ? If there is no plus-value in this sentence for the RA, cann' t it be just deleted ?
 
l. 67-71 ( roadmap, version July ) : I could agree with the initial wording of the revised guidance ( version 4 July ) or with the small amendements made by Moisés Burachik. 
I would however add the following elements in this § :
          - at the end of th 2nd sentence, after " ...Annex 1 of the Convention." , I would propose: " ….and related COP decisions. "
          - at the end of the §, I would propose: " In view of the objective and preamble of the Protocol, it should be clear, anyway, that pure economic considerations should not bypass environmental considerations and protection goals as guided by the Convention of biodiversity. "
 
 
Concerning Uncertainty:
 
Some participant ( Lucia de Souza ) seem to consider that too much emphasis is put on the chapter on Uncertainty, that brings confusion rather than clarification in the treatment of a  phenomenom current in science and in everyday life.
Since we are here trying to establish a guidance for risk analysis made as much as possible on a scientific basis, I consider that the treatment of uncertainty is very important ( should even be more visibly pointed as a title in the guidance ) and should be, as mentionned by Hiroshi Yoshikura on line 133, defined with precision ( place and size - with valuable statistics - on the incertitudes ) as long as we are inside the scientific process of the risk analysis. Because the politician decidors will normally have to take positions in face of various incertitudes.
 
Some participant found that the document makes confusion between "incertitude" and "lack of knowledge" .
The guidance anyway explains well that different "sources" and "natures" of uncertainty exist.
Maybe these different "sources" and "natures" should be a little bit more acurately separated, explained and treated in the document. For example, whereas it is clear for me in the document, maybe the difference between " lack of information " and "incomplete knowledge" should be explained a bit more.
Actually, as long as we are in the scientific process of risk analysis in a precise time, "incertitude" and "incomplete knowledge" are indeed different aspects and can be treated differently; but once we are in the risk assessment and the decision process, both "incertitude" and "incomplete knowledge" come under the general uncertainty to deal with.
"Incomplete knowledge" often concerns risks that are plausible ( through some scientific knowledge, through analogy, through empirical knowledge, … ), that can be expressed, but that cannot be tested at all or acurately at short term. Thus, it does well fall under the definition of the precaution principle of the Rio Declaration for its taking into account.
 
 
Concerning Comparators:
 
I agree with Jamie Schnell that comparator should not necessary be "as much as possible with a history of safe use", as proposed Hiroshi Yoshikura ( who made, besides, very pertinent comments, some of them difficult to deal with ). Comparators with history of safe use would apply mainly for GM plants intended for food/feed ( and even so, sometimes with difficulty as explained by J.Schnell ) , but we are here in the general roadmap, so it must apply to all GMOs. ( What would be non-GM mosquitoes transmitting malaria with a history of safe use ?? ) .
 
I find it should still be better explained, in summary, by some examples, why the isogenic non-modified organism, which, theoretically, should be the best comparator, is not always available or is not the ideal comparator.
 
We are all inevitably influenced by the fact that most GMOs till now are GM plants, and mostly intended for food/feed and having simple GM traits, and so are we in our reasonings on the general roadmap.
As such also the comments of Wadzi Mandivenyi on the comparators.
Similarly, I feel that the changes brought by Hector Quemada in the chapter on comparators could in any case not fit for a general roadmap intended for all types of LMOs.
As an example of comparator in the case of GM plants one could propose, in addition or replacement of the isogenic non-GM comparator, the cultivar of the same species the most commonly cultivated in the foreseen receiving environment of the LMO and that the LMO would replace.
 
 
Concerning Monitoring - Management of risks :
 
I do not totally agree with Jamie Schnell comments.
Monitoring is a particular aspect of management of risks.
Risk management measures aimed at avoiding specific identified risks ( like refuge zones for Bt cultures ) should indeed be established only if an unacceptable risk has been identified and can be avoided by some specfic tool.
But monitoring is part of the management process that is intended to look at the appearance of adverse effects that would appear in spite of the specific measures established to avoid those risks and, besides, to look for the appearance of uncertain and, at the same time, unforeseen risks.
Monitoring can thus be useful even in cases where other specific management measures have not been judged necessary to be put in place.
 
 
Concerning the guidance on GM Mosquitoes:
 
Dr. Marshall has to be acknowledged for his careful trials to take into account peculiar characteristics of mosquitoes and especially of self-propagating LM Mosquitoes  with invasive gene-drive systems.
However, if GM mosquitoes in contained use are sent from one Party to another one where they will first be kept in contained use, there is indeed no requirement neither for a risk assessment neither for a AIA procedure and a "generic RA" falls outside the prescriptions of the Protocol. It would be the responsabiliy of the importing country to make a RA before deliberate release. 
If they are sent from contained use to be immediately released into the environment, then a AIA procedure would be needed, and it is left to the option of the importing Party to make itself the RA or to ask the exporting Party to do it.
Regulation 1946/2003 does not either impose a RA or AIA in case the mosquitoes are sent for contained use.
Import permits are national requirements that have no international specifications.
 
 
Whereas I also doubt that Dr. Marshall' s proposal for bilateral, multilateral or regional agreements falls within the mandate of the AHTEG, this suggestion is surely good to remember to propose in another context of discussioon around the case of GM mosquitoes, in view of the impossibility to confine these organisms. Anyway, in case his proposal under Unintentional transboundary movements § 3 would be accepted, I propose the following addition after Dr. Marshall' s text:
" These agreements should be based on risk assessment, respecting Art.14 § 1 of the Protocol, and at best established with all the Parties where the concerned LM mosquitoes could propagate, taking into account the various ways of propagation and taking care that the genetic modification would not broaden the propagation and survival distribution of the concerned mosquitoes. "
 
I consider that peculiar precautions should be taken in the ERA of these organisms I view of their wide ability to spread, their complex ecological variety and interactions and the role they play in the transmission of diseases. Thus, all plausible risks that are not proved to be impossible should be considered even if estimated as "rare" possibilities following the common knowledge. The magical word  "as appropriate" could maybe be used for the "Points to consider" after l. 1150, if some of these considerations do not apply to all mosquitoes or all types of genetic changes.
Maybe a more detailed kind of flowchart specific to GM mosquitoes could be established to facilitate the progressing in the ERA ( with yes/no answers to guide the progression in the RA., whereas this is maybe rather difficult in view of the complex interactions of this kind of organisms and of the lacks of knowledgs ) . As presented now in the document, the "points to consider" are presented in a rather disordered fashion.
This kind of ERA should in any case not be left to beginners neither in the concerned GM- technology neither in the science of tropical mosquitoes. 
 
 
With best regards.
 
Lucette Flandroy

THIS MESSAGE WAS RECEIVED SHORTLY AFTER CLOSING OF THE DISCUSSION AND IS BEING POSTED ON BEHALF OF CAMILO RODRIGUEZ-BELTRAN

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Dear all,
Thank you for this intense discussion on the proposed text, I´m sorry to also coming late to the discussion. You will find attached my version of the text and would like only to express my respect to the great work of the AHTEG, I agree with the views that expressed the need for suggesting, but retaining some of the  important issues that have been already discussed and agreed.
Best regards,
Camilo

THIS MESSAGE WAS RECEIVED SHORTLY AFTER CLOSING OF THE DISCUSSION AND IS BEING POSTED ON BEHALF OF GEORGINA CATACORA

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Dear all,

The document attached contains the comments and suggestions on the RA Roadmap from the Plurinational State of Bolivia.

We would like to thanks and congratulate the Secretariat and the AHTEG for the progressive improvements of this important document. We also would like also to share general comments and concerns about the current Raodmap document:

-       In general terms, we feel that the Roadmap has a strong and imbalance focus on molecular biology issues in terms of approaches to identify potential adverse effects. Probably (we are not sure) the AHTEG is missing some ecologist (?) We believe that explicit and COMPLEMENTARY text on approaches and points to consider to effectively identify potential adverse effects at population, habitat and ecosystem level are certainly needed in the Roadmap.

-       In line to the previous comment, the Roadmap needs to include more complementary insights for the assessment of potential adverse effect that may arise from the “transfer, handling and use” of the LMO (now it has a strong focus on potential adverse effect that may arise from molecular / genetic changes). This not only to have a more comprehensive approach in the RA planning, process and decision-making, but to be consistent to the CPB which aims at “ensuring an adequate level of protection in the field of the safe transfer, handling and use of living modified organisms” (Art. 1).

-       We are concerned on the stress placed on the “comparative / choice of comparator” approach. This due to the following reasons: 1) it is too restrictive since there are other approaches different from the comparative approach (and others may arise) to effectively assess potential adverse effects of LMOs. We should aim at suggesting a pool of complementary approaches and not stressing on one only; 2) As described now, the comparative /choice of the comparator approach is restricted to molecular biology without effectively including the analysis of the “transfer, handing and use” of the LMO to assess potential adverse effects; 3) the CPB deals with adverse effects of LMOs regardless they are intrinsic or not to the LMO or non-LMOs. Accordingly, the relevant comparison should be framed in relation to the baseline information of the receiving environment (baselines should not be restricted to non-LMOs or parental varieties). Therefore, we believe that the strong focus on the comparative approach (including the choice of comparator in terms of molecular biology parameters only) needs to be changed.

-       In the first part of the Roadmap, in some places there is an unnecessary and misleading focus on LM plants and agriculture. The inclusion of other LMOs or at least text that do not restrict the RA planning and process to LM plants is needed. We have suggested some changes to achieve this.

-       We read some suggestions that try to substantially change the spirit of the Roadmap and that even are not inline to the CPB. We suggest to avoid opening issues that we are sure were intensively discussed already in the AHTEG. Someone said that we need to be cautious with the changes suggested. We agree with that.

Looking forward to further developments of this process.

Kind regards,

Georgina Catacora-Vargas
Viceminsitry of Environment
Plurinational State of Bolivia