If the event is unique and is the multiplication of genetic material occurs by cloning, from the same founding event, the analysis will be unique and ends in the genotype and phenotype of this event, and the interactions with human and animal health and the environment.

1. In the Overarching Issues Section, regarding the identification and consideration of uncertainties, it is proposed to distinguish the uncertainties associated to the information, from those derived from the experimental systems.

2. In Related issues we propose to include the cost-benefit analysis.

3. We think that the importance of the selection of comparators should be addressed largely.

4. The “(near-)isogenic” term should be defined.

5. The experts suggested to include the analysis of individual risks for each adverse effect identified, prior to the overall estimate of risk.

6. In step 1, specifically at the points to consider about adverse effects, we proposed to be more specific about the potential effects on human health (toxicity and allergenicity).

7. In the same step, it is important to consider agricultural practices used in the trial, type of irrigation, number and doses of herbicide applications and the used method for harvesting and waste disposal.

8. From line 334 to 343, in the Receiving Environment topic, it is necessary to incorporate the aspects exposed in the example to facilitate the work of assessor (paragraph 20 at the end of the page).

9. In step 3, points to consider, subsection a) (i) and (ii), add soil microorganisms.

10. The roadmap is applicable to all LMOs in general, but very enclosed to plants and does not reflect the specifications of other cases.

11. It is suggested the use of examples that are not circumscribed only to plants but also to microorganisms and animals.

12. Previous experiences are required for the understanding and use of the guidance.

13. In the Roadmap, specifically into the strategies of risk management, the monitoring plans should be expressly mentioned.

14. The guidance on risk assessment of genetically modified mosquitoes should be a little more illustrative due to the complexity of the case and the uncertainties related to the topic.

The concept of choice of comparators induces an uncertainty by use of words like: can and may. This may be because comparators is not a very good concept. Instead an assessment (CASE BY CASE) of the insert in its background could be a suggestion.

Nos parecería positivo añadir en este último apartado alguna definición suplementaria, como la de heterocigosidad , isogénico, re-transformación y co-transformación.

Consideramos que la monitorización y los planes de seguimiento son un elemento clave para la mejora continua de las evaluaciones de riesgo ya que supone el elemento clave de contraste entre los datos teóricos o de laboratorio con la experiencia real en campo, lo que permite una fuente muy valiosa de información de cara a rectificar la evaluación de riesgo o emprender evaluaciones nuevas. Por ello, convendría que fuera claramente indicada en el texto de la guía.

Por último, creemos que es importante seguir con el trabajo emprendido y desarrollar nuevas guías específicas, considerando como prioritarias por su importancia y desarrollo actual las referentes a peces, microoorganismos y virus.

The following further observations were made:

1. It is recognized that Annex III of the protocol was a "political" compromise on a highly dynamic technical issue, reached during a dynamic period for biotechnology development, which required continuous up-dating.

2. Reference to the Precautionary principle in the preface is highly commended, but this is not adequately reflected in the "points to consider" as closely linked to "uncertainties". Reference to the importance of RA in the "potential receiving environment", country policies and regulations, local practices and habits related to the handling and use of GMOs are also commendable and should be an explicit cardinal principle.

3- While "part II" touches rightly on 2 of the non-crop plants GMOs this does not clearly anticipate further developments in biotechnologies which would bring about new elements and approaches in RA. From an environmental perspective, the rationale for emphasis on crop plants and managed ecosystems may be a practical approach but lacks in scientific validity. Reference in "Background" of part I needs to be more explicit in considering need for RA methods in response to future developments in biotechnology, hence release of new GMOs in addition to mosquitos and plants with abiotic stress traits.

4- The section on "choice of protection goals" is too narrow and would not accommodate the environmental protection goals of the CBD and the Protocol, where decisions are based on RA and all articles of the Protocol. . It needs to be categorically broadened to include socio-economic, public perception, religious, spiritual, ethical and other considerations which vary from community to community.

5- In the "choice of comparators of Part I, reference needs to be made to all articles of the Protocol and the fundamental goal which the CBD targets, including: ecological functions and services and ecological balances in both managed and un-managed ecosystem. This is now restricted to the sections on LMO mosquitos and needs to cover the entire roadmap. While reference to "additional points not explicitly mentioned in Annex III" in the section on "conducting the RA" is commendable, the rationale should include phenomena such as: gene interactions, "gene scrambling" and the possibility that gene expression and the interactions of the gene product may be influenced by environmental factors. Step I needs to include ecological services and balances, and "novel characteristics" needs to include certainty, accuracy and precision of the transformation event and interaction with other genetic constituents whether expressed naturally or not: this being reflected in several elements of the "points to consider regarding characterization of the LMO". In Step 2, the rationale needs to reflect the LMO and its products which may find its way into the environment. In Step 5, the recommendations need to take into consideration socio-economic, public perception, religious, spiritual, ethical and other considerations which vary from community to community. In the same Step, reference to "benefits" analysis is unscientifically suggestive and is best modified to "cost-benefit" analysis.

6- The "points to consider" section could benefit from reference to: in situ conservation goal of the CBD, Identity preservation, countries' capabilities and priorities and alternative options.

7- In the section of Effects on the abiotic environment and ecosystem, in "Risk Assessment of Living modified plants with tolerance to abiotic stress", the last paragraph would benefit from reference to "cost in terms of ecological services?

8- The section on Risk assessment of living modified mosquitoes is more elaborate, balanced and "frank. It is an example showing that when a non-"trade related" GMO is considered, a more open, less restricted, scientifically sound and more ecologically-relevant RA becomes more likely. RA should not be unduly biased by trade-interests. Here, species, habitats, ecosystem function and services etc. are more prominent (see Steps 2 and 3 of the roadmap. Fish and other aquatic GMOs are not much different from mosquitos but received less attention because of trade considerations.

- Les exigences en termes d'analyses statistiques devraient être plus développées.

- Il devrait être clarifié que les résultats bruts doivent pouvoir être obtenus sur demande s'ils ne sont pas inclus dans le dossier.

- Problèmes éventuels liés aux pays non signatairesdu P de C (ex: obtention de données supplémentaires d'une société d'un pays non signataire? obtention de méthodes de détection / identification de LMO importé d'un pays non signataire?) à clarifier.

- Définir "ecological function" (p. 6 l. 207).

- La question des méthodes de détection/identification des LMOs devrait être développée.

Définir "Party involved" (l. 187 et suivantes).

- le cas des essais expérimentaux n'est pas abordé

- la surveillance des points d'entrée et voies de transports lors d'introduction de LMO pour transformation et alimentation n'est pas développée

- les cas particuliers de LMO destinés à des usages industriels spécifiques, des utilisations pharmaceutiques ou de la phytorémédiation, ne sont pas discutés.

les plans de surveillance post-commercialisation.

The guidance does not explain that some importing countries do not regulate stacked events. In addition, the scope restricts this guidance to LMOs comprising LM events that have been assessed previously. There is a strong possibility that assessors will need to consider LMOs containing multiple events in which all of the individual events have not been considered before.

En el enfoque simplificado utilizado en Honduras, el Análisis de Riesgo se define como "el uso sistemático de la información disponible que permita la toma de decisiones, con base en los riesgos y beneficios evaluados, de la adopción de una tecnología en particular". En el Análisis de Riesgo deben ser considerados los aspectos de la bioseguridad, así como las consecuencias económicas y sociales de las nuevas tecnologías. Bajo este enfoque de consecuencias económicas, se debe también tomar en cuenta el riesgo de no adoptar una tecnología que sea valiosa para los productores y para el país.

Siguiendo este enfoque , la Evaluación de Riesgo (diferente al Análisis de Riego que es mas global e incluye la Evaluación de Riego) se define como "el uso sistemático de la información disponible sobre bioseguridad, con base en los riesgos identificados y los objetivos de protección elegidos, que permite inferir con certeza razonable acerca de la seguridad de la nueva tecnología al medio ambiente y a la salud humana y animal". En la Evaluación del Riesgo no se debe tomar en cuenta los aspectos sociales y económicos como consecuencia de la adopción de la nueva tecnología, pues éste utiliza el método científico como herramienta para responder preguntas estrictamente de carácter biológico cuantificable.

El éxito del Análisis de Riesgo depende de la correcta Evaluación de Riesgo, y que los riesgos identificados sean reales y no sólo percibidos. Una evaluación correcta es necesaria para poder concentrar los esfuerzos en las preguntas importantes para la bioseguridad ambiental. Es importante formular preguntas coherentes para obtener respuestas coherentes, siguiendo el método científico. De lo contrario, el analista ambiental o los órganos regulatorios tendrán que enfrentarse a los daños imprevistos, o tendrán que dedicar su atención, esfuerzo y recursos financieros limitados (especialmente en países pequeños en vías de desarrollo) a un conjunto de elementos que no presentan un riesgo real. Es así, que la formulación del problema es el paso más importante en cualquier proceso de Evaluación de Riesgo.

Línea 584: La Hoja de Ruta sugiere considerar "Aspectos Releacionados" (Related Issues) como aspectos socio- económicos y éticos, entre otros. Nuestro comité considera que estos aspectos son parte de la Gestión del Riesgo y la Toma de Decisiones.

Considerar que estos aspectos son parte de la Evaluación de Riesgo, puede resultar confuso para reguladores sin experiencia, ya que sale de los márgenes a tomar en cuenta, al realizar una evaluación en bioseguridad bajo el mètodo científico, que involucra mediciones biológicas cuantificables.

Glosario: Aunque consideramos que el glosario es un componente necesario en la Hoja de Ruta, es necesario que incluya todos los términos técnicos utlizados en el texto (ejemplo "near-isogenic lines" no incluído ) y considere hacer una revisión mas objetiva de la fuente utilizada para definir los términos, ya que las definiciones pueden variar, dependiendo de la fuente utilizada. La mayoria de terminos ya estan definidos en la literatura científica y no es necesario tratar de definirlos otra vez.

Por ejemplo, la definición de los términos "Análisis de Riesgo y "Evaluación de Riesgo" pueden tener diferentes interpretaciones (favor ver relacion en la pregunta 8)

Consideramos que para los reguladores de Honduras la presente Hoja de Ruta es demasiado compleja y difícil de conceptualizar, ya que la Evaluación del Riesgo debe tomarse como un componente integral del Análisis holístico del Riesgo ( favor ver comentarios a la pregunta 8 con definiciones de "Análisis de Riesgo" vs. "Evaluación de Riesgo"). Sería útil ver un flujograma que integre los pasos del proceso en forma vertical, relacionando en forma trasnversal, los aspectos inherentes a cada paso del proceso.

El Análisis de Riesgo conceptualizado en la Hoja de Ruta no parece incluir los beneficios que deben ser considerados al momento de tomar decisiones. Si las desciones solo consideraran el riesgo ineherente de la aplicación de la tecnología, nuestro grupo (CNBB) no hubiera podido aprobar su liberación.

Consideramos que es inconsistente medir un riesgo y tomar una desición basada en la medición (dificil) de este riesgo, sin realizar una Analisis de Riesgo-Beneficio. La Hoja de Ruta no considera este aspecto.

The effects on the ecosystem services should be considered more during the assessment.

It should also be considered to assess the effect of abiotic stress in line 293.

Posttranslational effects should also be considered in line 332, point e) regarding the characterization of the LMO.

Also for clarity would it be helpful to list steps referred to in line 251 (page 7) so as to improve overall structure?

(i) the use of examples that include microorganisms and animals;

(ii) an ecosystemic approach during the RA.

1.To the introduction please add this reference:

Guidance on the environmental risk assessment of genetically modified plants EFSA Journal 2010;8(11):1879 [111 pp.]. http://www.efsa.europa.eu/it/efsajournal/pub/1879.htm

2. to para. Step 5: Points to consider related to risk management strategies:monitoring:please add this reference:

Guidance on the Post-Market Environmental Monitoring (PMEM) of genetically modified plants -EFSA Journal 2011;9(8):2316 [40 pp.]. http://www.efsa.europa.eu/it/efsajournal/pub/2316.htm

3. To "The Choice of Comparators" please add this reference:

EFSA Guidance on selection of comparators for the risk assessment of genetically modified plants and derived food and feed EFSA Journal 2011; 9(5):2149 [20 pp.]. ttp://www.efsa.europa.eu/it/efsajournal/pub/2149.htm

Although it seems (k) in points to consider is similar to (n), they are not listed side by side. What rule is applied to ordering points to consider? As many points to consider exist, the way of ordering should be reexamined.

It is stated in the text that Step4 is a step to determine the level of the overall risk based on all information from Step1, Step2 and Step3. However, there is no arrow from Step1 to Step4. It is inconsistent with the text.

1) line63-64, line177-178: In order to consistent with the Annex III of the Protocol and the line 221-222 of the Roadmap, and to make it clear that the assessment is performed by comparative way, “in relation to the likely potential receiving environment” should be replaced to “in the context of the risks posed by the non-modified recipients or parental organisms in the likely potential receiving environment”.

2) line123: The sentence of “Where appropriate, in the risk assessment and be described in the risk assessment report.” may be incomplete sentence.

3) line 350: As the changes caused by the change of farm management practices, such as the change in the herbicide application followed with adoption of LMO, are not effects of the LMO, those effects should be out of the objective of assessment in the Roadmap. Therefore the words of “changes in farm management practices” should be deleted.

4) As the cumulative effects of LMO would not be the common understanding of the Parties,

a) line365:The words of “Cumulative effects with any other LMO present in the environment” should be deleted.

b) line 469:The words of “and cumulative” should be deleted.

c) line507-508:The words of “, including cumulative effects due to the presence of various LMOs in the receiving environment” should be deleted.

5) line543: The sentence of “Monitoring can be applied as a tool to detect unexpected and long-term adverse effects” should be deleted.

It is recognized that the General Surveillance (GS), which is shown in the first draft of Monitoring Document distributed on Aug.30, is based on this part.

GS will cover the monitoring of particular indicators or parameters that reflect important protection goals where no particular hypothesis for an adverse effect has been established. On the other hand, the monitoring in the Roadmap is quoted from Annex III, paragraph 8(f) of the Protocol, and is implemented where there is uncertainty regarding the level of risk (line147-150). Thus the monitoring in the Roadmap, which is implemented in case that the uncertainty exists after the risk assessment based on the risk hypothesis, is different from GS, which has no risk hypothesis.

Therefore this part is beyond the Annex III. It is not appropriate to contain this sentence in the Roadmap which complements Annex III.

(2) Part II A. Risk assessment of living modified plants with stacked genes or traits

1) As the cumulative effects of LMO would not be the common understanding of the Parties,

a) line725,739,756:The words of “and cumulative” should be deleted.

b) line765-766:The words of “and DNA fragments that could result in cumulative effects” should be deleted.

2) line741-743: As the changes caused by the change of farm management practices, such as the change in the herbicide application followed with adoption of LMO, are not the direct effects of the LMO, those effects should be out of the objective of assessment in the Roadmap. Therefore the sentence of “Also, indirect effects due to changed agricultural management procedures, combined with the use of the transgenic event LMOs, may occur.” should be deleted.

The roadmap may be easier for those with experience in risk assessment. Clarification of the information that is specified in some of the points considered necessary. We consider that regulators from developing countries must have a intensive trainning course provided by experienced evaluators international organization.

The risk assessment is a very relevant activity that must be shared with biotech companies. Regulator must check the "available literature" to evaluate the risks. In some cases the problem is that literature is scarse International Organizations must develop some protocolos that must be part of the acompanies research duties during the GMO development as happens with synthetic pesticides.

However, this is a problem that can only partly be solved by revising the text of the Roadmap. We think that the text, being a general guidance, will never be able to fully inform the uninitiated about all the intricacies of environmental risk assessment of the specific case that they are dealing with. For that reason, the Roadmap refers to background documents, so that the available experience of others can be taken into account. For the usefulness of the document it will be vital that a mechanism is devised for continuously assembling lists of references, and for updating and managing these lists. This is a task for the AHTEG, and it is of vital importance that the AHTEG delivers a thoroughly considered proposal for a process that takes this issue into account, especially taking into account the needs of uninitiated users of the Roadmap.

The Document is well written and thought out but difficult to apply because of the subjective nature of the assessments. I would suggest that no two people could come up with anything like a similar assessment for an application. An improvement in this direction would be a semi-quantitative approach as described by Morris, 2011. Transgenic Research DOI 10.1007/s11248-010-9480-8.

The 'approach' taken by this roadmap should be more clearly explained. The leap is too big from the framework/strategy that we are accustomed to.

1) Not accurate, because:

- The Guidance does not adequately reflect the experience worldwide with evaluating the impact of LMOs in the environment; in the current draft it gives the wrong impression that there is little experience with evaluating LMOs, and wrongly suggests that experience with the use of other GMOs, or indeed with the use of other organisms, cannot be used in a risk assessment;

- The Guidance does not adequately reflect the experience worldwide with the safe use of LMOs in the environment.

2) Not useful, because in its current form it raises more questions than it answers. See for example the questions raised in the submissions of the UK, for example.

In particular, the "points to consider," are a mixed bag of relevant general principals and others which are ill thought out and not much related to the text of the section in which they appear.

It might also be useful to put the flowchart at the beginning of the document, instead of at the end.

Second, although there is nothing wrong with the structure (i.e. headings and subsections) of the document, the text underneath is often bizarrely disorganized, bouncing from topic to topic without much rhyme or reason, frequently mixing important considerations with highly specific or trivial ones while making no distinctions between them.

As a rule, when providing guidance on how to perform an assessment it is better to provide a solid understanding of the foundational elements and then address the various complexities that may arise using case studies or examples. The Roadmap seems to do the opposite, bypassing the foundation in order to pile on potential considerations that may have limited practical applicability.

Line 280: “It may be important to define a causal link or pathway between a characteristic of the LMO and a possible adverse effect, which may be direct or indirect, immediate or delayed”.

Q: in which type of cases would identification of a causal pathway not be required?

Line 311: “its taxonomic relationships”;

Q: What is meant by “its taxonomic relationships”: is this what the calls CPB “taxonomic status” (and the EU Directives “taxonomy”) or does it refer to crossable species of maize or both?

Line 313: “its ecological function”:

Q: to what does this refer? the ecological function of maize as grown as a crop or the ecological function of the wild relatives?

Line 314: “whether it is a component of biological diversity that is important for the conservation and sustainable use of biological diversity”.

Q: What would be an example of a non modified crop plant that is a component of biological diversity that is important for the conservation and sustainable use of biological diversity?

Line 318: “ Characteristics related to the transformation method, including the characteristics of the vector such as its identity, source or origin and host range”

Q: Is this information also necessary if none of the vector DNA went into the final LMO?

Line 323: “with particular attention to characteristics in the recipient organism that could cause adverse effects”

Q: What does this mean? Does this mean that for maize, for example, there are none?

Line 326: “characteristics of the modified genetic elements”

Q: what does this mean? Example please

Line 412: "biogeographic".

Q: What is the definition of this term?

Line 466: "the behaviour of agricultural or relevant wild-type populations of unmodified animal or insect species, including interactions between predators and prey, disease transmission and interaction with humans or animal species; "

Q:What is meant by « behavior »? How would would determine what are relevant wild-type populations?

Line 507:

Q: what does the term 'broader' mean here, what is the definition of landscape considerations, how are cumulative effects related to these considerations, and why are these mentioned in particular?

Line 562: (d) 'Ability to identify, evaluate and confine adverse effects as well as to take appropriate response measures':

Q: does this refer to the ability, so the 'capability' of the risk assessor?

Line 1418: definition of cumulative effects.

Q: What is the difference between cumulative and additive (see definition of "combinatorial effects").