Special event on the risk assessment of new plant breeding techniques

Transcription

1 Special event on the risk assessment of new plant breeding techniques Summary Authors: Anita Greiter 1 Marion Dolezel 1 Michael Eckerstorfer 1 Alexandra Ribarits 2 Walter Stepanek 2 Markus Wögerbauer 2 Helmut Gaugitsch 1 1 Environment Agency Austria 2 Austrian Agency for Health & Food Safety

2 The event was organised on behalf of the Austrian Federal Ministry of Health and Women s Affairs 1

3 Content Content Introduction... 2 Key note presentations... 3 Opportunities of New Plant Breeding Techniques (Jan Schaart)... 3 EFSA`s activities in relation to risk assessment of new plant breeding techniques (Elisabeth Waigmann). 4 Food & Feed safety assessment approaches vs. current practice for GMOs: innovations, convergences, and divergences (Gijs Kleter)... 5 Risks for the environment by new plant breeding techniques and how to assess them (Odd-Gunnar Wikmark)... 5 Discussion on the topics of the key note presentations... 7 Differences between conventional breeding and new plant breeding techniques... 7 Implications for the risk assessment... 8 Off-target effects & DNA changes... 9 The use of comparators & baselines in risk assessment... 9 The role of omics technologies for NPBT Risk assessment experience Discussion on the way forward Experiences with NPBTs in different countries Challenges for the risk assessment of NPBT Next steps Closing remarks

4 Introduction Introduction The use of new plant breeding techniques (NPBTs) is promoted as an alternative to currently used techniques of genetic engineering as well as to complement conventional breeding. Past events on NPBTs mainly focussed on regulatory issues. Therefore, the Austrian Federal Ministry of Health and Women s Affairs decided to host a respective event bringing risk assessment issues in the focus. On 17 th October 2017 the special event on the risk assessment of new plant breeding techniques took place in Vienna. The event was organised by the Environment Agency Austria, supported by the Austrian Agency for Health & Food Safety. The goal of the event was to discuss risk assessment issues of NPBTs with experts from different EU Member States, Norway and Switzerland and to facilitate the scientific and technical exchange. 96 people from 21 countries registered for the event. Four keynote presentations by experts gave an overview on NPBTs relevant for the near future, the work done on this aspect so far by EFSA and risk assessment aspects for both food & feed safety assessment and the environmental risk assessment. During the event keynote speakers and participants were invited to discuss and exchange views. The event concluded with a panel discussion focusing on risk assessment challenges and the way forward. 2

5 Key note presentations Key note presentations Opportunities of New Plant Breeding Techniques (Jan Schaart) This presentation provided an overview of selected applications of NPBTs and the differences to conventional breeding. Applications of cisgenesis and intragenesis, sequence-specific nuclease techniques (e.g. zinc-finger nucleases, TALEN and CRISPR/Cas9), oligo-directed mutagenesis, transgrafting, reverse breeding and induced early flowering were discussed. NPBTs are a powerful tool for plant breeding and crop improvement, in particular in polyploid species and species with long generation times (e.g. trees). A single step modification of multiple genes or alleles as well as knocking out of several genes is facilitated by the use of NPBTs. Specific genomic sequences can be specifically targeted and replaced, and breeding cycles can be accelerated. Differently from previously applied techniques of genetic modification the production of proteins can be efficiently knocked out, even in polyploid species with multiple allelic versions of a gene. However, challenges of these methods include the delivery of the genome edited constructs into the cell, and the removal of the genome edited construct by segregation and backcrossing. In addition, off-target effects are possible and are influenced by the specific design of the application. Such off-target effects are, however, not considered an issue for plant breeders, as they also occur during traditional mutagenesis by chemicals or irradiation. During the selection process in subsequent breeding steps unwanted mutations are eliminated. Similarly for NPBTs, such breeding steps may be necessary to eliminate plants with unwanted characteristics. In the case of cisgenesis and intragenesis an extra copy of a gene from the gene pool of a sexually compatible plant is added, employing Agrobacterium-mediated transformation of plant cells. In this case, the insertion occurs at random locations in the plant genome. Usually additional short DNA sequences are also introduced, either as T-DNA right and left border sequences (< 20 bp) or due to rearrangements at the insertion site. Methods are already available to detect and identify cisgenic/intragenic plants. As an example, cisgenesis was successfully applied to achieve scab resistance in apple trees by the introduction of the hcrvf1 and hcrvf2 genes of Malus floribunda into the apple variety Gala. The use of special transformation vectors allows the stacking of different genes with different modes of action which results in a stable resistance. Insertion of these Vf genes from resistant wild relatives by conventional breeding would take 50 years. The necessary development time for a disease-resistant tree can therefore be reduced with cisgenesis approaches to only a few years. Cisgenic modification of a potato line with three resistance genes against Phytophthora was also described as another successful example of this technique. Another technique applicable for many crops is the use of sequence-specific nucleases (SSN including CRISPR/Cas 9). The advantage of this technique is that multiple alleles of a target gene can be simultaneously modified. Examples are: potato (starch, carotenoid content), 3

6 Key note presentations tomato, Camelina/Crambe (6x; oil content), bread wheat (removal of gluten), Chrysanthemum (haploid induction), Nicotiana (model organism), rice (susceptibility to bacterial blight). Several examples using other techniques were mentioned. Oligo-directed mutagenesis (ODM) has been successfully used to target the AHAS/ALS enzyme in order to generate tolerance to sulfonylurea herbicides. RNA-directed DNA Methylation is used predominantly for gene silencing. Transgrafting makes use of a genetically modified rootstock which can function as source for small RNAs which may be transported from root to scion mediating systemic silencing of genes via RNAi. Induced early flowering is relevant for fruit trees which usually have long generation times (5-10 years). Fire blight resistance was incorporated in apple varieties within a short time period. Questions and comments regarding the presentation addressed the efficacy of the removal of off-target mutations via segregation as well as the reliability of techniques applied to detect such off-target effects. Off-target effects can be predicted in silico by sequence alignment studies. Unintended modifications are theoretically detectable by whole genome sequencing. Sequences are identified with similarity to the target sequence in the genome and checked for mutations. It was emphasized that due to the use of tissue culture the background variations (somaclonal variation) in the genome are considerable. Therefore the identified mutations cannot be unequivocally assigned to the applied genome editing technique. EFSA`s activities in relation to risk assessment of new plant breeding techniques (Elisabeth Waigmann) The role and remit of EFSA and EFSA`s previous activities concerning the risk assessment of NPBTs was presented. The focus was on two EFSA opinions published on the risk assessment of plants produced with selected NPBTs based on a request by the European Commission. So far, opinions on cisgenesis and intragenesis as well as on zinc finger nucleases 3 and other site directed-nucleases with similar function have been published. The objective of the opinions was to evaluate whether there is a need for new guidance on the risk assessment or an update of existing guidance concerning specific NPBTs. Current EFSA guidelines on the risk assessment of GMOs were considered applicable for the respective NPBTs. Another objective was to evaluate the risks for human and animal health and the environment of NPBTs compared to either the application of conventional breeding techniques or classical GM techniques. In this context it was mentioned that somaclonal variations and mutations occur in all three types of breeding techniques. Questions by participants addressed the definition of GMO and the changed mandate of the European Commission to EFSA. The underlying reasons for the narrowing of the mandate of the European Commission to EFSA to provide guidance on the safety assessment on new breeding techniques from originally 8 to 3 techniques (zinc-finger nucleases, cis- and intragenesis) were explained. It was clarified that those three techniques were addressed by EFSA first. At that point the European Commission had put the mandate on hold. 4

7 Key note presentations Food & Feed safety assessment approaches vs. current practice for GMOs: innovations, convergences, and divergences (Gijs Kleter) The presentation covered approaches for the food & feed safety assessment of products derived from NPBTs as recommended in recent reports by various institutions, in particular the reports of the Scientific Advice Mechanism (SAM), the European Academies Science Advisory Council, the US National Academy of Sciences and the Australian Academy of Science. The following aspects were addressed: A wide array of different products can be produced with NPBTs. Therefore, a case-by case approach is needed for the safety assessment and no general safety statements addressing all NPBT-applications are thus justified. When classified into a group of breeding techniques, this classification does not automatically indicate the safety or the lack of safety of a particular product. The currently used comparative approach using a conventional variety as the baseline for the safety assessment has been acknowledged in the scientific reports mentioned above. Certain risk mitigation measures can already be built in when designing a certain approach (e.g. in the case of gene drives). These should, however, not replace the safety assessment. The issue that all types of breeding techniques cause unintended effects was raised. Small mutations or changes at the genetic or epigenetic level might have considerable and potentially adverse impacts, but vice versa large size genetic changes do not automatically lead to adverse effects. However, due to the large background variability in the plant genome changes due to genome editing might be small. The application of NPBTs can shorten the development time for new varieties and reduce breeding cycles. Therefore less time is available to discover unintended effects. Emerging approaches from other fields were considered relevant for the risk assessment of NPBT-applications. For example the use of omics-technologies for the identification of unintended changes and possibly off target effects was mentioned. Also approaches from veterinary epidemiology to identify health effects were addressed. Question and comments by participants referred to omics technologies and their usefulness in the risk assessment of new plant breeding techniques. It was noted that omics technologies are useful for the characterisation of GMOs but may not be useful for the risk assessment. Risks for the environment by new plant breeding techniques and how to assess them (Odd-Gunnar Wikmark) This presentation covered possible risks, the need for risk assessment and associated challenges of NPBTs. Currently perceived risks related to NPBT include off-target effects and the predictability of the intended outcome, gene flow, the novel mode of action, accessibility and speed of use and uptake as well as multiplexing. It was highlighted that a different context in which a specific technique is used may imply different risks (e.g. gene drives versus crop breeding). A lot of 5

8 Key note presentations products and traits may be generated, e.g. by multiplexing, and the techniques are new and different from classical mutagenesis. Since there have been only few NPBT products yet, there is limited experience with risk assessment and currently there are no environmental risk assessment data. Key elements and challenges to identify risks connected to NPBT were presented. Necessary elements for the risk assessment include e.g. a thorough molecular description of the modification and the identification of unintended effects. A comparative assessment is certainly needed. The application of omics approaches in the risk assessment was discussed. In this context the importance of metabolic pathway analysis was highlighted, which can reveal potential impacts on related metabolic pathways and functions. In addition, some aspects that need further research were highlighted. Questions and comments from the audience referred to whether novel challenges would arise for the risk assessment, as compared to GMO risk assessment and the role of omics techniques in this context. Difficulties with the interpretation of data from omics analyses were emphasized. Discussions related also to the relevance of the phenotype and the genotype for the risk assessment. It was emphasized that the genotype may be relevant to identify risks, e.g. in case of point mutations which may act as important indicators, but also the phenotype. It was highlighted that conventionally bred plants have a large natural genomic variation. Therefore, in order to detect small mutations induced by NPBTs, whole plant genomes need to be sequenced. In this context it was emphasized that genomic sequences of reference varieties may not be available for all crop plants. Related questions referred to the possible differentiation between natural mutations and induced mutation by NPBT. 6

9 Discussion of key note presentations Discussion on the topics of the key note presentations The participants of the events discussed a range of topics, among them regulatory and safety issues of NPBTs, the relevance of risk assessment, the differences between various breeding methods and their suitability as a baseline for comparison as well as technical aspects. Also the application of NPBT-derived products by farmers was discussed. Although in general, farmers may not support the use of GMOs, certain applications derived from novel genome editing techniques like hornless cows are likely to be welcomed by end-users. It was also mentioned that currently society makes high demands on the standards for food safety, sustainability, and consumer rights for products of conventional breeding. The requirements of the GMO regulatory framework can only partly address some of these demands. Differences between conventional breeding and new plant breeding techniques A major part of the discussions referred to the differences and similarities between conventional plant breeding and NPBTs. The relevance of the process to generate a plant variety and of the characteristics of the final product (the resulting plant variety) for the risk assessment was discussed. It was emphasized that there are fundamental differences between classical breeding and genome editing in plant breeding as novel modes of action are introduced into the breeding process, e.g. derived from bacterial systems. The CRISPR/Cas9 methodology used in plant breeding is based on mechanisms of the bacterial immune system not adapted to eukaryotic/plant cells. The necessary elements transferred to plant cells are working in a completely different metabolic context. It was also mentioned that conventional breeding is relying on naturally occurring alleles whereas products based on NPBTs have new alleles. Currently there is no sufficient experience available which would allow invoking a safe history of use for food and feed applications based on NPBTs. Therefore, the risk assessment approach would have to take into account the specifics of the process used to generate the product which also has to be assessed. Also socio-economic aspects of breeding were identified as important differences between conventional breeding and new breeding techniques. While conventional breeding is usually a longer process, the use of NPBTs aims at short breeding processes and fast market entry. This is partly due to the long adaptation and selection periods of the conventionally bred plants in the environment. It was stated that conventional breeding also uses laboratory techniques. In addition, some kind of selection is always applied in any plant breeding process. Discussions addressed also the difference of product- versus process-based risk assessment of plants derived from different breeding technologies. Considering plants derived from conventional plant breeding, only the final plant variety (the product) is usually evaluated, while for new plant breeding techniques also the breeding process is taken into account, if 7

10 Discussion of key note presentations these are regulated. It was put forward that if the final product with a specific trait is considered safe in the safety assessment, no differences should become evident between conventionally-bred plants and plants derived from NPBTs. In this context, the issue was raised that it is difficult to define what is similar. If the same trait has been produced with different methods some aspects may still be quite different, e.g. at the DNA level. On the other hand it was noted that the new trait of the final product can also be a major source of risk. Another discussion point was the question what difference between a product derived from conventional breeding and from NPBTs is of relevance for the safety of the product. Implications for the risk assessment The currently used framework for the risk assessment of GM plants was considered applicable for assessing the risks of plants derived from NPBTs. In this context, the specific technology applied was considered important for the risk assessment and can be accounted for in the problem formulation where the specific risk assessment questions are formulated. Thereby the technology used also influences and informs the risk assessment approach. The need to apply new innovative methods in risk assessment was highlighted which need to keep pace with product innovations. As an example, new conventional varieties with changes in compositions (e.g. cumarin in celery or glycoalcaloids in potato) were mentioned which may represent food safety issues. However, it has to be considered that not all unintended changes do necessarily result in environmental risks or food safety risks. The opinion was raised that CRISPR/Cas9 is the most important technology of NPBTs, since it is the most efficient way to introduce multiple changes to the plant genome, allowing a more targeted approach for gene modifications compared to conventional breeding and standard transgenic approaches using induced random mutations. This should also be reflected in less information requirements for the risk assessment. It was emphasized that for NPBTs a risk assessment should be performed. In this context, the importance of the precautionary principle in the risk assessment was discussed, e.g. in case of large remaining uncertainties regarding a specific risk. This implies however, that not all uncertainties can be eliminated as this principle can be invoked only when the associated uncertainties are substantial. This may be the case for NPBTs due to knowledge gaps when applying NPBTs and the lack of a history of safe use of these novel techniques. The discrepancy between product- and process-based risk assessment approaches was emphasized. Although the product is usually in the focus of the risk assessment, also the processes to generate the product need to be taken into account. It was mentioned that both approaches can benefit from each other. There was a strong consensus that the risk assessment has to be science-based and that a case-by-case approach is necessary. The currently available methods for risk assessment of GMOs are considered an adequate basis also for NPBTs but they should be refined further. 8

11 Off-target effects & DNA changes Discussion of key note presentations The point was raised that the changes in the DNA sequences are not necessarily related to the nature or the severity of effects. Therefore, not only large DNA changes, but also small changes in the DNA sequence may entail certain risks. As an example it was highlighted that even point mutations can change whole chemical pathways, thereby having large effects on the cellular metabolism. Several steps in the whole breeding process introduce variation into the plant genome. NPBTs are used at the start of the whole breeding process. Therefore, any introduced changes represent only a small part of changes which are due to the breeding process. However, these kinds of mutations may also appear naturally in any plant and may also be present in plants produced by conventional breeding. It was made clear that data are needed to check for off-target effects which may occur by the use of NPBTs. The severity of off-target effects depends on the experimental setup and the plant tissue (e.g. the duration of the presence of a site-specific nuclease in plant cells) and may be predictable at least to some extent. A case-by-case approach is therefore necessary to evaluate such off-target effects. Specific techniques must still be developed in order to detect and assess off-target effects. A challenge for the risk assessment is the fact that certain genetic changes comparable to off-target effects caused by NPBTs may be found in plants derived from conventional breeding (e.g. using induced mutations). The use of comparators & baselines in risk assessment It was considered important to select an appropriate baseline for comparison of products derived from NPBTs in order to be able to carry out a meaningful risk assessments of these products. Although it was advocated that classical breeding can be used for comparison purposes, it was also noted that in some cases the finding of a specific and appropriate comparator might be challenging. In this context it was also stated that baselines have changed during the last years, e.g. due to improved reference varieties from conventional breeding, which also has to be accounted for. There is a broad range of reference varieties available which can be used for comparison purposes. The question was raised whether there was mutual understanding that products of conventional breeding are safe. For plants derived from classical breeding it is assumed that these plant varieties are safe and these are not risk assessed. For plants derived from classical plant breeding the history of safe use is assumed. This safety of conventional plants would possibly have to be challenged. Hence, the choice of a safe comparator may therefore represent a challenge for the environmental risk assessment, as conventional varieties may have a significant environmental impact (e.g. due to ploughing, use of pesticides etc.). In this context, it was emphasized that there was no absolute status of safety of a product. It cannot be concluded that all conventional products are equally safe. Nevertheless, the products of conventional breeding are used as the baseline for comparison with GMOs or products derived from novel plant breeding techniques. All classical breeding techniques have to be taken into consideration for comparison purposes. However, on a case-by-case basis specific comparators have to be chosen. 9

12 Discussion of key note presentations The current guidance provided by EFSA for GMOs was considered a useful starting point as it recommends using a plant genetically as close as possible as conventional counterpart and at the same time takes into account the natural variability by the use of a range of reference varieties as a baseline for GM plants. From EFSA`s perspective conventional breeding is used for establishing a baseline for the comparative assessment. In this context, the term as safe as is used when GMOs are risk assessed with conventional (non-gm) plants, thereby implying no absolute status of safety but referring to the relative safety of the novel GM plant compared to its non-gm comparator. However, observed changes compared to the baseline may still be safe. It was mentioned that some of the methods used for new plant breeding techniques act as mutagens (e.g. CRISPR/Cas) although differences to conventional mutagenic approaches are evident. The use of plants derived by traditional mutagenesis as comparators was however questioned, due to their lack of documented safety. The role of omics technologies for NPBT The use of omics technologies was considered important for the risk assessment of plants derived by NPBTs. However, there is still a lack of knowledge regarding the variation in crop plants` genomes and the implications of observed differences between genomes for the risk assessment. Omics technologies produce many data but there is a lack of knowledge regarding how to handle the huge amount of information and how to interpret it correctly. The need for a systematic approach to allow the interpretation of data produced by omics technologies was emphasised. Also standardisation of omics would be paramount before it can be broadly applied for risk assessment purposes. One-Class modelling in transcriptomics (Van Dijk et al. (2014)) as introduced in one of the talks was mentioned as a way forward to identify biologically relevant genomic changes was discussed. The usefulness of omics techniques was also acknowledged for environmental analyses (e.g. for the characterisation of soil communities). It was also suggested that these technologies can be refined and used for the detection of unintended effects. Risk assessment experience Experience with the risk assessment of plants derived from NPBTs is largely limited. Although a few new plant breeding techniques are already applied in plant breeding (particularly in the Netherlands), no risk assessment data are so far available. In particular, the need to assess environmental effects of NPBTs was addressed. However, as there is currently no cultivation of plants derived from NPBTs in the environment no such assessments are available. 10

13 Panel discussion Discussion on the way forward A panel discussion took place with representatives of different EU member states, Switzerland and the OECD. Also the audience was invited to share their views on the topics. The discussion was guided by the following leading questions: How far are NPBT actively discussed in your country/ your organisation? Which aspects are in the focus of these discussions? Are there respective activities/projects? What issues are addressed? What are the most important challenges with respect to (the risk assessment of) NPBT? How may knowledge gaps relevant for the risk assessment be best addressed? What next steps should be taken - on international, EU or national level? Experiences with NPBTs in different countries The experts from the different countries/organisation elaborated on their experiences and the current national discussions regarding NPBTs. Only in the Netherlands breeders are already actively applying NPBTs. NPBTs are of relevance for all participants of the panel discussion. Breeding companies are urging the competent authorities to clarify the legal status of respective plants. As these technologies are rapidly developing international harmonisation of risk assessment procedures is necessary. Also the need to further exchange knowledge and experiences with NPBTs was emphasized. It should be kept in mind that the respective technologies are not only relevant for plant breeding but also for other uses. The Netherlands have put forward a proposal to exclude more or less all plants produced by NPBTs from the GMO legislative framework. According to this proposal a risk assessment for such plants would not be necessary, if these plants are considered to be as safe as conventionally bred plants. Such exemptions might be considered e.g. if no DNA from the genome editing process is detectable in the final product. This could be proven e.g. by whole genome sequencing. The aim should be to focus on risky applications of NPBTs. It was noted that breeders have only limited interest in carrying out risk assessments for NPBTs and therefore regulating those plants under GMO regimes could dramatically affect the development and commercial use of NPBTs. Several countries are actively discussing the development, use, risks and benefits of NPBTs and have commissioned studies on different topics. Many of the countries are awaiting the decision of the European High Court regarding the regulation of these plants. In addition, clarifications are needed for the contained use of such plants. Switzerland has a general moratorium on GMO cultivation that includes all NPBT-applications if these are considered GMOs according to the existing regulations. The need to regulate plants derived from NPBTs was emphasized by some experts while others favoured no regulation. 11

14 Panel discussion At the OECD level several workshops and working groups have addressed NPBTs, also in relation to risk assessment. These concluded that the existing knowledge with risk assessment approaches should suffice to tackle the risk assessment of these novel techniques. Challenges for the risk assessment of NPBT Some of the experts identified specific challenges for the risk assessment of NPBTs, while others did not see particular or novel challenges as these techniques were regarded as similar to conventional breeding. Among the challenges identified were risks to biodiversity and sustainable use, consideration of the receiving environment, as well as market access and labelling. Next steps There is currently no mutual understanding regarding the necessity to regulate NPBTs, neither on national nor at EU level. The need for a common approach and consensus on how to proceed regarding the regulation of NPBT at least at EU level was highlighted, as it has implications for trade, also on a global level. Such a consensus would be urgently necessary, particularly because the genome editing techniques used for plant breeding are rapidly evolving. Science is therefore needed to provide evidence-based qualitative and quantitative data. In cooperation with several stakeholders the acceptable levels of risk of novel technologies applied in plant breeding have to be determined. This implies also discussions which breeding goals should be met by any type of plant breeding. This must ensure that also environmental issues are incorporated into these breeding goals. Criteria have to be set to define which differences between NPBTs and conventional breeding are relevant to indicate specific risks. Also cost-benefit relationships for risk assessment will have to be addressed. Risk assessment for plants derived from certain NPBTs is deemed necessary. However, the triggers when a risk assessment has to be carried out are still unclear but have to be clearly defined. While some stakeholders support initiatives to discuss the necessary regulation of NPBTs others favour the exemption of these novel techniques from regulation in general. It was clearly emphasized that more discussions are needed as well as more exchange for mutual understanding of positions. It was mentioned that any decisions on the regulation of NPBTs would affect breeders in their uptake of these new techniques, mostly due to the costs implied with the regulatory requirements. It will therefore be a challenge for the regulators to balance societal and agricultural benefits with demands for food production as well as environmental and consumer safety. 12

15 Closing remarks Closing remarks In the closing remarks the discussions were positively highlighted. The importance of discussing emerging topics like NPBTs in a broad context and with a variety of experts and other stakeholders was emphasized. The event was seen as complementary to the high-level conference organised by the European Commission on 28 th September 2017 on modern biotechnology in agriculture. Both events will hopefully stimulate many other events and initiatives on this topic to follow. Some of the aspects discussed were specifically highlighted: The term new plant breeding techniques covers a wide range of methods and resulting products. In order to avoid an assumption-based approach, science-based risk assessment is crucial for NPBTs, which was also mentioned at the high-level conference in Brussels. An integrated risk assessment approach is required, covering both health assessment and environmental assessment. Currently available methods for the risk assessment of GMOs are an adequate basis also for the assessment of products produced by NPBTs. However, these methods should be refined and modified, where appropriate, according to the needs and progress in the field. A case-by-case risk assessment is necessary for NPBTs. The discussion should not focus on whether the risk assessment of NPBTs should be process-based or product-based. The product should be assessed, but in the assessment the characteristics of the process should be taken into account. However, criteria have to be set, for which cases a risk assessment is indicated. The development of risk assessment methods and product development is a tandem and should go hand-in-hand. The importance of omics approaches for the characterisation of NPBT-derived products and possibly also for risk assessment was highlighted. In order to assess risks of NPBTs the focus should be on evidence-based reasoning, robust methods and solid scientific data. The baseline for comparison was discussed, whether it is conventional breeding or traditional breeding A broader impact assessment would inform decision-making, but it cannot substitute decision-making. Decision making will include other aspects like public values. 13

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