Plants Developed by New Genetic Modification Techniques—Comparison of Existing Regulatory Frameworks in the EU and Non-EU Countries

The development of new genetic modification techniques (nGMs), also referred to as “new (breeding) techniques” in other sources, has raised worldwide discussions regarding their regulation. Different existing regulatory frameworks for genetically modified organisms (GMO) cover nGMs to varying degrees. Coverage of nGMs depends mostly on the regulatory trigger. In general two different trigger systems can be distinguished, taking into account either the process applied during development or the characteristics of the resulting product. A key question is whether regulatory frameworks either based on process- or product-oriented triggers are more advantageous for the regulation of nGM applications. We analyzed regulatory frameworks for GMO from different countries covering both trigger systems with a focus on their applicability to plants developed by various nGMs. The study is based on a literature analysis and qualitative interviews with regulatory experts and risk assessors of GMO in the respective countries. The applied principles of risk assessment are very similar in all investigated countries independent of the applied trigger for regulation. Even though the regulatory trigger is either process- or product-oriented, both triggers systems show features of the respective other in practice. In addition our analysis shows that both trigger systems have a number of generic advantages and disadvantages, but neither system can be regarded as superior at a general level. More decisive for the regulation of organisms or products, especially nGM applications, are the variable criteria and exceptions used to implement the triggers in the different regulatory frameworks. There are discussions and consultations in some countries about whether changes in legislation are necessary to establish a desired level of regulation of nGMs. We identified five strategies for countries that desire to regulate nGM applications for biosafety–ranging from applying existing biosafety frameworks without further amendments to establishing new stand-alone legislation. Due to varying degrees of nGM regulation, international harmonization will supposedly not be achieved in the near future. In the context of international trade, transparency of the regulatory status of individual nGM products is a crucial issue. We therefore propose to introduce an international public registry listing all biotechnology products commercially used in agriculture

An EU Perspective on Biosafety Considerations for Plants Developed by Genome Editing and Other New Genetic Modification Techniques (nGMs)

The question whether new genetic modification techniques (nGM) in plant development might result in non-negligible negative effects for the environment and/or health is significant for the discussion concerning their regulation. However, current knowledge to address this issue is limited for most nGMs, particularly for recently developed nGMs, like genome editing, and their newly emerging variations, e.g., base editing. This leads to uncertainties regarding the risk/safety-status of plants which are developed with a broad range of different nGMs, especially genome editing, and other nGMs such as cisgenesis, transgrafting, haploid induction or reverse breeding. A literature survey was conducted to identify plants developed by nGMs which are relevant for future agricultural use. Such nGM plants were analyzed for hazards associated either (i) with their developed traits and their use or (ii) with unintended changes resulting from the nGMs or other methods applied during breeding. Several traits are likely to become particularly relevant in the future for nGM plants, namely herbicide resistance (HR), resistance to different plant pathogens as well as modified composition, morphology, fitness (e.g., increased resistance to cold/frost, drought, or salinity) or modified reproductive characteristics. Some traits such as resistance to certain herbicides are already known from existing GM crops and their previous assessments identified issues of concern and/or risks, such as the development of herbicide resistant weeds. Other traits in nGM plants are novel; meaning they are not present in agricultural plants currently cultivated with a history of safe use, and their underlying physiological mechanisms are not yet sufficiently elucidated. Characteristics of some genome editing applications, e.g., the small extent of genomic sequence change and their higher targeting efficiency, i.e., precision, cannot be considered an indication of safety per se, especially in relation to novel traits created by such modifications. All nGMs considered here can result in unintended changes of different types and frequencies. However, the rapid development of nGM plants can compromise the detection and elimination of unintended effects. Thus, a case-specific premarket risk assessment should be conducted for nGM plants, including an appropriate molecular characterization to identify unintended changes and/or confirm the absence of unwanted transgenic sequences

Corrigendum: An EU Perspective on Biosafety Considerations for Plants Developed by Genome Editing and Other New Genetic Modification Techniques (nGMs)

The question whether new genetic modification techniques (nGM) in plant development might result in non-negligible negative effects for the environment and/or health is significant for the discussion concerning their regulation. However, current knowledge to address this issue is limited for most nGMs, particularly for recently developed nGMs, like genome editing, and their newly emerging variations, e.g., base editing. This leads to uncertainties regarding the risk/safety-status of plants which are developed with a broad range of different nGMs, especially genome editing, and other nGMs such as cisgenesis, transgrafting, haploid induction or reverse breeding. A literature survey was conducted to identify plants developed by nGMs which are relevant for future agricultural use. Such nGM plants were analyzed for hazards associated either (i) with their developed traits and their use or (ii) with unintended changes resulting from the nGMs or other methods applied during breeding. Several traits are likely to become particularly relevant in the future for nGM plants, namely herbicide resistance (HR), resistance to different plant pathogens as well as modified composition, morphology, fitness (e.g., increased resistance to cold/frost, drought, or salinity) or modified reproductive characteristics. Some traits such as resistance to certain herbicides are already known from existing GM crops and their previous assessments identified issues of concern and/or risks, such as the development of herbicide resistant weeds. Other traits in nGM plants are novel; meaning they are not present in agricultural plants currently cultivated with a history of safe use, and their underlying physiological mechanisms are not yet sufficiently elucidated. Characteristics of some genome editing applications, e.g., the small extent of genomic sequence change and their higher targeting efficiency, i.e., precision, cannot be considered an indication of safety per se, especially in relation to novel traits created by such modifications. All nGMs considered here can result in unintended changes of different types and frequencies. However, the rapid development of nGM plants can compromise the detection and elimination of unintended effects. Thus, a case-specific premarket risk assessment should be conducted for nGM plants, including an appropriate molecular characterization to identify unintended changes and/or confirm the absence of unwanted transgenic sequences

Spatial analysis of the occurrence of protected butterflies in six European biogeographic regions as a tool for the environmental risk assessment of Bt maize

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Limits of Concern: suggestions for the operationalisation of a concept to determine the relevance of adverse effects in the ERA of GMOs

Abstract Background The European Food Safety Authority proposed a concept for the environmental risk assessment of genetically modified plants in the EU that is based on the definition of thresholds for the acceptability of potential adverse effects on the environment. This concept, called Limits of Concern (LoC), needs to be further refined to be implemented in the environmental risk assessment of genetically modified organisms. Methods We analyse and discuss how LoC can be defined for the environmental risk assessment for three different types of genetically modified plants. We outline protection goals relevant to the genetically modified plants in question and discuss existing concepts and suggestions for acceptability thresholds from the environmental risk assessment of different regulatory areas. We make specific recommendations for the setting and use of LoC for each type of genetically modified plant. Results The LoC concept can be suitably applied for the environmental risk assessment of genetically modified organisms, if the different protection goals in agro-environments are specifically considered. Not only biodiversity protection goals but also agricultural protection goals need to be addressed. The different ecosystem services provided by weeds inside and outside agricultural fields have to be considered for genetically modified herbicide-tolerant crops. Exposure-based LoCs are suggested based on knowledge about dose–effect relationships between maize pollen and non-target Lepidoptera for insect-resistant maize. Due to the long-term nature of biological processes such as spread and establishment, LoCs for genetically modified oilseed rape should be defined for the presence of the genetically modified plant or its genetically modified traits in relevant protection goals. Conclusions When setting LoCs, the focus should be on protection goals which are possibly affected. Potential overlaps of the LoC concept with the ecosystem service concept have to be clarified to harmonise protection levels in the agro-environment for different stressors. If additional impacts on agro-biodiversity resulting from the cultivation of genetically modified plants are to be avoided, then high protection levels and low thresholds for acceptable effects (i.e. LoC) should be set

EU Perspective - Sampling for Testing of GM-Impurities

The distribution of a contaminant in a bulk mass greatly influences the effectiveness of sampling procedures. Most currently used sampling guidelines for genetically modified organisms (GMO) testing have stringent distribution requirements. Specifically, all these protocols are based upon the assumption that GM material, if present, is randomly distributed. Yet, assuming randomness is risky because the applied sampling plan may not provide an accurate estimate of the content of the contaminant. Despite the general consensus that an evaluation of the possibility of non-random distribution of GM materials within lots is a pre-requisite for the definition of effective sampling protocols, no experimental data on the distribution of GMOs in kernel lots are available anywhere in the world. Additionally, to date there is no distribution-free statistical model to estimate sampling errors, thus making the theoretical definition of optimal sampling technique impossible when randomness cannot be assumed. Here we presents preliminary results of the KeLDA project, which is the first study investigating the distribution of GM materials in large soybean lots imported within the European Union. The extensive variability of GM content, observable both within and among soybean lots, indicates that heterogeneity issues cannot be overlooked when defining sampling strategies for large lots of particulate materials and that randomness cannot be assumed a priori. A new statistical model free from any distribution assumptions, developed in order to estimate the sampling error associated with different sampling protocols together with the risk of false-negative results, is also presented. The new model, which is applicable to any consignment of particulate material with respect to any kind of contamination, presents two novelties: first, freedom from any distribution assumption; second, the possibility of estimating the magnitude of the sampling error associated with different sampling protocols as a function of specific distributional properties.JRC.I.6-Biotechnology and GMO

Biosafety of Genome Editing Applications in Plant Breeding: Considerations for a Focused Case-Specific Risk Assessment in the EU

An intensely debated question is whether or how a mandatory environmental risk assessment (ERA) should be conducted for plants obtained through novel genomic techniques, including genome editing (GE). Some countries have already exempted certain types of GE applications from their regulations addressing genetically modified organisms (GMOs). In the European Union, the European Court of Justice confirmed in 2018 that plants developed by novel genomic techniques for directed mutagenesis are regulated as GMOs. Thus, they have to undergo an ERA prior to deliberate release or being placed on the market. Recently, the European Food Safety Authority (EFSA) published two opinions on the relevance of the current EU ERA framework for GM plants obtained through novel genomic techniques (NGTs). Regarding GE plants, the opinions confirmed that the existing ERA framework is suitable in general and that the current ERA requirements need to be applied in a case specific manner. Since EFSA did not provide further guidance, this review addresses a couple of issues relevant for the case-specific assessment of GE plants. We discuss the suitability of general denominators of risk/safety and address characteristics of GE plants which require particular assessment approaches. We suggest integrating the following two sets of considerations into the ERA: considerations related to the traits developed by GE and considerations addressing the assessment of method-related unintended effects, e.g., due to off-target modifications. In conclusion, we recommend that further specific guidance for the ERA and monitoring should be developed to facilitate a focused assessment approach for GE plants

Recommendations for the Assessment of Potential Environmental Effects of Genome-Editing Applications in Plants in the EU

The current initiative of the European Commission (EC) concerning plants produced using certain new genomic techniques, in particular, targeted mutagenesis and cisgenesis, underlines that a high level of protection for human and animal health and the environment needs to be maintained when using such applications. The current EU biosafety regulation framework ensures a high level of protection with a mandatory environmental risk assessment (ERA) of genetically modified (GM) products prior to the authorization of individual GMOs for environmental release or marketing. However, the guidance available from the European Food Safety Authority (EFSA) for conducting such an ERA is not specific enough regarding the techniques under discussion and needs to be further developed to support the policy goals towards ERA, i.e., a case-by-case assessment approach proportionate to the respective risks, currently put forward by the EC. This review identifies important elements for the case-by-case approach for the ERA that need to be taken into account in the framework for a risk-oriented regulatory approach. We also discuss that the comparison of genome-edited plants with plants developed using conventional breeding methods should be conducted at the level of a scientific case-by-case assessment of individual applications rather than at a general, technology-based level. Our considerations aim to support the development of further specific guidance for the ERA of genome-edited plants

Kernel Lot Distribution Assessment (KeLDA)- A Study on the Distribution of GMO in Large Soybean Shipments

The reliability of analytical testing is strongly affected by sampling uncertainty. Sampling is always a source of error and the aim of "good" sampling practice is to minimize this error. Generally the distribution of GM material within lots is assumed to be random in order to use binomial distribution to make inferences. This assumption was never verified in practice and no experimental data investigating the distribution of GMOs exist. The objectives of the KeLDA project were: 1) to assess the distribution of GM material in soybean lots, 2) to estimate the amount of variability of distribution patterns among lots. The GM content of 15 soybean lots imported into the EU was estimated (using real-time PCR methodology) analyzing 100 increment samples systematically sampled from each lot at predetermined time intervals during the whole period of off-loading. The distribution of GM material was inferred by the one-dimensional (temporal) distribution of contaminated increments. All the lots display significant spatial structuring, indicating that randomness cannot be assumed a priori. The evidence that the distribution of GM material is heterogeneous highlights the need to develop sampling protocols based on statistical models free of distribution requirements.JRC.I.6-Biotechnology and GMO