Options to Reform the European Union Legislation on GMOs: Scope and Definitions

Abstract

We discuss options to reform the EU genetically modified organisms (GMO) regulatory framework, make risk assessment and decision-making more consistent with scientific principles, and lay the groundwork for international coherence. The first in a three-part series, this article focuses on reform options related to the scope of the legislation and the GMO definition. We discuss options to reform the EU genetically modified organisms (GMO) regulatory framework, make risk assessment and decision-making more consistent with scientific principles, and lay the groundwork for international coherence. The first in a three-part series, this article focuses on reform options related to the scope of the legislation and the GMO definition. A wide range of stakeholders have recently called for reform of the legal framework for GMOs in the EUi [1Eriksson D. et al.A welcome proposal to amend the GMO legislation of the EU.Trends Biotechnol. 2018; 36: 1100-1103Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 2Bratlie S. et al.A novel governance framework for GMO: a tiered, more flexible regulation for GMOs would help to stimulate innovation and public debate.EMBO Rep. 2019; 20: e47812Crossref PubMed Scopus (12) Google Scholar, 3Wasmer M. Roads forward for European GMO policy–uncertainties in wake of ECJ judgment have to be mitigated by regulatory reform.Front. Bioeng. Biotechnol. 2019; 7: 132Crossref PubMed Scopus (15) Google Scholar, 4Zetterberg C. Edvardsson Björnberg K. Time for a new EU regulatory framework for GM crops?.J. Agric. Environ. Ethics. 2017; 30: 325-347Crossref Scopus (25) Google Scholar]. One argument is that the implementation of the EU GMO law may lean too much towards precaution at the cost of stalling innovation [4Zetterberg C. Edvardsson Björnberg K. Time for a new EU regulatory framework for GM crops?.J. Agric. Environ. Ethics. 2017; 30: 325-347Crossref Scopus (25) Google Scholar,5Bogner A. Torgersen H. Precaution, responsible innovation and beyond – in search of a sustainable agricultural biotechnology policy.Front. Plant Sci. 2018; 9: 1884Crossref PubMed Scopus (10) Google Scholar]. There is also concern that the EU could forego potential benefits of technological innovations not only in transgenesis but also in gene editing; as a judgment of the Court of Justice of the European Union (CJEU) on the scope of the mutagenesis exemption in the GMO legislation (case C-528/16ii) implies, the products of targeted mutagenesis are also subject to the GMO legislative provisions [6Wanner B. et al.CJEU renders decision on the interpretation of the GMO directive.J. Intellectual Property Law & Practice. 2019; 14: 90-92Crossref Google Scholar,7Simas L. et al.Judgment of the Court of Justice of the European Union of July 25, 2018, in Case C-528/16 Confédération Paysanne and Others. WilmerHale, 2018Google Scholar]. The nondetectability of most products of gene editing has also made enforcement following the CJEU case C-528/16ii difficult, if not impossibleiii. Molecular breeding technologies, such as transgenesis and targeted mutagenesis, have the potential to contribute to sustainable agriculture and food security by increasing agricultural yields, reducing pesticide use [8Klumper W. Qaim M. A meta-analysis of the impacts of genetically modified crops.PLoS One. 2014; 9: e111629Crossref PubMed Scopus (369) Google Scholar,9Barrows G. et al.The impact of agricultural biotechnology on supply and land-use.Environ. Dev. Econ. 2014; 19: 676-703Crossref Scopus (27) Google Scholar], and increasing the nutritional value of food and feed crops [10Hansson S.O. et al.Breeding for public health: a strategy.Trends Food. Sci. Tech. 2018; 80: 131-140Crossref Scopus (8) Google Scholar]. In Box 1, we present a number of potentially beneficial applications. The use of molecular tools results in products facing regulatory environments that differ by country, with procedures that are more demanding in some countries than in others. While some stakeholders recognize stringent regulatory procedures as a means to prevent harm, others emphasize that overly strict regulations may act as a disproportionate threshold with the potential to hinder innovation [11Purnhagen K.P. Wesseler J.H. Maximum vs minimum harmonization: what to expect from the institutional and legal battles in the EU on gene editing technologies.Pest Manag. Sci. 2019; 75: 2310-2315Crossref PubMed Scopus (12) Google Scholar]. Regulatory procedures for the testing and commercial approval of GMOs are particularly lengthy and costly in the EU, as compared to the USA, Canada, and many other countries [12Lassoued R. et al.Regulatory uncertainty around new breeding techniques.Front. Plant Sci. 2018; 9: 1291Crossref PubMed Scopus (22) Google Scholar,13Smart R.D. et al.Trends in approval times for genetically engineered crops in the United States and the European Union.J. Agr. Econ. 2017; 68: 182-198Crossref Scopus (45) Google Scholar]. By contrast, authorization procedures provide a means to transfer information regarding the potential harm of these organisms from businesses to regulators, potentially closing the information gap between these two. If properly applied, the regulatory procedure is viewed as an enabler for more scientifically robust and socially acceptable public policies [14Sachs N. Rescuing the strong precautionary principle from its critics.Uni. of Illinois Law Rev. 2011; 4: 1285-1338Google Scholar]. At the same time, applications for cultivation authorization of GM crops as well as funding for GMO research have been decreasing in the EU [15Smyth S.J. Lassoued R. Agriculture R&D implications of the CJEU's gene-specific mutagenesis ruling.Trends Biotechnol. 2019; 37: 337-340Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar], which has been connected to a reduction in the overall level of innovation [16Martin-Laffon J. et al.Worldwide CRISPR patent landscape shows strong geographical biases.Nat. Biotechnol. 2019; 37: 613-620Crossref PubMed Scopus (35) Google Scholar]. These facts provide a strong indication that the current regulatory framework is no longer fit for purpose.Box 1Transgenesis and Gene Editing in Plant Research and BreedingPlant breeders depend on genetic variation for the development of new desirable traits in agricultural crops. To increase genetic variability in a particular species, breeders have for a long time used wide crosses, hybridization, randomly-induced mutagenesis, and other techniques. Transgenesis and gene editing has opened up new horizons as the genetic variation available for breeding has become much larger.The use of the CRISPR–Cas systems and other gene editing techniques to develop crops with new desirable traits is a very dynamic field of research. According to a recent review, around 100 market-relevant applications of gene editing in 28 different crop species have already been documented in scientific publications [20Modrzejewski D. et al.What is the available evidence for the range of applications of genome-editing as a new tool for plant trait modification and the potential occurrence of associated off-target effects: a systematic map.Environ. Evid. 2019; 8: 27Crossref Scopus (27) Google Scholar], and this number is increasing rapidly. Many of the applications involve resistance against fungal, bacterial, and viral diseases in crops, such as rice, wheat, maize, banana, and cassava. Disease resistance is a valuable trait to reduce crop losses and chemical pesticide sprays. Further, crops more tolerant to soil salinity, drought, and other climate stresses have been developed. Market-relevant applications also include crops with improved food and feed quality traits, such as wheat with reduced gluten content, vegetables with increased vitamin levels, and oil crops with improved oil composition and decrease of antinutritional compounds [10Hansson S.O. et al.Breeding for public health: a strategy.Trends Food. Sci. Tech. 2018; 80: 131-140Crossref Scopus (8) Google Scholar]. Many other gene editing applications are in the research pipeline and could help to make agriculture more sustainable and climate smart [21Bailey-Serres J. et al.Genetic strategies for improving crop yield.Nature. 2019; 575: 109-118Crossref PubMed Scopus (162) Google Scholar]. Under the current GMO legislation, such applications can hardly be developed and field tested in the EU, let alone commercially used. Plant breeders depend on genetic variation for the development of new desirable traits in agricultural crops. To increase genetic variability in a particular species, breeders have for a long time used wide crosses, hybridization, randomly-induced mutagenesis, and other techniques. Transgenesis and gene editing has opened up new horizons as the genetic variation available for breeding has become much larger. The use of the CRISPR–Cas systems and other gene editing techniques to develop crops with new desirable traits is a very dynamic field of research. According to a recent review, around 100 market-relevant applications of gene editing in 28 different crop species have already been documented in scientific publications [20Modrzejewski D. et al.What is the available evidence for the range of applications of genome-editing as a new tool for plant trait modification and the potential occurrence of associated off-target effects: a systematic map.Environ. Evid. 2019; 8: 27Crossref Scopus (27) Google Scholar], and this number is increasing rapidly. Many of the applications involve resistance against fungal, bacterial, and viral diseases in crops, such as rice, wheat, maize, banana, and cassava. Disease resistance is a valuable trait to reduce crop losses and chemical pesticide sprays. Further, crops more tolerant to soil salinity, drought, and other climate stresses have been developed. Market-relevant applications also include crops with improved food and feed quality traits, such as wheat with reduced gluten content, vegetables with increased vitamin levels, and oil crops with improved oil composition and decrease of antinutritional compounds [10Hansson S.O. et al.Breeding for public health: a strategy.Trends Food. Sci. Tech. 2018; 80: 131-140Crossref Scopus (8) Google Scholar]. Many other gene editing applications are in the research pipeline and could help to make agriculture more sustainable and climate smart [21Bailey-Serres J. et al.Genetic strategies for improving crop yield.Nature. 2019; 575: 109-118Crossref PubMed Scopus (162) Google Scholar]. Under the current GMO legislation, such applications can hardly be developed and field tested in the EU, let alone commercially used. With a focus on GM crops, we present details for a reform based on a rigorous application of a risk-based approach. In this article, which is the first in a series of three, we briefly describe the current EU regulatory framework and discuss reform options related to the scope of the legislation and the GMO definition (Figure 1). The subsequent two articles discuss reform options in terms of risk assessment and risk management as well as post-authorization requirements. The regulation of GMOs gained attention in the EU in the late 1980s. The first Council Directive 90/220/EEC covered their deliberate release into the environment and market introduction. Following a number of food crises and the requirement to realign with World Trade Organization law, several member states asked for a revision of the approval process and requirements for placing GMOs on the market by the end of the 1990s. In response to this, a new legal framework [inter alia Directive 2001/18/EC, Directive 2004/35/EC, Regulations (EC) No 178/2002, (EC) No 1829/2003, (EC) No 1830/2003, and Recommendations for Coexistence] additionally introduced labelling and traceability requirements, a liability framework for adventitious presence, a centralized authorization procedure for GMOs, and coexistence recommendations. Risk assessment and risk management are largely harmonized at the EU level. However, in line with the requirements of the treaties governing the EU, a member state may provisionally restrict or prohibit the use and/or sale of a particular GMO under the safeguard clause of Directive 2001/18/EC if new findings indicating potential environmental or health risks of the organism appear. Since 2015, member states may additionally restrict or prohibit the cultivation of GM crops on their territory based on other than risk-related criteria. GMOs obtained by techniques listed in Annex 1B of Directive 2001/18/EC are exempt from the specific risk assessment, authorization, labelling, and traceability procedures. This includes mutagenesis techniques that were in use before the Directive entered into force in 2001 but not newer forms of mutagenesis, according to the CJEU decision in case C-528/16ii. Three decades of research on GMOs have shown that potential risks associated with a new variety are related to the phenotypic traits of the plant and its derived products and not the technique that was used for breeding [17Gould F. et al.The study of genetically engineered crops by the National Academies of Sciences, Engineering, and Medicine.in: Genetically Engineered Crops: Experiences and Prospects. National Academies Press, 2016: 29-46Google Scholar]. This is in stark contrast to the emphasis on process as a trigger for the applicability of the GMO legislation in the EU. We propose to amend this framework to move away from process-based triggers for regulatory oversight and put a stronger emphasis on the product. One measure could be to establish a definition of GMO that is more in line with the definition of a Living Modified Organism (LMO) in the Cartagena Protocol on Biosafety (CPB) to the Convention on Biological Diversity, which stipulates that an LMO is ‘any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology.’ This is in line with the view expressed by some EU member states before the CJEU judgment on the mutagenesis exemption [18Eriksson D. The Swedish policy approach to directed mutagenesis in a European context.Physiol. Plant. 2018; 164: 385-395Crossref PubMed Scopus (14) Google Scholar]. Another alternative would be to amend Annex 1B of Directive 2001/18/EC, as proposed by the Dutch governmentiv, by which the exemption from the provisions of the Directive would apply to organisms not containing sequences foreign to the organisms’ gene pool and/or recombinant nucleic acids. This would imply that products harboring only point mutations and no foreign DNA would be exempt from harmonized regulation [1Eriksson D. et al.A welcome proposal to amend the GMO legislation of the EU.Trends Biotechnol. 2018; 36: 1100-1103Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar]. The CJEU ruling in Case C-528/16ii, however, also stipulated that exempted products of mutagenesis can be regulated at a national level, so this approach would carry the risk of further fragmentation of the EU internal market. Another possibility would be to introduce a stratified approach similar to that proposed by the Norwegian Biotechnology Advisory Board, according to which, regulatory requirements are adjusted based on the type of genetic change [2Bratlie S. et al.A novel governance framework for GMO: a tiered, more flexible regulation for GMOs would help to stimulate innovation and public debate.EMBO Rep. 2019; 20: e47812Crossref PubMed Scopus (12) Google Scholar]. More generally, we propose that products that are identical to those that can be developed using any conventional breeding technique, and/or may (to a reasonable degree of probability) occur without human intervention, should not be subject to the provisions of the EU GMO legislation as they currently stand. We believe it is reasonable from a risk perspective that identical products are subject to similar regulatory procedures. This would also be in line with the regulatory approach taken in many jurisdictions on the American continents and elsewhere [19Eriksson D. et al.A comparison of the EU regulatory approach to directed mutagenesis with that of other jurisdictions, consequences for international trade and potential steps forward.New Phytol. 2019; 222: 1673-1684Crossref PubMed Scopus (52) Google Scholar]. The recent CJEU ruling in case C-528/16ii provides an indication as to how the scope of Directive 2001/18/EC should be interpreted in relation to mutagenesis. However, many questions regarding what exactly is covered by the EU GMO laws remain, in particular, for techniques that are not a form of mutagenesis. In order to cope with the fast-moving pace of innovation, societal developments, and the need for predictability of legal systems, a designated expert committee could be entrusted with a mandate to issue nonbinding recommendations on the various legal terminologies and to decide whether specific genetically altered organisms should be within the scope. This approach would be similar to the ‘Am I regulated?’ approach of the United States Department of Agriculturev, which has offered nonbinding advice to applicants since 2011. The organization and mandate of such a designated expert committee needs to be designed in accordance with the requirements of EU law for the establishment of such bodies (as witnessed, e.g., by the Meroni doctrine) and has to make certain that the institutional balance within the EU is maintained. The composition of this expert group should be framed by EU law to ensure that the correct legal and scientific expertise is present and EU law is observed. Recital 17 of Directive 2001/18/EC stipulates that: ‘This Directive should not apply to organisms obtained through certain techniques of genetic modification which have conventionally been used in a number of applications and have a long safety record.’ The exemption currently applies to conventional, randomly-induced mutagenesis, however, it is not specified exactly what the requirement of a long safety record entails. The inclusion of Recital 17 demonstrates an early intention to shape a GMO regulatory framework that would evolve and take experience into account. We suggest implementation of a product-oriented approach when interpreting the requirement of a long safety record in Recital 17. This would resemble the practice of safety assessments, as safety assessments measure product-related features. It is not the mutagenesis technique itself that has a long safety record; it is the products that were introduced to the market or released into the environment after additional breeding and variety registration. Article 7 of Directive 2001/18/EC provides the possibility for differentiated (simplified) procedures for risk assessment and management whenever sufficient experience with a particular GMO has been gained [3Wasmer M. Roads forward for European GMO policy–uncertainties in wake of ECJ judgment have to be mitigated by regulatory reform.Front. Bioeng. Biotechnol. 2019; 7: 132Crossref PubMed Scopus (15) Google Scholar]. However, to date, Article 7 has never been used, which underlines that the original intention of an evolving regulatory practice is not being followed and that Directive 2001/18 is interpreted in a static way. This makes a reform of the Directive particularly important. In the next article, we continue discussing various details that may be reformed within the risk assessment and risk management procedures. D.E. took the initiative and prepared the first draft manuscript. All other coauthors contributed a section each to the manuscript and shared in the finalizing of the manuscript. This work was supported by the Swedish Foundation for Strategic Environmental Research (Mistra) through the Mistra Biotech research programme; and the German Federal Ministry of Education and Research through the project ‘Ethical, Legal and Socioeconomic Aspects of Genome Editing in Agriculture’ (grant reference number: 01GP1613C). ihttps://publications.europa.eu/en/publication-detail/-/publication/a9100d3c-4930-11e9-a8ed-01aa75ed71a1/language-en/format-PDF/source-94584603iihttp://curia.europa.eu/juris/documents.jsf?num=c-528/16iiiwww.infogm.org/IMG/pdf/comeur_note-detection-nveaux-ogm_nov2018.pdfivhttp://rijksoverheid.nl/binaries/rijksoverheid/documenten/kamerstukken/2017/09/13/proposal-for-discussion/proposal-for-discussion.pdfvwww.aphis.usda.gov/aphis/ourfocus/biotechnology/am-i-regulated Options to Reform the European Union Legislation on GMOs: Risk GovernanceEriksson et al.Trends in BiotechnologyFebruary 12, 2020In BriefHere, we discuss options to reform the EU genetically modified organism (GMO) regulatory framework, to make risk assessment and decision-making more consistent with scientific principles, and to lay the groundwork for international coherence. We discussed the scope and definitions in a previous article and, thus, here we focus on the procedures for risk assessment and risk management. Full-Text PDF Options to Reform the European Union Legislation on GMOs: Post-authorization and BeyondEriksson et al.Trends in BiotechnologyFebruary 12, 2020In BriefWe discuss options to reform the EU genetically modified organism (GMO) regulatory framework, make risk assessment and decision-making more consistent with scientific principles, and lay the groundwork for international coherence. In this third of three articles, we focus on labeling and coexistence as well as discuss the political reality and potential ways forward. Full-Text PDF

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