Familiarity in the Context of Risk Assessment of Transgenic Crops: Focus on Some Countries in the Americas.

Problem formulation is the formal opening stage of a risk assessment that determines its purpose and scope and hence guides the gathering of information data. The concepts of familiarity and history of safe use are an integral part of problem formulation. These concepts do not replace the case-by-case approach and are not taken as safety standards but are valuable components of the process that shape the generation of plausible, testable risk hypotheses. The International Life Sciences Institutes in Brazil and Argentina have facilitated numerous discussions on the scientific principles for risk assessment of transgenic crops in the Latin American region in the past 5-6 years. The session held at ISBR 15th elaborated on the familiarity concept and derived tools and their role in the evolution of risk evaluation criteria. Examples of how different countries in the Americas interpret and apply these conceptual tools show that familiarity is a valuable concept, although terms are very often confused and vaguely defined. Formalizing these terms with clear definitions and scope of application in guidelines and regulatory documents would reduce ambiguity, enhance predictability, and add transparency to the evaluation processes.

Policy-Led Comparative Environmental Risk Assessment of Genetically Modified Crops: Testing for Increased Risk Rather Than Profiling Phenotypes Leads to Predictable and Transparent Decision-Making.

We describe two contrasting methods of comparative environmental risk assessment for genetically modified (GM) crops. Both are science-based, in the sense that they use science to help make decisions, but they differ in the relationship between science and policy. Policy-led comparative risk assessment begins by defining what would be regarded as unacceptable changes when the use a particular GM crop replaces an accepted use of another crop. Hypotheses that these changes will not occur are tested using existing or new data, and corroboration or falsification of the hypotheses is used to inform decision-making. Science-led comparative risk assessment, on the other hand, tends to test null hypotheses of no difference between a GM crop and a comparator. The variables that are compared may have little or no relevance to any previously stated policy objective and hence decision-making tends to be ad hoc in response to possibly spurious statistical significance. We argue that policy-led comparative risk assessment is the far more effective method. With this in mind, we caution that phenotypic profiling of GM crops, particularly with omics methods, is potentially detrimental to risk assessment.

Bringing plant-based veterinary vaccines to market: Managing regulatory and commercial hurdles.

The production of recombinant vaccines in plants may help to reduce the burden of veterinary diseases, which cause major economic losses and in some cases can affect human health. While there is abundant research in this area, a knowledge gap exists between the ability to create and evaluate plant-based products in the laboratory, and the ability to take these products on a path to commercialization. The current report, arising from a workshop sponsored by an Organisation for Economic Co-operation and Development (OECD) Co-operative Research Programme, addresses this gap by providing guidance in planning for the commercialization of plant-made vaccines for animal use. It includes relevant information on developing business plans, assessing market opportunities, manufacturing scale-up, financing, protecting and using intellectual property, and regulatory approval with a focus on Canadian regulations.

Building Better Environmental Risk Assessments.

Risk assessment is a reasoned, structured approach to address uncertainty based on scientific and technical evidence. It forms the foundation for regulatory decision-making, which is bound by legislative and policy requirements, as well as the need for making timely decisions using available resources. In order to be most useful, environmental risk assessments (ERAs) for genetically modified (GM) crops should provide consistent, reliable, and transparent results across all types of GM crops, traits, and environments. The assessments must also separate essential information from scientific or agronomic data of marginal relevance or value for evaluating risk and complete the assessment in a timely fashion. Challenges in conducting ERAs differ across regulatory systems - examples are presented from Canada, Malaysia, and Argentina. One challenge faced across the globe is the conduct of risk assessments with limited resources. This challenge can be overcome by clarifying risk concepts, placing greater emphasis on data critical to assess environmental risk (for example, phenotypic and plant performance data rather than molecular data), and adapting advances in risk analysis from other relevant disciplines.

Genetic basis and detection of unintended effects in genetically modified crop plants.

In January 2014, an international meeting sponsored by the International Life Sciences Institute/Health and Environmental Sciences Institute and the Canadian Food Inspection Agency titled "Genetic Basis of Unintended Effects in Modified Plants" was held in Ottawa, Canada, bringing together over 75 scientists from academia, government, and the agro-biotech industry. The objectives of the meeting were to explore current knowledge and identify areas requiring further study on unintended effects in plants and to discuss how this information can inform and improve genetically modified (GM) crop risk assessments. The meeting featured presentations on the molecular basis of plant genome variability in general, unintended changes at the molecular and phenotypic levels, and the development and use of hypothesis-driven evaluations of unintended effects in assessing conventional and GM crops. The development and role of emerging "omics" technologies in the assessment of unintended effects was also discussed. Several themes recurred in a number of talks; for example, a common observation was that no system for genetic modification, including conventional methods of plant breeding, is without unintended effects. Another common observation was that "unintended" does not necessarily mean "harmful". This paper summarizes key points from the information presented at the meeting to provide readers with current viewpoints on these topics.

Selectable marker genes and unintended changes to the plant transcriptome.

The intended effect of a selectable marker gene is to confer a novel trait that allows for the selection and recovery of transgenic plants. Unintended effects may also occur as a result of interactions between the selectable marker gene or its regulatory elements and genetic elements at the site of insertion. These are called position effects. Other unintended effects may occur if the selectable marker gene has a range of pleiotropic effects related to the functional and regulatory domains within the coding region or the regulatory elements used to drive expression. Both pleiotropic and position effects may generate unpredictable events depending on the process used for transgenesis and the state of knowledge associated with the selectable marker gene. Although some selectable marker genes, such as the neomycin phosphotransferase type II gene (nptII), have no pleiotropic effects on the transcriptomes of transgenic plants, others, such as the bialaphos resistance gene (bar), have pleiotropic effects. These must be clearly understood and accounted for when evaluating the expression patterns conferred by other co-transforming transgenes under study. The number and kinds of selectable marker genes are large. A detailed understanding of their unintended effects is needed to develop transgenic strategies that will minimize or eliminate unintended and unpredictable changes to plants with newly inserted genes.

Regulation of Bt crops in Canada.

The Canadian Food Inspection Agency (CFIA) regulates environmental releases of plants with novel traits, which include transgenic plants such as Bt crops. Bt crops are regulated in Canada because they express insect resistance novel to their species. Commercialization of crops with novel traits such as the production of insecticidal Bt proteins requires an approval for environmental release, as well as approvals for use as feed and food. Environmental factors such as potential impacts on non-target species are considered. Insect resistance management (IRM) may be imposed as a condition for environmental release of Bt crops to delay the development of resistance in the target insect. Bt potato and European corn borer-resistant Bt corn have been released with mandatory IRM. The CFIA imposes an IRM plan consisting of appropriate refugia, education of farmers and seed dealers, and monitoring and mitigation. Industry, regulators, government extension staff and public researchers provide expert advice on IRM.