Armin Spök

Evolution of a regulatory framework for pharmaceuticals derived from genetically modified plants

The use of genetically modified (GM) plants to synthesize proteins that are subsequently processed, regulated and sold as pharmaceuticals challenges two very different established regulatory frameworks, one concerning GM plants and the other covering the development of biotechnology-derived drugs. Within these regulatory systems, specific regulations and guidelines for plant-made pharmaceuticals (PMPs)--also referred to as plant-derived pharmaceuticals (PDPs)--are still evolving. The products nearing commercial viability will ultimately help to road test and fine-tune these regulations, and might help to reduce regulatory uncertainties. In this review, we summarize the current state of regulations in different countries, discuss recent changes and highlight the need for further regulatory development in this burgeoning, new industry. We also make the case for the harmonization of international regulations.

Suggestions for the Assessment of the Allergenic Potential of Genetically Modified Organisms

The prevalence of allergic diseases has been increasing continuously and, accordingly, there is a great desire to evaluate the allergenic potential of components in our daily environment (e.g., food). Although there is almost no scientific evidence that genetically modified organisms (GMOs) exhibit increased allergenicity compared with the corresponding wild type significant concerns have been raised regarding this matter. In principle, it is possible that the allergenic potential of GMOs may be increased due to the introduction of potential foreign allergens, to potentially upregulated expression of allergenic components caused by the modification of the wild type organism or to different means of exposure. According to the current practice, the proteins to be introduced into a GMO are evaluated for their physiochemical properties, sequence homology with known allergens and occasionally regarding their allergenic activity. We discuss why these current rules and procedures cannot predict or exclude the allergenicity of a given GMO with certainty. As an alternative we suggest to improve the current evaluation by an experimental comparison of the wild-type organism with the whole GMO regarding their potential to elicit reactions in allergic individuals and to induce de novo sensitizations. We also recommend that the suggested assessment procedures be equally applied to GMOs as well as to natural cultivars in order to establish effective measures for allergy prevention.

A framework for stakeholder engagement during systematic reviews and maps in environmental management

People have a stake in conservation and environmental management both for their own interests and the sake of the environment itself. Environmental decision-making has changed somewhat in recent decades to account for unintentional impacts on human wellbeing. The involvement of stakeholders in environmental projects has been recognised as critical for ensuring their success and equally for the syntheses of evidence of what works, where, and for whom, providing key benefits and challenges. As a result of increased interest in systematic reviews of complex management issues, there is a need for guidance in best practices for stakeholder engagement. Here, we propose a framework for stakeholder engagement in systematic reviews/systematic maps, highlighting recommendations and advice that are critical for effective, efficient and meaningful engagement of stakeholders. The discussion herein aims to provide a toolbox of stakeholder engagement activities, whilst also recommending approaches from stakeholder engagement research that may prove to be particularly useful for systematic reviews and systematic maps.

Can systematic reviews inform GMo risk assessment and risk management

Systematic reviews represent powerful tools to identify, collect, synthesize, and evaluate primary research data on specific research questions in a highly standardized and reproducible manner. They enable the defensible synthesis of outcomes by increasing precision and minimizing bias whilst ensuring transparency of the methods used. This makes them especially valuable to inform evidence-based risk analysis and decision making in various topics and research disciplines. Although seen as a “gold standard” for synthesizing primary research data, systematic reviews are not without limitations as they are often cost, labor and time intensive and the utility of synthesis outcomes depends upon the availability of sufficient and robust primary research data. In this paper, we (1) consider the added value systematic reviews could provide when synthesizing primary research data on genetically modified organisms (GMO) and (2) critically assess the adequacy and feasibility of systematic review for collating and analyzing data on potential impacts of GMOs in order to better inform specific steps within GMO risk assessment and risk management. The regulatory framework of the EU is used as an example, although the issues we discuss are likely to be more widely applicable.

Inclusive development and prioritization of review questions in a highly controversial field of regulatory science

How to best assess potential health, environmental and other impacts of genetically modified organisms (GMOs) and how to interpret the resulting evidence base have been long-standing controversial issues in the EU. As a response, transparency and inclusiveness became a major focus of regulatory science activities in the GMO impact area. Nevertheless, nearly three decades of controversies resulted in a heavily polarized policy environment, calling for further efforts. Against this backdrop the EU funded project GRACE explored the value of evidence synthesis approaches for GMO impact assessment and developed an evidence synthesis framework with a strong emphasis on openness, stakeholder engagement, transparency, and responsiveness to tackle regulatory science challenges. This framework was tested and implemented in the course of 14 systematic reviews or maps conducted on selected review questions spanning potential health, environmental, and socioeconomic impacts of GMOs. An inclusive development and prioritisation of review questions is of key importance in evidence synthesis as it helps to provide a better link between stakeholder demands and concerns and policy relevant outcomes. This paper, therefore, places a particular focus on the stakeholder involvement strategy developed and experiences gathered during this particular step in the course of the GRACE project. Based on this experience, possible lessons for future engagement exercises in highly controversial fields of regulatory science are discussed.

Proposed criteria for the evaluation of the scientific quality of mandatory rat and mouse feeding trials with whole food/feed derived from genetically modified plants

In recent years, animal feeding trials conducted with whole food/feed have been a focal issue in the controversy on the safety assessment of genetically modified (GM) plants and derived food/feed. Within the scientific community and among stakeholders, quite different views have been expressed on how these studies should be conducted, analysed and interpreted, what they might add in terms of information relevant to safety and whether 90-day rodent feeding trials should be mandatory. Despite the fact that the Commission Implementing Regulation (EU) No. 503/2013 (specifying the requirements for the risk assessment of GM food/feed) requests mandatory 90-day feeding trials for GM plants with single transformation events, the controversy continues. This is due to the fact that in 2016 the European Commission will have to review this particular provision in the legislation (ibid, Article 12), and because of questions raised by long-term feeding studies with GM maize.

Status of microbial based cleaning products in statutory regulations and ecolabelling in Europe, the USA, and Canada

Cleaning products containing living microorganisms as active ingredients are increasingly being used in household, professional and industrial cleaning applications. Microorganisms can degrade soiling associated with dirt, food residues, and grease by enzymatic and metabolic action and out-compete microorganisms associated with odor problems. Their potential for odor control seems to result in a competitive advantage over conventional chemically-based cleaning products. Moreover, producers of microbial-based cleaning products (MBCPs) claim that their products are less harmful to the environment. These promising prospects have triggered interest from consumer and environmental organizations, professional users, and regulators in understanding if there are also possible negative health and environmental impacts which require attention and how the safety of these products is ensured. Unfortunately, there is little information on these issues in the public domain. Moreover, regulatory oversight in Europe is essentially limited to pathogenic properties in the context of worker protection. Canada, in contrast, has a regulatory framework in place to assess risks to human health and the environment from the manufacture, import and/or use of new microorganisms contained in MBCPs. In the absence of mandatory standards, safety assessment and hygienic practices seem to vary considerably across companies. Recently developed ecolabelling standards are - for the time being - the only option for transparent compliance to minimum standards in terms of safety as well as assessments of manufacturer information by third parties. These standards highlight in particular the need for precise taxonomic information for assessing the pathogenic properties and the need to ensure the absence of potentially harmful microorganisms as contaminants. Ecolabelling standards are, however, voluntary and do not cover all relevant safety issues. In order to develop a more comprehensive set of mandatory standards for health and safety, a number of areas would benefit from further research (e.g. the role in plant pathogenicity and other environmental properties of the microorganisms used; the relevance of chronic exposure to dusts and aerosols containing vegetative cells and spores; the relevance of strains which belong to species known to include opportunistic pathogens and possible hazards for particularly sensitive risk groups). Improved knowledge in these areas will contribute to a predictable level of product safety.