EU biotech crop regulations and environmental risk: a case of the emperor's new clothes?

European Union Commissioner for the Environment Stavros Dimas recently hailed 'upgraded' non-genetically modified (GM) crops as an alternative to GM crops. A comparative analysis of the environmental risks associated with such non-GM herbicide-resistant crops and GM herbicide-resistant crops is presented here. The analysis highlights serious weaknesses in the European Union (EU) regulatory framework, and the contradictory policy of the EU Commission on the precautionary principle is also shown. The continued political stance of ignoring these regulatory and policy inconsistencies is examined and found to be flawed. It is postulated that, even in the face of these flaws and coupled with recent statements from the UK drawing attention to inconsistencies in the EU regulatory framework, the EU will continue to ignore the real and present environmental risks associated with upgraded non-GM crops for biopolitical reasons.     

Development and implementation of a high nature value (HNV) farming indicator for Denmark

During the latest decades, conservation awareness have increased and conservation of biodiversity is no longer an agenda restricted to pristine natural areas of high value but is being integrated in cultivated landscapes characterized by increasing fragmentation and anthropogenic pressures. Conservation of species has become relevant even in agricultural areas especially in countries heavily influenced by intensive farming and ubiquitous infrastructure. Based on the UN biodiversity convention all EU membership countries are obliged to develop a high nature value (HNV) farming indicator. The purpose of such an indicator is to provide a basis for informed decisions in prioritizing agricultural subsidies allocating these to high nature value areas. Here, the development of a national HNV farming indicator for Denmark is presented and its application in the Danish government-controlled agricultural subsidy system is outlined. The Danish HNV farming indicator is based on landscape structural parameters, known occurrences of natural and semi-natural habitats, current land use and the distributions of rare and threatened species. It covers all agricultural areas as well as Natura 2000 areas and nationally protected sites in Denmark, ranking them on a 0–13 point scale from low to high nature value according to their estimated value for threatened and rare biodiversity. The Danish government recognizes areas reaching at least 5 points as HNV farming areas eligible to subsidy and from 2015 and onwards the HNV farming indicator will be implemented for allocating part of the agricultural subsidies under the Rural Development Program in Denmark. The indicator will be updated annually to include the growing knowledge of species occurrence and land use changes.     

药用植物分子农场研究进展

植物分子农场可以利用植物生产具有药物用途的重组蛋白或者次生代谢化合物,应用广泛。随着对动植物中具有药物用途的代谢途径的深入解析,代谢途径中关键限速酶或调控蛋白的功能不断被明确,如何选择植物分子农场的底盘植物和遗传改造途径等问题,特别是如何协同提高植物制药产量与品质一直是植物分子农场体系建立中面临的关键科学问题。综述了药用的植物分子农场的最新研究进展,着重介绍了底盘植物的选择与药用植物分子农场的构建策略,以期为提高分子农场应用效果提供有力的科技支撑。     

Golimumab

Golimumab, a human anti-TNFα IgG1κ monoclonal antibody, was approved in the US and Canada in April 2009 as a treatment for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, and is undergoing regulatory review in the EU for these indications. The product was developed by Centocor and Janssen Pharmaceutical KK (Johnson & Johnson subsidiaries), in collaboration with Schering-Plough and Mitsubishi Tanabe Pharma. Golimumab faces numerous protein therapeutic competitors on the market, but, as the first patient-administered, once-monthly dosed anti-TNFα drug, it will likely be an attractive option for patients.     

Tobacco,a highly efficient green bioreactor for production of therapeutic proteins

Molecular farming of pharmaceuticals in plants has the potential to provide almost unlimited amounts of recombinant proteins for use in disease diagnosis, prevention or treatment. Tobacco has been and will continue to be a major crop for molecular farming and offers several practical advantages over other crops. It produces significant leaf biomass, has high soluble protein content and is a non-food crop, minimizing the risk of food-chain contamination. This, combined with its flexibility and highly-efficient genetic transformation/regeneration, has made tobacco particularly well suited for plant-based production of biopharmaceutical products. The goal of this review is to provide an update on the use of tobacco for molecular farming of biopharmaceuticals as well the technologies developed to enhance protein production/purification/efficacy. We show that tobacco is a robust biological reactor with a multitude of applications and may hold the key to success in plant molecular farming.     

Grassland butterflies and low intensity farming in Europe

In this paper we describe the impact of the abandonment of traditional farming practices on butterflies and their habitats in traditional, often montane, pastoral systems. We link these declines to socioeconomic factors: illustrating how the failure of the CAP to support traditional farming leads to structural changes in farming enterprises??features which may be obscured by crude statistics on stock. We then call for the scheduled CAP reforms in 2013 to be radically realigned to support rather than destroy biodiversity so that any new EU agri-biodiversity commitments have an effective funding stream to support them.     

Plant molecular farming: systems and products

Plant molecular farming is a new and promising industry involving plant biotechnology. In this review, we describe several diverse plant systems that have been developed to produce commercially useful proteins for pharmaceutical and industrial uses. The advantages and disadvantages of each system are discussed. The first plant-derived molecular farming products have reached the marketplace and other products are poised to join them during the next few years. We explain the rationale for using plants as biofactories. We also describe the products currently on the market, and those that appear likely to join them in the near future. Lastly, we discuss the issue of public acceptance of molecular farming products.Communicated by P.P. Kumar     

Pharma-Planta: road testing the developing regulatory guidelines for plant-made pharmaceuticals

Significant advances over the last few years have seen plant-made pharmaceuticals (PMPs) move from the exploratory research phase towards clinical trials, with the first commercial products for human use expected to reach the market by 2009. Europe has yet to witness the commercial application of PMP technology, although at least one product has begun phase II clinical trials with others following close behind. These emerging products are set to challenge the complex and overlapping regulations that currently govern GM plants and ‘conventional’ pharmaceutical production. The areas of responsibility are being mapped out between the different EU regulatory agencies, with specific guidelines currently being drawn up for the regulation of PMPs. This article discusses issues surrounding the development of robust risk-assessment and risk-management practices based on health and environmental impact, while working with EU regulatory authorities to ensure appropriate regulatory oversight.     

Assessing the Effects of Climate Change on Waterborne Microorganisms: Implications for EU and U.S. Water Policy

Despite advances in water treatment, outbreaks of waterborne diseases still occur in developed regions including the United States and Europe Union (EU). Water quality impairments attributable to elevated concentrations of fecal indicator bacteria, and associated with health risk, are also very common. Research suggests that the impact of such microorganisms on public health may be intensified by the effects of climate change. At present, the major regulatory frameworks in these regions (i.e., the US Clean Water Act [CWA] and the EU Water Framework Directive [WFD]), do not explicitly address risks posed by climate change. This article reviews existing U.S. and EU water quality regulatory legislation for robustness to climate change and suggests watershed modeling approaches to inform additional pollution control measures given the likely impacts on microbial fate and transport. Comprehensive analysis of future climate and water quality scenarios may only be achievable through the use of watershed-scale models. Unless adaptation measures are generated and incorporated into water policy, the potential threat posed to humans from exposure to waterborne pathogens may be amplified. Such adaptation measures will assist in achieving the aims of the EU WFD and US CWA and minimize impacts of climate change on microbial water quality.     

Review: In vivo and postmortem effects of feed antioxidants in livestock: a review of the implications on authorization of antioxidant feed additives

The pivotal roles of regulatory jurisdictions in the feed additive sector cannot be over-emphasized. In the European Union (EU), antioxidant substances are authorized as feed additives for prolonging the shelf life of feedstuffs based on their effect for preventing lipid peroxidation. However, the efficacy of antioxidants transcends their functional use as technological additives in animal feeds. Promising research results have revealed the in vivo efficacy of dietary antioxidants for combating oxidative stress in production animals. The in vivo effect of antioxidants is significant for enhancing animal health and welfare. Similarly, postmortem effect of dietary antioxidants has been demonstrated to improve the nutritional, organoleptic and shelf-life qualities of animal products. In practice, dietary antioxidants have been traditionally used by farmers for these benefits in livestock production. However, some antioxidants particularly when supplemented in excess could act as prooxidants and exert detrimental effects on animal well-being and product quality. Presently, there is no exclusive legislation in the EU to justify the authorization of antioxidant products for these in vivo and postmortem efficacy claims. To indicate these efficacy claims and appropriate dosage on product labels, it is important to broaden the authorization status of antioxidants through the appraisal of existing EU legislations on feed additives. Such regulatory review will have major impact on the legislative categorization of antioxidants and the efficacy assessment in the technical dossier application. The present review harnesses the scientific investigations of these efficacy claims in production animals and, proposes potential categorization and appraisal of in vivo methodologies for efficacy assessment of antioxidants. This review further elucidates the implication of such regulatory review on the practical application of antioxidants as feed additives in livestock production. Effecting these regulatory changes will stimulate the innovation of more potent antioxidant products and create potential new markets that will have profound economic impacts on the feed additive industry. Based on the in vivo efficacy claims, antioxidants may have to contend with the legislative controversy of either to be considered as veterinary drugs or feed additives. In this scenario, antioxidants are not intended to diagnose or cure diseases as ascribed to veterinary products. This twisted distinction can be logically debated with reference to the stipulated status of feed additives in Commission Regulation (EC) No 1831/2003. Nonetheless, it is imperative for relevant stakeholders in the feed additive industry to lobby for the review of existing EU legislations for authorization of antioxidants for these efficacy claims.     

Business oriented EU human cell and tissue product legislation will adversely impact Member States’ health care systems

The transplantation of conventional human cell and tissue grafts, such as heart valve replacements and skin for severely burnt patients, has saved many lives over the last decades. The late eighties saw the emergence of tissue engineering with the focus on the development of biological substitutes that restore or improve tissue function. In the nineties, at the height of the tissue engineering hype, industry incited policymakers to create a European regulatory environment, which would facilitate the emergence of a strong single market for tissue engineered products and their starting materials (human cells and tissues). In this paper we analyze the elaboration process of this new European Union (EU) human cell and tissue product regulatory regime—i.e. the EU Cell and Tissue Directives (EUCTDs) and the Advanced Therapy Medicinal Product (ATMP) Regulation and evaluate its impact on Member States’ health care systems. We demonstrate that the successful lobbying on key areas of regulatory and policy processes by industry, in congruence with Europe’s risk aversion and urge to promote growth and jobs, led to excessively business oriented legislation. Expensive industry oriented requirements were introduced and contentious social and ethical issues were excluded. We found indications that this new EU safety and health legislation will adversely impact Member States’ health care systems; since 30 December 2012 (the end of the ATMP transitional period) there is a clear threat to the sustainability of some lifesaving and established ATMPs that were provided by public health institutions and small and medium-sized enterprises under the frame of the EUCTDs. In the light of the current economic crisis it is not clear how social security systems will cope with the inflation of costs associated with this new regulatory regime and how priorities will be set with regard to reimbursement decisions. We argue that the ATMP Regulation should urgently be revised to focus on delivering affordable therapies to all who are in need of them and this without necessarily going to the market. The most rapid and elegant way to achieve this would be for the European Commission to publish an interpretative document on “placing on the market of ATMPs,” which keeps tailor-made and niche ATMPs outside of the scope of the medicinal product regulation.     

A brief overview on the status and prospects of sturgeon farming in Western and Central Europe

This paper provides a short overview on the status of sturgeon farming in Europe, covering most of the EU and former East Block countries. Production trends are presented along with a listing of species cultured in various countries. Principle culture systems are described and an opinion is presented on possible constraints and perspectives of sturgeon farming, including market opportunities.     

Making the best of both worlds: Can high-resolution agricultural administrative data support the assessment of High Nature Value farmlands across Europe?

Worldwide, the role of farmlands for biodiversity conservation and the delivery of multiple ecosystem services has been widely acknowledged. In the European Union (EU), societal demands to include environmental conservation concerns within the Common Agricultural Policy (CAP) have resulted in the recognition of the importance of maintaining High Nature Value farmlands (HNVf).HNVf constitute complex social-ecological systems, which owe their nature conservation value to the maintenance of specific, mostly low-intensity farming systems, supporting high levels of species and habitats dependent on agricultural practices. Even though HNVf assessment in space and time is essential to evaluate the effectiveness of Rural Development Programmes, the diversity of rural landscapes across EU, the scarcity of data on farming systems, and the lack of common methodological guidelines has hampered the implementation of HNVf mapping and monitoring across Europe. Thus, there is a pressing need to develop and test methodological approaches that may support HNVf assessment across the EU.The Integrated Administration and Control System (IACS) which is mandatory for all EU Member States constitutes a system for the management and control of CAP payments to farmers. Essentially, IACS comprises high-resolution, spatially explicit information on the type and intensity of agricultural land-use. Even though such data exhibits high thematic, spatial and temporal resolution, IACS has seldom been used, due to significant access restrictions. Here, the potential to use IACS data to support the assessment of HNVf was evaluated within the German Federal State of Lower Saxony by implementing a recently developed methodological framework. Sets of indicators known to be essential for identifying potential HNVf and underlying farming systems (expressing landscape structure and composition, farming systems, and crop diversity), were derived from IACS. Spatial patterns of indicators were analyzed at two different scales to delineate the potential distribution of HNVf across Lower Saxony.Results highlighted that most regions in Lower Saxony were characterized by intensive farming practices including high livestock density, high share of intensive crops and low density of linear elements. Only 3% of the Utilized Agricultural Area (UAA) of Lower Saxony potentially constituted HNVf, with the majority of HNVf coinciding with mosaics of arable and/or permanent crops and semi-natural features under less intensive farming practices. Semi-natural grasslands, partially under agri-environment scheme management contracts, covered roughly 1% of the UAA and were mostly intermingled with other farmland habitats in extensively managed agricultural landscapes.In the context of the EU-wide HNVf assessment, IACS constitutes an important source of data, characterized by a high spatial, thematic and temporal resolution of data collected annually. Whilst having the potential for use in HNVf assessment, some challenges remain, especially due to significant access restrictions. Nevertheless, IACS constitutes a powerful tool to evaluate the extent and condition of HNVf across the EU countryside. Making use of IACS data in such a way could provide a stepping-stone towards achieving a more effective balance between the management and control of CAP support payments and the growing societal demands related to the maintenance and enhancement of farmland biodiversity and ecosystem services.     

Review on the worldwide regulatory framework for biosimilars focusing on the Mexican case as an emerging market in Latin America

The global biopharmaceutical market is worth over $100 billion USD. Nearly 90% of these products will lose their patent in the next ten years, leading to the commercialization of their subsequent versions, known as ‘biosimilars’. Biosimilars are much more complex molecules than chemically synthesized generics in terms of size, structure, stability, microheterogeneity, manufacture, etc. Therefore, a specific regulatory framework is needed in order to demonstrate their comparability with innovative products, as well as their quality, safety and efficacy. The EU published the first regulatory pathway in 2005 and has approved 14 biosimilars. Mexico has recently developed a clear regulatory pathway for these products. Their legal basis was established in Article 222 Bis of General Law of Health in 2009, clear specifications in the Regulation for Health Goods in 2011, and further requirements in the Mexican Official Norm NOM-EM-001-SSA1-2012. The aim of this review is to summarize the regulatory pathways for biosimilars in the world with a special focus on Mexican experience, so as contribute to the development of regulations in other countries.     

Comparison of regulatory pathways for the approval of advanced therapies in the European Union and the United States

Background aimsRegulatory agencies in the European Union (EU) and in the United States of America (USA) have adapted and launched regulatory pathways to accelerate patient access to innovative therapies, such as advanced therapy medicinal products (ATMPs). The aim of this study is to analyze similarities and differences between regulatory pathways followed by the approved ATMPs in both regions.MethodsA retrospective analysis of the ATMPs approved by EU and US regulatory agencies was carried out until May 31, 2020. Data were collected on the features and timing of orphan drug designation (ODD), scientific advice (SA), expedited program designation (EP), marketing authorization application (MAA) and marketing authorization (MA) for both regions.ResultsIn the EU, a total of fifteen ATMPs were approved (eight gene therapies, three somatic cell therapies, three tissue-engineered products and one combined ATMP), whereas in the USA, a total of nine were approved (five gene therapies and four cell therapies); seven of these were authorized in both regions. No statistical differences were found in the mean time between having the ODD or EP granted and the start of the pivotal clinical trial or MAA in the EU and USA, although the USA required less time for MAA assessment than the EU (mean difference, 5.44, P = 0.012). The MAA assessment was shorter for those products with a PRIME or breakthrough designation.. No differences were found in the percentage of ATMPs with expedited MAA assessment between the EU and the USA (33.3% versus 55.5%, respectively, P = 0.285) or in the time required for the MAA expedited review (mean difference 4.41, P = 0.105). Approximately half of the products in both regions required an Advisory Committee during the MAA review, and 60% required an oral explanation in the EU. More than half of the approved ATMPs (67% and 55.55% in the EU and the USA, respectively) were granted an ODD, 70% by submitting preliminary clinical data in the EU. The mean number of SA and protocol assistance per product conducted by the European Medicines Agency was 1.71 and 3.75, respectively, and only 13% included parallel advice with health technology assessment bodies. A total of 53.33% of the products conducted the first SA after the pivotal clinical study had started, reporting more protocol amendments. Finally, of the seven ATMPs authorized in both regions, the type of MA differed for only two ATMPs (28.6%), and four out of eight products non-commercialized in the USA had a non-standard MA in the EU.ConclusionsThe current approved ATMPs mainly target orphan diseases. Although EU and US regulatory procedures may differ, the main regulatory milestones reached by the approved ATMPs are similar in both regions, with the exception of the time for MAA evaluation, the number of authorized products in the regions and the type of authorization for some products. More global regulatory convergence might further simplify and expedite current ATMP development in these regions.     

Carbon sequestration potential in European croplands has been overestimated

Yearly, per‐area carbon sequestration rates are used to estimate mitigation potentials by comparing types and areas of land management in 1990 and 2000 and projected to 2010, for the European Union (EU)‐15 and for four country‐level case studies for which data are available: UK, Sweden, Belgium and Finland. Because cropland area is decreasing in these countries (except for Belgium), and in most European countries there are no incentives in place to encourage soil carbon sequestration, carbon sequestration between 1990 and 2000 was small or negative in the EU‐15 and all case study countries. Belgium has a slightly higher estimate for carbon sequestration than the other countries examined. This is at odds with previous reports of decreasing soil organic carbon stocks in Flanders. For all countries except Belgium, carbon sequestration is predicted to be negligible or negative by 2010, based on extrapolated trends, and is small even in Belgium. The only trend in agriculture that may be enhancing carbon stocks on croplands at present is organic farming, and the magnitude of this effect is highly uncertain. Previous studies have focused on the potential for carbon sequestration and have shown quite significant potential. This study, which examines the sequestration likely to occur by 2010, suggests that the potential will not be realized. Without incentives for carbon sequestration in the future, cropland carbon sequestration under Article 3.4 of the Kyoto Protocol will not be an option in EU‐15.     

Plant Biostimulant Regulatory Framework: Prospects in Europe and Current Situation at International Level

This review analyses the current regulatory procedures for plant biostimulants, both at an EU level and beyond the EU, and explores the future regulation of these substances in the EU. Plant biostimulants are defined as products that stimulate plant nutritional processes regardless of the product’s nutrient content, with the sole aim of improving one or more of the following characteristics of the plant and the plant rhizosphere or phyllosphere: the efficiency of nutrient use, tolerance to abiotic stresses, crop quality traits, availability of confined nutrients in the soil and rhizosphere, humification and degradation of organic compounds in the soil. This definition is reported in the proposals for new rules to regulate making CE-marked fertiliser products available on the market. This regulation, which includes a plant biostimulants category, will repeal the existing Fertilisers Regulation (EC) No. 2003/2003. This category of compounds is also used in non-European countries. Currently, as there are different market conditions and different national regulation requirements for plant biostimulants in different countries, the non-harmonised regulatory processes can lead to unfair competition between operators. The assessment of plant biostimulants should be harmonised as far as possible, to avoid fragmentation and ensure a level, reliable playing field. It is essential that a common market is created for these substances.

     

Can the EU agri-environmental aid program be extended into the coastal zone to combat eutrophication?

Eutrophication of coastal waters is a serious environmental problem with high costs for society globally. This is a development which demands immediate environmental action along many coastal sites. Since the 1980s, mussel farming has been recognized by Swedish environmental authorities as a possible measure to improve coastal water quality. Concepts and management strategies on how to increase mussel farming and thus combat coastal marine eutrophication has recently been developed in Sweden. The main principle of this development has been the implementation of nutrient trading as a management tool. This imposes demands on those who emit the pollution through the establishment of emission quotas, which are traded and bought by the emitter. The seller is a nutrient harvesting enterprise, e.g., a mussel farmer. This principle is particularly straightforward when the nutrients are discharged from a point source. When examining the nutrient supply from all diffuse sources, the situation is more complex. However, since the major part of the nutrient supply to coastal waters in many areas of Europe has its origin in agricultural operations, we suggest that the EU agro-environmental aid program could be extended into the coastal zone in order to combat eutrophication. In practice, this should involve support paid to mussel farming enterprises through their harvest of mussels (and thus their harvest of nutrients) in the same way as support is paid to agricultural farmers for operations that reduce nutrient leakage from their farmland. This is a simple, cost-effective and straightforward way of improving coastal water quality at many coastal sites that will, at the same time, provide coastal jobs. However, this eutrophication combat method depends on the EU agro-environmental aid program being extended beyond the shoreline. Guest editors: J. H. Andersen & D. J. Conley Eutrophication in Coastal Ecosystems: Selected papers from the Second International Symposium on Research and Management of Eutrophication in Coastal Ecosystems, 20–23 June 2006, Nyborg, Denmark     

The EU Biocidal Products Directive and the consequences for Dinsinfectants

The title of my presentation suggests or at least anticipates that the EU legislative process, to provide a harmonised regulatory platform for biocides in the EU, has been finalised when this symposium takes place.When adapted and subsequently implemented in the EU member states (estimation Q3 1999), this directive will have a major impact on the market of disinfectants for both the suppliers of active substances and formulators supplying disinfectant products to customers and consumers. This presentation will focus on (technical) regulatory consequences rather than economical or business effects.

• • scope: which products will fall under the regime of this directive, which are excluded?

• • principle: one product—one authorization and mutual recognition; lead times involved?

• • procedure: how will the simplified procedures foreseen (hopefully) help the disinfectant supplier?

• • data requirements: why do the dossier requirements for products and particularly actives need to be so excessively costly and what is the role of risk assessment?

• • transitional arrangements: what can and can't disinfectant suppliers do to keep their products on the market or to introduce new products?

• • review programme: what will happen to the availability of active substances?

The directive itself will not give sufficiient answers to all issues mentioned above to allow a harmonised interpretation across the EU. A number of technical guidance documents is therefore being developed covering Common Principles, Data Requirements and Conditions to include an Active Substance on Annex I. The workability of the whole directive will very much be dependent on the practical details to be dealt with in these documents.Disinfectant suppliers also do recognize the merits of the directive (improved protection of man and the environment, harmonisation across EU, etc.), provided however that it does not undermine the efforts of our industry to deliver better hygiene with safe, effective but also affordable disinfectants.     

Harnessing the biodiversity value of Central and Eastern European farmland

A large proportion of European biodiversity today depends on habitat provided by low‐intensity farming practices, yet this resource is declining as European agriculture intensifies. Within the European Union, particularly the central and eastern new member states have retained relatively large areas of species‐rich farmland, but despite increased investment in nature conservation here in recent years, farmland biodiversity trends appear to be worsening. Although the high biodiversity value of Central and Eastern European farmland has long been reported, the amount of research in the international literature focused on farmland biodiversity in this region remains comparatively tiny, and measures within the EU Common Agricultural Policy are relatively poorly adapted to support it. In this opinion study, we argue that, 10 years after the accession of the first eastern EU new member states, the continued under‐representation of the low‐intensity farmland in Central and Eastern Europe in the international literature and EU policy is impeding the development of sound, evidence‐based conservation interventions. The biodiversity benefits for Europe of existing low‐intensity farmland, particularly in the central and eastern states, should be harnessed before they are lost. Instead of waiting for species‐rich farmland to further decline, targeted research and monitoring to create locally appropriate conservation strategies for these habitats is needed now.