Methodology development in risk assessment

Deadline: Oct 6, 2016  
CALL EXPIRED

1. GRANT OPPORTUNITY AND CONDITIONS1

1.1 LEGAL FRAMEWORK

Article 36 of the Regulation (EC) 178/20022 of the European Parliament and of the Council of 28 January 2002 laying down the general principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in matters of food safety, foresees the possibility to financially support networking of organisations operating in the fields within the EFSA’s mission. Article 36 (1) stipulates that the aim of such networking is, in particular, to facilitate a scientific cooperation framework, the development and implementation of joint projects3, the exchange of expertise and best practices in the fields within the Authority`s mission.

On the 19 December 2006 the Management Board, drew up a list of competent organisations designated by the Member States which may assist EFSA with its mission. This list is regularly updated by EFSA’s Management Board and the updates are published on EFSA’s website.

Article 5 of the Commission Regulation (EC) 2230/20044 of 23 December 2004 laying down detailed rules for the implementation of the European Parliament and Council Regulation (EC) 178/2002 with regard to the network of organisations operating in the fields within the EFSA’s mission specifies that the financial support to the networking organisations shall take the form of subsidies (grants) awarded in accordance with the EFSA’s financial regulation and implementing rules.

The present Call for proposal and guide for applicants (hereinafter referred to as “the Call”) is procedurally governed by:

• Part 1, Title 6 of Commission Delegated Regulation (EU) No 1268/2012 of 29 October 2012 on the rules of application of Regulation (EU) No 966/2012 of the European Parliament and of the Council on the financial rules applicable to the general budget of the Union, as amended by Commission Delegated Regulation (EU) No 2015/2462 of 30 October 2015.

  The present Call for proposal is based on EFSA’s 2016 Work Programme for grants and operational procurements in science – Financing Decision as presented in Annex II of the Programming document 2016 - 2018, available on the EFSA’s website5.

1.2 MAIN OBJECTIVE OF THE CALL

The development, validation, implementation and harmonisation of methodologies and approaches for the assessment of health risks for humans, animals, plants and the environment is one of the key strategic objectives of EFSA. EFSA’s risk assessment methodologies have been described in the form of guidance documents of the Scientific Committee, Panels and Units. The implementation of these guidance documents is regularly reviewed and priorities are set for revision of existing and development of new risk assessment methods in various fields with potentially high impact on human, animal and plant health. To bring forward risk assessment in areas that are still under elaboration, new methods and tools need to be developed and validated in cooperation across EU Member States, reaching for commonly approved methods. Areas which EFSA considers as challenges for the future include the assessment of chemical mixtures, assessment of freedom of animal disease/infection, and the identification of emerging risks.

One of EFSA’s key areas is to support scientific cooperation in Europe and beyond, building on the scientific expertise of Member States, ensure that the scientific work carried out at national level is not duplicated at EU level, and stimulating Member States to contribute to consolidating the EU risk assessment community.
In the context of this call, the main objective is for projects to:

• boost scientific cooperation between EFSA and among Member States through the formation of consortia of national agencies from different EU countries with diverse technical capabilities and expertise,
• be of innovative nature, taking efforts of EFSA and other organisations (e.g. ECHA, EMA, EEA, FAO, WHO, OECD, EPPO, IPPC, ECVAM) into consideration, and

• ensure that the results of the project are transferable and their dissemination is sustainable, with the aim of further enhancing knowledge and competence sharing.
In particular, the action co-financed by this EFSA grant, to be awarded following the present call for proposals, shall develop and validate new methods/tools, making the best use of the scientific data available or generate new data, to be applied in a structured and transparent way for identifying emerging food risks, assessing the risk of mycotoxin mixtures in food and feed, and assessing the freedom of animal disease/infection.

The call for “methodology development in risk assessment” is divided into three different lots:

Lot 1: Methods and systems for the identification of emerging food risks

Lot 2: Integrated methodologies for the risk assessment of mycotoxin mixtures in food and feed

Lot 3:  Output-based methods for the assessment of the freedom of animal disease/infection

1.3 OBJECTIVES OF EACH LOT

Lot 1: Methods and systems for the identification of emerging food risks

Background

Researchers, governments, agencies, food producers and the civil society are increasingly concerned about ‘emerging food risks’. It is recognised that the successful identification of emerging risks is at the heart of protecting public health and the environment, and that this requires worldwide cooperation between all parties involved in the food supply chain.

Identification of emerging risks in the food chain is essential for EFSA to anticipate future needs in risk assessment both on data and methods as well as to support risk managers in anticipating potential risks and taking effective and timely measures to protect consumers. The general food law requires EFSA to establish monitoring procedures for systematically searching for, collecting, collating and analysing information and data with a view to the identification of emerging risks in the fields within its mission. Over the past years, EFSA has been implementing an approach to identify emerging risks. This consists of an operational definition of emerging risks and an overall strategy for the collection, analysis and evaluation of the relevant data and information6,7,8,9,10,11,12,13.

It is recognised that resources for addressing future risks are limited. Therefore, it is of paramount importance that there is coordination of resources, expertise and data across Europe and internationally. To facilitate such wide ranging networking, new methodologies and tools are required to help manage the sharing of complex and rapidly updated data.

MAIN OBJECTIVE

The overall objective of Lot 1 is the establishment of a collaborative platform to support the current EFSA procedure for emerging risks identification10. The platform should allow EU Member State authorities and EFSA to share knowledge, data and methods for the identification of emerging food-related risks in a rapid and effective manner. The project should ensure the interoperability of the information generated by the platform with the EFSA data repository currently under development.

The proponents should present their proposal to achieve the main objective, elaborating on the methodology proposed to create, structure and manage the platform; on the tools to sustain the activities of the platform; and on the coordination of existing knowledge and integration of additional competences, where relevant. The proposal should aim at establishing and testing the platform and methods proposed, and also consider its sustainability after the end of the project.

SPECIFIC OBJECTIVES
1. Development of new tools for automatic data retrieval and validation from multiple sources for emerging

risks identification

This would build on experience gained in text mining, webcrawling, media monitoring approaches, but would also include the development of tools for data mining, particularly of “big data”. Proposals should take into consideration work already existing in EU and non-EU organisations which are putting significant resources in developing and validating methods and tools for identifying emerging risks.

2. Integration of data and methodologies from social sciences into the emerging risk identification process on a farm to fork approach

Further elaboration of methods developed for expert elicitation14 into the emerging risks identification process, but also the use of crowd sourcing and social media. EFSA is also interested in aspects concerning the integration of behavioural science into understanding human behaviour as a driver of the emergence of new risks, and economic indicators and methodologies to assess system vulnerabilities.

3. Set up of a collaborative emerging risk platform to further strengthen EU emerging risks capacity

Propose and implement a methodology to structure, manage and maintain a collaborative platform in the area of emerging food risks. Such platform should enable national food agencies and EFSA to rapidly and effectively share knowledge on e.g. specific emerging risks, methodologies and relevant data sources. In addition, the development of structures and mechanisms for maintenance of such platform, beyond the duration of the grant, would be necessary. The proposal should also demonstrate how the project effectively contributes to the transfer of knowledge and capacity between countries and organizations, involved in emerging risks identification, having different technical expertise and resource availability.

Lot 2: Integrated methodologies for the risk assessment of mycotoxin mixtures in food and feed

Background

Mycotoxins as mixtures are produced mainly by fungi of the genera Aspergillus, Penicillium and Fusarium. They include many food commodities including cereals, fruit and vegetables. Their ubiquitous presence represents a challenge to the health of humans, animals and the environment. Over the last decade, EFSA has been very active in the area of risk assessment of mycotoxins food and feed:

• Scientific opinions dealing with risk assessment of mycotoxins in food and feed. These have included well characterised mycotoxins (e.g. aflatoxins, T-2 and HT-2 toxins, zearalenone, etc.) and emerging mycotoxins (e.g. alternaria toxins, beauvericin, enniatins, etc.) 15,16,17,18,19.

• A grant investigating “modelling, predicting and mapping the emergence of aflatoxins in cereals in the EU due to climate change”20.

  In addition, EFSA has initiated a series of projects dealing with the risk assessment of chemical mixtures in food and feed: review of the frameworks available for the human risk assessment of chemical mixtures, review of modern methods, including toxicokinetics (TK), OMICs and in silico tools, data collection activities, and an EFSA colloquium on the harmonisation of methods for human and ecological risk assessment of mixtures 21,22,23.

  From these activities and from the consultation with EFSA Panels and staff dealing with chemical risk assessment and with other experts from international bodies (ECHA, OECD, WHO, etc.), EFSA has formulated several recommendations to further develop methods for the risk assessment for mixtures. These include the refinement of:

1. The detection and reporting of realistic mixtures in food and feed samples for exposure assessment, and

2. The scientific basis to set cumulative assessment groups/assessment groups for chemicals based on their elimination patterns in a number of organisms (TK) and their combined toxicity profiles (dose addition, response addition, or interaction (i.e. synergistic effects/ antagonism) for further refinement of hazard characterization).

3. Combining the refinements of 1 and 2 for risk characterisation and uncertainty analysis based on realistic mixtures in food and feed 21,22,23.

These recommendations are directly applicable to the refinement of methodologies for risk assessment of mycotoxin mixtures. In practice, mycotoxin data for specific realistic co-occurrence of free and masked/modified mycotoxins are combined with food consumption patterns for exposure assessment, which are then further combined with TK/toxicity profiles for risk characterisation 24,25,26,27,28.

A major challenge is the understanding of the actual production of mycotoxin mixtures and consequently their realistic occurrence in plants and fruit 29. In order to address this challenge, the investigation of complex taxonomic,

biochemical, genetic and environmental variables and conditions that would influence the biosynthesis and occurrence of mycotoxin mixtures in plants is needed. These variables include biosynthetic pathways, species/strain specificity on host species, climate change, temperature, resistance of the individual strains to fungicides and associated mechanisms, availability of nutrients and mycotoxin precursors etc. to name but a few 30; Medina., 2013;31,32.

MAIN OBJECTIVE

The main objective of Lot 2 is to develop integrated innovative methods for the risk assessment of mixtures, using mycotoxins as a case study for the development of a holistic approach, from synthesis in primary production to effects on human health, animal health and environment. It is foreseen that these methods will be applied in the future by risk assessors dealing with mycotoxin mixtures for the food and feed area.

SPECIFIC OBJECTIVES
1. Extensive literature searches and structured data collection on biochemical, genetic and environmental

variables and their impact on mycotoxin production

These extensive literature searches (ELS) should review key environmental conditions and variables, that would influence the biosynthesis and occurrence of mycotoxin mixtures in plants of relevance to food and feed safety, including biosynthetic pathways, species or strain specificity of mycotoxin(s) production on host specie(s), resistance to fungicides and their mechanisms, influence of climate change, temperature, season, nutrient availability (e.g. amino acid etc.), other stressors, etc. The ELS should consider all available reviews, available Member States’ data and individual primary research studies of relevance such as laboratory studies, field studies, molecular, OMIC studies, occurrence data of free and masked/modified mycotoxins on plants and fruit, and available in silico computer models. The summary statistics from each individual study should be computed in a structured database that will be designed by the beneficiary in collaboration with EFSA.

2. Extensive literature searches and structured data collection on realistic occurrence of mycotoxin mixtures, toxicokinetics and combined toxicity in animals and humans

These ELS should review TK and toxicity data for single and combined mycotoxins in livestock, fish and humans. The ELS should consider all available reviews, available Member States’ data and individual primary research studies of relevance including laboratory studies, OMIC studies, blood, plasma and urine concentrations of parent/metabolite(s) free and masked/modified mycotoxins as single compound (s)/realistic mixtures, and available in silico computer models (e.g. TK, physiologically-based-TK, PB-TK-toxicodynamic). Summary statistics from each individual study should be computed in a structured database including TK and toxicity endpoints for each species (e.g. absorption, distribution, metabolism, excretion, half-life, clearance, acute, sub-chronic and chronic toxicity using lethal and sub-lethal endpoints etc.). Data describing and quantifying the metabolic or the toxicological basis for species tolerance to mycotoxins should also be collected. The structured database should follow the data model from EFSA‘s chemical hazards database that will be provided by EFSA at the kick-off meeting.

3. An integrated approach to the risk assessment of mycotoxin mixtures using modelling

The data from A and B should be integrated using modelling techniques (e.g. Monte Carlo modelling using frequentist/Bayesian methods) to develop an integrated method for the risk assessment of mycotoxin mixtures in humans and animals. The modelling should aim to combine the environmental variables with the TK and toxicity data to support risk assessment using a whole food chain approach (from the environment to the internal dose including carry over in farm animals and toxicity) and a comparative approach to mycotoxin toxicity in vertebrates. At least five realistic case studies should be developed for mycotoxin mixtures and illustrated for the risk characterisation of such mixtures in animal species and humans. Uncertainties and data gaps should be described and discussed.

Lot 3: Output-based methods to assess the freedom of animal disease/infection

BACKGROUND

Each year, the EU provides financial support to eradicate, control and prevent various animal diseases. A report from the Commission to the European Parliament and the Council on the outcome of the EU co-financed programmes over the period of 2005-201133 shows that, in most cases, the benefit of these activities is evidenced by the continuous expansion of disease-free zones in the EU34. For those diseases, the EU legislation defines and sets all the necessary standards for the Member States to carry over the relevant countermeasures.

However, not all animal diseases are regulated by relevant EU legislation and for these diseases Member States can adopt countermeasures on a voluntary basis. This means also that the choice of the type of intervention, and the way of implementing it, are left to the Member States. As a consequence, for the same disease, different types of interventions can be adopted with very different standards, making any comparison of the available information originating from those activities very difficult. Because of different regions and countries operating differently designed control programs, an assessment of the risk of introduction of infection arising from movements of susceptible species between regions or countries is difficult.

Output-based surveillance techniques (e.g. estimation of the surveillance system sensitivity, freedom from disease probability, etc.) provide a valid support to achieve harmonised and comparable surveillance activities while allowing flexible approaches that are adapted to the different populations under surveillance35.

However, despite the theoretical background for demonstrating ‘Freedom from Disease/Infection’ being well known and broadly accepted, the practical implementation in the field represents a challenging task. In recent works issued by EFSA, where the ‘Freedom from Disease/Infection’ methodology was adopted, gaps regarding the reporting tools and the certainty around the parameters needed to implement the ‘Freedom from Disease/Infection’ methodology (e.g. the target population size, the diagnostic test sensitivity, etc.) were identified.

MAIN OBJECTIVE

Considering all these aspects, the main objective of Lot 3 is to develop a framework that could enable to evaluate, standardise and compare the outcomes of different control programmes for non-regulated diseases, with particular emphasis on the confidence of freedom at different level of aggregation (animal, herd, area, country, etc.)36. The framework should allow estimating if a given entity is truly free from infection with a given non-regulated disease considering the control or eradication program applied37. Such a framework will also be useful in the context of the new Animal Health Law, which foresees the implementation of voluntary surveillance activities for non-regulated diseases by the Member States. Furthermore, the development and implementation of such a harmonised methodology would strengthen the European risk assessment capacity in the area of animal disease control.

SPECIFIC OBJECTIVES

1. Development of a method for the comparison of the outcomes of different control programmes for non- regulated diseases, with a view to confidence of freedom, for different epidemiological units. The method should allow heterogeneous data inputs, but generate comparable outputs. The uncertainty related to the latter, should be thoroughly assessed and described.

2. Development of a framework describing the non-regulated disease control activities implemented in the different EU Member States. The framework should include a database populated with the relevant parameters of the developed method (e.g. test performance, type and purpose of the sampling activity, etc.), in line with, but not

necessarily restricted to, the existing EFSA standards38, and of a descriptive summary of the available information.

3. Implementation of the framework in a case study on a specific disease for validation. It is expected that the outcome of this exercise will lead to the identification of the most problematic aspects in the harmonisation process, providing feedback to improve the developed framework. The case study could also be a good opportunity to explore the concept of “expected cost of error”, which combines probability and consequences of

surveillance failure: this parameter is of primary importance for the design of the surveillance activities, to set consistent design prevalence.

A plan for communicating the developed methodology and results with the aim of transferring the acquired knowledge to stakeholders and risk managers, with a special emphasis on the advantages that such a methodology could bring at all levels, from the farm, through trade, to the consumer.

Applicable to all lots:
Duration of the project - The Call for Proposals does not specify the duration and any details on the end date of the proposed projects. It is up to the applicant consortium to decide the duration of the project proposed.

1.4 ELIGIBLE ORGANISATIONS

In order to achieve the main objective of the call, the proposal must be submitted in a consortium of at least two eligible organisations, from (at least) two different EU countries, Norway or Iceland. One of the partners must be identified in the proposal as the consortium leader (= applicant). The applicant is responsible for identifying consortium partners.

The applicant may submit an application for one or more lots but each proposal should indicate clearly for which lot you apply. In the case you decide to apply for more than one lot, a separate proposal must be provided for each lot. For the material composition of the proposal, please consult the checklist in the Application Form (Annex 4).
To be eligible, the applicant and partner/s must be on the List of competent organisations designated by the Member States in accordance with Article 36 of Regulation (EC) 178/2002. This list is regularly updated by EFSA Management Board and the latest update is published on EFSA’s website.

Searching for consortium partner(s) among Article 36 organisations can be supported by contact persons of the Article 36 organisations accessing the Article 36 Search Tool39, or your EFSA national Focal Point40 for support.