European Union: EFSA Issues Guidance for the Risk Assessment of Genetically Modified Plants and Derived Food and Feed

Originally published March 2005

The European Food Safety Authority ("EFSA") has published guidance¹ to assist with the preparation and presentation of applications for authorisation of GM food and/or feed under Regulation 1829/2003 on GM food and feed and applications to authorise the placing on the market of genetically modified organisms ("GMOs") under Directive 2001/18 on the deliberate release into the environment of genetically modified organisms.

The guidance was prepared by the Scientific Panel on Genetically Modified Organisms ("GMO Panel") of the EFSA at the request of the European Commission. It was finalised and published in November 2004, following extensive stakeholder consultation that began in April 2004. It updates and replaces guidance issued by the Joint Working Group on Novel Foods and GMOs in March 2003 on the risk assessment of genetically modified plants and derived food and feed. However it does not replace a number of Council and Commission Decisions made within the framework of Directive 2001/18 which remain applicable.²

Under Regulation 1829/2003, only GM food and feed that has been authorised may be placed on the market in the EU. Authorisation requires a scientific assessment of any risks which they may present to human and/or animal health or to the environment. GM food and feed means: GMOs for food/feed use; food/feed containing or consisting of GMOs; food/feed produced from GMOs; and food containing ingredients produced from GMOs. Among others, Regulation 1829/2003, which has applied as of 18 April 2004, requires that in order to be authorised GM food/feed must not:

• Have adverse effect on human health, animal health or the environment

• Mislead the consumer/user

• Differ from the food/feed which it is intended to replace to such an extent that its normal consumption would be nutritionally disadvantageous for the consumer/animal.

Directive 2001/18 sets out the principles and conditions regulating the deliberate release into the environment of GMOs. It set out a step-by-step approval procedure for risk assessment in respect of human health and the environment prior to the approval and release into the environment of GMOs.

Regulation 1829/2003 and Directive 2001/18 are closely linked. In particular, in the case of food and/or feed containing or consisting of GMOs, the applicant has the choice of either supplying an authorisation of the deliberate release into the environment already obtained under part C of Directive 2001/18 (without prejudice to the conditions set out by that authorisation) or of applying for the environmental risk assessment carried out at the same time as the safety assessment under Regulation 1829/2003. The interplay between this legislation, and between these measures and other related Directives or Regulations, is discussed in detail in Part I of the guidance document.

The scope of the guidance is set out in Part I of the guidance document. The guidance covers applications for the authorisation of GM food and feed, including feed for animals not intended to be used for food production. Food additives, flavourings and feed additives containing, consisting of or produced from GM plants also fall within the scope of the guidance.

However the guidance does not cover:

• risk management issues such as traceability, labelling and co-existence

• socio-economic and ethical issues

• the deliberate release of GMOs into the environment for experimental purposes (under Part B of Directive 2001/18/EC)

• the contained use of genetically modified microorganisms ("GMMs") (under Directive 90/219/EEC)

• the placing of food and/or feed consisting of, containing or produced from GMMs (under Regulation 1829/2003)

• the deliberate release into the environment of genetically modified animals or

• the placing on the market of food and/or feed consisting of, containing or produced from genetically modified animals (under Regulation 1829/2003).

Separate guidance is being prepared by the EFSA's GMO Panel for food and feed containing, consisting of or produced from GMMs.

Part I of the guidance also sets out the legal background for the risk assessment of GMOS and GM food and feed at Community level. It summaries the main principles of the relevant EU Regulations, Directives and Decisions and explains how they interplay. In particular, in addition to Regulation 1829/2003 and Directive 2001/18, the key text is Regulation 178/2002 laying down the general principles of food law and procedures in food safety including the tasks of the EFSA³. Among others Regulation 178/2002 defines "hazard", "risk", "risk analysis", "risk assessment", "risk management" and "risk communication", all of which terms are used in the guidance document.

Part II of the guidance sets out the risk assessment strategy for GMOs. Risk assessment is defined in Regulation 178/2002 as "a scientifically based process consisting of four steps: hazard identification, hazard characterisation, exposure assessment and risk characterisation." In respect of GMOs, the guidance suggests that the sequential steps in risk assessment identify characteristics which may cause adverse effects, evaluate their potential consequences, assess the likelihood of occurrence and estimate the risk posed by each identified characteristic of the GMOs.

The risk assessment strategy envisaged in the guidance is essentially a comparative approach in which, using appropriate methods and tools, the GMO and its derived product(s) are compared with its non-GM counterpart(s). The underlying assumption is that traditionally cultivated plants have gained a history of safe use for the normal consumer or animal and the environment and therefore may serve as a baseline for the environmental and food/feed safety assessment of GMOs. This approach relies upon the concepts of "familiarity" and "substantial equivalence", both of which were developed originally by the OECD in 1993⁵ and elaborated further by the WHO/FAO in 2000.⁶ In summary, familiarity refers to the fact that most GM plants are developed from organisms or crop plants whose biology is well researched. Substantial equivalence, meanwhile, is based on the fact that an existing organism with a safe history of use as food or feed can serve as a comparator when assessing safety of GM food or feed.

On a case-by-case basis, data on composition, toxicity, allergenicity, nutritional value and environmental impact provide the cornerstones of the Community's risk assessment process. In particular, it describes the issues to be taken into account when carrying out a comprehensive risk assessment. These include:

• molecular characterisation of the inserts

• assessment of the modification to the agronomic characteristics of the GM plant, and

• evaluation of food/feed safety aspects of the GM plant and/or derived food and feed.

The risk assessment of GMOs and their derived products described in the guidance is a two step process. First, the differences (both intentional and non-intentional) between the GMO (and the derived products) and their non-GM counterparts are identified. Second, an assessment is made of the effect that these identified differences have on the environment and on food/feed safety and nutrition.

When a product is likely to be used both for food and feed purposes an application must fulfil the relevant requirements of both food and feed.

Part III considers in detail the type of information that is required in applications for authorisation of GM plants and/or derived food and feed. This includes, for example, general information requirements, such as those regarding the applicant, the title of the project and a description of the method of production and manufacturing and/or the conditions for placing on the market the food(s) or feed(s) produced from it, including specific conditions for use and handling.

In addition, detailed guidance is given in respect of the requirements for the provision of data and information in respect of, among others:

• molecular data

• the trait and the changes that the GM makes to the plant phenotype and related information

• the expression of the insert, on how the GM plant differs from the recipient plant in reproduction, dissemination and survivability

• genetic stability of the insert and phenotypic stability of the GM plant

• any change to the ability of the GM plant to transfer genetic material to other organisms

• any toxic, allergenic or other harmful effects on human or animal health arising from the GM food/feed

• the anticipated intake and/or extent of use

• nutritional assessment of GM food/feed.

Part IV of the guidance summarises the overall risk characterisation of GM plants in respect of food/feed safety and environmental impact. It describes how a risk characterisation should be carried out in a holistic manner and on a case-by-case basis, depending on the type of genetic modification, and what factors should be considered in doing so. Risk characterisation for these purposes is defined as "the quantitative or semi-quantitative estimate including attendant uncertainties, of the probability of occurrence and severity of adverse effect(s)/event(s) in a given population under defined conditions based on hazard identification, hazard characterisation and exposure assessment."⁷

The document notes that an extensive overview of risk assessment procedures is provided by the EU's Scientific Steering Committee ("SSC") in opinions issued in 2000⁸ and in 2003⁹. In addition, it highlights detailed strategies for risk assessment and risk characterisation of foods derived from GM plants described recently by the European Network on Safety Assessment of Genetically Modified Food Crops^{10 11}, for chemicals in food and diet by Food Safety in Europe¹², and for environmental risk assessment by the European Community¹³.

According to the guidance, the final risk characterisation should result in informed qualitative, and where possible quantitative, guidance to risk managers. It should state clearly what assumptions have been made during the risk assessment in order to predict the probability of occurrence and severity of adverse effect(s)/event(s) in a given population and/or on the environment, together with the nature and magnitude of uncertainties associated with establishing these risks.

To this end, it should, according to the guidance, include:

• whether the cultivation of GM plants is as safe for the environment as the cultivation as non- GM plants

• whether the consumption of foods/feed derived from GM plants is as safe for humans/animals as the conventional counterparts

• specific conditions for GM crop cultivation, if required

• the scientific basis for different options to be considered for risk management.

The guidance notes that the characterisation of risk may give rise to the need for further specific activities including, for example, post-market monitoring of the GM food/feed and/or for the environmental monitoring of GM plants.

The guidance also provides in Annex information and model formats for the presentation of applications and related data, including the format of technical dossiers, of the summary applications and the submission of samples to the European Commission's Joint Research Centre.

The guidance is available on the EFSA's website at: http://www.efsa.eu.int

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