(a) genetically modified plants for food or feed uses; (b) food or feed containing or consisting of genetically modified plants; (c) food produced from or containing ingredients produced from genetically modified plants or feed produced from such plants.
Commission Implementing Regulation (EU) No 503/2013 of 3 April 2013 on applications for authorisation of genetically modified food and feed in accordance with Regulation (EC) No 1829/2003 of the European Parliament and of the Council and amending Commission Regulations (EC) No 641/2004 and (EC) No 1981/2006 Text with EEA relevance
(a) be submitted in accordance with the requirements for the preparation and presentation of applications set out in Annex I; (b) contain all the information required by Annex I, in accordance with the specific requirements of Articles 4, 5 and 6.
(a) the summaries and results of the studies referred to in the application; (b) annexes where detailed information on those studies is provided.
(a) requirements of Directive 2004/10/EC; or (b) "OECD Principles on Good Laboratory Practice" (GLP), if carried out outside the Union.
(a) comply with the principles of Good Laboratory Practice (GLP) laid down in Directive 2004/10/EC; or (b) be conducted by organisations accredited under the relevant ISO standard.
(a) particular information is not necessary owing to the nature of the genetic modification or of the product; or (b) it is not scientifically necessary, or technically possible to supply such information.
(a) that specific recommendations of uses are followed by the consumer/animal owner; (b) the predicted consumption of the genetically modified food or feed; or (c) the relevance and intensity of effects and unintended effects detected during the pre-market risk assessment which can only be further characterised by post-market monitoring.
(a) developed to collect reliable information with respect to one or several of the aspects set out in paragraph 1. This information shall allow the detection of indications on whether any (adverse) effect on health may be related to genetically modified food or feed consumption; (b) based on strategies aiming at collecting relevant information from specific stakeholders including consumers and on a reliable and validated flow of information between the different stakeholders. More specific strategies shall be included when data on individual intakes of a specific food item or intakes of particular age groups have to be collected; (c) accompanied by adequate justification and a thorough description of the selected methodologies for the proposed post-market monitoring including aspects related to the analysis of the collected information.
(a) the methods for detection and identification of the transformation event; (b) samples of food or feed and their control samples, and information as to the place where the reference material can be accessed.
(a) the methods for detection and identification of the transformation event; (b) samples of food or feed and their control samples, and information as to the place where the reference material can be accessed,
(a) a thorough description of the quality assurance system under which such studies were performed; and (b) comprehensive information on the protocols and the results obtained from the studies including the raw data.
(1) Article 1 is replaced by the following: "Article 1 This chapter provides detailed rules concerning applications for authorisation submitted in accordance with Articles 5 and 17 of Regulation (EC) No 1829/2003 except for those applications covered by Commission Implementing Regulation (EU) No 503/2013 OJ L 157, 8.6.2013, p. 1 .";----------------------OJ L 157, 8.6.2013, p. 1 .";(2) Articles 5 to 19 are deleted.
(1) in Article 2, point (a) is replaced by the following: "(a) "full validation procedure" means: (i) the assessment through a ring trial involving national reference laboratories of the method performance criteria set by the applicant as compliant with the document entitled "Definition of minimum performance requirements for analytical methods of GMO testing" referred to: in the case of genetically modified plants for food or feed uses, food or feed containing or consisting of genetically modified plants and food produced from or containing ingredients produced from genetically modified plants or feed produced from genetically modified plants, in point 3.1.C.4 of Annex III to Commission Implementing Regulation (EU) No 503/2013 OJ L 157, 8.6.2013, p. 1 .";in all other cases, in point 1(B) of Annex I to Regulation (EC) No 641/2004;
and (ii) the assessment of the precision and trueness of the method provided by the applicant.
----------------------OJ L 157, 8.6.2013, p. 1 .";(2) in Article 3(2), the first and second subparagraphs are replaced by the following: "2. The CRL shall request the applicant to pay an additional contribution of EUR 60000 where a full validation procedure of a method of detection and identification for a single GMO event according to the requirements laid down in the following provisions is required:(a) Annex III to Implementing Regulation (EU) No 503/2013, when the application is related to: (i) genetically modified plants for food or feed uses; (ii) food or feed containing or consisting of genetically modified plants; (iii) food produced from or containing ingredients produced from genetically modified plants or feed produced from such plants; or
(b) point 1(B) of Annex I to Regulation (EC) No 641/2004, in all other cases.
That amount shall be multiplied by the number of GMO events to be fully validated.".
(a) Genetically modified food Food containing or consisting of genetically modified plants Food produced from genetically modified plants or containing ingredients produced from genetically modified plants (b) Genetically modified feed Feed containing or consisting of genetically modified plants Feed produced from genetically modified plants (c) Genetically modified plants for food or feed uses Products other than food and feed containing or consisting of genetically modified plants with the exception of cultivation Seeds and other plant propagating material for cultivation in the Union.
(i) family name; (ii) genus; (iii) species; (iv) subspecies; (v) cultivar, breeding line; (vi) common name;
(i) information concerning reproduction: mode(s) of reproduction; specific factors affecting reproduction (if any); generation time;
(ii) sexual compatibility with other cultivated or wild plant species; (iii) survivability: ability to form structures for survival or dormancy; specific factors, if any, affecting survivability;
(iv) dissemination: ways and extent of dissemination (to include, for example, an estimation of how viable pollen and/or seed declines with distance); special factors affecting dissemination, if any;
(v) geographical distribution within the Union of the sexually compatible species; (vi) where a plant species is not grown in the Union, a description of the natural habitat of the plant, including information on natural predators, parasites, competitors and symbionts; (vii) other potential interactions of the genetically modified plant with organisms in the ecosystem where it is usually grown, or used elsewhere, including information on toxic effects on humans, animals and other organisms.
(a) Plant to bacteria gene transfer; (b) Plant to plant gene transfer.
(a) The name and contact details of the applicant for a decision for domestic use; (b) The name and contact details of the authority responsible for the decision; (c) Name and identity of the GMO; (d) Description of the gene modification, the technique used, and the resulting characteristics of the GMO; (e) Any unique identification of the GMO; (f) Taxonomic status, common name, point of collection or acquisition, and characteristics of recipient organism or parental organisms related to biosafety; (g) Centres of origin and centres of genetic diversity, if known, of the recipient organism and/or the parental organisms and a description of the habitats where the organisms may persist or proliferate; (h) Taxonomic status, common name, point of collection or acquisition, and characteristics of the donor organism or organisms related to biosafety; (i) Approved uses of the GMO; (j) A risk assessment report consistent with Annex II to Directive 2001/18/EC; (k) Suggested methods for the safe handling, storage, transport and use, including packaging, labelling, documentation, disposal and contingency procedures, where appropriate.
(a) a proposal for labelling in all official languages of the Union, where a proposal for specific labelling is required in accordance with Articles 5(3)(f) and 17(3)(f) of Regulation (EC) No 1829/2003; (b) either a reasoned statement that the food or feed does not give rise to ethical or religious concerns or a proposal for labelling in all official languages of the Union as required by Articles 5(3)(g) and 17(3)(g) of Regulation (EC) No 1829/2003; (c) when appropriate a proposal for labelling complying with the requirements of point A(8) of Annex IV to Directive 2001/18/EC.
| No | | |
| Yes | | (in that case, specify) |
| Yes | | |
| No | | (in that case, provide risk analysis data on the basis of the elements of Part B of Directive 2001/18/EC) |
| No | | |
| Yes | | (in that case, specify) |
| No | | |
| Yes | | In that case, specify the third country, the date of application and, where available, a copy of the risk assessment conclusions, the date of the authorisation and the scope of the application |
(i) In the EU (ii) In EU export markets
1. "hazard identification" means the identification of biological, chemical and physical agents capable of causing adverse health effects and which may be present in a particular food and feed or group of foods and feeds; 2. "hazard characterisation" means the qualitative and/or quantitative evaluation of the nature of the adverse health effects associated with biological, chemical and physical agents which may be present in food and feed; 3. "risk characterisation" means the qualitative and/or quantitative estimation, including attendant uncertainties, of the probability of occurrence and severity of known or potential adverse health effects in a given population based on hazard identification, hazard characterisation and exposure assessment.
(a) stability of the transformation events; (b) expression of the transformation events; (c) potential synergistic or antagonistic effects resulting from the combination of the transformation events shall be subject to an assessment in accordance with Sections 1.4 (Toxicology), 1.5 (Allergenicity) and 1.6 (Nutritional assessment).
(a) evaluate all issues of potential concern, such as the presence of natural toxins or allergens; (b) identify the need for specific analyses.
(a) Complete name: (i) family name; (ii) genus; (iii) species; (iv) subspecies; (v) cultivar/breeding line or strain; (vi) common name.
(b) Geographical distribution and cultivation of the plant, including its distribution within the Union. (c) Information on the recipient or parental plants relevant to their safety, including any known toxicity or allergenicity. (d) Data on the past and present use of the recipient plant. This information shall include the history of safe use for consumption as food or feed, information on how the plant is typically cultivated, transported and stored, whether special processing is required to make the plant safe to eat, and describe the normal role of the plant in the diet (such as which part of the plant is used as a food or feed source, whether its consumption is important in particular subgroups of the population, what important macro- or micro-nutrients it contributes to the diet).
(a) to identify the nucleic acid(s) intended for transformation and related vector sequences potentially delivered to the recipient plant; (b) to characterise the nucleic acid(s) actually inserted in the plant.
(a) the method of genetic transformation including relevant references; (b) the recipient plant material; (c) the species and the strain of Agrobacterium and other microbes, if used during the genetic transformation process;(d) the helper plasmids, if used during the genetic transformation process; (e) the source of carrier nucleic acid(s), if used during the genetic transformation process.
(a) a physical map of the functional elements and other plasmid/vector components together with the relevant information needed for the interpretation of the molecular analyses (such as restriction sites, the position of primers used in polymerase chain reaction (PCR), the location of probes used in Southern analysis). The region intended for insertion shall be clearly indicated; (b) a table identifying each component of the plasmid/vector (including the region intended for insertion), its size, its origin and its intended function.
(a) the complete sequence of the nucleic acid(s) intended to be inserted, including information on any deliberate alteration(s) to the corresponding sequence(s) in the donor organism(s); (b) the history of safe use of the gene product(s) arising from the regions intended for insertion; (c) data on the possible relationship of the gene products with known toxins, anti-nutrients and allergens.
taxonomic classification; history of use regarding food and feed safety.
(a) the size and copy number of all detectable inserts, both complete and partial; this is typically determined by Southern analysis. Probe/restriction enzyme combinations used for this purpose shall provide complete coverage of sequences that could be inserted into the genetically modified plant, such as any parts of the plasmid/vector or any carrier or foreign nucleic acid(s) remaining in the genetically modified plant. The Southern analysis shall span the entire transgenic locus(i) as well as flanking sequences and include all appropriate controls. For the determination of copy number of the insert, complementary methods may also be used (such as real-time PCR); (b) the organisation and sequence of the inserted genetic material at each insertion site in a standardised electronic format, with the aim of identifying changes in the inserted sequences compared to the sequence intended for insertion; (c) in the case of deletion(s), size and function of the deleted region(s), whenever possible; (d) subcellular location(s) of insert(s) (nucleus, chloroplasts, mitochondria, or maintained in a non-integrated form) and methods for its/their determination; (e) sequence information in a standardised electronic format for both 5’ and 3’ flanking regions at each insertion site, with the aim of identifying interruptions of known genes. Bioinformatic analyses shall be conducted using up-to-date databases with the aim of performing both intraspecies and interspecies similarity searches. In the case of genetically modified plants containing stacked transformation events, the safety of potential interactions between any unintended modifications at each insertion site shall be assessed; (f) Open Reading Frames (hereafter referred to as "ORFs" and defined as any nucleotide sequence that contains a string of codons that is uninterrupted by the presence of a stop codon in the same reading frame) created as a result of the genetic modification either at the junction sites with genomic DNA or due to internal rearrangements of the insert(s). The ORFs shall be analysed between stop codons, not limiting their lengths. Bioinformatic analyses shall be conducted to investigate possible similarities with known toxins or allergens using up-to-date databases. The characteristics and versions of the databases shall be provided. Depending on the information gathered, further analyses (such as transcription analysis) may be needed to complete the risk assessment.
to demonstrate whether the inserted/modified sequence results in intended changes at the protein, RNA and/or metabolite levels; to characterise the potential unintended expression of new ORFs identified under point 1.2.2.2(f) as raising a safety concern.
(a) The method(s) used for expression analysis together with their performance characteristics; (b) Information on developmental expression of the insert during the life cycle of the plant. The requirement for information on developmental expression shall be considered on a case-by-case basis taking into account the promoter used, the intended effect(s) of the modification and scope of the application; (c) Parts of the plant where the insert/modified sequences are expressed; (d) Potential unintended expression of new ORFs identified under point 1.2.2.2(f) which raise a safety concern; (e) Protein expression data, including the raw data, obtained from field trials and related to the conditions in which the crop is grown. Data on expression levels from those parts of the plant used for food and feed purposes shall be provided in all cases. In addition, information shall also be provided on the expression of target genes in other parts of the plant when tissue-specific promoters have been used and when this is relevant for the safety assessment. The minimum requirement for protein expression shall be data provided from three growing sites or from one site over three seasons. Permutations of the sites and seasons shall be acceptable provided that the minimum requirement is met. When justified by the nature of the insert (such as silencing approaches or where biochemical pathways have been intentionally modified), specific RNA(s) or metabolite(s) shall be analysed. For silencing approaches by RNAi expression, potential "off target" genes should be searched by in silico analysis to assess if the genetic modification could affect the expression of other genes which raise safety concerns;(f) With regard to the stacking of transformation events by conventional crossing, expression data shall be provided to assess the potential interactions between the events which may raise any additional safety concerns over protein and trait expression compared with the single transformation events. The comparison shall be carried out with data obtained from plants grown in the same field trials. On a case-by-case basis, and where concerns arise, additional information may be necessary.
(a) to demonstrate the genetic stability of the transgenic locus(i) and the phenotypic stability and inheritance pattern(s) of the introduced trait(s); (b) in case of stacked transformation events, to establish that each of the transformation events stacked in the plant has the same molecular properties and characteristics as in the plants with the single transformation events.
(a) in composition, agronomic performance and phenotypic characteristics (intended and unintended alterations) between the genetically modified plant and its conventional counterpart; (b) in composition between the genetically modified food and feed and its conventional counterpart.
(i) a test of difference, to verify whether the genetically modified plant is different from its conventional counterpart and might therefore be considered a hazard depending on the type of the identified difference, and on the magnitude and type of exposure; (ii) a test of equivalence to verify whether the genetically modified plant is equivalent or not to non-genetically modified reference varieties, apart from the introduced trait(s).
(i) the conventional counterpart and, where appropriate, additional comparator(s) shall always occur together with the genetically modified plant in the same block; (ii) all the different genetically modified plants and their comparator(s) and all the non-genetically modified reference varieties used to test equivalence with those genetically modified plants shall be fully randomised within each block.
(i) the conventional counterpart shall always occur together with its particular genetically modified plant in the same block; (ii) all of the non-genetically modified reference varieties shall appear in each of the incomplete blocks and be fully randomised with the plants and their comparator(s).
(a) the assumptions underlying the analysis; (b) full specification of the mixed models chosen, including fixed and random effects; (c) results of any test of interaction between the test materials and sites; (d) fixed effects, together with the appropriate estimated residual variation with which they are compared, and variance components for the random factors; (e) estimated degrees of freedom; (f) any other relevant statistics.
A. Regarding test of difference, each outcome from the graph shall be categorised as follows and the respective appropriate conclusion shall be drawn. (i) Outcome types 1, 3 and 5: the confidence interval bar overlaps with the line of no-difference. The null hypothesis of no difference cannot be rejected and the appropriate conclusion is that there is insufficient evidence that the genetically modified crop and its conventional counterpart differ. (ii) Outcome types 2, 4, 6 and 7: the confidence interval bar does not overlap with the line of no-difference. The null hypothesis of no difference must be rejected and the appropriate conclusion is that the genetically modified crop is significantly different from its conventional counterpart.
B. Regarding test of equivalence, each outcome from the graph shall be categorised as follows, and the respective appropriate conclusion shall be drawn. (i) Outcome types 1 and 2 (category (i), Figure 1): both confidence limits lie between the adjusted equivalence limits and the null hypothesis of non-equivalence is rejected. The appropriate conclusion is that the genetically modified crop is equivalent to the set of non-genetically modified reference varieties. (ii) Outcome types 3 and 4 (category (ii), Figure 1): the mean of the genetically modified crop lies between the adjusted equivalence limits, but the confidence interval bar overlaps at least one of the adjusted equivalence limits on the graph. Non-equivalence cannot be rejected and the appropriate conclusion is that equivalence between the genetically modified crop and the set of non-genetically modified reference varieties is more likely to be the case than lack of equivalence. (iii) Outcome types 5 and 6 (category (iii), Figure 1): the mean of the genetically modified crop lies outside the adjusted equivalence limits, but the confidence interval bar overlaps with at least one of the adjusted equivalence limits. Non-equivalence cannot be rejected and the appropriate conclusion is that lack of equivalence between the genetically modified crop and the set of non-genetically modified reference varieties is more likely to be the case than equivalence. (iv) Outcome type 7 (category (iv), Figure 1): both confidence limits lie outside the adjusted equivalence limits. The appropriate conclusion is that there is lack of equivalence between the genetically modified crop and the set of non-genetically modified reference varieties.
In the case of significant difference and/or lack of equivalence for any particular endpoint, further statistical analysis shall be carried out to assess whether there are interactions between any of the test materials and site, possibly using a simple standard ANOVA approach. Whatever approach is adopted, details shall be given, for each endpoint analysed, listing: (a) the assumptions underlying the analysis, and, when appropriate: (b) degrees of freedom; (c) the estimated residual variation for each source of variation, and variance components; (d) any other relevant statistics. These additional analyses are intended to aid the interpretation of any significant differences found and to study potential interactions between test materials and other factors. More detailed guidance for the application of the requirements of this Section is available in the EFSA opinion on "Statistical considerations for the safety evaluation of GMOs" EFSA Journal 2010; 8(1):1250.
(a) whether agronomic and phenotypic characteristics of the genetically modified plant are, except for the introduced trait(s), different to the characteristics of its conventional counterpart and/or equivalent to the reference varieties, taking into account natural variation; (b) whether compositional characteristics of the genetically modified food and feed are, taking into account natural variation, different to the characteristics of its conventional counterpart and/or equivalent to the reference varieties, except for the introduced trait(s); (c) characteristics for which the genetically modified plant or the genetically modified food and feed are different to the characteristics of its conventional counterpart and/or not equivalent to the reference varieties taking into account natural variation, which need further investigation; (d) whether, in the case of transformation events stacked by conventional crossing, there are indications of interactions between the combined transformation events.
(a) demonstrate that the intended effect(s) of the genetic modification has no adverse effects on human and animal health; (b) demonstrate that unintended effect(s) of the genetic modification(s) identified or assumed to have occurred based on the preceding comparative molecular, compositional or phenotypic analyses, have no adverse effects on human and animal health; (c) identify potential adverse effects of new constituents and determine their highest dose level that does not result in adverse effects. From data obtained from an appropriate animal study, an acceptable daily intake (ADI) of single compounds by humans may be derived by using uncertainty or safety factors that take into account differences between test animal species and humans, and inter-individual variations among humans; (d) identify potential adverse effects on the whole genetically modified food/feed or address remaining uncertainties through the performance of 90-day feeding studies.
(a) A molecular and biochemical characterisation of the newly expressed protein, including determination of the primary structure, molecular weight (for example using mass spectrometry), studies on post-translational modifications and a description of its function. In the case of newly expressed enzymes, information on the enzyme activities including the temperature and pH range for optimum activity, substrate specificity, and possible reaction products shall also be provided. The potential interaction with other plant constituents shall also be evaluated. (b) An up-to-date search for homology to proteins known to cause adverse effects, such as toxic proteins. A search for homology to proteins exerting a normal metabolic or structural function may also contribute valuable information. The database(s) and the methodology used to carry out the search shall be specified. (c) A description of the stability of the protein under relevant processing and storage conditions and the expected treatment of the food and feed. The influences of temperature and pH changes shall be examined and potential modification(s) of the proteins (such as denaturation) and/or production of stable protein fragments generated through such treatments shall be characterised. (d) Data concerning the resistance of the newly expressed protein to proteolytic enzymes (such as pepsin), such as by in vitro investigations using appropriate and standardised tests. Stable breakdown products shall be characterised and evaluated with regard to the potential to cause adverse health effects linked to their biological activity.(e) A repeated-dose 28-day oral toxicity study with the newly expressed protein in rodents. When appropriate depending on the outcome of the 28-day toxicity study, further targeted investigations shall be provided, including an analysis of immunotoxicity.
(a) potential adverse effects identified in other parts of the safety assessment have been confirmed or discarded; (b) the available information on the newly expressed protein(s) and other new constituents resulting from the genetic modification gives indications of potential adverse effects in particular, whether and at which dose levels adverse effects were identified in specific studies; (c) the information on natural constituents of which the levels are different from those in its conventional counterpart provides indications of potential adverse effects, in particular, whether and at which dose levels adverse effects were identified in specific studies; (d) adverse effects have been identified from the studies made on the whole genetically modified food and feed and at which dose levels.
(a) Amino acid sequence homology comparison between the newly expressed protein and known allergens In every case, a search for sequence homologies and/or structural similarities between the expressed protein and known allergens shall be performed to identify potential IgE cross-reactivity between the newly expressed protein and known allergens. The applicant shall ensure that the quality and the comprehensiveness of the databases are state of the art. The alignment-based criterion involving 35 % sequence identity to a known allergen over a window of at least 80 amino acids is considered a minimal requirement. All sequence alignment parameters used in the analysis shall be provided including calculation of percent identity (PID). The calculation of PID shall be performed on a window of 80 amino acids with gaps so that inserted gaps are treated as mismatches. In some cases, for assessing short peptidic fragments such as ORFs, a search for sequences of contiguous identical or chemically similar amino acid residue can be conducted. However, this search shall not be carried out routinely for the identification of potential linear IgE binding epitopes because of its poor sensitivity or specificity. (b) Specific serum screening When there is an indication of sequence homology or structure similarities, an important procedure for assessing the potential that exposure to the newly expressed proteins might elicit an allergic reaction in individuals already sensitised to cross-reactive proteins, is based on in vitro tests that measure the capacity of specific IgE from serum of allergic patients to bind the test protein(s). There is inter-individual variability in the specificity and affinity of the human IgE response. In particular, the specificity of the IgE antibodies to the different allergens present in a given food/source and/or to the different epitopes present on a given protein may vary amongst allergic individuals. In order to optimise the sensitivity of the test, individual sera from well-characterised allergic individuals shall be used. The applicant shall perform specific serum screening in the following cases:(i) the source of the introduced gene is considered allergenic, even if no sequence homology of the newly expressed protein to a known allergen is demonstrated; or (ii) the source is not known to be allergenic, but there are indications of a relationship between the newly expressed protein and a known allergen, based on sequence homology or structure similarity.
Specific serum screening shall be undertaken with individual sera from individuals with a proven and well-characterised allergy to the source or to the potentially cross-reacting allergen using relevant immunochemical tests. IgE-binding assays (such as Radio or Enzyme Allergosorbent Assay (RAST or EAST), Enzyme Linked Immunosorbent Assay (ELISA) and electrophoresis followed by immunoblotting with specific IgE-containing sera) are adequate methods. (c) Pepsin resistance and in vitro digestibility testsStability to digestion by proteolytic enzymes has long been considered a characteristic of allergenic proteins. Although it has been established that no absolute correlation exists, resistance of proteins to pepsin digestion is an additional criterion to be considered in the weight-of-evidence approach for the assessment of allergenicity. The pepsin resistance test is generally performed under quite standardised conditions, at low pH values and high pepsin:protein ratios. It is recognised that the pepsin resistance test does not reflect the physiological conditions of the digestion. The digestibility of the newly expressed proteins in specific segments of the population, such as infants and individuals with impaired digestive functions, may be assessed using in vitro digestibility tests using different conditions. Also, since the protein encoded by the newly introduced genes will be present in the product as a complex matrix, the impact of the possible interaction between the protein and other components of the matrix, as well as the effects of the processing, shall be taken into account in additionalin vitro digestibility tests. Depending on the outcome of thein vitro digestibility test, a comparison of the intact, the heat-denatured and the pepsin-digested proteins for IgE binding shall be assessed since an altered digestibility may impact on the allergenicity of the newly expressed protein.(d) Additional tests Although additional tests including in vitro cell based assays orin vivo tests on animal models have not been validated to date for regulatory purposes, they may provide useful additional information, for example, on the potential of the newly expressed protein forde novo sensitisation.
(a) whether the novel protein(s) is likely to be allergenic; (b) whether the genetically modified food or feed is likely to be more allergenic than its conventional counterpart.
(a) the introduction of the genetically modified food and feed into the market is not nutritionally disadvantageous to humans and animals, respectively. This evaluation shall include the relevance for the nutrition of newly expressed proteins, other new constituents, and changes in the levels of food and feed constituents, as well as potential alterations in the total diet of the consumer or the animal; (b) unintended effects of the genetic modification that were identified or that may be assumed to have occurred based on the preceding molecular, compositional or phenotypic analyses, in accordance with Sections 1.2 and 1.3, have not adversely affected the nutritional value of the genetically modified food and feed.
(a) the composition of the genetically modified food and feed with regard to the levels of nutrients and anti-nutrients (see compositional studies as described in Section 1.3); (b) the bioavailability and biological efficacy of nutrients in the food and feed taking into account the potential influences of transport, storage and expected treatment of the food and feed; (c) the anticipated dietary intake of the food and feed (see Section 2) and resulting nutritional impact.
| Title | Reference of the method in Part B of the Annex to Regulation (EC) No 440/2008 |
|---|---|
| ACUTE TOXICITY (DERMAL) | B.3. |
| SKIN SENSITISATION | B.6. |
| REPEATED-DOSE (28 DAYS) TOXICITY (ORAL) | B.7. |
| REPEATED-DOSE (28 DAYS) TOXICITY (DERMAL) | B.9. |
| SUBCHRONIC ORAL TOXICITY TEST REPEATED-DOSE 90-DAY ORAL TOXICITY STUDY IN RODENTS | B.26. |
| CHRONIC TOXICITY TEST | B.30. |
| CARCINOGENICITY TEST | B32. |
| COMBINED CHRONIC TOXICITY/CARCINOGENICITY TEST | B.33. |
| ONE-GENERATION REPRODUCTION TOXICITY TEST | B.34. |
| TWO-GENERATION REPRODUCTION TOXICITY STUDY | B.35. |
| TOXICOKINETICS | B.36. |
| NEUROTOXICITY STUDY IN RODENTS | B.43. |
| Title | Reference of the method in Part B of the Annex to Regulation (EC) No 440/2008 |
|---|---|
| MUTAGENICITY — | B.11. |
| MUTAGENICITY — | B.12. |
| MUTAGENICITY: REVERSE MUTATION TEST USING BACTERIA | B.13/14. |
| MUTAGENICITY TESTING AND SCREENING FOR CARCINOGENICITY GENE MUTATION — | B.15. |
| MITOTIC RECOMBINATION — | B.16. |
| DNA DAMAGE AND REPAIR — UNSCHEDULED DNA SYNTHESIS — MAMMALIAN CELLS | B.18. |
| MUTAGENICITY — | B.17. |
| SISTER CHROMATID EXCHANGE ASSAY | B.19. |
| B.21. | |
| MAMMALIAN SPERMATOGONIAL CHROMOSOME ABERRATION TEST | B.23. |
(a) the genetically modified food and feed has no adverse effects on human and animal health; (b) the genetically modified food does not differ from the food which it is intended to replace to such an extent that its normal consumption would be nutritionally disadvantageous for the consumer; (c) the genetically modified food does not mislead the consumer; (d) the genetically modified feed does not harm or mislead the consumer by impairing the distinctive features of the animal products; (e) the genetically modified feed does not differ from the feed which it is intended to replace to such an extent that its normal consumption would be nutritionally disadvantageous for animals or humans.
(a) the performance characteristics of the submitted method(s); (b) technical requirements regarding the type of information that the applicant must submit so as to verify that those requirements are met; (c) samples of the food and feed and their control samples; (d) certified reference material.
(a) "certified reference material" means reference material as referred to in Articles 5(3)(j) and 17(3)(j) of Regulation (EC) No 1829/2003 and corresponds to any material or substance, one or more of whose property values are certified for calibration or quality control of methods. It is accompanied by a certificate that provides value of the specified property, its associated uncertainty and a statement of metrological traceability; (b) "method performance requirements" means the minimum performance criteria that the method shall demonstrate upon completion of the validation study carried out by the EURL, according to internationally accepted technical provisions.
1. The method(s) shall be specific to the transformation event (hereafter referred to as "event-specific") and thus shall only be functional with the genetically modified organism or genetically modified based product considered and shall not be functional if applied to other transformation events already authorised; otherwise the method cannot be applied for unequivocal detection/identification/quantification. This shall be demonstrated with a selection of non-target transgenic authorised transformation events and conventional counterparts. This testing shall include closely related transformation events. 2. The method(s) shall be applicable to samples of the food or feed, to the control samples and to the certified reference material. 3. The applicant shall take into consideration the following documents for the development of the detection method: (a) Foodstuffs — Methods of analysis for the detection of genetically modified organisms and derived products — General requirements and definitions: ISO 24276; (b) Foodstuffs — Methods of analysis for the detection of genetically modified organisms and derived products — Nucleic acid extraction: ISO 21571; (c) Foodstuffs — Methods of analysis for the detection of genetically modified organisms and derived products — Quantitative nucleic acid based methods: ISO 21570; (d) Foodstuffs — Methods of analysis for the detection of genetically modified organisms and derived products — Qualitative nucleic acid based methods: draft European standard ISO 21569.
4. The method shall also take into consideration the more detailed requirements set out in the common criteria set by the EURL, and the ENGL for minimum performance requirements for analytical methods for GMO testing. These criteria are part of the guidance provided by the EURL.
1. Scientific basis: the applicant shall provide an overview of the principles of how the method works. This overview shall include references to relevant scientific publications. 2. Scope of the method: the applicant shall indicate the matrix(es) (for example, processed food, raw materials), the type of samples and the percentage range to which the method may be applied. 3. Operational characteristics of the method: the required equipment for the application of the method shall be specified, with regard to the analysis as such and the sample preparation. Further information of any specific aspects crucial for the application of the method shall also be included. 4. Protocol: the applicant shall provide a complete optimised protocol of the method. The protocol shall present all the details as required to transfer and apply the method independently in other laboratories. 5. A prediction model (or a similar tool) needed to interpret results and to make inferences shall be described in full details. Instructions for the correct application of the model shall be provided by the applicant. 6. Breeding schemes that are to be applied for the production of genetically modified food and feed and their impact on the interpretation of results shall be provided by the applicant.
1. primer pairs tested and probe, if appropriate, including a justification as to how and why the proposed primer pair has been selected; 2. stability testing, which shall be established through the submission of experimental results from testing the method with different plant varieties; 3. specificity, which shall be established through the submission of the full sequence of the insert(s) in a standardised electronic format, together with the base pairs of the host flanking sequences so as to enable the EURL to assess the specificity of the proposed method by running homology searches in a molecular database; 4. precision, the relative repeatability standard deviation shall be less than or equal to 25 % related to mass fraction over the whole dynamic range of the method.
1. participating laboratories, time of the analysis and outline of the experimental design, including the details about the number of runs, samples, replicates, etc.; 2. description of the laboratory samples (such as size, quality, date of sampling), positive and negative controls as well as certified reference material, plasmids and alike used; 3. description of the approaches that have been used to analyse the test results and outliers; 4. any particular points observed during the testing; 5. references to relevant literature or technical provisions used in the testing.
1. Genetically modified reference material containers: (a) genetically modified reference material container (such as bottles, vials, ampoules) shall be tight and contain not less than the stated amount of material; (b) the commutability of the genetically modified reference material must be assured; (c) packaging shall be appropriate to the purpose; (d) labelling shall be of good aspect and quality.
2. Homogeneity testing: (a) samples shall have appropriate homogeneity; (b) between-bottle homogeneity shall be examined; (c) any possible between-bottle heterogeneity shall be accounted for in the overall estimated reference material uncertainty. This requirement shall apply even when no statistically significant between-bottle variation is present. In this case, the method variation or the actual calculated between-bottle variation, whichever is larger, shall be included in the overall uncertainty.
3. Stability testing: (a) samples shall have appropriate stability; (b) stability shall be positively demonstrated by appropriate statistical extrapolation for the genetically modified reference material shelf-life to be within the stated uncertainty; the uncertainty related to this demonstration is part of the estimated reference material uncertainty. Assigned values are valid only for a limited time and shall be subject to a stability monitoring.
4. Batch characterisation: 1. The methods used for verification and for certification shall: (a) be applied under metrologically valid conditions; (b) have been properly technically validated before use; (c) have precision and trueness compatible with the target uncertainty.
2. Each set of measurements shall: (a) be traceable to the stated references; (b) be accompanied by an uncertainty statement whenever possible.
3. Participating laboratories shall: (a) have the required competence for the execution of the task; (b) be able to achieve traceability to the required stated references; (c) be able to estimate their measurement uncertainty; (d) have in place a sufficient and appropriate quality assurance system.
5. Final storage: 1. To avoid degradation after sample production, all samples shall be stored under conditions designated for the final storage of the genetically modified certified reference material before measurements are started. 2. Otherwise, they shall be transported from door to door keeping them at all times under such storage conditions for which it has been demonstrated that there is no influence on the assigned values.
6. Establishment of a certificate for certified reference material: A certificate complemented by a certification report shall be established, containing all information relevant to and needed by the user. The certificate and report shall be made available when the genetically modified certified reference material is distributed. The information accompanying the certified reference material shall include information on the breeding of the plant which has been used for the production of the certified reference material and on the zygosity of the insert(s). The certified value of the GMO content shall be given in mass fraction and, where available, in copy number per haploid genome equivalent. Certified values (such as quantity of genetically modified material expressed in mass fraction) shall be traceable to stated references and be accompanied by an expanded uncertainty statement valid for the entire shelf-life of the genetically modified certified reference material.