Table 2.
Reference documents per sector that have been checked for relevancy for this Opinion, and for adequacy regarding the food/feed safety evaluation of SynBioMs
| Document no. | Reference document per sector in the remit of EFSA | Content explaining the relevance for the present Opinion |
| GMO | ||
| 1 | EFSA GMO Panel, 2011 – Guidance on the risk assessment of GMMs and their products intended for food and feed use | Focuses on the risk assessment of food and feed consisting, containing or produced from GMMs. It includes FF assessment. The aspects on the molecular characterisation of GMMs in this guidance are superseded by the FEEDAP guidance (EFSA FEEDAP Panel, 2018a) and the Statement of the CEP Panel (EFSA CEP Panel, 2019) replaced by the guidance of the EFSA CEP Panel (2021) |
| 2 | EFSA GMO Panel, 2017 – Guidance on allergenicity assessment of genetically modified plants | Provides supplementary guidance on specific topics for the allergenicity risk assessment of genetically modified plants. The topics addressed are non‐IgE‐mediated adverse immune reactions to foods, in vitro protein digestibility tests and endogenous allergenicity |
| FEED | ||
| 3 | EFSA FEEDAP Panel, 2018a – Guidance on the characterisation of microorganisms used as feed additives or as production organisms | Details the steps for characterisation of microorganisms (including GMMs) used as feed additives or as production organisms and introduced the Whole Genome Sequencing (WGS) analysis for RA for the first time. MC is however already addressed in Opinion 1. The sections regarding the use of WGS data for the characterisation and risk assessment have been updated by the EFSA statement (number 16 of this table) |
| 4 | EFSA FEEDAP Panel, 2018b – Guidance on the assessment of the efficacy of feed additives | Details specifically the assessment of the efficacy of feed additives for use in animal nutrition |
| 5 | EFSA FEEDAP Panel, 2017a – Guidance on the safety of feed additives for consumers | Comprises ADME (absorption, distribution, metabolism, and excretion) and toxicological studies of the FEED additive in the animal with a specific focus on metabolites that can affect the consumer |
| 6 | EFSA FEEDAP Panel, 2017b – Guidance on the assessment of the safety of feed additives for the target species | Details the in vivo toxicological studies with multilevel feed additives and its tolerance to and effects on the target animal species (Sections 4, 5 and 6) |
| 7 | EFSA FEEDAP Panel, 2017c – Guidance on the identity, characterisation and conditions of use of feed additives | Covers the identity, characterisation and conditions of use of the additives, including a section on the production process (Section 2.3) |
| 8 | EFSA FEEDAP Panel, 2012a ‐ Guidance on studies concerning the safety of use of the additive for users/workers | Provides guidance on how to conduct studies concerning safety for the user/workers: toxicology, effects on respiratory system, effects on eyes and skin (relevant for the allergenicity section), systemic toxicity and exposure assessment |
| 9 | EFSA FEEDAP Panel, 2021a – Guidance on the renewal of the authorisation of feed additives | Provides guidance on the principles of the assessment of applications for renewal of the authorisation, including the post‐market monitoring section |
| 10 | EFSA FEEDAP Panel, 2008a – Technical guidance: Compatibility of zootechnical microbial additives with other additives showing antimicrobial activity | Checked for adequacy; superseded by the FEEDAP guidances ( EFSA FEEDAP Panel, 2017b , 2018a ); addresses efficacy (compatibility in the gut) but does not address safety, therefore is not relevant for this Opinion |
| 11 | EFSA FEEDAP Panel, 2008b – Technical guidance microbial studies | Checked for adequacy; superseded by the FEEDAP guidance (EFSA FEEDAP Panel, 2018a ) and no longer used in detail for this Opinion |
| 12 | EFSA FEEDAP Panel, 2011 – Guidance on the assessment of microbial biomasses for use in animal nutrition | Checked for adequacy; superseded by the FEEDAP guidance ( EFSA FEEDAP Panel, 2018a ) and no longer used in detail for this Opinion |
| FOOD improvement | ||
| 13 | EFSA CEP Panel, 2021 – Guidance for the submission of dossiers on food enzymes | Updates the former guidance on the Submission of a Dossier on food enzymes (EFSA CEF Panel, 2009) taking into account the statements issued on the exposure assessment of food enzymes and the characterisation of microorganisms used in the production of food enzymes (EFSA CEP Panel, 2019) |
| 14 | EFSA FAF Panel, 2021 – Scientific guidance for the preparation of applications on smoke flavouring primary products | Focuses on toxicology and also covers the assessment of potential immunotoxicity |
| 15 | EFSA ANS Panel, 2012 – Guidance for submission for food additive evaluations | Covers exposure toxicokinetics, toxicity, reproductive and developmental toxicity, neurotoxicity. This guidance was meanwhile updated and republished in 2021 (https://doi.org/10.2903/j.efsa.2012.2760). |
| 16 | EFSA, 2021 – Statement on the requirements for whole genome sequence analysis of microorganisms intentionally used in the food chain | Provides recommendations on the analysis and results of WGS analysis of microorganisms, which should be provided to EFSA in the context of an application. Information on this Statement is included in the guidance of the EFSA CEP Panel ( 2021 ) and as such this statement per se is no longer used in detail for this Opinion |
| 17 | EFSA CEF Panel, 2009 – Guidance on the Submission of a Dossier on food enzymes for safety evaluation | Provides the requirements for a dossier submission on food enzymes for safety evaluation, including a section on the manufacturing process (Section 1.2) and the toxicological data needed (Section 2). This guidance is superseded by the guidance of the EFSA CEP Panel ( 2021 ) |
| 18 | EFSA CEP Panel, 2019 – Statement: Characterisation of microorganisms used for the production of food enzymes | Covers production organisms only and is focused on food enzyme applications. This statement was fully addressed in Opinion 1 and is superseded by the guidance of the EFSA CEP Panel ( 2021 ) |
| BIOHAZARDS/Food Improvement | ||
| 19 | EFSA BIOHAZ Panel, 2010 – Guidance document on the submission of data for the evaluation of the safety and efficacy of substances for the removal of microbial surface contamination of foods of animal origin for human consumption | Mentions in a general way the need for information on the identity of the substance, the manufacturing process and the toxicological potential; allergenicity is not mentioned in the guidance. This document has meanwhile been amended and republished in 2021 (https://doi.org/10.2903/j.efsa.2010.1544) |
| NUTRIENTS AND DIETARY PRODUCTS | ||
| 20 | EFSA NDA Panel, 2016a – Guidance on the preparation and presentation of an application for authorisation of a novel food in the context of Regulation (EU) 2015/2283 |
Provides the requirements for an application of a novel food, including the characterisation of microorganisms, fungi and algae (Section 2.2.3), the production process (Section 2.3), the ADME (Section 2.8), the nutritional (Section 2.9) and the toxicological (Section 2.10) assessment. This document has meanwhile been republished in 2021 (https://doi.org/10.2903/j.efsa.2021.6555). |
| 21 | EFSA NDA Panel, 2016b – Guidance on the scientific requirements for health claims related to the immune system, the gastrointestinal tract and defence against pathogenic microorganisms | Focuses on health claims (beneficial effects) which is by definition not a safety assessment. However, the guidance is informative on methods for how to assess/how to test possible clinical endpoints or parameters that maybe useful as intermediate indicators for adversity. |
| 22 | EFSA NDA Panel, 2014 – Scientific Opinion on the evaluation of allergenic foods and food ingredients for labelling purposes | Reviews the database on food allergens and the methods for establishing the potential for food to cause allergic reactions |
| PLANT PROTECTION PRODUCTS | ||
| 23 | Regulation (EU) No 283/2013, Annex part B on microorganisms as plant protection products (PPP), Setting out the data requirements for active substances, in accordance with Regulation (EC) No 1107/2009 of the European Parliament and of the Council concerning the placing of PPPs on the market | Provides data requirements for active substances consisting of microorganisms, including viruses e.g. in Chapters 5 and 6 data are requested on the effects on human health and on residues in or on treated products, food and feed |
| 24 | Regulation (EU) 2019/1009 – New regulation laying down rules on the making available on the market of EU fertilising products and amending Regulations (EC) No 1069/2009 and (EC) No 1107/2009 and repealing Regulation (EC) No 2003/2003 | Regulation including provisions for the use of (non‐GM) microorganisms in the EU and their assessment. This legal framework may be relevant for assessing translocation of the microorganisms and its metabolites to the edible plant parts leading to human exposure through the oral route |
| 25 | OECD, 2019 – Report of the 9th Biopesticides Expert Group Seminar on Test Methods for Microorganisms Series on Pesticides No. 100 (18 June 2018 in Paris, France) | Outcome discussion identifying the need to: (i) update the requirements for the registration of microbial biopesticides, (ii) revise existing methods for testing microbials, and (iii) develop more suitable alternative methods. Current methods were classified as technically challenging, relevancy of the administration route debated, appropriateness of the animal model used was questionable and the interpretation of the results deemed complex |
| 26 | OECD, 2020c – Report of the 10th Biopesticides Expert Group Seminar on Test Methods for Microorganisms Series on Pesticides No. 103 (24 June 2019 in Paris, France) | Outcome discussion concluded that is not yet envisioned that the use of genome sequencing, bioinformatics tools and databases would lead to new data requirements, despite possibility to use whole genome sequencing (WGS) to address data requirements for the registration of microbials, particularly for identification and characterisation. Further consideration should be given to the possibility of using WGS as a standard data requirement |
| 27 | OECD, 2010a – Guidance document on horizontal gene transfer between bacteria | Provides information on how to assess potential risks resulting from horizontal gene transfer (HGT) |
| MEDICINAL PRODUCTS | ||
| 28 | EMA, 2010 – Guideline on quality, non‐clinical and clinical aspects of live recombinant viral vectored vaccines | Covers immunologic pharmaceuticals or vaccines on how to address these beneficial and desired effects. The potential induction of autoimmunity is mentioned without any indication how to address this. The section on safety does not specify methodological details |
| 29 | EMA, 2012 – Guideline on requirements for the production and control of immunological veterinary medicinal products | For veterinary vaccines, the guideline is intended to supplement Directive 2001/82/EC ( European Commission, 2001b ) European Pharmacopoeia (2016a,b), and VICH guideline (EMA, 2016 ). The sections on safety and field trials do not specify methodological details |
| FERTILISING PRODUCTS | ||
| 30 | Regulation (EU) 2019/1009 of the European Parliament and of the Council of 5 June 2019 laying down rules on the making available on the market of EU fertilising products | Microbial plant biostimulants fall within the scope with 4 taxonomic families which can be used (Azotobacter spp., Mycorrhizal fungi, Rhizobium spp., Azospirillum spp). |