Scientific Opinion on development needs for the allergenicity and protein safety assessment of food and feed products derived from biotechnology

Abstract

This Scientific Opinion addresses the formulation of specific development needs, including research requirements for allergenicity assessment and protein safety, in general, which is urgently needed in a world that demands more sustainable food systems. Current allergenicity risk assessment strategies are based on the principles and guidelines of the Codex Alimentarius for the safety assessment of foods derived from 'modern' biotechnology initially published in 2003. The core approach for the safety assessment is based on a 'weight-of-evidence' approach because no single piece of information or experimental method provides sufficient evidence to predict allergenicity. Although the Codex Alimentarius and EFSA guidance documents successfully addressed allergenicity assessments of single/ stacked event GM applications, experience gained and new developments in the field call for a modernisation of some key elements of the risk assessment. These should include the consideration of clinical relevance, route of exposure and potential threshold values of food allergens, the update of in silico tools used with more targeted databases and better integration and standardisation of test materials and in vitro/in vivo protocols. Furthermore, more complex future products will likely challenge the overall practical implementation of current guidelines, which were mainly targeted to assess a few newly expressed proteins. Therefore, it is timely to review and clarify the main purpose of the allergenicity risk assessment and the vital role it plays in protecting consumers' health. A roadmap to (re)define the allergenicity safety objectives and risk assessment needs will be required to inform a series of key questions for risk assessors and risk managers such as 'what is the purpose of the allergenicity risk assessment?' or 'what level of confidence is necessary for the predictions?'.

Comprehensive COMPARE database reduces allergenic risk of novel food proteins

“…Conservative bioinformatic tools and thresholds have been developed to predict the cross-reactive risk among allergens. 2 , 3 Therefore, the robustness of these tools for predicting the allergenic risk of novel food proteins is largely dependent on the comprehensiveness of the allergen database that is used for the analysis.…”

“…The bioinformatic tools used to evaluate the potential cross reactivity of a GE protein with that of known allergens have been found to be very conservative for detecting true allergen cross reactivity. 2–4 From a regulatory perspective, sequences sharing >35% amino acid identity over a sliding window of ≥80 amino acids are considered a cross-reactive risk for a GE protein. However, the wider scientific literature suggests that statistical thresholds for amino acid similarity (E-values) across the entire sequence are equally conservative, yet have a much lower false-positive rate (fewer predictions of allergenicity for sequences with a history of no allergenicity).…”

Genetically engineered crops for sustainably enhanced food production systems

“…Since the Brazil nut is a common allergenic food, the allergenicity testing of transgenic soybean indicated allergenic reaction on three subjects through skin-prick testing. This allergenicity was associated to the introduction of 2S albumin gene of Brazil nut into the soybeans ( Nordlee et al., 1996 ; EFSA et al., 2022 ). There are also assumptions that GM crops can cause the development of cancerous cells in human beings ( Touyz, 2013 ).…”

Slow alignment of GMO allergenicity regulations with science on protein digestibility

“… 24 After the workshop, EFSA acknowledged that the evidence for digestive stability as a direct predictor of allergenic risk for food proteins is weak and that it is critical to consider the feasibility and practicality of inclusion of this parameter in the weight-of-evidence assessment; nevertheless, EFSA inexplicably continued to endorse the validity of including digestibility in the weight-of-evidence assessment of allergenicity. 25 Consequently, developers continue to be motivated to engineer digestively unstable proteins for expression in genetically engineered crops, potentially increasing the risk of sensitization.…”

“… 19 However, bioinformatic screening of all candidate newly expressed protein amino-acid sequences for similarity to known allergens is a very reliable indicator of the cross-reactive risk within those already sensitized to known allergens because very few truly novel allergens are discovered each year (high sequence homology within groups of cross-reactive allergens). 25–28 Additionally, the few new unique sequences are likely of minor clinical importance (low frequency of occurrence and not resulting in severe reactions) since they are primarily added to the database because they react with IgE antibodies, which is an often required attribute, but not sufficient in itself to indicate clinical relevance. 29 When a sequence is found to exceed the highly conservative amino acid thresholds for similarity to a known allergen, targeted IgE serum screening is typically conducted.…”