European Union
August 5, 2025

Published: 5 August 2025
Adopted: 30 June 2025

Wiley Online Library

Full article:
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DOI: https://doi.org/10.2903/j.efsa.2025.9568

Abstract

Current risk assessment strategies for protein safety of newly expressed proteins (NEPs) in genetically modified (GM) plants are based on chemical risk assessment principles and Codex Alimentarius guidelines for biotech‐derived foods, initially published in 2003. These guidelines were designed for proteins with multiple testing options and for GMOs expressing a low number of NEPs. However, two decades of experience in assessing GMO and biotech products, along with recent advances in the field, underscore the need to update best practices for protein safety assessment. Furthermore, new types of products challenge the application of the current international guidelines, as assessments become more complex due to NEPs that are difficult to test using existing approaches or products with numerous NEPs. This document outlines a strategy that strengthens the stepwise, weight‐of‐evidence approach, incorporating new methodologies as complementary or alternative studies. An improved strategy for protein safety assessment could include: (1) considering history of safe use (HoSU), read‐across and phylogeny defining the type of data required and remove the need for specific in vitro or in vivo studies; (2) applying advanced in silico tools, including predictive computational models and improved phylogenetic analysis to enable more accurate comparisons with known allergens, toxins or ‘safe’ proteins; (3) using standardised in vitro gastrointestinal models that replicate physiological conditions; (4) developing targeted in vivo studies; (5) evaluating the role of exposure in the safety assessment; and, where necessary, (6) considering post‐market monitoring for risk characterisation. Consensus on the definition of HoSU and the effective integration of novel methodologies into the current NEP safety assessment will be essential to meet society's demand for safer, healthier and more sustainable food/feed in a growing world. This calls for revisiting and refining the goals of protein safety risk assessment to ensure that NEPs in biotech products are evaluated appropriately, consistently and proportionately.

Website: http://www.efsa.europa.eu

Published: August 14, 2025