Substantial equivalence (developed by OECD/WHO) is a science-based safety assessment framework: if a GM food is compositionally, nutritionally, and toxicologically similar to its conventional counterpart, it is considered as safe. Assessment involves comparing: gene expression patterns, protein profiles, metabolite compositions, and allergenicity/toxicity indicators. Critics argue it focuses on known components and may miss novel unintended effects. It is the regulatory basis in the USA and Canada but is supplemented by pre-market approval in the EU.