What comes next for food enzymes in the EU?

After more than a decade of evaluations, the EU food enzyme framework is approaching a critical milestone. The long-awaited Union List of authorised food enzymes is moving closer to adoption, while discussions continue on how food enzymes should be assessed and communicated to consumers.

Although food enzymes have been used safely in food production for decades, important regulatory questions remain unresolved. How should enzyme safety be demonstrated in the future? When should enzymes appear on food labels? And what will the Union List mean for enzyme manufacturers and food business operators?

These questions are likely to shape the regulatory environment for food enzymes for years to come.

The Union List is finally taking shape

Food enzymes are regulated under Regulation (EC) No 1332/2008, which established a harmonised EU framework for the evaluation and authorisation of food enzymes. Under this system, all food enzymes require a safety evaluation by the European Food Safety Authority (EFSA) and must ultimately be included in an EU Union List before they can be fully authorised across the European Union.

However, unlike food additives or flavourings, the Union List of authorised food enzymes has still not been adopted. As a result, food enzymes remain in a transitional regulatory situation in which national rules continue to apply until the Union List becomes effective.

For many companies, this prolonged transition has created uncertainty. Once the Union List is finally established, companies will have greater clarity on authorised enzymes, conditions of use and regulatory expectations across the EU market.

Current industry timelines suggest that EFSA will deliver its opinions for the first Union List by Q1/2027, followed by its adoption in Q4/2028 and entry into force in Q4/2030. While the exact timing remains subject to regulatory progress, the industry is now beginning to see a realistic path towards a fully harmonised authorisation system for food enzymes across the European Union.

The introduction of the Union List is therefore not simply an administrative step. It marks the transition from a fragmented national system to a fully harmonised European framework.

Why enzyme labelling remains controversial

Perhaps the most difficult regulatory question related to the Union list concerns labelling. Food enzymes occupy a unique position in food production. Unlike many ingredients, they are generally added to facilitate a manufacturing process rather than to become part of the food consumed by the consumer. In many applications, the enzyme has already performed its technological function before the final product is placed on the market. What remains are, at most, residual traces of the enzyme or materials associated with its use during manufacturing.

This raises a fundamental question: should substances used as processing aids be labelled in the same way as ingredients that are intentionally present in the final food?

From a consumer perspective, transparency is important. However, regulatory requirements also need to be practical and scientifically meaningful. A case-by-case approach has the advantage of reflecting how an enzyme is actually used and what happens to it during food processing. It could therefore distinguish between uses where the enzyme remains relevant in the final food and those where it has fulfilled its technological purpose during processing.

At the same time, such an approach could create considerable practical challenges. Food enzymes may be used across numerous manufacturing processes and final products, making product-specific assessment of residual enzyme activity or presence difficult to implement on a large scale. Absolute absence is also an unrealistic criterion for many processing aids. Increasingly sensitive analytical methods may detect very small residues, even where these have no technological relevance in the final food.

In our view, a workable framework should therefore recognise food enzymes used as processing aids as such and avoid making the mere detection of residual traces a trigger for labelling. A more proportionate approach would consider the relevance of the enzyme in the final food and reserve additional labelling requirements for situations where its presence has genuine significance for the consumer.

Safety assessment is evolving

At the same time, the scientific approach to food enzyme safety assessment continues to develop.

Under the current EFSA guidance, toxicological data are generally required unless their omission can be scientifically justified. The package has commonly included genotoxicity testing and a repeated-dose 90-day oral toxicity study in rodents. The latter is used to identify potential systemic effects, establish a no-observed-adverse-effect level, or NOAEL, and compare that value with estimated dietary exposure through a margin-of-exposure calculation.

However, EFSA is now examining whether routinely requiring the 90-day study remains scientifically justified for food enzymes. This work is connected to the wider EU objective of reducing reliance on animal testing while maintaining scientifically robust safety assessments. EFSA has established a dedicated working group and conducted a retrospective review of 258 rodent studies submitted in support of food enzyme applications.

The preliminary results are noteworthy. EFSA reported that most of the reviewed studies identified no safety concern. In the small number of studies in which toxicological effects were observed, these were associated either with local gastric effects in rodents that were not considered relevant to humans, or with impurities and contamination linked to the manufacturing process rather than with the enzyme itself. EFSA therefore concluded at this preliminary stage that food enzymes are generally of low toxicological concern and that routine 90-day studies may provide limited additional value.

This does not mean that systemic toxicity would cease to be assessed. Instead, the focus could shift towards a more targeted weight-of-evidence approach. EFSA has identified possible sources of evidence including information on safe use, literature reviews, genomic and protein sequence analyses, digestibility data, detailed impurity profiles, manufacturing-process information and targeted in vitro methods. Together, these data could be used to determine whether a credible systemic toxicity concern exists and whether an animal study is needed in the individual case.

Such an approach could significantly reduce animal use and avoid studies that repeatedly confirm the same conclusion. It could also lower development costs and shorten study programmes for applicants. The trade-off is that producing a persuasive application may become less standardised. A study conducted according to an established guideline provides a relatively familiar regulatory endpoint. A weight-of-evidence assessment requires the applicant to demonstrate, through several complementary lines of evidence, why a conventional study is unnecessary.

The quality of strain characterisation, manufacturing-process descriptions and analytical data could therefore become even more important. Removing a routine animal study would not remove the applicant’s responsibility to address possible hazards arising from the enzyme protein, the production organism, fermentation materials, process-related impurities or contaminants. In fact, EFSA’s retrospective findings suggest that manufacturing-related factors may deserve greater attention because the limited effects observed in the reviewed studies were not generally attributed to the enzyme itself.