What is different about precision fermentation applications. GMM characterisation, host organism safety, and the specific requirements that catch applicants off guard.
Precision fermentation — using microorganisms as cell factories to produce specific target compounds — is one of the fastest-growing categories of novel food applications in the EU. The technology is used to produce proteins, fats, flavours, vitamins, and other ingredients that are identical or functionally equivalent to those found in conventional food sources.
From a regulatory perspective, precision fermentation products are novel foods. They fall under Regulation (EU) 2015/2283 and are assessed by EFSA's NDA Panel through the same ten-section framework as any other novel food application. But several aspects of the assessment are specific to fermentation-derived products, and understanding them early saves time.
If the production organism is a genetically modified microorganism — and in precision fermentation, it usually is — additional requirements apply. EFSA needs to assess the safety of the genetic modification, even if the production organism is removed from the final product and no viable GMOs or newly introduced DNA remain.
The assessment covers the host organism (its taxonomic identity, safety history, and any known pathogenicity), the genetic modification (what was inserted, deleted, or modified and why), and the production strain (its genetic stability and the absence of unintended changes). EFSA's 2025 guidance on characterisation of microorganisms used in food and feed production provides the current framework.
For the NDA Panel, the critical question is whether the production process — including the genetic modification — introduces any safety concern not already addressed by the characterisation of the final product. The panel may consult EFSA's GMO Panel or the Working Group on Microbiological Risk Assessment for specialised input.
Even if the target compound is identical to its conventionally produced counterpart (for example, a specific protein or fatty acid), EFSA still requires full characterisation of the final product as produced by the fermentation process. Substantial equivalence to the conventional version may reduce some data requirements, but it must be demonstrated with analytical data, not assumed.
Key characterisation requirements include: evidence that the target compound matches the expected structure and purity, a comprehensive impurity profile (including residual host cell proteins, DNA, and fermentation by-products), and demonstration that the purification process effectively removes process-related impurities.
1. Strain deposit. EFSA expects the production strain to be deposited in a recognised culture collection with a unique accession number. This provides an independent reference for the organism's identity and ensures traceability.
2. Absence of antimicrobial resistance genes. If the genetic modification involved selectable markers (such as antibiotic resistance genes), EFSA will assess whether these could pose a risk through horizontal gene transfer. The trend is strongly toward using production strains free of antimicrobial resistance markers.
3. Process contaminants specific to fermentation. Beyond the standard contaminant panel (heavy metals, mycotoxins, etc.), fermentation products may contain residual solvents from downstream processing, endotoxins from Gram-negative production organisms, or metabolites from the host organism that are not part of the target product.
4. Batch-to-batch consistency at scale. Five independent batches are required, and they must be representative of the routine commercial production process. Batches from a laboratory or pilot-scale process are not sufficient if the commercial process operates at a different scale with different parameters.
5. Genetic stability. EFSA needs evidence that the production organism maintains the intended genetic modification stably over the number of generations used in a typical production run. Instability — loss of the modification, rearrangements, or reversion — could affect the product's composition and safety.
EFSA's internal NORA extraction methodology identifies five categories that automatically trigger enhanced scrutiny during assessment: enzymes, nanoparticles, microorganisms, solvent steps, and catalysts. Precision fermentation products intersect with at least two of these (microorganisms and, frequently, solvent steps in downstream processing), which means the assessment receives additional attention by default.
Precision fermentation novel foods are being authorised. The regulatory pathway is the same as for any other novel food — there is no separate, dedicated procedure. The additional complexity lies in the GMM characterisation and the fermentation-specific impurity profile, both of which are well-defined in EFSA's guidance.
The applicants who move fastest are those who build the regulatory data package into the product development process from the start — selecting production strains with clean genetic backgrounds, establishing analytical methods early, and generating batch data at commercial scale rather than retrofitting regulatory evidence after the product is already in production.
- EFSA (2024). Scientific Guidance for the preparation of applications for authorisation of novel foods. *EFSA Journal*. - EFSA (2025). Guidance on the characterisation of microorganisms used as feed and food and in food and feed production. *EFSA Journal*. - Foley & Nicová (2024). NORA Standard Operating Procedure. *EFSA Supporting Publication*. - EFSA NDA Panel Working Group on Novel Foods, meeting minutes (WG 130–175, 2022–2026).
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