Registering a new microorganism as a feed additive or food microbe (as novel food) may be difficult to start with if one is not familiar with the EU legislation and specific guidance by the European Food Safety Authority (EFSA). We are often asked if there are studies that could tell the applicant if the microorganism is acceptable or not. This question does not have a simple answer.
There are at least two cases that will prevent the strain from being registered. The first one is an acquired antimicrobial resistance (AMR), which is always considered as a hazard. Microorganisms used in the food chain should not add to the pool of antimicrobial resistance genes already present in the gut bacterial population, or otherwise spread AMR. However, the determination if the AMR is of intrinsic or acquired nature is particularly challenging for novel species, or for species for which very few genomes or phenotypic resistance data are available for comparison. These cases require more research of the matter at hand.
The second case is related to the virulence of bacteria or to toxic metabolites typically produced by some fungi. Single genes linked to virulence in another species are usually not of concern in the absence of other genes needed for full virulence. If the strain is virulent / produces a toxin, it will not be accepted for food or feed use. The identified metabolites need to be carefully assessed for safety. In some cases the metabolite is needed for the microorganism to be efficacious in the intended use, and some precautionary measures may be sufficient to ensure safety to the user/worker.
There is a wide selection of in vitro toxicity tests to evaluate strain characteristics, but the choice requires understanding of the possible toxicity mechanism. Correct interpretation is also crucial. Sometimes a false positive test result can be due to e.g. acid formation and not to the presence of a specific toxin. To verify a a positive finding in a toxicity test, the compound should be identified.
Strains that qualify for QPS recommendation are presumed to be safe to the target species, consumer, and the environment without the need for specific safety studies. The QPS can thus be a fast lane for authorization. However, a microorganism does not need to be QPS to be acceptable. We are often asked how to apply the QPS status. Currently the QPS status cannot be applied separately, but once a dossier involving a new microorganism reaches EFSA, the QPS working group will examine the case. Currently under consideration is a possibility for a two-step process, in which the dossier would be submitted without toxicological studies, which would be added only if deemed necessary.
Today, the whole genome sequence is the golden standard for strain safety assessment. At its best, it can guide the safety tests in the right direction.
It is often the best study to start with, as the price of sequencing is quite reasonable. The genome serves as the basis for several key characteristics that must be included in the safety assessment: the unequivocal identification; screening for AMR genes and virulence factors; and looking for pathways possibly leading to toxic metabolites.
In short: There is no short-cut to safety assessment, and no best way to start. However, from the regulatory point of view, put the safety first!
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