Novel ingredients, such as those produced using precision fermentation, cell culturing, or plant molecular farming, must submit a novel food dossier to the European Food Safety Authority. Two legal experts guide us through the often lengthy process and identify common stumbling blocks.
In recent years, novel food technologies have exploded as food scientists try to produce high-value ingredients in a more sustainable way. Ingredients include meat and dairy proteins; health ingredients like human milk oligosaccharides; and fungi-derived food colours.
However, bringing these ingredients to market in Europe is not as easy as in other regions.
As an example, precision fermented ingredients that are based on recombinant dairy proteins or egg proteins would fall under Regulation (EU) No. 2015/2283.
To obtain novel food approval, an applicant must build a dossier following the relevant regulations and EFSA guidance documents to support the safety of their product under the proposed conditions of use, advised Hannah Lester, CEO and principal consultant at Atova Consulting.
“This means generating data to support the composition of the product in terms of its nutritional composition and also the level of impurities, its toxicological profile and allergenicity. Other pivotal data for precision fermentation derived ingredients is demonstrating that the genetically modified production organism is safe,” she explained.
She continued: “Once the applicant has built their dossier, they need to submit it to the EC, who will perform a suitability check and then send a mandate to EFSA for them to perform a risk assessment. Before EFSA starts their risk assessment, they perform a validation step to ensure that the dossier is complete. Once the dossier passes validation, EFSA starts their risk assessment during which time they may ask the applicant to provide clarification or more data.”
Lester said that the main stumbling blocks are the data requirements and knowing exactly what studies you need to perform (and EFSA will expect to see).
“EFSA offers general pre-submission advice but this is very limited in scope, and it is not possible to talk to EFSA regarding study design. This means applicants do their best to guess what EFSA will want to see and often, after the applicant has submitted their dossier, EFSA will ask for something different. This adds significant time to the risk assessment timeline,” she said.
In view of this, Lester would like to see provision for some kind of pre-application consultation whereby applicants are allowed to have non-binding pre-submissions calls with EFSA scientists.
“It would benefit both the applicant and EFSA, and would save time overall as the applicant would be able to prepare a better quality dossier.”
Justyna Pałasińska, who is regulatory affairs director for human nutrition at Argenta Barcelona, said that a particular challenge when assembling a dossier for alternative proteins is that conventional protocols for analysing the safety are not feasible.
“The typical pathway is to look at genotoxicity followed by subchronic toxicity. Subchronic toxicity is tested in a 90-day rat study where the animals are fed an abundance of the novel food. Over-consumption of protein could lead to liver failure and other serious illnesses so the conventional approach used for ingredients like enzymes is not feasible here.”
No specific guidance exists for an alternative approach, but Pałasińska’s advice is to study the microorganism itself to establish whether it has the potential to produce undesirable metabolites, for example.
Once EFSA has completed its risk assessment it publishes an opinion which is reviewed by the EC and EU member states at the Standing Committee on Plants, Animals, Food and Feed (SCoPAFF). The EC presents a draft implementing the regulation and the members of SCoPAFF vote on whether or not to approve the Novel Food.
The above process applies when precision fermented ingredients fall within the novel foods framework. If they stray into genetically modified territory, a GMO authorisation will be required.
But the question of when precision fermented foods become GM foods is a highly complex matter, according to Lester.
“The tipping point between a precision fermented food being a novel food or a GM food should be based on the presence of viable cells from the GMM in the final product,” she explained.
“In precision fermentation, the GMM is a processing aid and trace amounts of processing aids are permitted in final products if they are technologically unavoidable.”
She said there are no legal criteria for the trace amounts of the GMM in precision fermented products, but that there is an arbitrary threshold of 10 ng/g (limit of detection) referred to in one of the EFSA guidance documents.
“This is causing a lot of regulatory uncertainty and we have seen that Impossible Foods soy leghaemoglobin (in which there are trace amounts of the GMM, but no viable cells in the final product) is going through a GM food authorisation as well as a food additive authorisation in parallel. Impossible Foods submitted its GM food dossier in 2019 and it is still under EFSA risk assessment having been clock-stopped since December 2021.”
Asked whether this means that the product will never be granted EU approval, Pałasińska replied: “It certainly means that the approval process will be very, very lengthy.”
