Alternative proteins in the EU – regulatory roundup for 2021
Posted 20 December, 2021
In the past year, an increase in EFSA Scientific Opinions related to the protein alternative space was observed. Two plant proteins and three insect proteins were evaluated as novel foods in the EU. Pen & Tec has reviewed the EFSA Opinions and extracted the most note-worthy information that would be useful for applicants wishing to submit novel food applications for protein products.
From the five novel foods assessed (see Table for reference), EFSA could not conclude on the safety for ‘Water lentil powder from Lemnaceae’. After a very lengthy evaluation process (2 years 5 months) that included multiple requests for additional information and clarifications, EFSA could not decide on safety since the exposure to Manganese from consumption of the novel food from all the proposed food categories would increase the Mn intake by 12-25% across age groups and by 42% when used as a supplement in adults. Despite the absence of any established Tolerable upper levels, still EFSA considered that the estimates represent a substantial increase which is a safety concern. All the other information provided by the applicant on the presence of contaminants, microbiological quality, presence of antinutritional factors and biogenic amines, dioxins, mycotoxins and pesticides, toxicity and allergenicity did not raise any safety concerns. A decision on whether this novel food will be authorised has not yet been reached by the European Commission (expected publication of the Regulation in June 2022). Considering that water lentil powder from Lemnaceae has been assessed by the US FDA under a GRAS Notice and in Canada, Australia and New Zeeland the product is authorised to be used in foods, it will be interesting to see what the regulators will decide. This is another of many cases where the industry experiences why the European Union is considered to be one of the toughest markets to access.
An important deduction from the above analysis is that toxicological studies are not a guaranteed safe way to achieve a positive EFSA conclusion. EFSA can conclude positively on the safety of a novel food without the provision of these studies, as seen in the application for mung bean protein isolate, and the three insect proteins (Acheta domesticus, Locusta migratoria and Tenebrio molitor larva). The data provided on the identity, composition, nutritional analysis, dietary exposure and literature review on the history of use, toxicity and allergenicity of the novel food were sufficient to substantiate the safe use of the novel food under the proposed conditions of use.
Another observation from the analysis of the applications is that the stability studies are not crucial in concluding on the safety of the novel food. As seen in all three Opinions for the insect proteins, EFSA could not conclude on the stability in related food matrices because of limited number of samples analysed and absence of control samples, still because the novel food complied with the microbiological specifications and considering that the final foods placed on the market will have to agree with the existing legislative limits, EFSA considered that the provided stability data does not raise safety concerns.
It is also positive to note that in the case of allergenicity, EFSA was able to rely on the information from the literature and where there was a gap in the evidence, EFSA highlighted the need for more research from the scientific community, specifically on cross-reactivity to other allergens.
Lastly, it was interesting to observe the inconsistency in EFSA’s approach in regards to the ‘Total Aerobic Plate count’ limits. Where the specification limit for Total aerobic plate counts was higher than the reported analytical data in the five batches, EFSA considered that the specification limits should be lowered (see Mung bean protein, from 10,000 to <5000 cfu/g and water lentil powder from Lemnaceae, from 50,000 to 20,000 cfu/g) . However this was not the case in the Opinion published for ‘Locusta migratoria’ novel food. The results were below 1,000 cfu/g, whereas the specification proposed and not challenged by EFSA was 100,000 cfu/g. EFSA explains that they consider ‘Total Aerobic Plate count’ an ‘indicator of hygiene and that this quality parameter also contributes ultimately to the safety of a NF’. It is therefore crucial that applicants consider which batches they present in their novel food dossier, as based on the analytical results EFSA will scrutinize the specifications proposed.
With the rise in consumer demand for alternative proteins, it is expected that the industry will be investing in developing such products in the years to come. A lot of time and money is spent on R&D and regulatory approval and especially in the EU. From the time a batch sample is created until we see the product authorised to be placed on the market, it can take more than three years. With the uprise of more innovative products such as cell-cultured meat, certainly companies have preferred to test the waters first in those countries where the Authorities are inviting applicants to have consultations prior applications are submitted in order to help them decide on the data package most likely needed for the approval and reduce the likelihood of unexpected data requests that could postpone even further the successful market launch for their products. It is for this reason that Singapore was the first country to authorise a cell-cultured chicken nugget produced by Just Eat Inc. – a San-Francisco based company. The US FDA also invites applicants to set-up consultation calls prior submission of technical dossiers for premarket approval. These advisory calls don’t benefit just the applicant, but also the evaluators since they are preventively ‘educated’ on the latest novel technology and are made aware of some of the hurdles applicants are facing with the current regulatory framework, which often is more than 10 years behind the latest scientific and technological developments.
Protein type | Plant proteins | |
Novel food (NF) | Mung bean protein powder isolate from the seeds of Vigna radiata | Water lentil powder from Lemnaceae |
Applicant | Eat Just, Inc | Parabel Ltd |
EFSA conclusion | Safe | Safety could not be established |
EFSA evaluation timeline (from receipt of mandate until adoption of the Opinion) | 1 year 1 month | 2 years 5 months |
Proposed use | As an ingredient in protein analogues or substitutes of meat, fish and dairy. | As a food ingredient (FI) and as food supplement(FS) |
Proposed maximum use levels (g/kg food) | 200 | FI: 8-90g/kg food FS: 10g/day |
Nutritional composition | Min. 84% protein. Provides sufficient amounts of most EAA however it is not suitable as the sole source of dietary protein. | 35–55% plant protein, fibre/carbohydrates (30–62%) and fat(≤ 12%) |
Data provided |
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Data protection requested | Yes, for analytical data on phytic acid, lectins, trypsin inhibitors, cyanogenic glycosides and tannins | Yes, but EFSA did not conclude on it, which could mean that it might not be granted. |
Worth noting | No toxicological studies were provided. Safety was concluded based on worldwide consumption of the source, the protein not having been chemically modified and because the protein is structurally related to seed storage proteins present in other legumes (soy, lupin, peanut). EFSA proposes to lower specification limits for the parameter ‘ Total aerobic plate count’. | EFSA requested information on:
EFSA proposes to lower specification limits for the parameter ‘ Total aerobic plate count’. In regard to safety, EFSA stated that the conditions of cultivation of water lentils are expected to impact the toxicological profile of the NF. EFSA concluded that Mn levels from intake of the NF as ingredient or food supplement are of safety concern. |
Assessed/authorised in other countries? | Yes, GRAS Notice 684 (2017) by the US FDA | Yes, GRAS Notice 742 (2018) by the US FDA FSANZ declared in 2017 that the NF agrees with the definition of ‘non-traditional food’, no safety assessment needed. Health Canada: the NF is allowed in food. EFSA also assessed a traditional food notification for W. globosa and W. aarhiza vegetables |
Protein type | Insect proteins | ||
Novel food (NF) | Acheta domesticus (frozen and dried formulations from whole house crickets) | Locusta migratoria (frozen and dried formulations from migratory locust) | Tenebrio molitor larva (dried yellow mealworm) |
Applicant | Fair Insects BV | Fair Insects BV | SAS EAP Group |
EFSA conclusion | Safe | Safe | Safe |
EFSA evaluation timeline (from receipt of mandate until adoption of the Opinion) | 1 year 11 months | 1 year 9 months | 2 years 4 months |
Proposed use | As an ingredient in a variety of foods | As an ingredient in a variety of foods | As an ingredient in a variety of foods |
Proposed maximum use levels (g/kg food) | 100 | 100 | 100 |
Nutritional composition | protein, fat and fibre | protein, fat and fibre | protein, fat and fibre |
Data provided |
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Data protection requested | Yes, for the detailed description of the production process, proximate analysis, contaminants analysis, stability studies, microbiological analysis, data on novel food sales, solubility of test item for the genotoxicity tests, digestibility of protein study report and cytotoxicity/cellular toxicity study report. | Yes, for the description of the production process, analytical data on the composition of the NF, analytical data on contaminants in the NF, stability and microbiological status, data on NF sales, intake assessment, protein digestibility and DIAAS, genotoxicity and cytotoxicity study. | Yes, for analyses of contaminants in the NF, detailed description of the drying process, analytical data on chitin levels, data on the oxidative and microbiological status of the NF during storage, and allergenicity testing using the NF as testing material. EFSA did not conclude whether the allergenicity testing was crucial to reaching the conclusion on safety. |
Worth noting | EFSA requested analytical data on:
The applicant could not perform genotoxicity studies due to a lack of solubility of the NF in water, DMSO, ethanol and acetone. EFSA concluded that considering that no safety concerns arise from the history of use of A. domesticus or from the compositional data of the NF, the Panel identified no other safety concerns than allergenicity. EFSA recommended that research should be undertaken on the allergenicity to A. domesticus, including cross-reactivity to other allergens. | No toxicological studies were provided. The applicant relied on the studies available in the literature. The applicant could not perform genotoxicity studies due to a lack of solubility of the NF in water, DMSO, ethanol and acetone. EFSA requested analytical data on:
EFSA could not fully conclude on the stability of the NF, but concluding that there are no safety concerns. EFSA did not propose to lower the specification limits for the parameter ‘total aerobic count’, considering the results from the batch analysis. EFSA recommended that research should be undertaken on the allergenicity to Locusta migratoria, including cross-reactivity to other allergens. | No toxicological studies were provided. The applicant relied on the studies available in the literature. EFSA requested analytical data on:
EFSA requested the implementation of stricter controls for the drying step so that the peroxide value complies with proposed specification limits. EFSA could not conclude on the NF’s shelf life since appropriate data for intermediate timespans have not been made available by the applicant. EFSA recommended (not specifically to the applicant) that research is undertaken on the allergenicity to yellow mealworm, including cross-reactivity to other allergens. |
Assessed/authorised in other countries? | History of consumption in Madagascar, Cameroun, Congo, Zimbabwe, Suda, South Sudan, Papua New Guinea, Thailand, China and Morocco. Being sold in the EU since 2012. Can be legally introduced on the Swiss market as food. | History of consumption in Thailand, China, Mexico. Permitted to be consumed in Korea. In Australia and New Zealand are considered as non-traditional, not novel. Can be legally introduced on the Swiss market as food. |