An EU regulatory perspective on SynBio microorganisms for proteins

With food insecurity becoming an increasing reality, we need to leverage new technologies to produce food. The use of synthetic biology (SynBio) offers opportunities to create optimized new-to-nature proteins or genetically modified microorganisms (GMMs) that can express existing or new-to-nature proteins via precision fermentation.

In the European Union, the use of GMMs is not novel and they have been used since the 1990s to produce food enzymes, amino acids, vitamins, etc. More recently, GMMs have been approved to produce human milk oligosaccharides for use in infant formula.

However, one of the big questions is how will SynBio microorganisms (SynbioM) be regulated? We all know that the EU is extremely conservative when it comes to genetically modified (GM) food, so what can companies working with SynBioM expect?

The European Food Safety Authority (EFSA) defines SynBio as ‘the application of science, technology and engineering to facilitate and accelerate the design, manufacture and/or modification of genetic materials in living organisms’ and goes further to say ‘key features of synthetic biology include the ‘de novo’ synthesis of genetic material and an engineering-based approach to develop components, organisms and products’.

A GMM is a microorganism that has been genetically modified. GMMs fall into one of four categories: Categories 1 and 2 are products free from production strain DNA and viable cells; Category 3 are products containing DNA, but no viable cells; and Category 4 are products containing viable cells. It’s important to note that protein products that fall into Category 1 and 2 would be classified as novel foods, whereas those in Category 3 and 4 would be GM foods.

Although it is encouraging that the EC and EFSA are actively working on improving their knowledge and understanding of SynBio, there are still many gray areas

EFSA recently said that there are no clear criteria to differentiate between a GMM and a SynBioM and the current EFSA guidance documents are generally adequate for the risk assessment of SynBioM. However, they do identify some gaps such as assessing the risk of horizontal gene transfer and the impact on gut microbiota.

SynBio has been on the European Commission’s radar since 2005, but there is still a lot of uncertainty about what the EC’s view is and how EFSA will assess the safety of these products.

In 2014, the EC published a definition of SynBio. This was followed by two further opinions on risk assessment, methodologies and safety aspects and research priorities. EFSA has prepared three opinions on SynBioM for use in the agri-food sector, and is now preparing an opinion on new developments in biotechnology applied to microorganisms which will be published in 2024!

Although it is encouraging that the EC and EFSA are actively working on improving their knowledge and understanding of SynBio, there are still many gray areas, and it is challenging for applicants to know what to expect in terms obtaining regulatory approval.

For example, one question I get asked regularly is, what are the regulatory implications of modifying a known protein and then expressing it in a GMM? From the recent EFSA opinions and current guidance, the answer is not 100% clear. However, in the latest EFSA opinion on SynbioM, they refer to two cases that describe new-to-nature proteins, both of which would fall under GMM Category 1 and 2 as long as there are no viable cells and no DNA in the final product, which is interesting!

Due to a lack of precedents, time will tell how SynBioM products will fair in the EU but, overall, I am confident that with a strong dataset, it will be possible to demonstrate the safety of these products and obtain regulatory approval.

Dr Hannah Lester is the CEO & Principle Consultant of Atova Regulatory Consulting and also Head of Regulatory at Gourmey. This article was republished from the October/November 2022 edition of Protein Production Technology International, the industry's leading resource for alternative proteins. To subscribe to read future editions hot off the digital press, please click here