New Genomic Techniques applied to food cultures: a powerful contribution to innovative, safe, and sustainable food products.

Nontransgenic New Genomic Techniques (NGTs) have emerged as a promising tool for food industries, allowing food cultures to contribute to an innovative, safe, and more sustainable food system. NGTs have the potential to be applied to microorganisms, delivering on challenging performance traits like texture, flavour, and an increase of nutritional value. This paper brings insights on how nontransgenic NGTs applied to food cultures could be beneficial to the sector, enabling food industries to generate innovative, safe, and sustainable products for European consumers. Microorganisms derived from NGTs have the potentials of becoming an important contribution to achieve the ambitious targets set by the European 'Green Deal' and 'Farm to Fork' policies. To encourage the development of NGT-derived microorganisms, the current EU regulatory framework should be adapted. These technologies allow the introduction of a precise, minimal DNA modification in microbial genomes resulting in optimized products carrying features that could also be achieved by spontaneous natural genetic evolution. The possibility to use NGTs as a tool to improve food safety, sustainability, and quality is the bottleneck in food culture developments, as it currently relies on lengthy natural evolution strategies or on untargeted random mutagenesis.

Live Biotherapeutic Products, A Road Map for Safety Assessment.

Recent developments in the understanding of the relationship between the microbiota and its host have provided evidence regarding the therapeutic potential of selected microorganisms to prevent or treat disease. According to Directive 2001/83/EC, in the European Union (EU), any product intended to prevent or treat disease is defined as a medicinal product and requires a marketing authorization by competent authorities prior to commercialization. Even if the pharmaceutical regulatory framework is harmonized at the EU level, obtaining marketing authorisations for medicinal products remains very challenging for Live Biotherapeutic Products (LBPs). Compared to other medicinal products currently on the market, safety assessment of LBPs represents a real challenge because of their specific characteristics and mode of action. Indeed, LBPs are not intended to reach the systemic circulation targeting distant organs, tissues, or receptors, but rather exert their effect through direct interactions with the complex native microbiota and/or the modulation of complex host-microbiota relation, indirectly leading to distant biological effects within the host. Hence, developers must rely on a thorough risk analysis, and pharmaceutical guidelines for other biological products should be taken into account in order to design relevant non-clinical and clinical development programmes. Here we aim at providing a roadmap for a risk analysis that takes into account the specificities of LBPs. We describe the different risks associated with these products and their interactions with the patient. Then, from that risk assessment, we propose solutions to design non-clinical programmes and First in Human (FIH) early clinical trials appropriate to assess LBP safety.