Abstract
In the context of the circular economy and the increasing demand for safe and sustainable packaging, this work addresses the safety assessment of food contact materials (FCMs) derived from agro-industrial by-products. Despite growing interest in these bio-based materials, the literature still lacks a structured safety-assessment framework able to account for substrate-related contaminants, microbial processing, and downstream impurities. The novelty of this work lies in applying the European Food Safety Authority (EFSA) Technical Report perspective on natural mixtures to two representative case studies: bacterial cellulose (BC) produced by Komagataeibacter spp., as a promising microbial biopolymer for food packaging application, and nisin produced by Lactococcus lactis subsp. lactis, as an antimicrobial peptide, to functionalize the packaging material. This study aims to evaluate whether the EFSA-oriented framework can support the identification of potential substances of concern across the production chain when cellulose is produced starting from agro-industrial waste or nisin is applied. For this, a systematic literature review (SLR) was conducted to investigate potential substances of concern from agro-industrial substrates through fermentation to the final activated materials. The findings highlight the need to characterize natural carbon sources, including pesticide residues, consider the qualified presumption of safety (QPS) status of production microorganisms, and assess metabolites and fermentation by-products. The behavior of these substances during processing and their potential migration into food are critical aspects. A preliminary safety assessment at early development stages is therefore essential to guide material design and regulatory compliance. Overall, this study provides a practical framework to support researchers, developers, and risk assessors in identifying safety concerns and improving the regulatory readiness of innovative bio-based FCMs.