REGULATORY SCIENCE STRATEGIES TO ASSURE PATIENT ACCESSTO SAFE FOOD PRODUCTS IN THE HEALTHCARE SETTING

Abstract

This doctoral thesis investigates the regulatory, clinical and market dimensions of food products used for the dietary management of diseases and for the modulation of physiological functions, with a specific focus on foods for special medical purposes (FSMPs), food supplements and novel foods in the European Union and the United States. The work adopts a regulatory science perspective, analysing how legal classifications, evidence requirements and reimbursement arrangements influence both the safety of these products and patients’ access to them. Methodologically, the thesis combines comparative legal analysis, systematic reviews of the clinical and toxicological literature, and empirical examination of market data and reimbursement policies in key jurisdictions, including an in‐depth exploration of the Italian National Health Service and its National FSMP Registry. The first part of the thesis maps the global regulatory frameworks for medical foods and FSMPs, elucidating the criteria that distinguish them from both conventional foods and medicinal products and documenting the absence of systematic effectiveness assessment requirements comparable to those applied to medicines, despite their essential therapeutic role in conditions such as Glut‐1 Deficiency Syndrome (GLUT‐1 DS). Subsequent chapters examine the real‐world use of FSMPs in clinical practice and analyse reimbursement policies across G7 countries, highlighting cross‐national disparities and showing that Italy is currently the only European country guaranteeing comprehensive public coverage for FSMPs indicated in GLUT‐1 DS, with significant implications for equity of access and continuity of care. The thesis also reviews the evidence on the efficacy and safety of specific FSMPs, such as salt‐substitute products for arterial hypertension and ketogenic‐diet‐related FSMPs and discusses the methodological limitations of the available studies and their consequences for health technology assessment (HTA). The second part of the thesis addresses food supplements and novel foods, starting from an analysis of the global food supplements market and its rapid expansion, particularly in the segment of herbal products. Through a case study on hemp seed oil and an investigation of highly concentrated plant extracts used in supplements, the research shows how gaps in the application of Regulation (EU) 2015/2283 on novel foods and the American framework for new dietary ingredients can result in the marketing of products with potential hepatotoxicity in the absence of adequate pre‐market authorisation and post‐market surveillance. A systematic review of clinical cases of liver injury associated with herbal extracts demonstrates that only a small proportion of publications provide sufficient detail on composition, titration and history of consumption to allow a robust regulatory assessment, thereby underscoring the need for enhanced analytical characterisation and better integration between toxicological evidence and regulatory decision‐making. In its final part, the thesis articulates the original contributions of the research and their implications for policy, clinical practice and future studies. Conceptually, it proposes the tripartite tension between innovation, 3 safety and access as a unifying framework for understanding the regulatory challenges posed by FSMPs, food supplements and novel foods, and argues that these products should be more systematically integrated into HTA processes adapted to nutritional interventions. Empirically, it offers new comparative insights into European– American regulatory convergence and divergence, documents the unique role of the Italian FSMP Registry as a tool for guaranteeing access and enabling nutri‐surveillance, and quantifies key evidence gaps in the toxicological characterisation of high‐concentration plant extracts. The thesis concludes by outlining priority areas for future research and capacity building, including the development of long‐term observational studies on ketogenic diet use in GLUT‐1 DS, the refinement of criteria for determining novel food status in the context of herbal extracts, the extension of reimbursement analyses to additional jurisdictions, and the strengthening of interdisciplinary training in food regulatory science for healthcare professionals