Effects of Food on the Bioavailability of Medicinal Products in Bioequivalence Studies: A Comparative Analysis of Regulatory Documents

INTRODUCTION. Studying the effect of food on the bioavailability of medicinal products is important for selecting the right administration conditions for generics (in bioavailability and bioequivalence studies) and confirming the selection for originators in different patient groups (in clinical trials). However, there are currently no common harmonised requirements for food-effect bioavailability studies. AIM. This study aimed to evaluate the conditions for investigating the effect of food on the bioavailability of medicinal products in bioequivalence studies through an analysis of the national and international regulatory requirementsfor the conduct of clinical bioequivalence studies; additionally, this study aimed to identify common and unique requirements applied in different countries with a view to selecting the optimal conditions for conductingbioequivalence studies of medicinal products. DISCUSSION. Food-effect bioavailability studies of medicinal products should rely on the Biopharmaceutics Classification System (BCS) and the Biopharmaceutical Drug Disposition and Classification System (BDDCS), whichclassify medicinal products by solubility, permeability, and metabolism. This study analysed documents reflecting the approaches of international organisations to bioequivalence studies, including documents by the WorldHealth Organisation (WHO), the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), and regulatory bodies of the Eurasian Economic Union, the European Union(European Medicines Agency (EMA)), and the United States of America (Food and Drug Administration (FDA)). The analysis revealed differences in the conditions for studying the effect of food on the bioavailability of medicinalproducts. A common approach is to require that bioequivalence studies should be conducted under standardised conditions. The differences lie in the expected scope of postprandial studies; the recommended mealcomposition with regard to the energy, protein, carbohydrate, and fat content and local dietary preferences; and approaches to food-effect bioavailability studies of high-risk medicinal products, medicinal products withlinear and non-linear pharmacokinetics, and modified-release formulations. CONCLUSIONS. The differences identified in the national and international requirements for the conduct of food-effect bioavailability studies of medicinal products underscore the need for regulatory standard harmonisation, which will contribute to ensuring the safe and effective use of medicinal products, to implementing uniform approaches to the interpretation of the results of food-effect bioavailability studies, and to bringing medicinal products to the global pharmaceutical market.