Controle de impurezas em insumos farmacêuticos ativos: Nitrosaminas

Abstract

The control of impurities in active pharmaceutical ingredients, particularly in the class of N-nitrosamines, is a highly relevant topic in the contemporary pharmaceutical industry as they belong to the "Cohort of Concern," classified by the ICH M7 (R1) guideline. The emphasis on the control of N-nitrosamines lies in their mutagenic properties and, according to the International Agency for Research on Cancer (IARC), the potentially carcinogenic and genotoxic influences under conditions of prolonged high exposure. The growing awareness of these impurities has prompted a continual review and enhancement of pharmacovigilance regulatory standards. In this context, the intention is to provide a comprehensive review of the impacts of N-nitrosamines on the pharmaceutical industries, including the measures and actions taken by regulatory agencies worldwide. Thus, the main objectives of this Thesis will be to provide information on studies related to the origin and presence of N-nitrosamines in medications. Additionally, it aims to present an overview of the evolution of the regulatory model in impurity control, highlighting factors that led to the current model. The goal is also to explore and discuss acceptable limits of exposure to impurities, as well as analytical methods.