Регуляторные исследования и экспертиза лекарственных средств (Apr 2024)
Assessment and Control of Organic Impurities in Medicinal Products: A Review
Abstract
INTRODUCTION. The determination of impurities is a key requirement for the quality assessment of medicines because impurities can significantly impact the quality and therapeutic effectiveness. Pharmacopoeias are the most important scientific and methodological guidelines for manufacturers developing medicinal product specifications and regulators assessing these specifications as part of registration dossiers. Therefore, it is essential to harmonise national and international approaches to impurities.AIM. This study aimed to analyse and summarise pharmacopoeial requirements for and methodological approaches to the control, evaluation, and identification of organic impurities in medicines.DISCUSSION. The authors compared requirements for the control of organic impurities in small-molecule medicines set forth in national and international pharmacopoeias and guidelines of the International Council for Harmonisation of Technical Requirements for Medicinal Products for Medical Use (ICH) and the Eurasian Economic Union (EAEU). This comparison highlighted the differences in current approaches that require further harmonisation of the existing regulatory documentation. Additionally, this study analysed the popularity, advantages, and disadvantages of different options for determining impurities in two-component combination products (i.e. identified and/or unidentified impurities in one or each of the active substances). The analysis demonstrated the need to control nitrosamines and genotoxic impurities and to use selective and highly sensitive chromatographic methods.CONCLUSIONS. When drafting pharmacopoeial monographs for medicinal products, experts should consider the general approach set forth in the EAEU pharmacopoeia and regulations and in the ICH Q3B guideline. This approach recommends that process-related impurities of active substances should not be controlled at the medicinal product level. Therefore, pharmacopoeial monographs for active substances should distinguish degradation products from process-related impurities. Impurities should be determined for each active substance to ensure the quality and safety of fixed combination medicinal products. Priorities for improving the methodological approach to the control of organic impurities include using reference standards for impurities and acknowledging the necessity of impurity quantification.
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