Risk management aspects for quality in pharmaceutical development

Currently, for the pharmaceutical development of both original and generic drugs, a systematic scientifically based approach is used to create model formulations and dosage form technology. The use of this approach is expressed in the paradigm of Quality-by-Design (QbD) and the application of quality risk management (QRM) methods. The use of these concepts and their deep integration with each other is due to the presence of uncertainty properties in the manifestation of risks that have different degrees of severity of consequences, the probability of occurrence and their detectability. In the case of the use of original pharmaceutical substances, innovative methods or dosage forms, uncertainty increases, and with them the need to use methods for assessing, analyzing, controlling, accepting and communicating risks. The purpose of this article is to analyze the possibilities for introducing the QRM system into the pharmaceutical development process, identify the project field and critical indicators of quality and process, analyze the features and systematize the initial risk assessment methods, in particular risk identification. The article demonstrates possible methods for assessing and managing risks in pharmaceutical development using solid dosage forms as an example, in particular, in terms of such key characteristics as polymorphism, particle size, solubility of pharmaceutical substances, their interaction with excipients, etc. In addition, when considering risk identification methods such as: brainstorming, Delphi method, interviews, documentation review, application of checklists and construction of cause-and-effect diagrams, etc. an assessment of the advantages and disadvantages of the approaches and the main problems characteristic of all QRM methods was carried out.