Разработка и регистрация лекарственных средств (May 2020)
Assessing the Correlation Between GMP Deviations and Potential Quality Defects of Medicinal Products: the Result of the Survey of Qualified Persons
Abstract
Introduction. One of the key issues in the field of assessing the conformity of drug manufacturers with the requirements of good manufacturing practice (GMP) is a systematic methodology for classifying revealed deficiencies (deviations, non-conformities) by their level of criticality. Today the information included into regulatory documents regarding the definitions of critical, major and minor (other) deficiencies is not always sufficient for the use in GMP inspection practice, as well as in quality management systems of the pharmaceutical manufacturers. In terms to study approaches to the classification of GMP deviations applied in the practice of the Qualified persons of drug manufacturers in the Russian Federation, a survey was conducted in the form of a questionnaire. This work became a logical continuation of a previous study among employees of the pharmaceutical inspectorate of the Russian Federation.Aim. To identify the correlation between the classification of critical and major GMP deviations and potential class I and II quality defects of medicinal products.Materials and methods. The study was based on a survey of Qualified persons of drug manufacturers (56 respondents) using a questionnaire specially designed. The main hypothesis of the study is that specialists (Qualified persons) who make decisions on the classification of GMP deviations are guided by potential quality defects that may be caused by the indicated deviations. In the framework of the study, authors used the model of gradation of quality defects of the medicinal products into 3 classes (class I, II and III) according to the rate of their significance as indicated in the PIC/S and EMA guidelines. At the same time, for GMP deviations a three-level gradation system is also used: Critical, Major and Minor (Other). In designing of questionnaires for the survey, the focus was made on examples of quality defects of classes I and II and, accordingly, Critical and Major GMP deviations.Results and discussion. The results of the processing and analysis of questionnaires summarize the opinion of the majority of respondents about the direct relationship between product quality defects of the high risk (class I) and critical GMP deviations. Respondents also expressed the opinion that deviations that could trigger the occurrence of the class II quality defects in most cases will be classified as critical. The results obtained during the study also indicate the similarity of existing approaches of the classification of GMP deviations (deficiencies) between QPs of the drug manufacturers and pharmaceutical inspectors.Conclusion. The results of the study show that for the purpose of classifying (determining the criticality) of GMP deviations (deficiencies) , it is possible to use the rating system for the quality defects of medicinal products by the rate of their significance for the patient which is presented in EU regulatory documents and PIC/S guidelines. The results of the study also will facilitate the drawing of conclusions that today, not only from the position of regulatory authorities, but also for the pharmaceutical industry, there is a need to develop methodological guidelines with a focus on a risk-based classification of GMP deviations (deficiencies). These guidelines should take into account the potential impact of the mentioned GMPdeviations on the occurrence of the quality defects of medicinal products and, as a result, threats to the life and health of patients.
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