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Introduction. The article discusses significant changes in the procedure for pharmaceutical inspection of drug manufacturers for compliance with the requirements of the rules of good manufacturing practice (GMP) of the Eurasian Economic Union (EAEU), related to restrictions due to the COVID-19 pandemic.Text. The article presents the main international guidelines describing the remote conduct of pharmaceutical inspections, which is the basis for further updating the relevant procedures in the law of the EAEU. An overview of the foreign practice of pharmaceutical inspection during the pandemic is given. In addition, the changes in the Russian regulatory approaches to control and supervision in the Russian legislation are presented.Conclusion. These data give an idea that, with considering the above, there is a need for further convergence of the requirements, the practice of conducting pharmaceutical inspections for compliance with the requirements of GMP Rules in order to harmonize the norms between Russian regulatory documents, the norms of the EAEU law and international standards. This requires the development of a dialogue with the participation of stakeholders.

Introduction. The article is focused on differences in quality assurance-related obligations and responsibilities between Marketing Authorisation Holders (MAHs) and manufacturing authorisation holder (manufacturers) in pharmaceutical industry. In case of outsourcing and technical agreements there is a need to differentiate responsibilities related to quality assurance between the above mentioned categories.Text. The guidelines for the pharmaceutical sector of the European Union (EU) provide guidance on the responsibilities of the MAHs in relation to the GMP rules, which are scattered throughout the various chapters of the GMP and its appendices. In addition, certain provisions on this topic are contained in the EU directives. With this in mind the European Medicines Agency (EMA) issued in January 2020 a draft Reflection paper on Good manufacturing practice and Marketing Authorisation Holders. The draft clarifies that while certain activities of an MAH may be delegated to the manufacturer, MAH retains ultimate responsibility for the performance of a medicinal product, its safety, quality and efficacy. The important obligation of MAH in this context is to facilitate GMP compliance by establishing a robust two-way communication system with national competent authorities, manufacturing sites, Qualified Persons (QPs) certifying batches before release, and other interested parties. The MAH ought to communicate to manufacturing personnel, normally through QPs, production processes and related quality control procedures, including subsequent variations, described in registration dossiers.Conclusion. A general one conclusion: in view of rapid developments in the EU GMP Guide, the Eurasian Economic Union GMP requirements ought to be updated. In respect of specific responsibilities of MAH pertaining to GMP compliance the EMA draft Reflection paper merits attention as a guidance regarding separation of obligations and responsibilities between MAH and personnel of manufacturing sights.

Introduction. This paper is devoted to analysis of a new risk-based regulatory approach to the classification of deficiencies found by inspections of medicines manufacturers, which is undoubtedly relevant.Text. The article describes the new definitions for the deficiencies found in the medicinal products manufacturing, the proposed gradation of non-conformances distinguishes from the one that is currently used. The proposed innovation in regulatory activity is that a critical deficiency can consist of several related nonconformities, none of which can be critical on their own, but which together can constitute a critical nonconformity or system failure. The proposed approach to the classification of deficiencies, which is based on a risk assessment for the patient, is described. The main stages of the risk-based algorithm are characterized: a detailed assessment of the deficiency for its preliminary classification; assessment of risk increase or decrease factors, regardless of the initial classification; making a decision on the final classification, taking into account the factors of increasing, reducing risk or their absence. Block diagrams and illustrative examples are described, on the basis of which preliminary assignment of a revealed deficiency of one or another level of criticality is carried out. The factors of increasing or decreasing risk are considered. These factors are extrapolated to the category of deficiency and they can both increase the preliminary assigned category or decrease it, and can leave the preliminary classification unchanged.Conclusion. A new risk-oriented regulatory approach to the classification of non-conformances with the requirements of Good Manufacturing Practice, proposed by the Pharmaceutical Inspection Co-operation Scheme PIC / S, is described. An analysis of this approach and its characterization are made. The new approach is based on the systematic and methodological application of risk management tools, aimed at justifiably assigning a certain criticality category to a revealed deficiency. The implementation of the new approach allows to increase the objectivity and transparency of inspection procedures. Further detailed study and possible step-by-step implementation of this new approach is very important for regulators so for medicines manufacturers.

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.

The main requirements for a quality system of GMP-inspectorate in terms of inspectors’ appropriate training were described and analyzed. The existing international recommendations in this area were summarized. It was shown that the training of inspectors should be organized and carried out on such principles as systemacy, consistency, professionalism and performance of the international recommendations on training. The additional professional retraining program for GMP inspectors/auditors was developed, tested, and approved. The developed program can be used successfully for training of GMP-inspectors from regulatory authorities of the states that are members of Eurasian Economic Union. The program can be used successfully for training of GMP-inspectors from regulatory authorities of the states that are members of BRICS after some adaptation also.

The regulatory requirements are constantly increasing in the medicines manufacturing sphere, which is reflected in the good manufacturing practice rules. The changes in the GMP regulations relating to personnel, premises and equipment, production, quality control, complaints, quality defects and product recalls, as well as a new version of qualification and validation annex and certification by a Qualified Person and batch release annex have been characterized and analyzed in a review. The related information sources have also been analyzed in order to facilitate the interpretation and implementation of these innovations in the practice of company-producers and, in the long term, the work of the regulatory authorities. The review provides recommendations on the priorities and points of application of efforts to implement the changes discussed.

The matter presents the analysis of results for GMP inspections of foreign manufacturing sites in 2017 and gives the comparison of them with the results from 2016. Statistical evaluation of the results obtained is also given. In comparison with the corresponding results from 2016, there is a significant increase in the total number of inspections conducted. The changes also reflected in the percentage of discovered GMP non-conformities both in terms of criticality and in the categories of good manufacturing practices. The article also presents some examples of discovered GMP non-conformities.

This articles is devoted to major principles of import substitution regarding drugs within the scope of restriction lists at various levels of the health care system. The article reviews the methodology of import substitution of drugs represented as a systematic and consistent process aimed at reduction or termination of import of medical and drug products by its substitution with similar domestic products at the domestic market of the country.