The Use of Digital Technologies for the Purpose of Improving Methodological Approaches to the Creation of a Pharmaceutical Quality System at Enterprises for the Production of Medicines

Introduction. The article is devoted to the aspects of improving methodological approaches to the creation of a pharmaceutical quality system (PQS) at enterprises for the production of medicines, taking into account the possibility of using tools and means of digitalization. The relevance of the study is associated with the enduring importance of comprehensive high quality assurance in the development, production and release of medicines into circulation. The implementation of PQS requires numerous transformations of management and production processes, which can be facilitated by tools and elements of digitalization.Aim. To consider the potential and specific areas of application of digital technologies to improve the methodology and practice of developing and implementing PQS.Materials and methods. The state in the subject area was assessed on the basis of the results of economic and statistical analysis and forecasting of the implementation of PQS at Russian pharmaceutical enterprises that have positive and comparatively long experience in this area: the companies LLC "OZON" and JSC "AKRIKHIN". The assessment was carried out by calculating the integral indicator of the effectiveness of the functioning of PQS, which is a set of weighted key performance indicators (KPI) for quality.Results and discussion. The importance of the introduction of PQS for the development of pharmaceutical enterprises and the presence of numerous difficulties in the implementation of PQS, which necessitates the improvement of methodological approaches in the subject area, are stated. It has been proven that even at those enterprises where PQS has been introduced with varying degrees of success, the use of digitalization tools would contribute to a faster, more systematic and high-quality implementation of PQS. Among the key areas of application of digital tools, the authors propose monitoring of quality indicators (using neural network cards) and the use of blockchain platforms and smart contracts to register the release of drugs of appropriate quality.Conclusion. Digital tools contribute to complex improvement in many areas of socio-economic activity. Their active use at pharmaceutical enterprises is intended to contribute to ensuring the proper implementation and uninterrupted functioning of pharmaceutical quality systems, through constant monitoring of the quality of manufactured products and registration of manufactured batches in high-precision information storage systems.

PROBLEMS OF MAKING QUALITY ASSURANCE DOCUMENTATION

The article is devoted to the development of quality system documents for the pharmacy organization. The legislation of the Republic of Belarus, as well as the Eurasian Economic Union, requires the development and maintenance of the quality assurance system, the quality management system, the pharmaceutical quality system in a pharmacy organization, a distributor or manufacturer of medicinal products. The article presents the comparative analysis of regulatory requirements as well as approaches of the international standards ISO series to the construction of the quality systems and processes documentation. Such documents as the Quality Manual or its equivalent, Standard Operating Procedures (SOP) and Process Instructions are the most difficult to develop. The distribution of responsibility for processes within the organization is difficult to understand. On the example of RUE «BELPHARMATSIYA» it is shown how the processes in the pharmacy organization can be documented and responsibility for their implementation can be stated. The functioning of the quality system depends on the clarity of the documentation structure and its development and circulation organization. It is the responsibility of the organization authorities to maintain effective functioning of this system.

Risk Management: How Not To Do It

Regulations worldwide tell us that a Pharmaceutical Quality System has to be risk-based. In reviewing best practices and ICH Q9 guidelines on QRM, the author shares insights on what not to do, using examples the author has come across over the more than 30 years in industry.

EXTEMPORAL MANUFACTURE OF MEDICINES. PROBLEMS AND SOLUTIONS

Despite the decrease in the number of pharmacies having prescription and manufacturing departments the need for extemporally manufactured dosage forms remains high. Pharmaceutical organization dealing with medicines manufacture is currently facing a number of problems: lack of modern pharmaceutical substances at pharmacies, manufacture of medicines containing narcotic substances, psychotropic substances and their precursors, high costs, low profitability of in-pharmacy manufacture and etc. The urgency to preserve and revive ex tempore formulations at pharmacies is highlighted. The groups of patients for whom individual manufacture of medicines is most relevant are identified: children, especially newborn and children under 1 year old, elderly patients, as well as patients with orphan diseases and patients requiring palliative care. The advantages of the extemporal formulation are noted, in particular, the selection of an individual composition and dosage taking into account body characteristics, age, concomitant diseases of the patient, tolerance of medicinal substances and their excipients, etc. Some ways to solve problems arising are suggested. Promising directions for the development of extemporal manufacture are noted: the use of modern excipients, technologies, packaging facilities, the development of internal regulatory documentation for the pharmaceutical quality system and etc.

The risk-oriented approach to the development and implementation of the pharmaceutical quality system in the production of in-bulk finished products

Aim. To determine the areas of the risk-based approach to the development and implementation of the pharmaceutical quality system with the emphasis on the production of in-bulk finished products, identify the main factors affecting the stability of the functional characteristics of drugs in order to provide their compliance with the international quality standards, Good Manufacturing Practice and quality risk management. Results. 29 pharmaceutical companies with the license in Ukraine for dispensing and packing of medicines from in-bulk products have been identified. The control strategy for the production of medicines for in-bulk products has been developed as a set of measures covering the incoming control of in-bulk products, the primary, secondary packing and their labeling, patient information leaflets, finished drug at release and shelf life, control of operating conditions of premises and equipment, parameters of dispensing and packing stages. The analysis of the specificity of the production of finished drugs from in-bulk products has been performed, and the areas of the risk-oriented approach have been determined to the development and implementation of the pharmaceutical quality system in this type of production based on the risk assessment of significant factors affecting the pharmaceutical production and the use of the appropriate risk management methods for quality in the production of medicines from in-bulk products. Conclusions. It has been determined that the risk-oriented approach to the development and implementation of the pharmaceutical quality system in the production of medicines from in-bulk products is a strategic direction. It allows increasing the effectiveness of the quality management system at a qualitatively new level, achieving goals in order to prevent adverse effects on quality and safety, and it means the best possible customer satisfaction. In our research, the quality guarantees that the pharmaceutical quality system should provide in the production of medicines from in-bulk products have been identified, and the control strategy has been developed. Key words: in-bulk products; medicines; drug quality; risk-based approach; pharmaceutical quality system; Good Manufacturing Practice; quality risk assessment

Documentation of Pharmaceutical Development. Part 1. Study of the Documentation of the Site

Introduction. The trends in the modern pharmaceutical industry demonstrate the need for proper documentation of all stages of the life cycle of a medicinal product to ensure its quality and eliminate risks to patients. Therefore, documenting pharmaceutical development, as the first stage of this cycle, is relevant. It will allow regulating technological processes, product quality indicators, as well as ensuring the integrity of the data received. It is advisable to document the pharmaceutical development taking into account the requirements established at the enterprise where the industrial production of this drug is planned.Aim. Development of documentation for pharmaceutical development within the pharmaceutical quality system of the enterprise. One of the objectives of the study was to analyze the document flow of the pharmaceutical quality system of the enterprise planning the production of suppositories for the proper development of documentation for the pharmaceutical development of a medicinal product in this dosage form.Materials and methods. During the research the following methods were used: content analysis; system analysis; sociological (survey method); SWOT analysis technology; systems approach.Results and discussion. In order to get acquainted with modern trends related to pharmaceutical development and pharmaceutical quality system, at the first stage, an analysis of the ICH (International Council on Harmonization) guidance document Quality Implementation Working Group on Q8, Q9 and Q10 Questions & Answers was carried out. An important preparatory stage for the optimal documentation of a pharmaceutical development was the study of the document flow of the pharmaceutical quality system of an enterprise planning to produce two-component suppositories. For this purpose, in the course of the research, a questionnaire was developed containing questions related to the functioning of the quality system, documentation processes and production. The analysis of the received responses made it possible to obtain information on documenting the pharmaceutical development of medicinal products, as well as to identify the main trends associated with this process within the pharmaceutical quality system.Conclusion. The documentation of the pharmaceutical quality system of the enterprise planning the production of suppositories has been analyzed. The strengths and weaknesses of the documentation are identified, a number of proposals for improving the documentation system are highlighted. Based on the results obtained, proposals will be developed for the optimal documentation of pharmaceutical development and a set of documents for an enterprise planning to produce two-component suppositories will be formed.