Development Of Quality Management System Research Articles

Organization of reviews of a pharmaceutical enterprise quality management system functioning

Aim. To determine the state of organizing the process of analyzing the quality management system of a typical pharmaceutical enterprise in accordance with the current industry requirements of Good Manufacturing Practice and the ISO 9001:2015 standard, as well as substantiating effective approaches to improving this activity. Materials and methods. We used analysis, comparison, questionnaires, surveys and direct observations. The results were processed and verified using licensed Microsoft Office Excel software products. Results. The relevance of the development of quality management systems (QMS) of domestic pharmaceutical organizations in the period of martial law has been proven. The requirements of the DSTU ISO 9001:2015 standard, as well as the requirements of the guidelines on Good Manufacturing Practice (GMP) of medicines for reviewing and analyzing QMS of pharmaceutical enterprises (PhE) have been analyzed. Approaches to the organization of QMS review at a number of domestic PhE have been studied; as a result, typical inconsistencies of these procedures have been determined. Based on the results of the study and the experience analyzed in supporting the QMS functioning of PhE, effective organizational approaches have been identified, and recommendations are given for the effective analysis of QMS of PhE. Conclusions. In the study conducted, a review of the practice of analyzing QMS at a number of domestic and foreign PhE has been carried out, and typical inconsistencies of this process have been identified and systematized. The requirements of the DSTU ISO 9001:2015 standard, as well as the industry requirements of the GMP guidelines for reviewing and analyzing the quality system of PhE have been analyzed. Based on the results of the research and the authors’ own experience in implementing and supporting the QMS functioning of PhE, the main organizational approaches and recommendations for analyzing QMS of PhE have been determined.

Impact of biogenic impurities on catalytic synthesis of multi-walled carbon nanotubes and hydrogen from polyolefin resins

Biogenic impurities are common contaminants of plastic waste. This study investigated the effects of biogenic impurities on the conversion of a polyolefin mixture (6 wt% low-density polyethylene, 24 wt% high-density polyethylene, and 70 wt% polypropylene) into multi-walled carbon nanotubes (MWCNTs) and hydrogen via pyrolysis-chemical vapor deposition (CVD). Biogenic components from diverse sources were added to the polyolefin mixture, including lignocellulosic materials (pine sawdust, coconut coir pith), biosolids from wastewater treatment (municipal sewage sludge), animal-based waste (crustaceans), and bio-based plastic (polylactic acid). At contamination levels up to 9.1 wt%, 3 out of 5 impurities (coconut coir pith, sewage sludge and crustaceans) caused a decline in the conversion efficiency of feedstock into MWCNTs (33 ± 7% for polyolefins only compared with 20 ± 6%, 16 ± 1% and 16 ± 2% for polyolefins with 9.1 wt% coconut coir pith, sewage sludge and crustaceans, respectively). According to gas analysis, impurities led to a loss of catalyst activity, resulting in a decreased concentration of H2 and increased concentrations of methane and ethylene in the CVD gas. Furthermore, for polyolefins containing 9.1 wt% coconut coir pith, sewage sludge, crustaceans and polylactic acid, microscopy data revealed changes in the growth of filamentous carbon, leading to the appearance of carbon nanofibers in MWCNT samples. On the contrary, biogenic impurities barely changed outer diameters, ID/IG ratios, interlayer spacing, crystallite sizes of graphite-like sites, and the surface chemistry of MWCNT samples. The results suggest the development of quality management system for contaminated plastic feedstock could be advantageous to ensure consistent outcomes of pyrolysis-CVD process.

Ризик-орієнтований підхід до управління підприємством сфери послуг

The article is devoted to the study of features of the introduction of a risk-oriented approach in the context of the development of quality management systems, which ensures the integration of risk management with the mechanism of enterprise management in compliance with the principles of consistency, economy and coherence of business processes to solve the problems of ensuring their risk tolerance and competitiveness. The article discloses economic essence of risk as an integral part of each business process in activity of an enterprise in the service sector under conditions of uncertainty and its essential characteristics – negative consequences, optional nature of occurrence and the impossibility of their complete exclusion. The features of the manifestation of risks of service enterprises, the main aspects of the process approach in quality management systems and its integration with the business processes of service enterprises, the implementation of risk management in the quality management system of service enterprises, introduced in accordance with ISO 9001:2015, are considered. The practical significance of the obtained results of the study lies in the possibility of using the proposed risk-oriented approach to management and its integration into the quality management system of an enterprise in the service sector through the allocation of responsibility centers for risk management within the framework of the implementation of the main groups of business processes of the Quality Management System in the context of the requirements of the international standard ISO 9001:2015.

Методика впровадження системи менеджменту якості в організації

The article considers in detail the problem of introduction and certification of quality management systems in organizations, substantiates their importance in ensuring the competitiveness of economic entities in the context of globalization. In this regard, there is a need to introduce quality management systems that meet international ISO standards. The aim of the article is to provide a theoretical and practical substantiation of the methodology for the formation of the quality management system of an organization, which is determined by the allocation of key stages of development and introduction of the quality system. The related study should reflect the significance and impact of a reasonable approach to the introduction of the quality management system on the efficiency of management and competitiveness of the organization. The authors note that modern stakeholders demand from organizations not only guarantees of the quality of goods and services, but also social responsibility. The article analyzes contemporary approaches to the formation of the quality management system, identifies the advantages of the project approach to the introduction of the quality management system, identifies the main elements and stages of introduction of the quality management system in the organization. The aim and objectives of the study were achieved through the use of the following methods: analysis and synthesis – to study information sources on the subject of research and modern approaches to the development of quality management systems; comparative analysis – to characterize different approaches to the formation and introduction of quality management systems; system approach – to study the quality management system as an integral system with interrelated elements; empirical methods – to obtain information on the experience of introducing quality management systems in different organizations. Particular attention is paid to the project approach to the formation of quality management systems, which ensures a structured process of their introduction. The key stages of an alike project are highlighted, such as planning, introduction of tasks, monitoring and audit, certification and continuous improvement. The introduction of quality management systems provides organizations not only with compliance with market requirements, but also with the development of the professional potential of staff, increases its involvement in business processes. The authors compare different approaches to the introduction of quality management systems: independent development or with involvement of external experts. The use of the organization’s internal resources can reduce costs and increase the adaptability of the system, but there are risks of not having the necessary competencies. External consultants are able to ensure the speed and efficiency of introduction, but their services require financial resources. The introduced quality management system ensures not only high quality of products or services, but also increases the reputation of the organization in the market, attracts new customers and partners, and also minimizes the risks associated with management of business processes. Also, the quality management system is focused on identifying, eliminating or minimizing risks associated with inconsistencies and deviations in individual processes of the system. This will help the organization to be competitive in the market and attract more consumers. Thus, the quality management system allows the organization to become more efficient, sustainable and focused on strategic development. Prospects for further scientific developments in the field of research on the construction of quality management systems will be directed towards adapting modern technologies and innovative approaches to improving the efficiency and effectiveness of such systems, in particular, through the use of Big Data to track the performance of quality management systems, forecast changes and make decisions based on the analysis of large amounts of information and the development of international standards ISO 9001 to the needs of the global economy and new challenges related to digitalization and globalization.

Quality Management System in Clinical Digital Pathology Operations at a Tertiary Cancer Center

Digital pathology workflows can improve pathology operations by allowing reliable and fast retrieval of digital images, digitally reviewing pathology slides, enabling remote work and telepathology, use of computer-aided tools, and sharing of digital images for research and educational purposes. The need for quality systems is a prerequisite for successful clinical-grade digital pathology adoption and patient safety. In this article, we describe the development of a structured digital pathology laboratory quality management system (QMS) for clinical digital pathology operations at Memorial Sloan Kettering Cancer Center (MSK). This digital pathology–specific QMS development stemmed from the gaps that were identified when MSK integrated digital pathology into its clinical practice. The digital scan team in conjunction with the Department of Pathology and Laboratory Medicine quality team developed a QMS tailored to the scanning operation to support departmental and institutional needs. As a first step, systemic mapping of the digital pathology operations identified the prescan, scan, and postscan processes; instrumentation; and staffing involved in the digital pathology operation. Next, gaps identified in quality control and quality assurance measures led to the development of standard operating procedures and training material for the different roles and workflows in the process. All digital pathology–related documents were subject to regulatory review and approval by departmental leadership. The quality essentials were developed into an extensive Digital Pathology Quality Essentials framework to specifically address the needs of the growing clinical use of digital pathology technologies. Using the unique digital experience gained at MSK, we present our recommendations for QMS for large-scale digital pathology operations in clinical settings.

Інтеграція ризик-менеджменту в систему управління якістю торговельного підприємства

The article is aimed at studying the features of the risk-oriented approach in the context of the development of quality management systems as an instrument for management of trading enterprises to solve the problems of increasing their competitiveness, ensuring risk resistance and risk protection. The economic essence of risk as an integral element of the economic and financial activity of the enterprise, which in its manifestation poses a threat to the achievement of the established goals of this activity in conditions of uncertainty and lack of complete information at the time of making decisions on planning, management, coordination, control of the enterprise’s activities, is covered. The list of risks inherent in the activities of commercial enterprises is considered. The classification of risks depending on the type of trade object, group of goods, functional divisions of the trading enterprise and the subsystems has been improved, which allows to deepen research in this direction and objectively determine the areas in which the degree of risk corresponds to the characteristics of the activity. The content and sequence of the main stages of risk management in a trading enterprise are characterized. The article considers features of various approaches to risk management: adaptive, functional, system, process-oriented. It is argued that the lack of an integrated risk management policy of a trading enterprise aimed at implementing strategic development goals leads to: insufficient coordination of individual managerial decisions in this area of various functional services; low level of implementation and use of modern methods and tools for identification and assessment of risks; insufficient substantiation of risk management models in various operations of the trade and technological process; use of inefficient forms of control over the result of the chosen risk solution. A conception of implementing the risk management in the quality management system of a trading enterprise, implemented in accordance with ISO 9001: 2015, is proposed. This conception will provide integrated management of material, financial, information, service flows in business processes between the functional areas of procurement, transportation, warehousing, production, implementation in the performance of management functions of analysis, planning, organization, coordination, motivation, control in compliance with the principles of consistency, efficiency, continuity, cyclicality, variateness, adaptability, mutual consistency, as well as the completeness of the functions of such management and the use of a unified approach to the mechanism of enterprise management. The normative-methodological base of risk management within the documented quality management system of the enterprise is considered.

Implementation and development of quality management system in the tourism sector

Implementation and development of quality management system in the tourism sector

Determination of Optimum Conditions with Regression Analysis within the Scope of 6 Sigma for Eliminating Caking Problem in Nitrogen Fertilizers

In the nitrogen fertilizer industry, the nitrogen content of chemical fertilizers is an important parameter that determines its physical strength, storage capacity and storage life. The production variables that determine this physical parameter, which is characterized as degradation and caking, can be expressed as the characteristics that determine the course of the chemical process. Although there are improvements in reaction conditions to solve the caking problem, the cost problem of the manufacturer limits the processing conditions. For this reason, in order to minimize the cost problem in any nitrogen fertilizer production process, the analysis of working conditions and the development of quality management systems accordingly constitute the focus of the manufacturer. In this study, within the scope of lean production, regression analysis of the 6-sigma quality method system was performed, the process parameters during the production were analyzed, the optimum conditions were determined and the effect on the production cost was investigated by comparing with the current production conditions.

An Innovative Framework for Sustainable Development in Healthcare: The Human Rights Assessment.

Healthcare providers are investing considerable resources for the development of quality management systems in hospitals. Contrary to these efforts, the number of tools that allow the evaluation of implementation efforts and the results of quality, security and sustainable development is quite limited. The purpose of the study is to develop a reference framework for quality and sustainable development in healthcare, Sanitary-Quality (San-Q) at the micro system level, which is compatible with applicable national and international standards in the field. The research method consisted of the study of literature, identification and analysis of good sustainability practices in healthcare, which allowed identification of the areas of the new San-Q framework: quality, economic, environmental, social, institutional and healthcare. These areas are incorporated into the core topics of social responsibility mentioned by ISO26000. A total of 57 indicators have been defined that make up the new reference framework. The evaluation format of the indicators is innovative through a couple of values: completion degree–significance. In the experimental part of the research, a pilot implementation of the San-Q framework at an emergency hospital was performed, the results recorded in terms of responsibility for human rights being presented. The conclusions of the study reveal the innovative aspects of the framework that facilitate the development of a sustainability strategy promoted through performance indicators, the results obtained after evaluation being useful in establishing a reference level of sustainability but also in developing sustainability policies.

Напрями підвищення ефективності управління якістю послуг підприємств залізничного транспорту України

The article identifies directions to improve the efficiency of quality management of services of the railway transport enterprises. It is noted that today the transport sector of Ukraine is going through extremely hard times, caused both by the strengthening of internal contradictions in the development of entities of this sphere and the influence of external negative factors associated with economic and political instability in the country and in the world. In turn, the prospects for the development of railway transport require addressing issues related to the integration of the railway industry of Ukraine into the European transport system and improving the quality of services provided by the associated enterprises. It is determined that the organization of work on quality management at railway transport enterprises involves the development of quality management systems and the adoption of the necessary measures to ensure their effective functioning. In this direction, it is considered necessary to establish and implement the following procedures: development; approval; maintaining and providing all documents and data that belong to the system. It is further noted that the dynamics of profits of railway transport enterprises largely depend not only on the enterprise’s technical and technological capabilities, but also on socioeconomic factors, that is, on the needs and ability of the population to use high-quality transport services. There are five main disagreements and problems that are the causes of consumer dissatisfaction with the services of railway transport enterprises. It is found out that the presence of the above disagreements and problems significantly affects the level of quality management of services of railway transport enterprises. Elimination of discrepancies between expectations and perception of the quality of service provision by consumers is possible only if there is a clear awareness of the problems characteristic of this process at the present stage of integration of the railway industry of Ukraine into the European transport system. It is concluded that it is necessary to improve the efficiency of quality management of services of railway transport enterprises based on the use of modern approaches to careful studying the consumer requests (population demand for transport services) and further improve the consumer qualities of transport services towards achievement of profit, increasing the social significance of railway transportation, and gaining competitive advantages in the future

ОЦЕНКА ЗАТРАТ НА КАЧЕСТВО В СИСТЕМЕ МЕНЕДЖМЕНТА КАЧЕСТВА МОЛОДЕЖНОЙ ПЛОЩАДКИ ПО ПОДГОТОВКЕ КАДРОВ

The development of quality management systems in accordance with the requirements of GOST R ISO 9001-2015 entailed the gradual development and implementation of quality cost management systems. Created youth platforms for personnel training with the support of customer enterprises are not yet actively implementing quality management systems, but at the same time they are aimed at identifying and reducing costs in their activities. Existing quality costing models have already proven their appeal. The purpose of the study is to apply quality cost models in a youth training platform, to propose approaches to reducing financial and time costs, and to assess the costs of preventing risks in the activities of the platform. The essence of the research methodology: on the basis of the obtained results of assessing the costs for quality in the main areas of activity of the youth platform, identify unnecessary costs and propose measures to reduce them. The main results of the research: the model of costs for the process Organization and holding of the All-Russian Olympiad for schoolchildren XXX the most costly stage - the purchase of premium products; for activities on the development and design of educational complexes, the applied model of prevention, assessment and failure showed unnecessary costs of prevention; the economic assessment of risks has confirmed that prevention activities are significantly more profitable than losses from the occurrence of risks. Specific measures are proposed to improve the activities of the youth platform for personnel training by reducing the cost of quality and preventing risks.

Development of Quality Management System for Construction Services Procurement to Improve the Quality of Contractor Performance in Universitas Indonesia

Purpose: Construction work was one of Key Performance Indicators (KPI) that stated in Universitas Indonesia (UI) Strategic Plan. Therefore, the success in the implementation of construction work had quite an influence in overall UI performance achievement, both the activities performance and financial performance. However, in the practice, the construction work implementation in UI was not always in line with the plan/expectation. The construction work was often delayed until the termination of contract that resulted in the obstruction of operational activities. This research had a purpose to develop the Quality Management System (QMS) for the Construction Services Procurement Process to Improve the Quality of Contractor Performance in Universitas Indonesia.Methodology: Research methods used were literature study, survey, and statistical analysis. Results: The development of Quality Management System (QMS) for the construction services procurement process in Universitas Indonesia. Applications/Originality/Value: With the development of this QMS, it is expected that the construction services procurement process could improve the quality of contractor performance and reduce the stoppage rate of projects.

Data Analysis Model of High Self-Organization Processes

The article is devoted to the development of quality management systems in terms of the growth of process self-organization. Formulas for calculating the share and level of self-organization of processes are given based on the transaction expenses, compliance, and non-compliance costs. Forms of maps and schemes for monitoring processes of quality management systems with a high degree of self-organization are proposed.

A Rule-Based System for Quality Control in Brake Disc Production Lines

Currently, challenges in quality improvement have driven various enterprises to create quality management systems in smart factories. The development of quality management systems enables quality control for reviewing product quality, identification, and eliminating product failures. However, process adjustment in quality control decisions may be hard to determine when failures are detected. To overcome this problem, an expert system (ES) that applies the failure mode and effects analysis (FMEA) method for developing quality control systems in brake disc production lines is considered. This quality control system concentrates on analyzing product defects that occur frequently in the production line and will lead to an improved performance of the braking system; the selected product defects are disc thickness variation (DTV), runout, and parallelism. This quality control system developed two modules, the designed FMEA (DFMEA) and component FMEA, which apply a rule-based algorithm for selecting actions. We propose the rules of configuration into the expert system code. The results indicate that the operator can carry out a quality control system with decision-making that can be supported by intelligent searching and reasoning in an expert system.

ФУНДАМЕНТАЛЬНІ ЗАСАДИ СИСТЕМИ УПРАВЛІННЯ ЯКОСТИ ВИЇЗНОГО ТУРОПЕРЕЙТИНГУ В КОМПАНІЇ «ІНТЕРАВІАСЕРВІС»

This article summarizes the arguments and counterarguments within the scientificdiscussion on quality management in outgoing tour operating. The main purpose of the studyis the increase in profitability and competitiveness of tourism enterprise due to improvementof the quality of tourist products; consolidation of economic stability of the enterprise andcost reduction; ensuring systemic and targeted influence on the parameters of the quality oftourism services in the direction of their continuous increase; compliance with therequirements of legislative acts in the field of consumer protection. Systematization ofliterature sources and approaches to solving the problem of quality management in outgoingtour operating is shown in the works of Tkachenko T. I., Brych V. Ya., Kovalskyi V. S.,Goncharenko V. G., Royina O. M. The urgency of solving this scientific problem is thatquality management has become the main driver of the development of outgoing touroperating. The study of quality management in outgoing tour operating in the article iscarried out in the following logical sequence: analysis of quality management system,investigation of the essence of outgoing tour operating and investigations of "Interaviaservis"Tourism Company. The methods of formalization, algorithm development, descriptive,analytical and synthetic methods have become methodical tools of the conducted research.The process of quality management in outgoing tour operating in "Interaviaservis" companyis the object of the study, because it is a set of theoretical, methodological and practicalissues related to the development of quality management strategies of outgoing touroperating. The article presents the results of an empirical analysis of "Interaviaservis"Tourism Company that realizes the mechanisms of outgoing tour operating, which has shownthe development of quality management strategies. The study empirically confirms andtheoretically proves the system of successive procedures of outgoing tour operating presentedin "Interaviaservis" Tourism Company. The results of this study may be useful for varioustourism companies for the development of quality management system in outgoing touroperating.

History of development of quality management system and its application in practice of healthcare institutions

The review considers the evolutionary process of development of the world economy, which implies the need and inevitability of the implementation of quality management system in all areas of production and services, in particular health care to improve the efficiency and quality of care and increase patient satisfaction in the quality and volume of services received.

ТЕХНОЛОГИИ УПРАВЛЕНИЯ: ОТ ТЕОРИИ К ПРАКТИКЕ ПРИМЕНЕНИЯ В УЧРЕЖДЕНИЯХ ЗДРАВООХРАНЕНИЯ

Significance. Development and implementation of new medical and information technologies in healthcare, development of quality management system and digitalization are prioritized by the Decree of the President of the Russian Federation as of June 6, 2019 No.254 «On Strategy on healthcare development in the Russian Federation for the period until 2025». They are also mentioned in the list of key activities of the Ministry of Health of the Russian Federation in 2019-2024. Modern evidence-based management approaches are necessary to work in the mentioned fields, while the system development requires improvements including improvements in the management process based on best Russian and international practices in modern management in healthcare. Purpose. To assess the possibility of using modern management technologies to increase flexibility and efficiency of the medical organization. Material and methods. Analysis of domestic and foreign literature, normative legal documents for the period from 2015 to 2020 was carried out by means of theoretical analysis and synthesis using databases of the Russian Science Citation Index, Google Scholar, «Garant» reference system, open Internet sources and keywords search in Yandex search system. Results. Based on the analysis and guided by the functional principle, the authors have proposed a three-group classification of modern management technologies in healthcare allowing to structure the management process in a health care organization depending on the objectives. The groups include: 1) technologies that ensure development and implementation of organizational solutions; 2) technologies that ensure treatment and diagnostic process, quality and safety of health care; and 3) technologies for human resource management. Each group of technologies is represented by a set of organizational solutions, the characteristics of which are presented in this study. Conclusion. Application of flexible technologies is determined by the need to cope with changes in the business environment and to adapt the management system to new conditions. Due to objective restrictions related to the normative nature of the facility functioning and existing personnel limitations preventing development of the necessary managerial competencies of the staff, managers of health care organizations may not be able to properly attend to these issues. At the same time, the accumulated successful experience in implementing individual project management tools, the Agile method and other modern management technologies in the international practice suggest their possible replication to improve management processes in health care organizations in Russia. Scope of application. The study results can be used by healthcare managers, heads of health care organizations in developing and implementing managerial decisions, selecting modern tools and management technologies in order to achieve flexibility and efficiency of the institution's performance, as well as by regional authorities in public health in determining priorities for organizational development of health care organizations. Keywords: modern tools and methods of management in healthcare; project management; flexible management technologies.

REGULARITIES OF THE PREPARATION OF RUSSIAN ENTERPRISES FOR CERTIFICATION OF COMPLIANCE WITH ISO 9000 SERIES

The authors' task was to analyze the development of quality management systems at the current stage in Russia, as well as at the previous stage in the USSR. As a result, we came to the conclusion that the factors stimulating the implementation of ISO 9000 standards are the need to promote products on the world market, as well as the possibility of receiving orders from the state. In the future, strict adherence to these standards will allow enterprises to significantly reduce the likelihood of lawsuits from consumers, which is important in the context of the development of the legislative framework and increased control over the business. The practical significance of the article is the possibility of familiarizing management and personnel with quality services, whose task is to prepare for certification for compliance with ISO 9000 standards in how this process took place in other companies. The originality of this work is to summarize the experience of implementation of ISO 9000 standards at enterprises and to analyze the factors contributing to or hindering this process.

Development of conceptual model as a means of forming effective quality management systems for engineering services enterprises

Introduction. Integration of Ukraine into the European Economic Area, membership in the World Trade Organization put forward strict requirements on the quality of goods (services, jobs) to the activities of domestic enterprises, in particular in the field of engineering. The formation of quality management systems (QMS) at engineering services enterprises in the context of the requirements of the international standard ISO 9001: 2015 can become an effective mechanism for ensuring their competitiveness as a decisive factor for commercial success. Along with the obvious advantages of designing and implementing quality management systems according to the requirements of the international standard ISO 9001: 2015 at enterprises, today there are a lot of problems, in particular in the field of engineering, to resolve which companies require methodological developments, practical tools and quality specialists.
 Aim and tasks. The aim of the study is to develop a conceptual model for the formation of the quality management system of an engineering enterprise according to the requirements of international standard ISO 9001: 2015 as a tool to improve its performance and ensure integration with the overall management of the company.
 Research results. The article substantiates the relevance of the formation of quality management systems at the enterprises of engineering services in the context of the requirements of international standard ISO 9001: 2015 and proves that they are an effective mechanism for ensuring their competitiveness as a decisive factor of commercial success. The existing models of quality management as a basis for the development of quality management systems in the leading countries of the world been analyzed. The model of processes of quality management system of the engineering enterprise according to requirements of standard ISO 9001: 2015 has been investigated and the essence of all its components has been revealed. The conceptual model of quality management system formation of an engineering enterprise in the context of the requirements of international standard ISO 9001: 2015 has been developed.
 Conclusions. The developed conceptual model of quality management system formation of the engineering enterprise is an effective methodological tool of quality management that will allow providing its integration into the general management of the company. Further developments are aimed at expert assessment of quality management system processes of engineering services companies in the context of the requirements of international standard ISO 9001: 2015.

Development of Reference Materials for Noninvasive Prenatal Aneuploidy Testing by Massively Parallel Sequencing: A Proof-of-Concept Study

Noninvasive prenatal aneuploidy testing (NIPT) represents the first large-scale clinical application of massively parallel sequencing technology. However, no NIPT reference material (RM) has yet been widely adopted, impeding the development of quality management systems and standardization. Developing an NIPT RM from a biological sample is complicated by the low concentration of cell-free DNA (cfDNA), which implies pooling specimens and frequent resampling. We tested the feasibility of using DNA from immortalized cell lines of a woman and her aneuploid offspring to spike an artificial plasma matrix. Enzymatic fragmentation of extracted DNA was optimized to achieve fragment size profiles with a mode of 150 to 200 bp, similar to biological cfDNA. This synthetic material was compared with routine biological samples from pregnant women by a targeted NIPT assay in a multiplex sequencing run on a Proton platform. Sequencing statistics were similar between artificially prepared material and routine biological samples, as well as relative chromosomal representation, and no matrix effects could be detected. Estimate of fetal fraction (FF) was within the range of expected value, and aneuploidy detection statistic (z-score) was also comparable between both types of samples. Artificial plasma spiked with DNA from cell lines of mother and offspring is a promising strategy for developing NIPT RM. This type of material would offer the advantage of a constant and stable composition, allowing for greater standardization of NIPT assays. Moreover, it preserves the parental relatedness used by targeted assay to estimate FF by identification of paternal alleles in single-nucleotide polymorphisms or other variable regions.