INTERDISCIPLINARY APPROACH TO THE LABELLING OF ORGANIC PRODUCTION FOOD

Labelling — the final stage of production, which determines its characteristics and properties. In addition to the main regulated elements of labeling, information about the product distinctive features can be applied to the label, which can influence the potential consumer choice. Complete and reliable information allows not only to identify the product, but also to prevent possible consumer deception. Information falsification is one of the most common ways of misleading consumers.There are several types of marking: consumer, warning, conformity, environmental and special protective. In order to protect the consumer from information falsification for food products, clear rules for marking for mandatory application have been developed, established in the technical regulations of the Customs Union 022/2011 «Food products in terms of its marking» and technical regulations for certain types of products (industry products features). In recent years, the organic products production is actively developing, the requirements for which in the countries of the Eurasian Economic Union (EEU) are at the design stage. Organic production is based on the principles of environmental friendliness and humanity, as well as the prohibition of the use of means of production intensification (chemical fertilizers, chemotherapy drugs, artificial food additives, etc.). To control the implementation of these requirements, it is necessary to conduct a full analysis of the production of the product «from the field to the counter», which can be carried out only by highly qualified experts. Confirmation of compliance with the requirements is a organic products sign. In world practice, there are several types of eco-labels. The essence of the developed interdisciplinary approach is a comprehensive application of mandatory and voluntary requirements for the organic food products labeling.Labelling — the final stage of production, which determines its characteristics and properties. In addition to the main regulated elements of labeling, information about the product distinctive features can be applied to the label, which can influence the potential consumer choice. Complete and reliable information allows not only to identify the product, but also to prevent possible consumer deception. Information falsification is one of the most common ways of misleading consumers.There are several types of marking: consumer, warning, conformity, environmental and special protective. In order to protect the consumer from information falsification for food products, clear rules for marking for mandatory application have been developed, established in the technical regulations of the Customs Union 022/2011 «Food products in terms of its marking» and technical regulations for certain types of products (industry products features). In recent years, the organic products production is actively developing, the requirements for which in the countries of the Eurasian Economic Union (EEU) are at the design stage. Organic production is based on the principles of environmental friendliness and humanity, as well as the prohibition of the use of means of production intensification (chemical fertilizers, chemotherapy drugs, artificial food additives, etc.). To control the implementation of these requirements, it is necessary to conduct a full analysis of the production of the product «from the field to the counter», which can be carried out only by highly qualified experts. Confirmation of compliance with the requirements is a organic products sign. In world practice, there are several types of eco-labels. The essence of the developed interdisciplinary approach is a comprehensive application of mandatory and voluntary requirements for the organic food products labeling

An experience of scaling and intensifying the industrial production of the Gam-COVID-Vac vector adenovirus vaccine in the limiting conditions of the pandemic

The COVID-19 pandemic has presented a global challenge to the health system. More than 200 years of world epidemiological experience since the first mass use of vaccines have convincingly shown that effective vaccines are the key tools in the fight against dangerous infectious diseases, especially epidemic and pandemic ones. In the context of a rapidly spreading pandemic of a new infectious agent, it is crucial not only to develop fundamentally new vaccines, but also to be able to quickly organise their large-scale production. In the Russian Federation, in 2020, a team of the National Research Centre for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya developed an innovative vector vaccine, Gam-COVID-Vaс, for the prevention of coronavirus disease caused by the SARS-CoV-2 virus. A number of pharmaceutical companies faced the challenge of producing the vaccine. The aim of the study was to optimise the production technology of Gam-COVID-Vac for scaling and increasing the production capacity. In the course of the work, the authors established critical quality attributes of the product, optimised analytical methods for their control, identified poorly scalable technological stages, streamlined the technological process before its transfer to production, and modified non-scalable and technologically unfeasible stages. The work resulted in the launch of industrial-scale production of active pharmaceutical ingredients for both components of Gam-COVID-Vac, which made it possible not only to meet the critical need for COVID-19 immunoprophylaxis in the Russian Federation, but also to supply this vaccine to a number of foreign countries

Методические подходы к валидации технологических процессов получения терапевтических рекомбинатных белков на основе концепции «Quality by Design»

Validation of production processes based on the Quality by Design (QbD) principles calls for thorough scientific understanding of the processes and enhancement of their stability by implementation of new technologies. The aim of the study consisted in substantiating a QbD-based technological approach to validation of commercial production of dornase alfa. For this purpose a design space was established in a scale-down model, i.e. 2 L reactors; the model was shown to be representative in terms of all parameters except for the reactor size; the similarity of hydrodynamic conditions, design characteristics and operation modes of laboratory, pilot and commercial scale reactors was established; the process scalability was demonstrated by using the PCA (Principal Component Analysis) multivariate mathematical model including the volume range of 2–1000 L, input and output process parameters and product quality attributes for a number of recombinant therapeutic products derived from the same CHO cell line and expression construction as dornase alfa producer. The article demonstrates the applicability of engineering space, which includes bioreactor design features and production process parameters, to different production scales by implementing 3 processes at the pilot scale (100 L) and 2 processes at the commercial scale (1000 L) and building a PCA model based on the obtained data.Валидация технологических процессов на основе концепции «качество, встроенное при разработке» (Quality by Design, QbD) требует глубокого научного понимания процессов и повышения их устойчивости путем внедрения новых технологий. Цель данной работы заключалась в обосновании методологического подхода на основе концепции QbD к валидации промышленного производства активной фармацевтической субстанции (АФС) дорназы альфа. Для этого было определено технологическое пространство процесса в демасштабированной модели — реакторах объемом 2 л; доказана репрезентативность данной модели по независимым от масштаба реактора параметрам; установлено сходство гидродинамических условий, конструкционных особенностей и режимов работы реакторов лабораторных, опытно-промышленных и промышленного объемов; показана масштабируемость процесса посредством демонстрации многовариантной математической модели РСА (Principal Component Analysis), перекрывающей объемы 2–1000 л, включающей входные, выходные параметры процесса и параметры качества продукта для ряда продуцентов рекомбинантных терапевтических белков, созданных на основе той же клеточной линии CHO и экспрессионной конструкции, что и продуцент дорназы альфа. Обоснована применимость инженерного пространства, которое определяется сочетанием конструкционных особенностей биореакторов и технологических параметров процесса, к различным масштабам путем проведения трех процессов в опытно-промышленном масштабе 100 л и двух процессов в промышленном масштабе 1000 л и построении на основе полученных данных модели РСА

Опыт масштабирования и интенсификации промышленного производства векторной аденовирусной вакцины Гам-КОВИД-Вак в лимитирующих условиях пандемии

The COVID-19 pandemic has presented a global challenge to the health system. More than 200 years of world epidemiological experience since the first mass use of vaccines have convincingly shown that effective vaccines are the key tools in the fight against dangerous infectious diseases, especially epidemic and pandemic ones. In the context of a rapidly spreading pandemic of a new infectious agent, it is crucial not only to develop fundamentally new vaccines, but also to be able to quickly organise their large-scale production. In the Russian Federation, in 2020, a team of the National Research Centre for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya developed an innovative vector vaccine, Gam-COVID-Vaс, for the prevention of coronavirus disease caused by the SARS-CoV-2 virus. A number of pharmaceutical companies faced the challenge of producing the vaccine. The aim of the study was to optimise the production technology of Gam-COVID-Vac for scaling and increasing the production capacity. In the course of the work, the authors established critical quality attributes of the product, optimised analytical methods for their control, identified poorly scalable technological stages, streamlined the technological process before its transfer to production, and modified non-scalable and technologically unfeasible stages. The work resulted in the launch of industrial-scale production of active pharmaceutical ingredients for both components of Gam-COVID-Vac, which made it possible not only to meet the critical need for COVID-19 immunoprophylaxis in the Russian Federation, but also to supply this vaccine to a number of foreign countries.Пандемия COVID-19 явилась глобальным вызовом для системы здравоохранения. За более чем 200 лет, прошедших с момента первого массового применения вакцин, эпидемиологи всего мира убедились, что именно эффективные вакцины являются ключевым инструментом в борьбе с опасными инфекционными заболеваниями, особенно эпидемического и пандемического характера. В условиях быстро распространяющейся пандемии нового инфекционного агента, не только разработка принципиально новых вакцинных препаратов, но и возможность быстро организовать крупномасштабное производство приобретают решающее значение. В Российской Федерации коллективом ФГБУ «НИЦЭМ им. Н.Ф. Гамалеи» Минздрава России в 2020 г. была разработана инновационная векторная вакцина Гам-КОВИД-Вак для профилактики коронавирусной инфекции, вызываемой вирусом SARS-CoV-2. Перед рядом отечественных биофармацевтических предприятий была поставлена задача ее производства. Цель работы – оптимизация технологии производства вакцины Гам-КОВИД-Вак для масштабирования и наращивания объема выпуска. В ходе работы были решены следующие задачи: установлены критические атрибуты качества продукта и оптимизированы аналитические методы для их контроля; выявлены технологические стадии, плохо поддающиеся масштабированию; оптимизирован технологический процесс перед переносом в производство; модифицированы не масштабируемые/нетехнологичные стадии. В результате работы был налажен массовый выпуск субстанции обоих компонентов Гам-КОВИД-Вак, позволивший не только обеспечить высокую потребность в вакцине для иммунопрофилактики COVID-19 в Российской Федерации, но и осуществлять поставки данной вакцины в ряд зарубежных стран

Methodological Approaches to Validation of Therapeutic Recombinant Proteins Production Based on the Quality by Design Concept

Validation of production processes based on the Quality by Design (QbD) principles calls for thorough scientific understanding of the processes and enhancement of their stability by implementation of new technologies. The aim of the study consisted in substantiating a QbD-based technological approach to validation of commercial production of dornase alfa. For this purpose a design space was established in a scale-down model, i.e. 2 L reactors; the model was shown to be representative in terms of all parameters except for the reactor size; the similarity of hydrodynamic conditions, design characteristics and operation modes of laboratory, pilot and commercial scale reactors was established; the process scalability was demonstrated by using the PCA (Principal Component Analysis) multivariate mathematical model including the volume range of 2–1000 L, input and output process parameters and product quality attributes for a number of recombinant therapeutic products derived from the same CHO cell line and expression construction as dornase alfa producer. The article demonstrates the applicability of engineering space, which includes bioreactor design features and production process parameters, to different production scales by implementing 3 processes at the pilot scale (100 L) and 2 processes at the commercial scale (1000 L) and building a PCA model based on the obtained data