Use of Vanadium for Low-alloy Steel Manufacturing at JSC “EVRAZ NTMK”

Joint Stock Company “EVRAZ Nizhniy Tagil Metallurgical Plant” ( JSC “EVRAZ NTMK”) is the World’s largest processor of vanadium-rich titanium magnetite ores. This work describes the results of the research performed to test various combinations of vanadium and nitrogen microalloying targeted at repeatable quality and strength properties of the rolled steel products. In particular the benefits are described of using vanadium mass fractions in steel for manufacturing railway steel (rails, wheels, rings/tires), railcar body products (Z-beams, I-beams, etc.), API grades including large diameter X70 and X80 pipes. To optimize the analysis of different steel grades for the shaped sections manufacturing EVRAZ NTMK has taken efforts to identify the impact of the vanadium mass fraction in steel grade 09G2S on the mechanical properties of rolled steel with the elements of various thickness. During the effort, the mechanical tests were performed, the extent of vanadium reduction in the form of carbonitrides during the rolling and cooling process and its impact on the mechanical properties, the macrostructuring of rolled products was also studied. Recommendations were given on the chemical composition of steel 09G2S for manufacturing rolled steel of strength classes 375 and 390. Keywords: EVRAZ NTMK, vanadium, I-beams, mechanical properties, impact strengt

Organisational and methodological challenges of CAR-T manufacturing in the Russian Federation

Despite their widespread clinical implementation, chimeric antigen receptor T-cell (CAR-T) therapy products, including those manufactured by industrial processes, are still not legally available or used in the Russian Federation.The aim of the study was to describe the current challenges associated with specific aspects of CAR-T manufacturing in the Russian Federation and the potential ways to overcome them.This article discusses the regulatory, legal, organisational, and methodological challenges of CAR-T manufacturing. It analyses differences in the interpretation of CAR-T therapy products under national and supranational law. According to Russian Federal Law No. 180-FZ “On Biomedical Cell Products” of 23 June 2016, CAR-T therapy products are considered biomedical cell products. However, according to Decision No. 78 of the Council of the Eurasian Economic Commission “On the Rules of Marketing Authorisation and Assessment of Medicinal Products for Human Use” of 3 November 2016, CAR-T therapy products are considered advanced therapy medicinal products (ATMPs). This article provides a detailed overview of the difficulties in obtaining starting biological materials (i.e. the inability to consider the patient as a donor) and transferring the materials for CAR-T manufacturing (i.e. the inapplicability of national law). In addition, this article describes export aspects specific to biological materials. The authors reckon that CAR-T therapy products should be categorised as ATMPs and that the corresponding active pharmaceutical ingredients, genetically modified autologous lymphocytes, should be defined as starting materials. Therefore, genetically modified autologous lymphocytes should be regulated under the requirements for starting materials for the manufacturing of active pharmaceutical ingredients that are set forth in Decision No. 77 of the Council of the Eurasian Economic Commission “On the Adoption of the Rules of Good Manufacturing Practice of the Eurasian Economic Union” of 3 November 2016. In conclusion, the authors recognise the need for national and supranational law harmonisation. For this task, it is necessary to establish expert groups that will include clinicians, legal experts, and representatives from the relevant authorities and the pharmaceutical industry

Организационно-методические проблемы производства CAR-T в Российской Федерации

Despite their widespread clinical implementation, chimeric antigen receptor T-cell (CAR-T) therapy products, including those manufactured by industrial processes, are still not legally available or used in the Russian Federation.The aim of the study was to describe the current challenges associated with specific aspects of CAR-T manufacturing in the Russian Federation and the potential ways to overcome them.This article discusses the regulatory, legal, organisational, and methodological challenges of CAR-T manufacturing. It analyses differences in the interpretation of CAR-T therapy products under national and supranational law. According to Russian Federal Law No. 180-FZ “On Biomedical Cell Products” of 23 June 2016, CAR-T therapy products are considered biomedical cell products. However, according to Decision No. 78 of the Council of the Eurasian Economic Commission “On the Rules of Marketing Authorisation and Assessment of Medicinal Products for Human Use” of 3 November 2016, CAR-T therapy products are considered advanced therapy medicinal products (ATMPs). This article provides a detailed overview of the difficulties in obtaining starting biological materials (i.e. the inability to consider the patient as a donor) and transferring the materials for CAR-T manufacturing (i.e. the inapplicability of national law). In addition, this article describes export aspects specific to biological materials. The authors reckon that CAR-T therapy products should be categorised as ATMPs and that the corresponding active pharmaceutical ingredients, genetically modified autologous lymphocytes, should be defined as starting materials. Therefore, genetically modified autologous lymphocytes should be regulated under the requirements for starting materials for the manufacturing of active pharmaceutical ingredients that are set forth in Decision No. 77 of the Council of the Eurasian Economic Commission “On the Adoption of the Rules of Good Manufacturing Practice of the Eurasian Economic Union” of 3 November 2016. In conclusion, the authors recognise the need for national and supranational law harmonisation. For this task, it is necessary to establish expert groups that will include clinicians, legal experts, and representatives from the relevant authorities and the pharmaceutical industry.Несмотря на широкое внедрение в клиническую практику терапии Т-клетками с химерным антигенным рецептором (chimeric antigen receptor T-cell, CAR-T), на территории Российской Федерации данные препараты до сих пор официально не представлены и не используются, в том числе и произведенные промышленным (индустриальным) способом.Цель работы — описание текущих проблем, связанных с особенностями производства CAR-T в Российской Федерации, и потенциальных путей их решения.Рассмотрены трудности, связанные c регуляторными, юридическими и организационно-методическими аспектами производства CAR-T. Проанализированы расхождения в трактовке понятия CAR-T в национальном и наднациональном праве: как биомедицинского клеточного продукта согласно Федеральному закону от 23.06.2016 № 180-ФЗ «О биомедицинских клеточных продуктах» и как высокотехнологического лекарственного препарата (ВТЛП) согласно Решению Совета Евразийской экономической комиссии от 03.11.2016 № 78 «О Правилах регистрации и экспертизы лекарственных средств для медицинского применения». Подробно рассмотрены трудности на этапе получения исходного биологического материала (невозможность рассматривать пациента как донора биологического материала); на этапе передачи биологического материала для производства CAR-T (невозможность применения национального права); особенности экспорта биологического материала. По мнению авторов статьи, CAR-T следует относить к ВТЛП, активной фармацевтической субстанцией (АФС) которых являются генетически модифицированные аутологичные лимфоциты, а последние должны быть определены как «исходный материал», и к ним должны применяться требования как к исходному материалу для производства АФС, указанные в Решении Совета Евразийской экономической комиссии от 03.11.2016 № 77 «Об утверждении Правил надлежащей производственной практики Евразийского экономического союза». Сделано заключение о необходимости гармонизации национального и наднационального права, что требует формирования экспертных групп, объединяющих врачей-клиницистов, специалистов в области права, представителей профильных ведомств и фармацевтической индустрии