mesЭкстремальная биомедицинаExtreme Medicine3033-89643033-8972Centre for Strategic Planning of the Federal Medical and Biological Agency10.47183/mes.2024-26-4-74-81mes-234Research ArticleПРОФИЛАКТИЧЕСКАЯ МЕДИЦИНАPREVENTIVE MEDICINEВозможные риски профессионального воздействия инновационных биологических лекарственных препаратов: обзор литературыPotential risks of occupational exposure to innovative biopharmaceuticals: a reviewhttps://orcid.org/0000-0003-1444-6591КлимовВ. И.KlimovV. I.

Климов Владимир Иванович, канд. мед. наук, старший научный сотрудник

Москва

Moscow

klimov@expmed.ruhttps://orcid.org/0000-0002-9279-1377ЛалыменкоО. С.LalymenkoO. S.

Лалыменко Ольга Сергеевна, канд. мед. наук

Москва

Moscow

yaloposta@gmail.comhttps://orcid.org/0000-0003-4068-2870КорсунЛ. В.KorsunL. V.

Корсун Лилия Владимировна, канд. биол. наук

Москва

Moscow

korsunlilia27@gmail.comНаучный центр экспертизы средств медицинского применения Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian FederationЦентр стратегического планирования и управления медико-биологическими рисками здоровью Федерального медико-биологического агентстваРоссияCentre for Strategic Planning of the Federal Medical and Biological AgencyRussian Federation2024131120242647481Copyright © Климов В.И., Лалыменко О.С., Корсун Л.В., 20242024Климов В.И., Лалыменко О.С., Корсун Л.В.Klimov V.I., Lalymenko O.S., Korsun L.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.extrememedicine.ru/jour/article/view/234Введение

Введение. Активные фармацевтические ингредиенты для производства лекарственных препаратов, воздействующих на генетический аппарат (генотерапевтических, высокотехнологических, биотехнологических), являются реакционноспособными соединениями с плейотропной активностью, что сопряжено с рисками здоровью работников, занятых на различных этапах их производства. Клинически значимый фармако/токсикологический эффект инновационных лекарственных препаратов, воздействующих на работающих, имеющих производственный контакт с данными компонентами, с точки зрения риск-ориентированного подхода в медицине труда является небезопасным.

Цель

Цель. Оценка потенциальных рисков профессионального воздействия инновационных биологических лекарственных препаратов на работающих в условиях производства/лаборатории и методических подходов их гигиенической регламентации.

Материалы и методы

Материалы и методы. Поиск научной литературы выполнен в электронных библиографических базах данных на русском (eLibrary, CyberLeninka) и английском (Web of Science, Scopus, PubМed) языках, нормативных документах в справочной правовой системе КонсультантПлюс.

Обсуждение

Обсуждение. Рассмотрены отдельные аспекты особенностей разработки биологических лекарственных препаратов нового поколения (генотерапевтических/высокотехнологических/биотехнологических лекарственных средств) и сопряженных с этим рисков профессионального воздействия на работников в условиях фармацевтического или лабораторного производства. Выявлено, что работники подвергаются сочетанному воздействию неблагоприятных факторов производственной среды различной природы: биологических, физических, химических. Отмечается неполнота информации о разработке аналитических методов идентификации компонентов генотерапевтических/высокотехнологических/биотехнологических лекарственных средств в воздухе рабочей зоны, на рабочих поверхностях, в сточных водах. Обозначены актуальные проблемы гигиены труда, связанные с отсутствием законодательных инструментов, научно обоснованных управленческих решений по идентификации факторов риска здоровью работников, диапазонов контроля потенциального производственного воздействия инновационных биологических лекарственных препаратов на основе принципов гигиенической регламентации, направленной на устранение или уменьшение негативного производственного воздействия и обеспечение безопасности и сохранения здоровья работников.

Выводы

Выводы. Проведенная работа позволила определить основные методические подходы по оценке потенциального производственного воздействия генотерапевтических/высокотехнологических/биотехнологических лекарственных средств на работников соответствующих фармацевтических предприятий. К таким подходам относятся: токсикологическая оценка соединений с установлением возможных параметров токсикометрии, исследование фармако/токсикокинетических особенностей компонентов генных препаратов, разработка методик их количественного определения в различных средах, установление биомаркеров экспозиции и эффекта с последующим гигиеническим нормированием и обоснованием основных профилактических мероприятий.

Introduction

Introduction. Gene-targeted therapies (gene-targeted, high-tech, and biopharmaceuticals) are developed based on active pharmaceutical ingredients, which are reactive compounds with pleiotropic activity. Such ingredients are associated with health hazards to workers employed at various stages of their production. Clinically significant pharmacological or toxicological effects of innovative medications on employees exposed to these components are unsafe from the perspective of a risk-based approach in occupational medicine.

Objective

Objective. Assessment of potential risks of occupational exposure to innovative biopharmaceuticals in production or laboratory conditions and approaches to their hygienic management.

Materials and methods

Materials and methods. The relevant scientific publications were searched and retrieved via electronic bibliographic databases both in the Russian language (eLibrary, CyberLeninka) and in the English language (WoS, Scopus, PubMed). Regulatory documents were analyzed using the Consultant Plus legal information system.

Discussion

Discussion. Specific features of production of new-generation biopharmaceuticals (gene-targeted, high-tech, or biotechnological medications) and the associated risks of occupational exposure to workers in pharmaceutical or laboratory production are considered. It was established that employees of such enterprises are exposed to the combined influence of adverse — biological, physical, and chemical — production environment factors. There is a lack of information on the development of analytical methods for identifying gene-targeted components (high-tech or biotechnological medications) in the workplace air and wastewater, as well as on workplace surfaces. The identified problems of occupational health are related to the lack of legislative instruments and knowledgebased management decisions on the identification of risk factors and control ranges of potential work-related effects of innovative biopharmaceuticals. Such approaches should be based on the principles of hygienic regulation aimed at eliminating or reducing negative industrial effects and ensuring the safety and preservation of employee health.

Conclusions

Conclusions. Major methodological approaches to assessing the work-related impact of gene-targeted, high-tech, or biotechnological therapies on employees of pharmaceutical enterprises are determined. These approaches include: (1) toxicological assessment of compounds with the establishment of possible parameters of toxicometry; (2) evaluation of the pharmacological and toxicokinetic features of gene-targeted therapeutical components; (3) development of methods for their quantitative determination in various environments; (4) establishment of biomarkers of exposure and related effects followed by hygienic rationing and justification of preventive measures.

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The authors declare that there are no conflicts of interest present.