vedomostiregmedРегуляторные исследования и экспертиза лекарственных средствRegulatory Research and Medicine Evaluation3034-30623034-3453Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/1991-2919-2024-660vedomostiregmed-660Research ArticleКОНТРОЛЬ КАЧЕСТВАQUALITY CONTROLМеждународные подходы к разработке, валидации и внесению изменений в аналитические методики (обзор)International Approaches to the Development, Validation, and Change Management of Analytical Procedures (Review)https://orcid.org/0009-0006-4575-705XФетисоваА. В.FetisovaA. V.

Фетисова Анна Владимировна.

ул. Верейская, д. 29, стр. 134, Москва, 121357

Anna V. Fetisova.

29/134, Vereyskaya St., Moscow 121357

afetisova@pharm-sintez.ruhttps://orcid.org/0000-0002-2441-3542АладышеваЖ. И.AladyshevaZh. I.

Аладышева Жанна Игоревна - канд. мед. наук, доцент.

ул. Трубецкая, д. 8, стр. 2, Москва, 119991

Zhanna I. Aladysheva - Cand. Sci. (Med.), Associate Professor.

8/2 Trubetskaya St., Moscow 119991

https://orcid.org/0000-0003-4901-4625ПятигорскаяН. В.PyatigorskayaN. V.

Пятигорская Наталья Валерьевна - д-р фарм. наук, профессор, член-корреспондент РАН.

ул. Трубецкая, д. 8, стр. 2, Москва, 119991

Nathalia V. Pyatigorskaya - Dr. Sci. (Pharm.), Professor, Corresponding Member of RAS.

8/2 Trubetskaya St., Moscow 119991

https://orcid.org/0000-0001-9038-8720ЗыряновО. А.ZyryanovO. A.

Зырянов Олег Анатольевич - канд. фарм. наук.

ул. Трубецкая, д. 8, стр. 2, Москва, 119991

Oleg A. Zyryanov - Cand. Sci. (Pharm.).

8/2 Trubetskaya St., Moscow 119991

https://orcid.org/0000-0002-5281-7771МаршаловаМ. М.MarshalovaM. M.

Маршалова Марина Максимовна.

ул. Трубецкая, д. 8, стр. 2, Москва, 119991

Marina M. Marshalova.

8/2 Trubetskaya St., Moscow 119991

Акционерное общество «Фарм-Синтез»РоссияPharm-Sintez AORussian FederationФедеральное государственное автономное образовательное учреждение высшего образование «Первый Московский государственный медицинский университет имени И.М. Сеченова» (Сеченовский Университет) Министерства здравоохранения Российской ФедерацииРоссияI.M. Sechenov First Moscow State Medical University (Sechenov University)Russian Federation202409102024145561571Copyright © Фетисова А.В., Аладышева Ж.И., Пятигорская Н.В., Зырянов О.А., Маршалова М.М., 20242024Фетисова А.В., Аладышева Ж.И., Пятигорская Н.В., Зырянов О.А., Маршалова М.М.Fetisova A.V., Aladysheva Z.I., Pyatigorskaya N.V., Zyryanov O.A., Marshalova M.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.vedomostincesmp.ru/jour/article/view/660ВВЕДЕНИЕ

ВВЕДЕНИЕ. В связи с изданием в 2023 г. нового руководства Международного совета по гармонизации технических требований к лекарственным средствам для медицинского применения ICH Q14 «Разработка аналитических методик» и пересмотром руководства ICH Q2 по валидации аналитических методик используемый в настоящее время на территории стран ЕАЭС подход к разработке и валидации аналитических методик должен быть в значительной степени пересмотрен. Также подлежат пересмотру процедуры оценки значимости и внесения изменений в регистрационное досье, касающееся аналитических методик.

ЦЕЛЬ

ЦЕЛЬ. Анализ существенных изменений международных подходов к разработке аналитических методик, оценка их преимуществ и недостатков при внедрении фармацевтическими предприятиями и регуляторными органами стран Евразийского экономического союза.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. Рассмотрены основные положения и практические аспекты введенного руководством ICH Q14 расширенного подхода к разработке аналитических методик, включая концепции жизненного цикла аналитической методики (ЖЦАМ) и модифицированного подхода «качество через дизайн» (AQbD), разработку аналитического целевого профиля, управление рисками для качества испытаний, планирование экспериментов и стратегии контроля, валидацию аналитической методики и последующую верификацию, трансфер и управление изменениями аналитической методики. Также определены сопутствующие этой новой регуляторной парадигме обновления руководства ICH Q2 (R2).

ВЫВОДЫ

ВЫВОДЫ. Указанные руководства восполняют дефицит рекомендаций в отношении разработки аналитических методик, а использование концепций ЖЦАМ и AQbD обеспечивает гибкость подходов как для фармацевтических компаний, так и для регуляторных органов. Эти подходы применимы как к новым разрабатываемым аналитическим методикам, так и к уже используемым на предприятиях. Для их эффективного внедрения в российскую фармацевтическую отрасль и регуляторную систему требуется широкая дискуссия специалистов и экспертов регуляторных органов, возможно, в рамках пилотного проекта, последующее обучение специалистов, занимающихся аналитической разработкой, а также внесение изменений в Правила регистрации и экспертизы лекарственных средств для медицинского применения.

INTRODUCTION

INTRODUCTION. In 2023, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) published a new Guideline on Analytical Procedure Development (ICH Q14) and a revised version of the Guideline on Validation of Analytical Procedures (ICH Q2(R2)). Consequently, there is a need for a considerable revision of the approach to the development and validation of analytical procedures that is currently used in the Eurasian Economic Union (EAEU). A revision is also needed for the processes for evaluating and introducing variations to the analytical procedures described in medicinal product registration dossiers.

AIM

AIM. This review aimed to analyse the significant changes made to international approaches to the development of analytical procedures, as well as to study the advantages and disadvantages of these approaches for pharmaceutical manufacturers and regulatory agencies in the EAEU.

DISCUSSION

DISCUSSION. This review covers the key provisions and practical aspects of the enhanced approaches to the development of analytical procedures introduced by the ICH Q14 guideline. In particular, the review addresses the concepts of the analytical procedure life cycle (APLC) and the modified analytical quality-by-design (AQbD) approach; the development of the analytical target profile (ATP); analytical quality risk management; planning of the design of experiments (DoE) and the analytical procedure control strategy; and the validation, subsequent verification, transfer, and change management of analytical procedures. Additionally, the review describes the ICH Q2(R2) updates that accompany this new regulatory paradigm.

CONCLUSIONS

CONCLUSIONS. The above guidelines fill the existing gap in recommendations for the development of analytical procedures. The use of the APLC and AQbD concepts provides both pharmaceutical companies and regulatory authorities with flexible approaches that are applicable to analytical procedures both during the development phase and once they have been implemented. Effective implementation of these international approaches in the Russian pharmaceutical industry and regulatory system requires a broad discussion between pharmaceutical industry professionals and regulatory agency experts, possibly, as part of a pilot project. After that, there will be a necessity to provide training for specialists involved in the development of analytical procedures and to amend the EAEU Rules for Marketing Authorisation and Expert Assessment of Medicinal Products for Human Use.

разработка аналитической методикивалидация аналитических методикуправление рискамиICH Q14ICH Q2внесение изменений в аналитическую методикуdevelopment of analytical proceduresvalidation of analytical proceduresrisk managementICH Q14ICH Q2changes to the analytical procedureanalytical quality by designAQbDanalytical procedure life cycleAPLCReferencesBastogne T, Caputo F, Prina-Mello A, Borgos S, Barberi-Heyob M. A state of the art in analytical quality-by-design and perspectives in characterization of nano-enabled medicinal products. J Pharm Biomed Anal. 2022;219:114911. https://doi.org/10.1016/j.jpba.2022.114911Bastogne T, Caputo F, Prina-Mello A, Borgos S, Barberi-Heyob M. A state of the art in analytical quality-by-design and perspectives in characterization of nano-enabled medicinal products. J Pharm Biomed Anal. 2022;219:114911. https://doi.org/10.1016/j.jpba.2022.114911Tome T, Žigart N, Časar Z, Obreza A. Development and optimization of liquid chromatography analytical methods by using AQbD principles: overview and recent advances. Org Process Res Dev. 2019;23(9):1784–802. https://doi.org/10.1021/acs.oprd.9b00238Tome T, Žigart N, Časar Z, Obreza A. Development and optimization of liquid chromatography analytical methods by using AQbD principles: overview and recent advances. Org Process Res Dev. 2019;23(9):1784–802. https://doi.org/10.1021/acs.oprd.9b00238Chavan AV, Gandhimathi R. Quality by design approach: progress in pharmaceutical method development and validation. Biomed Pharmacol J. 2023;16(3):1669–79. https://doi.org/10.13005/bpj/2745Chavan AV, Gandhimathi R. Quality by design approach: progress in pharmaceutical method development and validation. Biomed Pharmacol J. 2023;16(3):1669–79. https://doi.org/10.13005/bpj/2745Orlandini S, Hancu G, Szabó ZI, Modroiu A, Papp LA, Gotti R, Furlanetto S. New trends in the quality control of enantiomeric drugs: quality by design-compliant development of chiral capillary electrophoresis methods. Molecules. 2022;27(20):7058. https://doi.org/10.3390/molecules27207058Orlandini S, Hancu G, Szabó ZI, Modroiu A, Papp LA, Gotti R, Furlanetto S. New trends in the quality control of enantiomeric drugs: quality by design-compliant development of chiral capillary electrophoresis methods. Molecules. 2022;27(20):7058. https://doi.org/10.3390/molecules27207058Mishra V, Thakur S, Patil A, Shukla A. Quality by design (QbD) approaches in current pharmaceutical set-up. Expert Opin Drug Deliv. 2018;15(8):737–58. https://doi.org/10.1080/17425247.2018.1504768Mishra V, Thakur S, Patil A, Shukla A. Quality by design (QbD) approaches in current pharmaceutical set-up. Expert Opin Drug Deliv. 2018;15(8):737–58. https://doi.org/10.1080/17425247.2018.1504768Ermer J, Aguiar D, Boden A, Ding B, Obeng D, Rose M, et al. Lifecycle management in pharmaceutical analysis: how to establish an efficient and relevant continued performance monitoring program. J Pharm Biomed Anal. 2020;181:113051. https://doi.org/10.1016/j.jpba.2019.113051Ermer J, Aguiar D, Boden A, Ding B, Obeng D, Rose M, et al. Lifecycle management in pharmaceutical analysis: how to establish an efficient and relevant continued performance monitoring program. J Pharm Biomed Anal. 2020;181:113051. https://doi.org/10.1016/j.jpba.2019.113051Melissa H-B, Ermer J, Katzenbach S, Rignall A, Gervais A, Hoffmann J, et al. Analytical procedure lifecycle management: сurrent status and opportunities. Pharm Technol. 2018;42(12):18–23.Melissa H-B, Ermer J, Katzenbach S, Rignall A, Gervais A, Hoffmann J, et al. Analytical procedure lifecycle management: сurrent status and opportunities. Pharm Technol. 2018;42(12):18–23.Chaursiya AC, Dumpala RL. A review on revision of ICH Q2 (R1) and new ICH Q14 guidance. Glo J Pharm All Sci. 2020;1(6):1–6. https://doi.org/10.47583/gjfpas.2020.v01i06.001Chaursiya AC, Dumpala RL. A review on revision of ICH Q2 (R1) and new ICH Q14 guidance. Glo J Pharm All Sci. 2020;1(6):1–6. https://doi.org/10.47583/gjfpas.2020.v01i06.001Argentine M, Barnett K, Buhse L, Burgess C, Ermer J, Jackson P, et al. Stimuli to the Revision Process. Proceedings of the workshop on lifecycle approach of analytical procedure. Pharm Forum. 2017;43(6).Argentine M, Barnett K, Buhse L, Burgess C, Ermer J, Jackson P, et al. Stimuli to the Revision Process. Proceedings of the workshop on lifecycle approach of analytical procedure. Pharm Forum. 2017;43(6).Borman PJ, Guiraldelli AM, Weitzel J, Thompson S, Ermer J, Roussel JM, et al. Ongoing analytical procedure performance verification using a risk-based approach to determine performance monitoring requirements. Anal Chem. 2024;96(3):966–79. https://doi.org/10.1021/acs.analchem.3c03708Borman PJ, Guiraldelli AM, Weitzel J, Thompson S, Ermer J, Roussel JM, et al. Ongoing analytical procedure performance verification using a risk-based approach to determine performance monitoring requirements. Anal Chem. 2024;96(3):966–79. https://doi.org/10.1021/acs.analchem.3c03708Borman P, Campa C, Delpierre G, Hook E, Jackson P, Kelley W, et al. Selection of analytical technology and development of analytical procedures using the analytical target profile. Anal Chem. 2021;94(2):559–70. https://doi.org/10.1021/acs.analchem.1c03854Borman P, Campa C, Delpierre G, Hook E, Jackson P, Kelley W, et al. Selection of analytical technology and development of analytical procedures using the analytical target profile. Anal Chem. 2021;94(2):559–70. https://doi.org/10.1021/acs.analchem.1c03854Grangeia HB, Silva C, Simões SP, Reis MS. Quality by design in pharmaceutical manufacturing: a systematic review of current status, challenges and future perspectives. Eur J Pharm Biopharm. 2020;147:19–37. https://doi.org/10.1016/j.ejpb.2019.12.007Grangeia HB, Silva C, Simões SP, Reis MS. Quality by design in pharmaceutical manufacturing: a systematic review of current status, challenges and future perspectives. Eur J Pharm Biopharm. 2020;147:19–37. https://doi.org/10.1016/j.ejpb.2019.12.007Parr MK, Schmidt AH. Life cycle management of analytical methods. J Pharm Biomed Anal. 2018;147:506–17. https://doi.org/10.1016/j.jpba.2017.06.020Parr MK, Schmidt AH. Life cycle management of analytical methods. J Pharm Biomed Anal. 2018;147:506–17. https://doi.org/10.1016/j.jpba.2017.06.020Verch T, Campa C, Chery CC, Frenkel R, Graul T, Jaya N, et al. Analytical quality by design, life cycle management, and method control. AAPS J. 2022;24(1):34. https://doi.org/10.1208/s12248-022-00685-2Verch T, Campa C, Chery CC, Frenkel R, Graul T, Jaya N, et al. Analytical quality by design, life cycle management, and method control. AAPS J. 2022;24(1):34. https://doi.org/10.1208/s12248-022-00685-2Schmidtsdorff S, Neumann J, Schmidt AH, Parr MK. Analytical lifecycle management for comprehensive and universal nitrosamine analysis in various pharmaceutical formulations by supercritical fluid chromatography. J Pharm Biomed Anal. 2021;197:113960. https://doi.org/10.1016/j.jpba.2021.113960Schmidtsdorff S, Neumann J, Schmidt AH, Parr MK. Analytical lifecycle management for comprehensive and universal nitrosamine analysis in various pharmaceutical formulations by supercritical fluid chromatography. J Pharm Biomed Anal. 2021;197:113960. https://doi.org/10.1016/j.jpba.2021.113960Abreu JC, Mahr AG, do Lago CL. Stability-indicating method development for quantification of bromopride, its impurities, and degradation products by ultra-high performance liquid chromatography applying Analytical Quality by Design principles. J Pharm Biomed Anal. 2021;205:114306. https://doi.org/10.1016/j.jpba.2021.114306Abreu JC, Mahr AG, do Lago CL. Stability-indicating method development for quantification of bromopride, its impurities, and degradation products by ultra-high performance liquid chromatography applying Analytical Quality by Design principles. J Pharm Biomed Anal. 2021;205:114306. https://doi.org/10.1016/j.jpba.2021.114306Mahr AG, Lourenco FR, Borman P, Weitzel J, Roussel JM. Analytical Target Profile (ATP) and Method Operable Design Region (MODR). In: Breitkreitz MC, Goicoechea H, eds. Introduction to Quality by Design in Pharmaceutical Manufacturing and Analytical Development. Cham: Springer International Publishing; 2023. P. 199–219. https://doi.org/10.1007/978-3-031-31505-3_9Mahr AG, Lourenco FR, Borman P, Weitzel J, Roussel JM. Analytical Target Profile (ATP) and Method Operable Design Region (MODR). In: Breitkreitz MC, Goicoechea H, eds. Introduction to Quality by Design in Pharmaceutical Manufacturing and Analytical Development. Cham: Springer International Publishing; 2023. P. 199–219. https://doi.org/10.1007/978-3-031-31505-3_9Sousa VL, Gonçalves R, Menezes JC, Ramos A. Analytical method lifecycle management in pharmaceutical industry: a review. AAPS PharmSciTech. 2021;22(3):128. https://doi.org/10.1208/s12249-021-01960-9Sousa VL, Gonçalves R, Menezes JC, Ramos A. Analytical method lifecycle management in pharmaceutical industry: a review. AAPS PharmSciTech. 2021;22(3):128. https://doi.org/10.1208/s12249-021-01960-9Deidda R, Orlandini S, Hubert P, Hubert C. Risk-based approach for method development in pharmaceutical quality control context: a critical review. J Pharm Biomed Anal. 2018;161:110–21. https://doi.org/10.1016/j.jpba.2018.07.050Deidda R, Orlandini S, Hubert P, Hubert C. Risk-based approach for method development in pharmaceutical quality control context: a critical review. J Pharm Biomed Anal. 2018;161:110–21. https://doi.org/10.1016/j.jpba.2018.07.050Lidija Kovač L, Časar Z, Lušin TT, Roškar R. Development of an analytical method for determination of related substances and degradation products of cabotegravir using analytical quality by design principles. ACS Omega. 2022;7(10):8896–905. https://doi.org/10.1021/acsomega.1c07260Lidija Kovač L, Časar Z, Lušin TT, Roškar R. Development of an analytical method for determination of related substances and degradation products of cabotegravir using analytical quality by design principles. ACS Omega. 2022;7(10):8896–905. https://doi.org/10.1021/acsomega.1c07260Pasquini B, Orlandini S, Furlanetto S, Gotti R, Bubba MD, Boscaro F, et al. Quality by Design as a risk-based strategy in pharmaceutical analysis: development of a liquid chromatography-tandem mass spectrometry method for the determination of nintedanib and its impurities. J Chromatogr A. 2020;1611:460615. https://doi.org/10.1016/j.chroma.2019.460615Pasquini B, Orlandini S, Furlanetto S, Gotti R, Bubba MD, Boscaro F, et al. Quality by Design as a risk-based strategy in pharmaceutical analysis: development of a liquid chromatography-tandem mass spectrometry method for the determination of nintedanib and its impurities. J Chromatogr A. 2020;1611:460615. https://doi.org/10.1016/j.chroma.2019.460615Nayak R, Narenderan ST, Meyyanathan SN, Babu B. Analytical quality by design-based LC-MS/MS method for the determination of Riociguat in its formulations. J Appl Pharm Sci. 2021;11(12):100–6. https://doi.org/10.7324/japs.2021.1101208Nayak R, Narenderan ST, Meyyanathan SN, Babu B. Analytical quality by design-based LC-MS/MS method for the determination of Riociguat in its formulations. J Appl Pharm Sci. 2021;11(12):100–6. https://doi.org/10.7324/japs.2021.1101208Prabhu RC, Maruthapillai A. New RP-UPLC method development using QbD approach for determination of mebendazole, quinfamide, its impurities and antioxidants in mebendazole and quinfamide fixed dose combinations (FDC). Mater Today Proc. 2021;40:120–6. https://doi.org/10.1016/j.matpr.2020.04.243Prabhu RC, Maruthapillai A. New RP-UPLC method development using QbD approach for determination of mebendazole, quinfamide, its impurities and antioxidants in mebendazole and quinfamide fixed dose combinations (FDC). Mater Today Proc. 2021;40:120–6. https://doi.org/10.1016/j.matpr.2020.04.243Gurrala S, Raj S, Cvs S, Anumolu PD. Quality-by-design approach for chromatographic analysis of metformin, empagliflozin and linagliptin. J Chromatogr Sci. 2022;60(1):68–80. https://doi.org/10.1093/chromsci/bmab030Gurrala S, Raj S, Cvs S, Anumolu PD. Quality-by-design approach for chromatographic analysis of metformin, empagliflozin and linagliptin. J Chromatogr Sci. 2022;60(1):68–80. https://doi.org/10.1093/chromsci/bmab030Santana IM, Rostagno MA, Breitkreitz MC. Analytical quality-by-design (AQbD) approach for comprehensive analysis of bioactive compounds from Citrus peel wastes by UPLC. Anal Bioanal Chem. 2023;415(18):4411–22. https://doi.org/10.1007/s00216-023-04588-9Santana IM, Rostagno MA, Breitkreitz MC. Analytical quality-by-design (AQbD) approach for comprehensive analysis of bioactive compounds from Citrus peel wastes by UPLC. Anal Bioanal Chem. 2023;415(18):4411–22. https://doi.org/10.1007/s00216-023-04588-9Rácz N, Molnar I, Zöldhegyi A, Rieger HJ, Kormany R. Simultaneous optimization of mobile phase composition and pH using retention modeling and experimental design. J Pharm Biomed Anal. 2018;160:336–43. https://doi.org/10.1016/j.jpba.2018.07.054Rácz N, Molnar I, Zöldhegyi A, Rieger HJ, Kormany R. Simultaneous optimization of mobile phase composition and pH using retention modeling and experimental design. J Pharm Biomed Anal. 2018;160:336–43. https://doi.org/10.1016/j.jpba.2018.07.054Ermer J, Aguiar D, Boden A, Ding B, Obeng D, Rose M, Vokrot J. Lifecycle management in pharmaceutical analysis: how to establish an efficient and relevant continued performance monitoring program. J Pharm Biomed Anal. 2020;181:113051. https://doi.org/10.1016/j.jpba.2019.113051Ermer J, Aguiar D, Boden A, Ding B, Obeng D, Rose M, Vokrot J. Lifecycle management in pharmaceutical analysis: how to establish an efficient and relevant continued performance monitoring program. J Pharm Biomed Anal. 2020;181:113051. https://doi.org/10.1016/j.jpba.2019.113051Kalyane D, Raval N, Polaka S, Tekade RK. Quality by design as an emerging concept in the development of pharmaceuticals. In: Tekade RK, ed. The Future of Pharmaceutical Product Development and Research. Academic Press, 2020. P. 1–25. https://doi.org/10.1016/B978-0-12-814455-8.00001-3Kalyane D, Raval N, Polaka S, Tekade RK. Quality by design as an emerging concept in the development of pharmaceuticals. In: Tekade RK, ed. The Future of Pharmaceutical Product Development and Research. Academic Press, 2020. P. 1–25. https://doi.org/10.1016/B978-0-12-814455-8.00001-3Patel A, Jin C, Handzo B, Kalyanaraman R. Measurement of moisture content in pharmaceutical tablets by handheld near-infrared spectrometer: adopting quality by design approach to analytical method lifecycle management. J Pharm Biomed Anal. 2023;229:115381. https://doi.org/10.1016/j.jpba.2023.115381Patel A, Jin C, Handzo B, Kalyanaraman R. Measurement of moisture content in pharmaceutical tablets by handheld near-infrared spectrometer: adopting quality by design approach to analytical method lifecycle management. J Pharm Biomed Anal. 2023;229:115381. https://doi.org/10.1016/j.jpba.2023.115381Zagalo DM, Sousa J, Simões S. Quality by design (QbD) approach in marketing authorization procedures of non-biological complex drugs: a critical evaluation. Eur J Pharm Biopharm. 2022;178:1–24. https://doi.org/10.1016/j.ejpb.2022.07.014Zagalo DM, Sousa J, Simões S. Quality by design (QbD) approach in marketing authorization procedures of non-biological complex drugs: a critical evaluation. Eur J Pharm Biopharm. 2022;178:1–24. https://doi.org/10.1016/j.ejpb.2022.07.014

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