基因治疗制品质量评价技术与方法专栏(一)

重组腺相关病毒(rAAV)基因治疗制品质控检验技术重点考量*

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  • 中国食品药品检定研究院 卫生部生物技术产品检定方法及其标准化重点试验室, 北京 100050
第一作者 秦 玺 Tel:(010)67095586;E-mail:qinxi@nifdc.org.cn
于 雷 Tel:(010)67095426;E-mail:yulei@nifdc.org.cn
** 史新昌 Tel:(010)67095426;E-mail:shixc@nifdc.org.cn
周 勇 Tel:(010)67095308;E-mail:zhouyong@nifdc.org.cn

收稿日期: 2023-03-16

  网络出版日期: 2024-06-21

基金资助

* 国家质量基础设施资助(2021YFFO600804);北京市科学技术委员会资助(Z221100007922015)

Critical considerations for quality control testing technology of recombinant adeno-associated virus(rAAV) gene therapy products*

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  • Key Laboratory of the Ministry of health for Research on Quality and standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing 100050, China

Received date: 2023-03-16

  Online published: 2024-06-21

摘要

近些年,国内基因治疗行业迅速发展,创新制品不断涌现,如何对该类制品进行有效的质量控制成为业界十分关心的问题。本文借鉴基因治疗制品质量控制领域中相对成熟的、有效的、实用性被证明的方法,以重组腺相关病毒基因治疗制品为例,从检测项目与检测方法的选择、注意事项、质量标准的拟定等方面出发,阐述了其质量控制检验项目及相关技术要求。希望本文能为从业者开展该类制品的质量控制研究提供参考,并通过后续的交流讨论可达成一定共识,进而加速推动我国基因治疗行业的发展。

本文引用格式

秦玺, 于雷, 陶磊, 毕华, 王光裕, 史新昌, 周勇 . 重组腺相关病毒(rAAV)基因治疗制品质控检验技术重点考量*[J]. 药物分析杂志, 2023 , 43(11) : 1813 -1819 . DOI: 10.16155/j.0254-1793.2023.11.01

Abstract

In recent years, the domestic gene therapy industry has developed rapidly, and innovative gene therapy products are emerging constantly. How to effectively control the quality of such products has become a highly concerned issue in the industry. This article draws inspiration from relatively mature, effective, and practical methods in the field of quality control of gene therapy products. Taking recombinant adeno-associated virus gene therapy products as an example, starting from the selection of testing items and methods, precautions, and formulation of quality standards, it elaborates on their quality control inspection items and related technical requirements. We hope this article can provide reference for practitioners to conduct quality control research on such products, and through subsequent communication and discussion, a certain consensus can be reached, thereby accelerating the development of gene therapy industry in China.

参考文献

[1] 中华人民共和国药典2020年版.三部[S]. 2020: 52
ChP 2020. Vol Ⅲ[S]. 2020: 52
[2] 夏训明.美国FDA批准一种基因疗法药物治疗RPE65双等位基因突变型遗传性视网膜变性病[J]. 广东药科大学学报,2017,33(6):752
XIA XM. The US FDA approved a gene therapy drug for the treatment of RPE65 biallele mutant hereditary retinal degeneration[J]. J Guangdong Pharm Univ,2017,33(6):752
[3] 夏训明.美国FDA批准Zolgensma(onasemnogene abeparvovec-xioi)治疗儿童脊髓性肌萎缩症[J]. 广东药科大学学报,2019,35(3):332
XIA XM. The US FDA approved Zolgensma (onasemnogene abeparvovec-xioi) for the treatment of spinal muscular atrophy in children[J]. J Guangdong Pharm Univ,2019,35(3):332
[4] MILLER NE. Glybera and the future of gene therapy in the European Union [J]. Nat Rev Drug Discov, 2012, 11(5):419
[5] 徐洋,闫荟羽,陶娌娜,等.基因治疗药物Alipogene tiparvovec的研究进展[J]. 中国药房,2015,26(11):1579
XU Y,YAN HY,TAO LN, et al. Research progress of gene therapy drug Alipogene tiparvovec[J]. China Pharm,2015,26(11):1579
[6] DARROW JJ. Luxturna: FDA documents reveal the value of a costly gene therapy[J]. Drug Discov Today, 2019, 24(4): 949
[7] 国家药品监督管理局药品审评中心[DB/OL]. (2023-4-30)[2023-06-07]. https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d
Center for Drug Evaluation[DB/OL]. (2023-4-30) [2023-06-07]. https://www.cde. org. cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d
[8] Specifications: Test Procedures and Acceptance Criteria for Biotechnological:Biological Products. ICH Q6B[S]. 1999:8
[9] 曹雪涛.医学免疫学[M]. 第6版.北京:人民卫生出版社,2013: 35
CAO XT.Medical Immunology[M]. 6nd Ed. Beijing: People’s Medical Publishing House, 2013:35
[10] ZHONG YM, XU F, WU JH, et al. Application of next generation sequencing in laboratory medicine[J]. Ann Lab Med,2014,41(1):25
[11] LIN B, HUN JN, MAO HJ. Nanopore technology and its applications in gene sequencing[J]. Biosensors (Basel), 2021, 11(7): 214
[12] TAKEDA H, YAMASHITA T, UEDA Y, et al. Exploring the hepatitis C virus genome using single molecule real-time sequencing[J]. World J Gastroenterol,2019,25(32):4661
[13] DENG JZ, LANCASTER C, WINTERS MA, et al. Multi-attribute characterization of pneumococcal conjugate vaccine by Size-exclusion chromatography coupled with UV-MALS-RI detections[J]. Vaccine, 2022,40(10):1464
[14] YARAWSKY AE, ZAI-ROSE V, CUNNINGHAM HM, et al. AAV analysis by sedimentation velocity analytical ultracentrifugation: beyond empty and full capsids[J]. Eur Biophys J,2023,52(4-5):353
[15] DICKERSON R, ARGENTO C, PIERACCI J, et al. Separating empty and full recombinant adeno-associated virus particles using isocratic anion exchange chromatography[J]. Biotechnol J, 2021, 16(1):e2000015
[16] COLE D, YOUNG G, WEIGEL A, et al. Label-free single-molecule imaging with numerical-aperture-shaped interferometric scattering microscopy[J]. ACS Photonics, 2017,4(2):211
[17] ALLEN JM, DEBELAK DJ, REYNOLDS TC, et al. Identification and elimination of replication-competent adeno-associated virus (AAV) that can arise by nonhomologous recombination during AAV vector production[J]. J Virol, 1997,71(9):6816
[18] SCHALK JA, DE VRIES CG, ORZECHOWSKI TJ, et al. A rapid and sensitive assay for detection of replication-competent adenoviruses by a combination of microcarrier cell culture and quantitative PCR[J]. J Virol Methods, 2007,145(2):89
[19] 金奇.医学分子病毒学[M]. 北京:科学出版社,2001:34
JIN Q. Medical Molecular Virology [M]. Beijing:Science Press,2001:34
[20] 国家食品药品监督管理局药品审评中心.体内基因治疗产品药学研究与评价技术指导原则(试行) [S]. 2022:40
Center for Drug Evaluation. Technical Guidelines for Pharmaceutical Research and Evaluation of in vivo Gene Therapy Products (Trial Version) [S]. 2022:40
[21] EMA. Guideline on the Quality, Non-Clinical and Clinical Aspects of Gene Therapy Medicinal Products[EB/OL]. (2015-03-23) [2023-05-06]. http://www.ema. europa. eu/docs/en_GB/document_library/Scientific_guideline/2015/05/WC500187 020. pdf
[22] FDA. Guidance for Industry: Guidance for Human Somatic Cell Therapy and Gene Therapy[EB/OL]. (1998-03) [2023-06-06]. https://www.fda. gov/downloads/BiologicsBloodVaccines/GuidanceCompliance RegulatoryInformation/Guidances/CellularandGeneTherapy/ucm 081670. pdf
[23] VELOURS C,ZHOU JJ,ZECCHIN P, et al. Determination of the absolute molar mass of [Fe-S]-containing proteins using size exclusion chromatography-multi-angle light scattering(SEC-MALS)[J]. Biomolecules,2022,12(2): 270
[24] COLE D,YOUNG G,WEIGL A, et al. Label-free single-molecule imaging with numerical-aperture-shaped interferometric scattering microscopy[J]. ACS Photonics,2017,4(2):211
[25] 国家食品药品监督管理局. 人基因治疗研究和制剂质量控制技术指导原则[EB/OL]. (2003-03-20) [2023-06-06]. http://www.sda. gov. cn/WS01/CL0237/15708.html
China Food and Drug Administration. Technical Guidelines for Human Gene Therapy Research and Preparation Quality Control [EB/OL]. (2003-03-20) [2023-06-06]. http://www.sda. gov. cn/WS01/CL0237/15708.html
[26] 中华人民共和国卫生部. 人间传染的病原微生物名录[S]. 2006:12
Ministry of Health of the People’s Republic of China. List of Pathogenic Microorganisms Transmitted from Human to Human[S]. 2006:12
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