摘要
目的 探讨生物类似药相似性评价及临床试验设计的关键技术考虑。方法 通过梳理近年来国内外生物类似药临床研发情况,调研国内外生物类似药相关技术指南进展和核心内容,基于研发和审评的实践经验,形成相关技术考虑。结果与结论 生物类似药相似性评价应基于药学、非临床、临床的相似性比对研究结果进行整体相似性评价。对于药学及非临床对比研究中存在的不确定性,应针对性开展临床比对试验。临床试验设计应重点关注研究人群选择、给药途径和剂量、有效性终点、评价时间点、研究周期等一系列关键要素,以建立敏感模型,进而充分评估临床相似性并支持适应症的科学外推。
Abstract
OBJECTIVE To explore the essential technical considerations for the similarity assessment and the design of clinical trials of biosimilars. METHODS By sorting out the clinical research and development of biosimilars at home and abroad in recent years, the progress and core contents of relevant technical guidelines for biosimilars at home and abroad, and forming relevant technical considerations based on the practical experience of research and development as well asreview. RESULTS AND CONCLUSION The similarity evaluation of biosimilars should be carried out as overall similarity evaluation, based on the results of pharmaceutical, non-clinical and clinical similarity comparison studies. For uncertainties in pharmaceutical and non-clinical comparative studies, clinical comparative trials should be carried out specifically.A series of key elements such as the selection of the study population, route of administration and dose, efficacy endpoints, evaluation time points, and research periods, etc. for the clinical trial design should be paid attention to. Sensitive models should be established to adequately assess clinical similarities, which supports scientific extrapolation of indications.
关键词
生物类似药 /
临床试验设计 /
敏感模型 /
相似性评价 /
适应症外推
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Key words
biosimilar /
clinical trial design /
sensitive model /
similarity assessment /
indication extrapolation
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葛玉梅, 钱思源, 宋丽娜, 徐刚领, 赵聪, 唐崇淇, 韩鸿璨, 黄芳华, 谢松梅.
生物类似药相似性评价及临床试验设计的关键技术考虑[J]. 中国药学杂志, 2022, 57(23): 1962-1966 https://doi.org/10.11669/cpj.2022.23.002
GE Yu-mei, QIAN Si-yuan, SONG Li-na, XU Gang-ling, ZHAO Cong, TANG Chong-qi, HAN Hong-can, HUANG Fang-hua, XIE Song-mei.
Essential Technical Considerations for the Similarity Assessment and the Design of Clinical Trials of Biosimilars[J]. Chinese Pharmaceutical Journal, 2022, 57(23): 1962-1966 https://doi.org/10.11669/cpj.2022.23.002
中图分类号：
R979.1
Q798
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参考文献
[1] CFDA. Technical guidelines for development and evaluation of biosimilars(trial) [EB/OL]. (2015-02-28) [2021-06-25]. http: //samr. cfda. gov. cn /WS01 / CL1616 /115104. html.
[2] FDA. Biosimilar product information [EB/OL]. [2021-04-02]. https://www.fda.gov/drugs/biosimilars/biosimilar-product-Information.
[3] NMPA. Technical guidelines for similarity evaluation and indication extrapolation of biosimilars [EB/OL]. (2021-02-18) [2021-06-25]. https://www.cde.org.cn/zdyz/domesticinfopage?zdyzIdCODE=5e15021b72cb2d884afded50850 ed1f0.
[4] XIE S M, GAO C Y, BAI Y, et al. Considerations for design of clinical similarity comparison trials and evaluation of biosimilars[J]. Chin Pharm J(中国药学杂志), 2015, 50(6):490-493.
[5] EMA. Guideline on similar biological medicinal products containing monoclonal antibodies [EB/OL]. (2010-11-18) [2020-08-12]. https://www.ema.europa.eu/en/documents/scientific-guideline/draft-guideline-similar-biological-medicinal-products-containing-monoclonal-antibodies_en.pdf.
[6] WHO. Questions and answers: similar biotherapeutic products. Complementary document to the WHO guidelines on evaluation of similar biotherapeutic products (SBPs) [EB/OL]. (2018-03-19) [2021-06-12]. https://www.who.int/publications/m/item/who-questions-and-answers-similar-biotherapeutic-products.
[7] WHO.Guidelines on evaluation of monoclonal antibodies as similar biotherapeutic products (SBPs), Annex 2, TRS No 1004, [EB/OL]. (2011-01-16) [2021-06-04]. https://www.who.int/publications/m/item/mAbs-trs-no-1004-a2.
[8] RUGO H S, RIFKIN R M, DECLERCK P, et al. Demystifying biosimilars: development,regulation and clinical use[J]. Future Oncol, 2019,15(7):777-790.
[9] FDA. Scientific considerations in demonstrating biosimilarity to a reference product [EB/OL]. (2015-4) [2020-04-24]. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/scientific-considerations-demonstrating-biosimilarity-reference-product
[10] WHO. Guidelines on evaluation of similar biotherapeutic products (SBPs), Annex 2, TRS No 977 [EB/OL]. (2010-01-01) [2020-09-04]. https://www.who.int/publications/m/item/sbp-trs-977-Annex-2
[11] FDA. Guidance for industry clinical pharmacology data to support a demonstration of biosimilarityto a reference product [EB/OL]. (2020-08-12) [2020-09-04]. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-pharmacology-data-support-demonstration-biosimilarity-reference-product.
[12] WEISE M, KURKI P, WOLFF-HOLZ E, et al. Biosimilars: the science ofextrapolation [J]. Blood, 2014, 124(22):3191-3196.
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