Contains Nonbinding Recommendations
Draft — Not for Implementation 包含不具约束力的建议 草案 — 不用于实施
protocols for the botanical drug substance and/or drug product. A biological assay that reflects the drug’s known or intended mechanism of action is preferred.
在只靠化学检验不足以确保质量和疗效一致性的情况下，申请人应在植物药原料药和/或药品放行质量标准和稳定性方案中纳入生物检定。反映药物已知或预期作用机制的生物检定为首选。
Because results from a biological assay are inherently more variable than most of the chemical assays, the batch potency and activity should be measured relative to a suitable reference standard or material; results should be expressed in units of activity calibrated against the reference standard or material. The applicant should incorporate system suitability criteria and quality controls to ensure that the assay will perform in a reproducible and predictable manner.
由于生物检定结果在本质上比绝大多数的化学含量测定存在更多易变性，应相对于适用的标准品或材料测定批含量和活性。申请人应整合系统适用性标准和质量控制，确保检定以可重复和可预测的方式开展。
At the time of the NDA submission, the biological assay should be appropriately validated. At a minimum, the validation should demonstrate accuracy, precision, specificity, linearity, and range.
在新药申请提交时，生物检定应做适当验证。在最低程度上，验证应证明准确度、精度、专属性、线性和范围。
When the same botanical drug product is intended for multiple indications, the applicant should consult with the appropriate OND review division regarding whether it is necessary to develop a separate biological assay for each indication. 37
当同一植物药品拟用于多个适应症时，申请人应向恰当的新药办公室审评部门咨询，是否有必要针对每种适应症开发单独的生物检定法。37
d. Specifications d. 质量标准
The experience and data accumulated during the development of a botanical drug should form the basis for setting clinically relevant specifications. Analytical procedures should be properly validated. In addition, when multiple orthogonal methods are used, the totality of the data from all analytical procedures should be able to demonstrate the mass balance in the test sample on the basis of the different classes of chemicals and, if appropriate, among the individual constituents detected within a chemical class.
植物药研发阶段积累的经验和数据应成为设定临床相关质量标准的基础。应正确验证分析规程。此外，当使用多个正交法时，来自于所有分析程序的数据汇总，应能在不同类化学物质基础上，以及如果适用，包括一个化学物质类型中检测到的单个成分基础上，证明试样的质量平衡。
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37 See ICH Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products
and USP Biological Assays <1032>: Design and Development of Biological Assays and USP <1033>: Biological Assay Validation.
37 参见《ICH Q6B 质量标准：用于生物技术制品/生物制品的检验规程和可接受标准》，《美国药典（USP）生物检定<1032>：生物检定设计与研发》及《美国药典（USP）<1032>：生物检定验证》。
北京大学药物信息与工程研究中心?comments@cpier.pku.edu.cn?
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Contains Nonbinding Recommendations
Draft — Not for Implementation 包含不具约束力的建议 草案 — 不用于实施
The following tests on the drug substance should be included, if possible (see § 312.23(a)(7)):
? Amount by weight of each known chemical constituent, ? Area percentage of each unknown peak,
? Relative Retention Time (RRT) of each unknown quantifiable peak, ? Amounts by weight of total lipids and individual fatty acids, ? Amounts by weight of total amino acids and individual amino acids, ? Total amount by weight of simple carbohydrates, ? Total amount by weight of complex carbohydrates,
? Amounts by weight of total vitamins and individual vitamins, and ? Ash content (see USP <561 >, Articles of Botanical Origin).
如果可能，应涵盖对原料药的下述检验(参见§ 312.23(a)(7))：
? Amount by weight of each known chemical constituent, ? 以重量计的每种已知化学成分量， ? Area percentage of each unknown peak, ? 每个未知峰的面积百分比，
? Relative Retention Time (RRT) of each unknown quantifiable peak, ? 每个未知可量化峰的相对驻留时间（RRT），
? Amounts by weight of total lipids and individual fatty acids, ? 以重量计的总脂质和单个脂肪酸量，
? Amounts by weight of total amino acids and individual amino acids, ? 以重量计的总氨基酸和单个氨基酸量， ? Total amount by weight of simple carbohydrates, ? 以重量计的简单碳水化合物总量，
? Total amount by weight of complex carbohydrates, ? 以重量计的复杂碳水化合物总量，
? Amounts by weight of total vitamins and individual vitamins, and ? 以重量计的总维生素和单个维生素量，以及
? Ash content (see USP <561 >, Articles of Botanical Origin). ? 灰分含量（参见美国药典（USP）<561 >，植物源制品）。
If a biological assay is needed for quality control, the mass balance should be evaluated in conjunction with the biological assay.
如果生物检定对质量控制是必需的，应与生物检定一起评价质量平衡。
f. Stability f. 稳定性
The applicant should develop, validate, and use stability-indicating analytical methods and/or a biological assay to monitor the stability of the botanical drug substance and drug product. The applicant also should perform stress stability studies to identify degradation products in the drug substance and drug product, assess the potential toxicity, and provide adequate control of these degradation products.
北京大学药物信息与工程研究中心?comments@cpier.pku.edu.cn?
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