翻译：JULIA 来源：Julia法规翻译

15. What material can be used as instrument calibration standards for chromatographic systems? 色谱分析系统可使用什么物料作为仪器校正标准品？

For chromatographic systems, instrument calibrationstandards should be chosen from highly purified materials that are well characterized and can be accurately weighed. Standards can be compendial (from USP) or non-compendial (e.g., from NIST, a chemical supplier, or produced in-house). Substances obtained from a chemical supplier or produced in-house should be purified and characterized using validated purification processes and validated characterization methods. Purification is necessary because impurities can add variation and interfere with analytical methods. Finished dosage forms generally should be avoided as standards because excipients in the finished dosage form may interfere with analysis.

对于色谱系统，仪器标准标准品应从已知特性可准确称量的高度纯化的物料中选取。标准品可以是药典（来自USP）或非药典的（例如，来自NIST，化学品供应商或自制）。来自化学品供应商或自制的物质应采用经验证的精制工艺和经验证的特征鉴别方法经过纯化和特征鉴别。精制是必须的，因为杂质可能会增加分析方法的波动性，对分析方法形成干扰。通常应避免使用制剂作为标准品，因为制剂中的辅料可能会干扰分析。

References: 参考文献

FDA guidance for industry, 2015, Analytical Procedures and Methods Validation for Drugs and Biologics

FDA行业指南，2015，药品和生物药品分析方法验证

21 CFR 211.160(b)(4): Instrument calibration

21 CFR 211.160(b)(4)：仪器校正

21 CFR 211.194(a)(2) and (c): Methodvalidation and reference standards

21 CFR 211.194(a)(2) 和(c)：方法验证和对照品

USP General Chapter <621> Chromatography, section on System Suitability

USP通则<621>色谱技术中的系统适用性部分

Date: 8/12/2019 日期：20190812

16. What material can be used for system suitability? 系统适用性可使用什么物料？

FDA expects system suitability to be checked using qualified primary or secondary reference standards and any materials necessary to ensure adequate method performance. A new batch of highly pure reference standard material (e.g., from a chemical supplier or produced in-house) should be qualified against the primary reference standard. Finished dosage forms or APIs that have not been qualified as reference standards should not be used for system suitability testing. Even when API or a finished dosage form has been properly qualified as a reference standard, it should not be used for system suitability testing if it is from the same batch as sample(s) being tested. Written procedures must be established and followed (21 CFR 211.160 and 211.194). All data — including obvious errors and failing, passing, and suspect data — must be in the CGMP records and subject to review and oversight. Records must be complete (e.g., 21 CFR 211.68(b), 211.188, and 211.194) and subjected to adequate review (21 CFR 211.68(b), 211.186(a), 211.192, and 211.194(a)(8)).

FDA要求使用经过确认的一级或二级对照品和任何必要的物料进行系统适用性检查，以确保足够的方法性能。一个新批次高度纯化的对照物料（例如来自化学品供应商或自制）应采用一级对照品进行确认。未确认为对照品的制剂或API不应用于系统适用性测试。即使API或制剂经过恰当确认成为对照品，如果是来自待检样品相同批次，则亦不能用于系统适用性测试。应制订并遵守书面程序（21XFR211.160和211.194）。所有数据----包括明显错误和不合格、合格和可疑数据----均必须记录在CGMP记录里，并经过审核和监管。记录必须完整（例如21 CFR 211.68(b), 211.188, 和211.194）并经过足够审核（21CFR 211.68(b), 211.186(a), 211.192, 和211.194(a)(8)）。

References: 参考文献

FDA guidance for industry, 2015, Analytical Procedures and Methods Validation for Drugs and Biologics

FDA行业指南，2015，药品和生物药品分析方法验证

FDA guidance for industry, 2018, Data Integrity and Compliance With Drug CGMP: Questions and Answers

FDA行业指南，2018，数据完整性和药品GMP合规问答

USP General Chapter <621> Chromatography, section on System Suitability

USP通则<621>色谱技术中的系统适用性部分

Date: 8/12/2019 发布日期：2019-08-12

17. Is it ever appropriate to perform a “trial injection” of samples? 对样品进行“试针”合适吗？

No. FDA has observed at some drug manufacturers the practice of a trial injection where a sample of a lot is injected into the chromatographic system with the intention of obtaining an unofficial result (e.g., passing or failing). This is in contrast to the appropriate practice where an injection of a standard is performed with the sole intention of determining if the chromatographic system is fit for purpose. The injection of trial samples is not acceptable, in part, because all data from analysis of product samples must be retained and reviewed (21 CFR 211.22, 211.165, 211.192, and 211.194). Furthermore, uncertainty about system performance may also suggest a potential insufficiency of the method’s design, validation status, analyst training, equipment maintenance, or other fundamental problem(s) in the laboratory that should be promptly corrected.

不合适。FDA已在有些药品生产商处发现其使用试针的做法，他们将样品批次进样色谱系统，意图得到非正式的结果（例如合格或不合格）。这与采用对照品进样的合适做法是相反的，采用对照品只是为了确定色谱系统是否适合其用途。试针是不可接受的，原因之一就是产品样品分析的所有数据均必须保存并经过审核（21 CFR 211.22, 211.165, 211.192, 和211.194）。另外，系统性能的不确定度亦说明方法设计、验证状态、化验员培训、设备维护可能是不充分的，或存在其它实验室基本问题，应及时整改。

Column conditioning does not involve injecting a sample from a lot and is not considered a trial injection. When its use is scientifically justified, column conditioning should be fully described in the method validation package as to the conditions needed to make the measurement (i.e., based on data from the method validation) and should be clearly defined in an approved and appropriate procedure. Only validated test methods that demonstrate accuracy, sensitivity, specificity, and reproducibility may be usedto test drugs (21 CFR 211.165(e)). Consistent and unambiguous injection nomenclature should be used, and all data from the column conditioning, including audit trail data, should be maintained and subject to review.

不采用待检样品进样对柱子平衡并不是试针。如果其用途经过科学论证，则应在方法验证包中完整描述检验达到所需的条件而需要执行的柱平衡要求（即，基于方法验证中的数据），并应在批准的恰当程序中清楚规定。只有经过验证的检测方法，证明了其准确度、灵敏度、专属性和重复性，才可用于检测药品（21 CFR 211.165(e)）。应使用清楚一致的进样命名，柱平衡的所有数据包括审计追踪数据，均应保存并经过审核。

Therefore, FDA considers it a violative practice to perform a trial injection (including under the guise of column conditioning). FDA also considers it a violative practice to use an actual sample in test, prep, or equilibration runs as a means of disguising testing into compliance.

因此，FDA认为试针是违规的（包括打着柱平衡的旗号）。FDA亦认为使用实际待检样品、样品溶液或平衡运行作为掩盖“检测直至合格”的手段是违规的。

References: 参考文献

FDA guidance for industry, 2015, Analytical Procedures and Methods Validation for Drugs and Biologics

FDA行业指南，2015，药品和生物药品分析方法验证

21 CFR 211.194(a)(2): Method validation

21 CFR 211.194(a)(2)：方法验证

Date: 8/12/2019 发布日期：2019-08-12