CDER评审官指南《色谱分析方法的验证》CenterforDrugEvaluationWord下载.docx

1、and Research （CDER）Reviewer GuidanceValidation ofChromatographic MethodsNovember 1994CMC 3率. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16G. Robustness耐久性. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16H. Sample Solut

2、ion Stability供试品溶液的稳定性. . . . . . . . . . . . . . . . . . . . . .17I. Specificity/selectivity专属性/选择性 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17J. System Suitability Specifications and Tests系统适用性规定和试验 . . . . . 211. Capacity factor容量因子 . . . . . . . . . . . . . . . . . . . . . . . . .

3、 . . . . . . .222. Precision/Injection repeatability精密度/进样重复性 . . . . . . . . . . . .223. Relative retention相对保留时间. . . . . . . . . . . . . . . . . . . . . . . . . . . . .224. Resolution分离度. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225. Tailing factor拖尾因子. . . . . . . . . . .

4、. . . . . . . . . . . . . . . . . . . . . . . . .236. Theoretical plate number 理论塔板数 . . . . . . . . . . . . . . . . . . . .26K. General Points to Consider要点 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .28V. COMMENTS AND CONCLUSIONS注解和结论. . . . . . . . . . . . . . . . . . . . . . .

5、 . . .29VI. ACKNOWLEDGEMENTS致谢. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .29VII. REFERENCES参考文献. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .291This guidance has been prepared by the Analytical Methods Technical Committee of the Chemi

6、stry Manufacturing Controls Coordinating Committee （CMC CC） of the Center for Drug Evaluation and Research at the Food and Drug Administration. Although this guidance does not create or confer any rights for or on any person and does not operate to bind FDA or the industry, it does represent the age

7、ncys current thinking on the validation of chromatographic methods. For additional copies of this guidance, contact the Division of Communications Management, HFD-210, CDER, FDA, 5600 Fishers Lane, Rockville, MD 20857 （Phone: 301-594-1012）.Send one self-addressed adhesive label to assist the offices

8、 in processing your request. An electronic version of this guidance is also available via Internet the World Wide Web （WWW） （ connect to the FDA Home Page at WWW.FDA.GOV/CDER and go to the “Regulatory Guidance” section）.REVIEWER GUIDANCE1 VALIDATION OF CHROMATOGRAPHIC METHODSI. INTRODUCTIONThe purpo

9、se of this technical review guide is to present the issues to consider when evaluating chromatographic test methods from a regulatory perspective. The document discusses the points to note and weaknesses of chromatography so that CDER reviewers can ensure that the methods performance claims are prop

10、erly evaluated, and that sufficient information is available for the field chemist to assess the method. Analytical terms, as defined by the International Conference of Harmonization （ICH）, 1993, have been incorporated in this guide.本技术指南的目的是给审评人员审评验证色谱方法的, 该文件讨论色谱方法的要点和不足, 以便CDER的审评人员能够保证方法的良好性能，也使

11、化学工作者了解为通过审评应给出的足够的信息。国际协调会议（ICH）1993年定义的分析术语，已在这一指南中运用。Chromatographic methods are commonly used for the quantitative and qualitative analysis of raw materials, drug substances, drug products and compounds in biological fluids. The components monitored include chiral or achiral drug, process impuri

12、ties,residual solvents, excipients such as preservatives, degradation products, extractables and leachables from container and closure or manufacturing process, pesticide in drug product from plant origin, and metabolites.色谱方法通常用于原料、药物、药物制剂和生物体液中化合物的定性和定量。涉及的成分包括手性的或非手性的药物、过程杂质、残留溶媒、附加剂如防腐剂、分解产物、从容器

13、和密闭包装或制造过程中带入的可提取和可过滤的杂质、植物药中的农药和代谢物等。The objective of a test method is to generate reliable and accurate data regardless of whether it is for acceptance, release, stability or pharmacokinetics study. Data are generated for the qualitative and quantitative testing during development and postapproval

14、 of the drug products. The testing includes the acceptance of raw materials,release of the drug substances and products, in-process testing for quality assurance,and establishment of the expiration dating period.试验方法的目的是得到可信赖的和准确的数据，无论是用于验收、出厂、稳定性或药物动力学研究。得到的数据用于药品开发或批准后的定性和定量，试验包括原料的验收、药物和药物制剂的出厂、过

15、程检验（In- process testing）的质量保证和失效期的建立。Validation of a method is the process by which a method is tested by the developer or user for reliability, accuracy and preciseness of its intended purpose. Data thus generated become part of the methods validation package submitted to CDER. 方法的验证是由药品的开发者或使用者来检验其方法是否达到预期的可靠性、准确度和精密度的过程。得到的数据成为方法的验证资料的一部分交给CDER.。Methods validation should not be a one-time situation to fulfil Agency filing requirements, but the me