分析方法验证、转移和确认概念解析

分析方法验证、转移和确认的目的是证明分析方法的适用性,对保证检测结果的一致性、可靠性和准确性具有重要作用。方法验证、转移和确认的概念不同,适用范围不同,在实际工作中存在一些模糊概念,而且也存在使用不当的情况。鉴于上述情况,本文详细阐述药品方法验证、方法转移、方法确认的联系、区别、适用范围,为药品检验检验相关工作提供参考。     

杂质检查分析方法建立过程中破坏性试验的意义和存在的问题分析

破坏性试验是杂质检测方法建立时验证专属性、检测灵敏度的重要试验内容之一,能提供药品可能的降解途径和降解产物的信息.由于破坏性试验的实验过程复杂,在技术审评过程中经常发现该项实验的实验条件设计不合理、实验参数确定依据不充分、实验结果评价分析不全面等问题.现对如何有效、全面测定破坏性试验中产生的降解产物,合理开展破坏性试验研究做一分析.     

生物药物分析方法验证体系的研究

目的:探讨生物药物分析方法验证中存在的问题及改良策略。方法:分析国内外对于生物药物分析方法验证的理念、特点及研究进展,将质量源于设计的理念同传统方法验证理念进行比较研究。结果与结论:将指标化、终点化控制的传统验证体系改良为可视化、可溯源、立体化过程控制的方法验证系统。将方法建立及验证工作有机融合一体,为高质量数据提供保障。这个体系不但可有效整理记录方法建立及验证过程,利于分析方法转移过程中有效信息的传递,也有利于生物药物分析方法的评价和研究。     

对药物研发中分析方法验证的几点考虑

本文对分析方法验证的内涵进行了进一步阐述,指出了 目前药物研发中在分析方法验证方面存在的问题以及误区,给出了作者的见解和建议,并提出了更高的要求和期望.     

清洁验证中的分析方法验证

目的:论述如何验证清洁验证中所采用的分析方法.方法:制定验证方案,对方法的专属性、线性和范围、准确度、精密度、定量限等一一进行验证.结果:通过方法验证,确认可适用于清洁验证的分析方法.结论:采用经过验证的分析方法,是保证分析结果真实可靠的前提条件.清洁验证所采用的分析方法,同样也不能忽略方法验证.     

HPLC检查非残溶杂质分析方法验证的实例解析

目的:对于用HPLC检查非残留溶剂杂质的分析方法验证问题,通过实例解析进行探讨,以便更好地操作和指导工作。方法:通过具体介绍,解析实例,更直观、全面地阐述分析方法验证的要求。结果与结论:分析方法验证,无论在质量保证工作,还是在药品注册活动中,都非常重要,企业必须结合具体情况,提出适宜方案,并且认真贯彻实施。     

药品微生物经典分析方法的验证探讨

本文通过研读分析药品、食品和环境微生物分析方法验证的相关规范性文件,结合药品微生物分析实践,对药品微生物经典分析方法的验证进行了研究,总结了微生物分析方法验证的考察指标,包括专属性、灵敏度、精密度、检测限和定量限、线性、范围、耐用性及方法适用性等,并阐述了各指标在药品微生物分析中的含义、测量方法、影响因素和可接受标准。为规范经典微生物分析方法的验证,获得可靠的微生物检验结果及建立相关指导原则,提供了参考依据。     

有关物质的研究与新药注册

讨论有关物质检查方法建立与验证、限度确定的基本原则,同时指出有关物质研究在新药注册中需要关注的几个问题.     

人体苯磺酸氨氯地平生物分析方法验证问题的探讨

目的探讨国内进行生物分析方法验证存在的问题。方法分析2001年至2013年含测定人体苯磺酸氨氯地平浓度的生物分析方法验证的20篇文献(除去相同试验的文献),并与欧盟生物分析方法验证指导原则进行对比。结果与结论国内的试验单位进行生物分析方法验证时在基质效应、稳定性的验证方面需要加强;建议增加残留、稀释完整性、已测样品再分析、系统适用性等方面的内容以提高生物分析的质量。我国的药品申报者、生物分析研究单位,应充分认识到生物分析方法验证的意义和重要性,关注科学和法规的不断发展,开展系统、合理的方法学验证工作,以保证药物安全性、有效性研究的科学性。     

欧美原料药进口注册文件中的分析方法验证

目的:促进我国企业原料药的国际注册工作。方法:结合欧美原料药注册管理的要求,对其中的分析方法验证部分进行全面阐述,并提出具体的操作方法。结果与结论:分析方法验证无论在质量控制中,还是在国际药品注册活动中,都是非常重要的内容,我国企业必须给予高度的重视。     

HPLC分析方法验证问题解析

方法验证虽然有包括《中国药典》在内的许多指南,但《指南》一般较为原则性,没有具体操作指导,如有关物质测定方法的线性范围如何确定？耐用性进行哪些项目较为科学？验证项目是否都需要加入样品以考察干扰？精密度误差接受标准是什么？这些都是在实际验证中非常纠结的问题,而且《指南》也未必所有内容都科学,诸如强降解试验的物料平衡问题、峰纯度测定问题等,笔者结合近30年的工作经验,对HPLC分析方法验证的实际操作的疑点和难点进行探讨。     

GLP实验室计算机化系统基础设施的验证和管理

网络和系统基础设施是GLP实验室计算机化系统的基本构架,其验证和管理工作对计算机化系统在GLP机构中的有序运行至关重要。基础设施可在计算机化系统的系统生命周期中被验证,也可独立验证。基础设施验证应全面考虑其特殊方面如基础设施配置、规模和复杂性、硬件和软件以及网络通信等,从而实现以监管为目的的计算机化系统验证。简述了计算机化系统基础设施的验证方法和管理工作特性,以期为建立符合我国GLP原则和法规要求的计算机化系统提供支持和参考。     

浅议有关物质分析方法验证的接受标准

目的：阐述HPLC有关物质分析方法各验证项目的接受标准。方法与结果：介绍HPLC有关物质分析方法各验证项目的目的和操作,参阅文献并结合实际工作经验,通过对比分析提出其接受标准。结论：正确理解有关物质分析方法验证的目的,是制定合理接受标准的基础;规范的方法验证需要一个较为公认的接受标准,但是,分析方法验证本身也是一个无止境的系统过程,因此在看待接受标准时,我们不能陷入形而上学的本本主义。     

Impact of metal-induced degradation on the determination of pharmaceutical compound purity and a strategy for mitigation

Case studies are presented demonstrating how exposure to traces of transition metals such as copper and/or iron during sample preparation or analysis can impact the accuracy of purity analysis of pharmaceuticals. Some compounds, such as phenols and indoles, react with metals in the presence of oxygen to produce metal-induced oxidative decomposition products. Compounds susceptible to metal-induced decomposition can degrade following preparation for purity analysis leading to falsely high impurity results. Our work has shown even metals at levels below 0.1 ppm can negatively impact susceptible compounds. Falsely low results are also possible when the impurities themselves react with metals and degrade prior to analysis. Traces of metals in the HPLC mobile phase can lead to chromatographic artifacts, affecting the reproducibility of purity results. To understand and mitigate the impact of metal induced decomposition, a proactive strategy is presented. The pharmaceutical would first be tested for reactivity with specific transition metals in the sample solvent/diluents and in the HPLC mobile phase. If found to be reactive, alternative sample diluents and/or mobile phases with less reactive solvents or addition of a metal chelator would be explored. If unsuccessful, glassware cleaning or sample solution refrigeration could be investigated. By employing this strategy during method development, robust purity methods would be delivered to the quality control laboratories, preventing future problems from potential sporadic contamination of glassware with metals.     

Validation protocol of analytical procedures for quantification of drugs in polymeric systems for parenteral administration: Dexamethasone phosphate disodium microparticles

In this work a protocol to validate analytical procedures for the quantification of drug substances formulated in polymeric systems that comprise both drug entrapped into the polymeric matrix (assay:content test) and drug released from the systems (assay:dissolution test) is developed. This protocol is applied to the validation two isocratic HPLC analytical procedures for the analysis of dexamethasone phosphate disodium microparticles for parenteral administration. Preparation of authentic samples and artificially “spiked” and “unspiked” samples is described. Specificity (ability to quantify dexamethasone phosphate disodium in presence of constituents of the dissolution medium and other microparticle constituents), linearity, accuracy and precision are evaluated, in the range from 10 to 50 μg mL⁻¹ in the assay:content test procedure and from 0.25 to 10 μg mL⁻¹ in the assay:dissolution test procedure. The robustness of the analytical method to extract drug from microparticles is also assessed. The validation protocol developed allows us to conclude that both analytical methods are suitable for their intended purpose, but the lack of proportionality of the assay:dissolution analytical method should be taken into account.     

Validation of an HPLC Analytical Method for the Quantitative/Qualitative Determination of Fluticasone Propionate in Inhalation Particles on Several Matrices

Fluticasone propionate is a highly potent corticosteroid used to treat asthma and allergic rhinitis. It is a very effective drug, but has the inconvenient factor of being insoluble in water. Cyclodextrins were used to improve this limitation because of their ability to form inclusion complexes with guest drug molecules as well as increase the stability and bioavailability of the drugs. A rapid and simple HPLC method was developed to detect and quantify fluticasone propionate in inhalation particles on several matrices. Liquid chromatography with a UV detector at a wavelength of 236 nm, using a C18 column, was employed in this study. Isocratic elution was employed using a mixture of acetonitrile and water (60:40, v/v). The analytical method validation was performed in accordance with ICH guidelines, which included selectivity, range, linearity, accuracy, detection limit, quantitation limit, precision, robustness, and stability of solutions. This method showed to be selective and specific. Acceptable assay precision and accuracy (100 ± 5.0%) were obtained at 50– 150% of the analytical concentration of fluticasone propionate at the target concentration of 0.060 mg/mL, and good linearity (0.9958) was achieved over a range of 0.03 to 0.09 mg/mL for fluticasone propionate. The proposed HPLC method proved to be reliable. The validation and application of this method can be adopted for determining the fluticasone propionate in: assays, impingers and impactors, diffusion cells, dissolutions, and other tests. In addition, this method can be adapted and used in the pharmaceutical industry for routine analysis.     

Application issues in bioanalytical method validation,sample analysis and data reporting

Although some degree of consensus has been reached concerning the requirements for acceptable method validation, the procedures used to establish them vary significantly between laboratories. Also, issues arising from application of these requirements during validation and subsequent sample analysis need to be addressed. The purpose of this paper is to discuss application issues concerning prerequisites to method validation, and all validation criteria for evaluation of method reliability and overall performance. Other poorly addressed issues such as re-validation, cross-validation, partial sample volume, multicomponent analysis and reporting will also be discussed. Although many issues discussed are of a general nature, the scope of this presentation is primarily to address issues arising from the validation and routine application of chromatographic methods.     

Validation of a dissolution method with HPLC analysis for lasofoxifene tartrate low dose tablets

A dissolution method with high performance liquid chromatography (HPLC) analysis was validated for an immediate release low dose tablet formulation. The method was validated to meet requirements for a global regulatory filing and this validation included specificity, precision, linearity, accuracy and range. Validation of precision included an intermediate precision study using an experimental design in order to satisfy Japanese regulatory requirements. In addition, filter suitability, standard and sample solution stability and method robustness were demonstrated. A statistical design of experiments was used for the robustness evaluation of both the dissolution method and the HPLC analysis method. All results were acceptable and confirmed that the method is suitable for its intended use.     

非临床研究中大分子生物分析方法验证报告审核方法

目的：掌握大分子生物分析方法验证报告审核的方法和原则,确保验证报告的科学性、合规性和完整性。方法：将完整的生物分析方法验证报告和原始记录拆分为原始记录、数据及数据处理、验证报告,分别对三部分进行全面系统性审核,最后将审核的结果进行分析和汇总。结果与结论：通过系统性的审核,熟练掌握审核的方法和要点,提高大分子生物分析方法验证报告的审核效率,提升报告质量,满足机构SOPs和国内外法律法规的要求,推进客户药物研发和申报进程。