药品质量控制分析的毛细管电泳显影方法

简介

在早期到后期的研究阶段，毛细管电泳(CE)程序的药物质量控制(QC)分析被开发和应用。早期方法和高分子量化合物都可以从后期开发中受益。对于注册稳定性研究和原料药(DS)和药品(DP)验证批次的放行，药品QC执行后期方法开发。这些方法旨在转移到操作QC实验室进行生产批次的放行测试，最好是开发成快速、可靠、可靠和可转移的方法。因此，分配足够的时间、注意力和金钱来开发这些方法是至关重要的。对于QC测试来说，精确、准确、持久、可靠和可转移的方法是必要的。

关于研究

在方法开发的经典方法中，方法是在分析开发(AD)实验室中构建的。在移交给QC或稳定性实验室之前，AD实验室开发程序。开发实验室通常有能力与应用实验室交流，以寻求构建可能的最佳方法。另一方面，应用实验室主要关注测试样本，与开发实验室交谈可能被认为是浪费时间。因此，在方法开发过程中没有考虑到客户的需求，这可能会导致转移过程中的并发症，甚至在应用过程中出现投诉。此外，在客户端进行实际分析时，开发实验室并不知道该方法的性能。因此，抱怨往往被认为是主观的，而不是客观的。该方法的真正挑战是在转移研究期间进行的。在这个阶段，经常会出现许多与方法相关的意外。在更严重的情况下，转移失败，必须重新设计方法，导致延迟，这可能会严重影响产品开发时间表，并可能威胁到申请日期。 CE procedures frequently fail due to poor development and a lack of experience in receiving labs. Recently a more advanced approach towards chromatographic method development was introduced in pharmaceutical product development that also is beneficial for CE methods. In the advanced approach (i) the voice of the "customer" is captured, (ii) key process input variables are identified, (iii) Critical To Quality (CTQ) factors are determined, (iv) several method verification tests are installed, (v) proactive evaluation of method performance during development is performed, (vi) continuous customer involvement and focus is institutionalized, and (vii) method capability assessment is established. The aim of the advanced approach in method development is a first time right development process for late phase methods, with targeted customer focus, robust, reliable, and transferable methods. These methods result in reduced customer complaints, less rework, improved quality of the methods, objectively monitored method performance, improved partnership with the customers, and a high probability for success during method transfer. In contrast to the classical approach, a redesigned process is needed that starts with the generation of a Method Definition Requirement (MDR). This form contains target values that are set for many CTQ's prior to the start of method development process. Design of Experiment (DOE) techniques and Measurement System Analyses (MSA) 3 studies are systematically carried out during the method development process. The performance of the process is continuously monitored by a formal feedback round and Improving the quality attributes of methods is the goal, resulting in a reduction of complaints at the customers. This is achieved through continuous involvement with the application labs early in the method development process. The customer's voice is captured early and accounted for during development of the method. General needs are translated into CTQ attributes and treated as such during development. The MDR records product-specific customer requirements. All requirements described in the MDR are considered during method development. Either an intuitive or an experimental design approach may be applied when optimizing methods, resulting in an optimal separation of the main compound and all relevant impurities in a reasonable analysis time using typical CE conditions.

结论

AD实验室负责大部分的开发工作(方法开发阶段)。在提交方法之前，应评估其稳健性和日常实验室对实验室应用性能(方法评估阶段)。在开发和评估阶段之后，编写最终的方法描述，完全验证(方法验证阶段)，并转移到应用程序实验室(方法转移阶段)。在开发过程中进行彻底的评估后，转让活动将顺利进行。流程转换几乎肯定是成功的，因为应用程序实验室已经熟悉了这种方法。每次应用实验室对样品进行分析时，都会对方法性能进行监控(方法性能监控阶段)并进行评估。收集到的信息提供给开发实验室;因此，他们不断地被告知方法性能的好坏(性能反馈)。根据客观数据讨论潜在问题，并在彼此密切合作下解决问题。先进的方法开发方法具有主动控制(方法需求)、性能检查(方法评估)和在过程中构建的反应性控制，允许减少客户投诉、避免返工、提高方法质量、跟踪方法性能、让客户参与并促进合作关系。