The proposed ICH Q14 guideline “Analytical procedure development” describes science and risk-based approaches for development and maintenance of analytical procedures suitable for the assessment of the quality of drug substances and drug products. As a case study, the systematic development and validation of a supercritical fluid chromatography (SFC)-based purity method for carbamazepine is presented. Systematic analytical quality by design (AQbD) principles were applied using the software package Fusion QbD to the method development approach. The relationship between chromatographic parameters and the responses of interest were examined to improve the reliability of the method by understanding, reducing, and controlling sources of variability. Method performance qualification in terms of method robustness was finally carried out with the parameters that were classified as critical after method development and a validation study met previously set acceptance criteria. The developed SFC purity method for carbamazepine demonstrated readiness as a viable alternative to the official HPLC method published in the Ph.Eur. with improved peak resolution, improved peak symmetry, and faster analysis times (3 min vs. 80 min for the official method). Its inherent reliability illustrates the superiority of AQbD in method development and application for drug quality assurance.

中文翻译：

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受 ICH Q14 启发，建立基于 SFC 的卡马西平纯度方法

拟议的 ICH Q14 指南“分析程序开发”描述了用于开发和维护适合原料药和药品质量评估的分析程序的科学和基于风险的方法。作为案例研究，介绍了基于超临界流体色谱 (SFC) 的卡马西平纯度方法的系统开发和验证。使用软件包 Fusion QbD 将系统分析设计质量 (AQbD) 原则应用于方法开发方法。检查色谱参数和感兴趣的响应之间的关系，以通过了解、减少和控制变异性来源来提高方法的可靠性。最终使用方法开发后被归类为关键的参数进行方法鲁棒性方面的方法性能鉴定，并且验证研究满足先前设定的验收标准。开发的卡马西平 SFC 纯度方法已证明可以作为欧洲药典中发布的官方 HPLC 方法的可行替代方法。具有改进的峰分辨率、改进的峰对称性和更快的分析时间（官方方法为 3 分钟，而官方方法为 80 分钟）。其固有的可靠性说明了 AQbD 在药物质量保证方法开发和应用中的优越性。