Kirkpatrick Douglas, Gupta Nirzari, Gopalaswamy Ramesh, Kolhatkar Rohit, Hudson-Davis Morgan, Keire David
United States Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, 645 S Newstead Ave, St. Louis, 63110, Missouri, USA.
Office of Pharmaceutical Quality Assessment II, CDER, U.S. FDA, White Oak, Maryland, USA.
AAPS J. 2025 Mar 14;27(2):61. doi: 10.1208/s12248-025-01037-6.
Enabling greater flexibility for lifecycle management of analytical procedures is one of the primary features of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q12 Lifecycle Management guideline. Rather than rely on a comparatively slower and burdensome post-approval change supplement process, ICH Q12 created a new pathway to facilitate changes to chemistry, manufacturing, and controls. The new framework utilized key concepts such as established conditions (ECs), post-approval change management protocols, and the product lifecycle management document to allow modifications to analytical procedures based upon pre-approved conditions. Shortly after the publication of ICH Q12, the ICH Q14 Analytical Procedure Development guideline provided further guidance on how knowledge gained during analytical procedure development could be incorporated with the ICH Q12 framework to support scientifically sound and risk-based post-approval changes. However, to date, the full potential of ICH Q12 and Q14 remains unrealized, likely due to uncertainty over how analytical procedure development data can be effectively utilized to gain regulatory flexibility for post-approval changes. In this case study, an example of determining, proposing, and justifying analytical procedure ECs, reporting categories, and identification of elements not considered ECs is presented. In addition, how such information could be presented in a regulatory submission is described. Importantly, this case study serves as an example of the application of ICH Q12 and Q14 principles for analytical procedures, but it is not intended to serve as official guidance nor to define the full scope of information required in a regulatory submission.
增强分析程序生命周期管理的灵活性是国际人用药品技术协调理事会（ICH）Q12生命周期管理指南的主要特点之一。ICH Q12并未依赖相对缓慢且繁琐的批准后变更补充程序，而是创建了一条新途径来促进化学、生产和控制方面的变更。新框架利用了既定条件（ECs）、批准后变更管理协议和产品生命周期管理文件等关键概念，以便在预先批准的条件下对分析程序进行修改。ICH Q12发布后不久，ICH Q14分析程序开发指南就如何将分析程序开发过程中获得的知识与ICH Q12框架相结合以支持科学合理且基于风险的批准后变更提供了进一步指导。然而，迄今为止，ICH Q12和Q14的全部潜力尚未实现，这可能是由于在如何有效利用分析程序开发数据以获得批准后变更的监管灵活性方面存在不确定性。在本案例研究中，给出了一个确定、提议和论证分析程序ECs、报告类别以及识别非ECs要素的示例。此外，还描述了此类信息在监管申报中应如何呈现。重要的是，本案例研究作为将ICH Q12和Q14原则应用于分析程序的一个示例，但并非旨在作为官方指导，也未定义监管申报所需信息的全部范围。
