Purpose

Lean stability is a science- and risk-based initiative which utilizes the enhanced understanding of drug substance and drug product physical and chemical characteristics to (1) reduce and optimize the design of standard stability protocols; (2) expedite the generation of stability data without impact to safety, efficacy, or quality of the product; and (3) decrease time to market for innovative drugs. Lean stability was introduced in the early 2000s [ICH: Guideline Q1A(R2) (2003), ICH: Guideline Q1D (2002)] followed by reduced stability protocols, focusing on the critical quality attributes and critical time points, being reported in the literature [Skrdla et al. (J Pharm Biomed Anal 50: 794–796, 2009)]. While the concept of lean testing is not entirely new, and it is currently a part of several regulatory guidances, it continues to evolve and gain acceptance of the industry and regulators.

Methods

In this review, twelve case studies are presented where stability data was collected during clinical, registration, and post-approval phases of the product development.

Results

Case studies summarize the lean stability testing design, the strategies applied during the regulatory filing and the outcomes of the regulatory filings.

Conclusion

The authors expect that the case studies presented in this review will increase the visibility of lean stability, facilitate overcoming of the existing challenges, and accelerate the global regulatory acceptance of lean stability practices in the industry.

中文翻译：

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精益稳定性案例研究-利用基于科学和风险的方法来实现有意义的特定于阶段的药物稳定性策略

目的

精益稳定是一项基于科学和风险的举措，它利用对药物物质和药品理化特性的增强理解，以（1）减少和优化标准稳定性方案的设计；（2）加快稳定性数据的生成，而不会影响产品的安全性，功效或质量；（3）缩短创新药物的上市时间。在2000年代初期引入了精益稳定性[ICH：Guideline Q1A（R2）（2003），ICH：Guideline Q1D（2002）]，其后降低了稳定性协议，重点关注关键的质量属性和关键的时间点，已有文献报道。 [Skrdla等。（J Pharm Biomed Anal 50：794–796，2009）。精益测试的概念并不是一个全新的概念，目前已成为一些监管指南的一部分，

方法

在这篇综述中，提出了十二个案例研究，其中在产品开发的临床，注册和批准后阶段收集了稳定性数据。

结果

案例研究总结了精益稳定性测试设计，在监管文件中应用的策略以及监管文件的结果。

结论

作者期望本次审查中提出的案例研究将提高精益稳定性的可见性，促进克服现有挑战，并加速全球法规对精益稳定性实践的接受。