Global Preclinical & Product Safety, Abbott Healthcare Pvt Ltd., Mumbai, India.
Global Preclinical & Product Safety, Abbott Healthcare Pvt Ltd., Mumbai, India.
Regul Toxicol Pharmacol. 2021 Oct;125:105016. doi: 10.1016/j.yrtph.2021.105016. Epub 2021 Jul 21.
Although the 3Rs are broadly applied in nonclinical testing, a better appreciation of the 3Rs is needed in the field of differentiated or value-added pharmaceutical generics because the minor changes in formulation, dosage form, indication, and application route often do not require additional safety testing. The US FDA and the EU EMA have comprehensive regulations for such drugs based on quality, therapeutic equivalence, and safety guidelines. However, no scientific publications on how the concept of replacement and reduction from 3Rs principles can be applied in the safety assessment of differentiated generics were found in the public domain. In this review, we discuss the application of 3Rs in nonclinical testing requirements for differentiated generics. Practical examples are provided in the form of case studies from regulated markets. We highlight the need for utilization of existing data to establish equivalence (differentiated generic vs innovator) in efficacy and safety. The case studies indicate that data requirements from animal experiments have been reduced to a large extent in some major markets without compromising quality and safety. In this context, we also highlight the problem that on a global scale, a true reduction of animal experiments will only be achieved when all countries adopt similar practices.
虽然 3R 原则已广泛应用于非临床测试，但在差异化或增值仿制药领域，人们需要更好地理解 3R 原则，因为配方、剂型、适应证和给药途径的微小变化通常不需要额外的安全性测试。美国 FDA 和欧盟 EMA 基于质量、治疗等效性和安全性指南，对这类药物有全面的规定。然而，在公开领域中，并未发现关于如何在差异化仿制药的安全性评估中应用替代和减少 3R 原则的概念的科学出版物。在这篇综述中，我们讨论了 3R 在差异化仿制药非临床测试要求中的应用。以来自监管市场的案例研究的形式提供了实际示例。我们强调需要利用现有数据来建立等效性（差异化仿制药与创新药）在疗效和安全性方面的等效性。案例研究表明，在一些主要市场，在不影响质量和安全性的情况下，动物实验的数据要求已大大减少。在这方面，我们还强调了一个问题，即在全球范围内，只有当所有国家都采用类似的做法时，才能真正减少动物实验。
