最近的FDA指导文件标题为“Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations”概述了关于对比较分析研究的设计和评估的建议,该研究旨在支持治疗蛋白质产品。这包括进行所提出的产品,加速和应力稳定性研究的稳定性曲线的适当的物理化学和功能比较,以及强制降解研究。
A common approach for drug development includes the use ofich稳定conditions to subject the product to varying environmental conditions. Subsequent stability pulls are tested against a battery of tests to ensure the safety, purity, and potency of the drug product. Take the case of an injectable biologic product. Depending on the firm’s risk appetite and the regulatory pathway, the initial GMP batches are; filled in a vial or pre-filled syringe, packaged, and carefully carted to the stability chambers for their iterative cadence of stability followed by analytical testing. Acceptable stability profiles against the various product tests keep the program alive. Fast forward to design verification, where the device portion of the combination product is put through the ringer. Typically, this includes a bombardment of physical stressors on the final-finished package configuration, which simulates a variety of transit conditions one would expect for the mode of distribution chosen for the given product. The resultant units are commonly placed into ICH stability conditions where an iterative cadence of stability is followed by physical testing to ensure the functionality of the device. Such tests include机械测试,particulate analysis, 和容器闭合完整性, to name a few.
Where’s the gap? The early stage GMP batches put on stability were never subjected to physical stressors, from a dynamic perspective. During design verification, the product was subjected to physical stressors, from a dynamic perspective, but was not scrutinized from an analytical perspective. Furthermore, recurring stability studies during commercial production will likely not account for the stress put on the product during transit and distribution.
Where’s the problem? Injectable biologic products are some of the most sensitive therapies in development and on the market. Using the example of proteins, the efficacy of these highly complex molecules can sometimes depend on low-energy interactions such as hydrogen bonding and van der Waals forces. Subjection of these molecules to the harsh conditions of transit and distribution can; alter their conformations, cause precipitation or aggregation, or accelerate degradation. By not testing the product against the analytical battery of tests after transit and distribution simulation, application holders run the risk of an adverse event happening in the field.
无论发展阶段,研发科学家和工程师都应考虑执行稳定性研究时的动态分量。此外,生物纤维单模应用持有者应在逆向工程产品时密切检查创新者包配置。注射器放置,托盘设计和纸箱设计的微妙选择可以将不同的力赋予装置内的药品。最后,随着生物制品进化为家庭管理的笔注射器,申请持有人应该考虑药房和患者家用冰箱或冰箱之间可能发生的条件。
虽然包装和分配实验室通常位于地下室(由于要求将振动表放在坚实的基础上),或者在第三方测试实验室,但它不是一个可怕的地方,一个研发科学家应该考虑访问更多经常。
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