基于USP<1207>39中关于真空衰减法的描述与应用详解

真空衰减法原理简介：

“对放置样品的密闭测试腔抽取真空，达到稳定状态后观察真空度的变化，若真空度的变化值小于设定的阈值，或比对值小于设置的参数，则样品包装视为合格；若真空度的变化值大于设定的阈值，或比对值大于设置的参数，则样品包装视为不合格。”

Selection of Containers/Closures for Use in Lyophilization Applications: Possibilities and Limitations

Abstract
The unit operation of freeze-drying is commonly employed in the pharmaceutical industry to enhance the storage stability of relatively fragile biopharmaceuticals. Yet without a suitable container closure system, the advantages of freeze-drying a biopharmaceutical product cannot be fully realized and appreciated. Primary packaging provides the first line of defense for all pharmaceutical products by maintaining the critical quality attributes (CQAs) throughout the product shelf life. Although primary packaging components are intended to provide a stable environment for the pharmaceutical products, without proper understanding they can affect the product adversely by adsorption, absorption, leaching and permeation. For biologic products, proper selection of container and closure (c/c) components is even more important as they are more sensitive compared to other small molecule pharmaceuticals. Additionally, c/c also impacts the lyophilization process development and ultimately the drug product characteristics. The composition and processing history of the packaging components can play significant role as the impurities and residuals can induce destabilization and alter the drug product characteristics. It is critical, therefore, to understand and address all of these concerns related to c/c selection for successfully developing a stable biologic product to avoid potential product incompatibilities.

基于USP<1207>39中关于压力衰减法的描述与应用详解

压力衰减法原理简介：

“对放置样品的密闭测试腔体施加一定的气体压力，达到稳定状态后观察测试腔体内压力值的变化，若压力值的变化值小于设定的阈值，或比对值小于设置的参数，则样品包装视为合格；若压力值的变化值大于设定的阈值，或比对值大于设置的参数，则样品包装视为不合格。”

Container Closure Integrity Testing Method Development and Validation for Prefilled Syringes

"In order to function both as a container closure system and as a drug delivery device, prefilled syringes feature many unique design elements.”

如何正确选择容器密闭完整性检测（CCIT）的方法？

导言
USP39中对容器密闭完整性检测（CCIT）列取了10种方法，其中6种方法为无损检测，USP称为之确定性方法，包括了：真空衰减法、压力衰减法、激光顶空气体分析法、高压放电法、质量提取法、真空模式下示踪气体法；另外4中方法为有损检测，USP称之为概率性方法，包括了气泡法、微生物法、染色法、嗅探模式下示踪气体法；用户的包装类型与内在产品不尽相同，检测的方法也之所以不同。