仿制药注射剂一致性评价之包装密封性测试阳性样品制备

鑫天地

Qualificationoftestmethodseaksimulationandflowtest
CCIT测试方法验证：漏孔模拟以及漏孔泄漏率测量
Whatis a simulated/artificial leak?何为漏孔模拟？
·Packages with intentional defects or known leaks.
Simulates naturally occurring defects and leaks
认为模拟贴合于自然发生在容器上的漏孔以及裂痕等缺陷。
Examples of natural defects 存在自然缺陷的不良品
Photos by Schott(Bauer,2019)
Simulated leak 模拟漏孔
By Solmonth

Purpose of a simulated leak in CCIT
为何需要漏孔模拟？
1.Acts as the positive control in leak test equipment qualification, method development and validation, and system suitability tests
作为阳性样品，用于验证色水法或微生物挑战法，用于验证仪器测试能力
·Accuracy
·Precision
·Specificity
·Detection limit
·Quantitative limit
·Linearity
·Range
·Robustness
2.Acts as a positive control during routine testing for some methods
作为阳性样品，在测漏方法或仪器的日常使用中协助进行持续验证
USP <1207.1>, 2016

Simulatedleakaser drill onactualpackaging
漏孔模拟：在实际容器上进行激光打孔
·Customizable hole geometry to simulate the non-cylindrical and tortuous path of natural defects. 激光可加工出曲折通道的孔型，更贴切于自然的漏孔
·Minimum hole sizes＜2μm，dependent on thickness. 最小可加工孔径：＜2μm
·Result consistency and tolerance highly dependent on material variability.
激光加工的批次一致性主要取决于材料以及材料厚度的一致性

Simulated leak : Laser drill on actual packaging
漏孔
模拟：在实际容器上进行激光打孔
·No foreign materials. 无人为加的部件和材料
·Works for all packaging (IV Bags, Blister packs, glass vials, pre-filled syringes, ampoules,etc). 可加工所有医药包装
·Risk of holes clogging during use.
不当存放和使用可能导致漏孔堵塞
·Careful handling is critical.
需适当存放
Semi-clogged holes due to debris
因空气中的尘埃而部分堵塞的漏孔
Image by Solmonth
Brown et al., 2017

Simulated leak : Laser drill on actualpackaging
漏孔模拟：在实际容器上进行激光打孔
·Drill location typically above or below product fill level, or close to critical seal areas. Precise location depends on varying requirements.
激光打孔在容器上的位置可依据各公司内孔标准和要求而定

Simulated leak : Laser drill on actualpackaging
漏孔模拟：在实际容器上进行激光打孔
·Beyond justv”holes”,recentadvancement towards customizable geometries to better simulate natural defects
随着激光打孔技术的进步，可更好的模拟实际自然发生的漏孔孔型和性能

Simulated leak : Laser drill on actualpackaging
漏孔模拟：在实际容器上进行激光打孔
·Beyond justv”holes”,recentadvancement towards customizable geometries to better simulate natural defects
随着激光打孔技术的进步，可更好的模拟实际自然发生的漏孔孔型和性能

Simulatedleak: Hole sizemeasurementbymicroscopy
漏孔模拟：通显微镜进行孔径测量及验证
·At times, measurement of hole size can be challenging. Further complicated by micro cracks in glass and irregular shapes
有时显微镜测量不容易：不规则孔型，不一致的出入孔，以及微裂纹的

Simulatedleak: Hole sizemeasurementbymicroscopy
漏孔模拟：通显微镜进行孔径测量及验证
·If microscopic measurement prove challenging, hole sizes can also be certified by gas flow test calibration.
如果微观测量具有挑战性，也可以通过气体流量测试校准来确定孔的尺寸。(Flow Test)
·Main principe原理
·Under set conditions, measure the gas flow rate of standard thin orifices plates of different nominal hole sizes. The results are used to create a calibration currelatingrelationship between the hole sizes and flow rate.
在设定的条件下，测量不同公称孔尺寸的标准薄孔板的气体流量。这些结果被用来建立孔尺寸和流量之间的校准关系。
·Under the same conditions, measure the flow rate of the actual laser-drilled simulated leaks.
在相同条件下，测量实际激光打孔模拟泄漏的流量。
Guazzo, 2010; USP<1207.1>, 2016

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