轧盖效果与产品密封性-量化的相关性研究

hisun，sanofi

今天和大家分享一篇文章
试验人员研究了RSF 与 CCI之间的关系。
理解这个试验先要看张图

研究者将研究的目标锁定在CCI与1、2、3密封面之间的关系上，然后通过RSF量化轧盖工艺过程确定RSF的变化后是否影响1、2、3面的密封性并同时判断CCI是否受影响。最后的研究结论是 1面主要和组件尺寸有关与RSF相关性弱，3面受RSF的影响较大，但3面不是影响CCI的关键密封面。

实验设计


试验通过改造胶塞的形状进行了单因素的研究（针对1、3面的研究）


Valve Seal: The valve seal, provided by the
plug of the stopper, was isolated by cutting off the
land seal area (i.e., the flange) from a lyophilization
stopper. A stainless-steel spacer was inserted in the
top of the plug to prevent the plug from being dis-
lodged during capping (Figure 3A). Vials in this con-
figuration do not have an RSF because they lack the
land seal. Twenty vials of this configuration were
tested by the He-leak. All vials showed a leak rate
＜1.0 *10^-7 mbar L/s (passed the test). This data set
confirmed that for lyophilization stoppers, the valve
seal is the primary sealing area for CCI even when the
stopper is not under measurable compression (RSF
value of 0 N). The valve seal is extremely important
for lyophilized products, as the seal can maintain
vacuum in the vial and prevent contamination prior to
crimp capping. Therefore, stoppers with well-fitting
valve seals would hinder the identification of the cor-
relation between RSF and CCI.

Land Seal: The land seal, provided by the
flange of the stopper, was isolated by cutting off the
plug from a lyophilization stopper (Figure 3B). This
essentially transformed the stopper into a line seal.
One hundred vials (without the valve seal) were
capped with RSFs ranging from 6.2 N to 26.6 N and
tested for the He-leak. Forty-five of these vials failed
the test with a leak rate ＜1.0 *10^-7 mbar L/s. Figure
10 (plotting of increasing RSF with He-leak pass/fail
data) displayed a correlation between RSF and He-
leak: the lower the RSF, the more likely the vial would
leak. All vials with an RSF＜10.2 N failed the He-leak
test, while all vials with RSF ＞20.1 N passed the CCI
test.



文章简述

Capping completes the closure of parenteral drug products in the final packaging container and is critical
in maintaining an integral seal to ensure product quality. Residual seal force (RSF) is considered the sole quantifiable
attribute for measuring seal “goodness” and potentially enables nonsubjective, consistent setting of cappers across
manufacturing sites. However, the consistency and reliability of RSF measurement and data have been scarcely
reported, and the relationship between RSF and container closure integrity (CCI) remains poorly understood.
Here, we present a large data set generated from a commercial capper and the results from a laboratory capper of glass
vials and rubber stoppers with aluminum caps. All RSF values exhibited significant variability. We evaluated four potential
sources of variability: the capper, the RSF tester, the time-dependent nature of RSF, and the components. We determined
that the capper, the tester, and the time-dependent nature are not main sources. Dimensional tolerances of the packaging
components were the root cause for the container closure system (CCS) configurations tested in this study.
This study correlated RSF with CCI (via helium leakage), although CCI is not sensitive to RSF; CCI was maintained
even for loosely capped vials with no measurable RSF. This was attributed to the stopper’s two sealing surfaces: the
valve seal and the land seal. A methodology capable of differentiating the two seals’ functions demonstrated that vials
with only the valve seal always passed leakage testing for a selected CCS configuration in this study, while vials with
only the land seal failed CCI at low RSF values. This observation allows proposal of a low RSF limit that is safe even
when the valve seal is defective. Simplified statistical analysis of commercial capping data, with the input of sample
size, allowed the relationship between RSF’s low limit and an allowable failing rate to be established. Overall, despite
the inherent variability of RSF, this study shows that it is a feasible parameter for capping process quantification and
demonstrates the potential of RSF measurement in capper setup.

hisun，sanofi

看图理解一下RSF的研究过程，利用RSF 测试仪器，模拟胶塞的受力情况。（RSF： Residual seal force剩余的密封力）

小金库

感谢分享。