Why do biological products leak at low temperatures?
Biological products such as live viruses, vaccines, cells and so on usually need to be stored in low temperature or even ultra-low temperature environment. The physical and chemical properties of many packaging components of biological products packaging system in low temperature environment are quite different from room temperature environment. For example, the glass conversion temperature of the commonly used butyl rubber plug is between -55℃ and -70℃. If the silin bottle containing the rubber plug is stored at a lower temperature than the glass conversion temperature (such as -80℃ dry ice storage or -196℃ liquid nitrogen storage), the rubber plug will lose viscoelasticity, coupled with the physical characteristics of thermal expansion and contraction of the rubber plug at low temperature. At this time, there will be a leakage channel between the rubber plug and the glass bottle mouth, making the top air body inside and outside the package exchange, and the microorganism in the refrigerated environment will invade into the package, making the packaging system inside the risk of infection or change of the top air body risk. When the vial is placed at room temperature and gradually returned to room temperature, the vial will 'stop' leaking due to the physical characteristics of thermal expansion and contraction of the rubber plug. At this time, it will be difficult to identify the leakage of the vial with CCIT technology at room temperature (such as vacuum attenuation method).
In addition, some sillin bottles have good sealing performance at room temperature but the cap is not tight enough. Because of the shrinkage of the rubber plug at low temperature, the cap becomes loose and the sealing integrity is problematic.
Difficulties and countermeasures of sealing test of biological products packaging
Vaccine schering bottles, cell SAP cryopreserved tubes, frozen storage bag of biological products packaging systems generally need to be preserved in low temperature even under cryogenic transportation, remove biological products at room temperature detection, in the surface of biological products packaging system may produce condensate most CCIT disturbance attenuation, quality (including vacuum extraction, etc.), high pressure discharge detection, Before the test, the sample needs to be pre-treated (at least 4 hours at room temperature or surface drying), which affects the detection efficiency and is cumbersome to operate. Moreover, it can only detect leakage at room temperature, but not in low-temperature environment. Cryogenic helium is recommended for process leak testing.
Principle of cryogenic helium detection for low-temperature leakage: Place filled with helium packaging system under test in the vacuum chamber, the vacuum chamber placed in low or ultra-low temperature environment, through to the vacuum chamber, in the packaging of helium leak into the cavity in the body, and then enter into helium mass spectrometry detector, the number of helium mass spectrometry detector test helium molecules, translates into electrical signals, then further converted into helium leak rate of the unit.
Most CCIT methods are likely to produce false negative results for liquid biological products with high viscosity and very little headspace. When no suitable CCIT method is available, a residual seal method may be considered as an alternative to CCIT testing of finished products and routine process control testing to ensure that the cap is tightly rolled to prevent subsequent low-temperature leaks.
Biological products packaging system low temperature process leakage prevention measures
The key to maintaining the integrity of packing seal in the form of silin bottle is the rolling cover part of the sealing. If there is a problem in the rolling cover process or the packaging seal component does not match, it may cause the process leakage in low temperature environment.
In view of the problem of rolling cap technology, the method of residual sealing force can be used to control the production process. The residual sealing force obtained by optimizing the technological parameters of rolling cap can ensure that the rolling cap is tight enough to ensure that it does not leak out of the factory and in the subsequent low-temperature storage and transportation.
If the packing and sealing components have poor matching and are difficult to identify using the conventional CCIT method, the vacuum helium method can be used for matching and screening to ensure the best match of the full set of sealing components, because the sensitivity of the vacuum helium method is high enough to identify the leak aperture less than 0.1 micron.
Zhongxun can provide low temperature refrigerated biological products full life cycle packaging seal integrity test solution, Includes the choice of sealing components, sealing components fit examination, selection of rolling machine, rolling process parameters optimization, cover effect validation, rolling cover quality process control, process validation, production release testing, production line automation 100% full inspection, sample inspection, extreme stability of CCIT research production conditions, bad transportation CCIT, normal temperature CCIT distribution environment , low temperature CCIT research, special products (high viscosity) CCIT research, special packaging system (abnormal packaging) CCIT research and other research content related to CCIT.
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