Solution of airtight integrity of vials

Effects of leakage of vials: vials are generally filled with sterile drugs, including the form of powder injection and water injection For powder injection vials, they are usually sealed with high vacuum or micro negative pressure Once the powder injection vials leak, the oxygen, water vapor and microorganism in the air will invade the container, which may cause the products filled inside to be oxidized, hydrolyzed and damped, and affect the stability of the products; moreover, if the filled products are suitable for the growth of microorganisms after the invasion of microorganisms, the microorganisms will propagate rapidly, thus laying a hidden danger to the life safety of patients The water needle cylinder is usually sealed with nitrogen Once it leaks, the oxygen and microorganism in the air will invade the container, so that the nitrogen will be replaced by oxygen, and the product may be oxidized, which affects the stability of the product Moreover, if the filled product is suitable for the growth of microorganism, the microorganism will propagate rapidly, and then the patient's life safety will be hidden danger Traditional leak detection methods and shortcomings of vials traditional leak detection methods are mainly color water method and microbial challenge method These two methods are generally subjective, qualitative and destructive The color water method is applicable to the filling of vials, which can be used for the detection of production links, while the microbial challenge method is more applicable to the detection of empty containers, which is applicable to the verification links Although these two methods have been used in the industry for many years, their disadvantages are obvious The disadvantages of color water method are destructive testing, low sensitivity, subjective results, time-consuming and hard to trace; the disadvantages of microbial challenge method are destructive testing, time-consuming and hard to trace, and high leakage rate when the leakage path is zigzag path At present, FDA in the United States tends to replace the traditional two methods with physical quantitative methods The physical quantitative methods suitable for leak detection are vacuum attenuation method, laser method and high voltage discharge method Vacuum attenuation method is suitable for freeze-drying and water injection vials, laser method is suitable for vials with nitrogen filling or negative pressure and high-voltage discharge method is suitable for water injection vials If there are protein particles in the vials, the high-pressure discharge method should be selected; if water needle vials and freeze-dried vials are to be detected, the vacuum attenuation method can be used; if there are freeze-dried vials or water needle vials with a certain head space filled with nitrogen, the laser method can be used In contrast, the vacuum attenuation method is more applicable, because it can be used to detect not only water needle vials full of liquid, but also water needle vials with atmospheric air headspace, and freeze-dried powder needle vials The laser method can only detect the freeze-dried powder vials in the above three samples, and the high-voltage discharge method can only detect the first two of the above three samples Jinan Sanquan Zhongshi Experimental Instrument Co., Ltd designed and developed a sealability tester mfy-05s for testing the sealing integrity of sterile vials according to a number of national and international standards This tester is mainly used for the sealing and sealability test of vials The development and verification of leak detection method of Xilin bottle sealing integrity tester take vacuum attenuation method as an example For specific product packaging, such as different specifications and different filling quantities of freeze-dried powder injection Xilin bottle and water injection Xilin bottle, different method parameters, including pressure and time parameters, need to be developed The optimized parameters must ensure that both large and small leaks can be detected, especially for small capacity vials, if there is a large leak, in the vacuumizing stage, the headspace gas will be pumped out, in the subsequent pressure maintaining and testing stage, there will be no gas leakage, leading to false negative results In addition, the optimized parameters must ensure enough separation between the negative sample and the positive sample when testing the negative sample and the positive sample At the same time, the optimized parameters should ensure the good repeatability and stability of the negative samples, and the background vacuum attenuation value of the negative samples is relatively low The optimized parameters need to be verified by negative samples and positive samples According to the test data of negative samples, a qualified and unqualified leakage standard value can be preliminarily established According to the standard value, when testing negative samples, all results should be qualified; when testing positive samples, all results should be unqualified Taking vacuum attenuation method as an example, there are two parameters: absolute pressure and differential pressure The absolute pressure value shall be set to ensure that large leakage and medium leakage can be detected, and the differential pressure value shall be set to ensure that small leakage can be detected The correlation between the differential pressure value and the size of the leakage hole is generally realized by the micro flowmeter The conversion between the flow rate and the leakage hole of the micro flowmeter can be obtained by the formula or by looking up the table The formulation end of the leakage standard of vials is now the size of the leakage, and the leakage range is generally between the lower detection limit of the instrument and the detection limit of the traditional method At the same time, it is necessary to ensure that the developed leakage level should reduce the risk of microbial invasion as much as possible Many studies have shown that the microbial leakage will significantly invade the packaging container when it is more than 5 μ m, and the leak detection accuracy of the traditional color water method is generally ≥ 5 μ M The accuracy of vacuum attenuation equipment is generally more than 1 μ M Therefore, the final leakage standard can be set between 1 and 5 μ m, and the specific setting value needs to be adjusted according to the actual production situation.