Solution of sealed integrity of pre syringe container

The effect of pre syringe leakage: the pre syringe is generally filled with sterile liquid preparation It may be filled with clean air or nitrogen Once the pre syringe leaks, the oxygen and microorganism in the air will invade the container, which may oxidize the filled product and affect the stability of the product; and after the invasion, if the filled product is suitable for the growth of the microorganism, the microorganism will propagate rapidly, thus laying a hidden danger to the life safety of the patient The traditional leak detection methods of pre syringe and their shortcomings the traditional leak detection methods of pre syringe are mainly color water method and microbial challenge method These two methods are generally subjective, qualitative and destructive The color water method is suitable for the pre syringe of filling products and can be used for the detection of production links, while the microbial challenge method is more suitable for the detection of empty containers and is suitable for 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 of pre syringe are vacuum attenuation method, laser method and high voltage discharge method The vacuum attenuation method is suitable for the pre syringe with clear and transparent liquid without particles, the laser method is suitable for the pre syringe with a certain headspace volume and filled with nitrogen, and the high-pressure discharge method is suitable for the pre syringe filled with emulsion or suspension Development and validation of leak detection method for pre syringe: Taking vacuum attenuation method as an example, different method parameters, including pressure and time parameters, need to be developed for specific product packaging, such as pre syringes with different specifications and different loading The optimized parameters must ensure that both large and small leaks can be detected, especially for small volume pre syringes If there is a large leak, in the vacuumizing phase, the headspace gas will be pumped out In the subsequent pressure maintaining and testing phase, 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 The establishment of leakage standard of pre syringe: take vacuum attenuation method as an example, the establishment of leakage standard requires two parameters: absolute pressure value and differential pressure value 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 final formulation of the pre syringe leakage standard 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.