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    Home > Active Ingredient News > Drugs Articles > Solution of sealed integrity of pre syringe container

    Solution of sealed integrity of pre syringe container

    • Last Update: 2019-12-18
    • Source: Internet
    • Author: User
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    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.
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