09,08,2026 8 views
The sealing performance of a packaging system refers to the ability of a drug packaging system to prevent loss of contents, microbial invasion, and the entry of other gases. The packaging system for sterile products is the key to ensuring product safety and quality. The methods used to check the sealing of packaging systems include microbial challenge method (immersion or aerosol method), high-voltage discharge method, laser headspace analysis method, etc.
The methods for testing the sealing of drug packaging are detailed in the table below:
| category |
detection method | General scope of application |
Literature reports Detection limit level a |
Quantitative/qualitative |
| 概率性方法 |
Microbial Challenge Method (Intrusion or aerosol method) |
The packaging must be able to withstand immersion conditions, may require tools to limit the expansion or movement of the soft package, and can be used for filling culture media; Commonly used for packaging sealing verification. | Level 4 |
qualitative |
| Colorimetric method | It must be able to withstand immersion and may require tools to limit the expansion or movement of the soft pack, mainly suitable for liquid formulations. | Level 4 | Qualitative or quantitative | |
| Bubble release method | Packaging with top air, capable of withstanding immersion, small volume, and less than a few liters | Level 4 | qualitative | |
| Deterministic method |
High voltage discharge method | The product has a certain degree of conductivity, while the packaging components are relatively non-conductive and the product is not flammable. | Level 3 | quantitative |
| Laser headspace analysis method | Transparent packaging: products that require low oxygen or low carbon dioxide headspace content; Products requiring low moisture content; Products with low internal packaging pressure | Level 1 | quantitative | |
| Quality extraction method | Packaging with top air or filled with liquid | Level 3 | quantitative | |
| Pressure attenuation method | Having top air | Level 3 | quantitative | |
| Vacuum attenuation method | Packaging with top air or filled with liquid | Level 3 | quantitative |
Common sealing integrity inspection methods:
The 2025 edition of the Chinese Pharmacopoeia "Draft of the Guiding Principles for the Sealing of Aseptic Drug Packaging Systems (Second Edition)" and the 2020 release of the "Technical Guidelines for Sealing Research of Chemical Drug Injection Packaging Systems (Trial)" and "Technical Requirements for Quality and Efficacy Consistency Evaluation of Chemical Drug Injection Generic Drugs" by the Drug Evaluation Center indicate that for sterile preparations, appropriate and validated sealing inspection methods need to be selected for sample testing. The preferred sealing inspection method is a deterministic method that can determine the maximum allowable leakage limit of the product. If the sensitivity of the method cannot reach the maximum allowable leakage limit of the product, it is recommended to use at least two methods for sealing verification, one of which is the microbial challenge method.
USP<1207.2>Package Integrity Leak Test Technologies also states, "Immersion microbial challenge testing is used when there is no validated physical and chemical leak testing method or when the test results require direct evidence of preventing microbial entry
Introduction to Microbial Challenge Method
The microbial challenge method evaluates the integrity of packaging by immersing it in a bacterial suspension containing growth promoting medium and exposing it (liquid load challenge test). Proving leakage by challenging the growth of microorganisms in the packaging contents is a probabilistic inspection method.
Introduction to Microbial Challenge Sealing Detection Instrument
Shandong Puchuang has developed and produced according to the requirements of the 2025 edition of the Chinese Pharmacopoeia and other standardsMicrobial Challenge Sealing TesterLT-PNP is suitable for microbial invasion method sealing test, meeting four test modes. It is widely used for sealing testing of sterile packaging bags such as penicillin bottles, ampoules, infusion bags, pre filled needles, eye drops, etc. It is suitable for pharmaceutical factories, medical device enterprises, drug testing, quality inspection departments, etc
LT-PNP Microbial Invasion Tester
Experimental principle:
Microbial challenge method, also known as microbial invasion test method, is a common sealing integrity testing method, usually performed simultaneously with simulated filling. By simulating the filling of the culture medium according to the simulation filling verification plan, followed by plugging and capping, the visual inspection is qualified. After sterilization in the validated sterilization cabinet, the sealing surface of the container is immersed in a high concentration of bacterial solution, so that the culture medium in the sample container fully contacts the inner surface of the seal. The neck of the sample and the outer surface of the seal should be immersed in the bacterial suspension. After soaking for a certain period of time, it is taken out and regularly cultured to check for microbial invasion, in order to determine the integrity of the container sealing system. At the same time, a positive control test needs to be conducted to confirm the growth promoting ability of the culture medium.
The sealing performance of sterile drug packaging containers is crucial for maintaining the sterility requirements of drugs. Microbial challenge method can be used to verify the sealing performance of drug packaging containers. Welcome to inquire and learn more.
