Stability test of syringe manufacturing process

Update:14 Mar 2020
Summary:

The plunger in the syringe is allowed to move along the […]

The plunger in the syringe is allowed to move along the syringe within a certain range. During storage and transportation, and when in a low-pressure environment, plunger movement caused by pressure changes may potentially affect the integrity of the seal. Therefore, it is necessary to evaluate the integrity of the plunger seal under these special conditions.

In addition to the complicated design of pre-filled syringes, the drugs packaged in the syringes need to be considered. For example, pre-filled syringes have been widely used in biologicals, and some of them may require extremely low temperature storage (eg -70 degrees). Due to the sealing characteristics of the syringe composition, especially the elastomers (such as needle shields and plungers) are temperature dependent, if the theoretical reasons for the characteristics of the elastomers are insufficient, the CCI test may need to be performed at extremely low temperatures. Furthermore, drug and packaging interactions can affect the sensitivity and choice of methods. For example, protein products may hinder mass transfer through the CCI defect opening, reducing the sensitivity of the vacuum attenuation method.

CCI test development strategy

Many different CCI failure modes can occur throughout the life cycle of a syringe, from component manufacturing, drug filling and sealing, equipment assembly and packaging, to subsequent distribution and storage. Throughout the life of the syringe, it is necessary to develop an overall strategy to apply a series of CCI tests.

CCI test strategy development begins with a thorough understanding of syringe construction, design, and manufacturing processes. The first step is to identify CCI failure modes and the impacts associated with all aspects. Using a risk-based approach, we further determine if a CCI test is required, and if so, the expected usage and test frequency. For example, knowing that the integrity of the needle guard room seal is tested by the component supplier, we choose to apply unconventional CCI tests to confirm the integrity of the seal during the filling and sealing of pharmaceuticals and assembly into equipment. In contrast, for syringe barrels filled with pharmaceutical products, we have incorporated an extensive set of CCI tests into the entire product development cycle, including initial design validation, cutting performance studies, and product stability testing to ensure CCI implementation and maintenance.

Method selection

Note that all technologies have significant limitations. In choosing the appropriate method, the following key aspects should be considered:

1. Suitable for intended use. The method chosen must be suitable for the intended use and the scope of the specific CCI test. For example, the microbial invasion test, although it is a better choice for the filling process verification for the medium filling syringe, can not be used for stability testing because it is not suitable for the sample filling of drugs. If one method does not meet all testing requirements, then supplementary methods may be applied to arrive at clear and comprehensive test conclusions.

2. suitable for specific drug packaging. As mentioned earlier, drugs may interact with CCI defects in different ways, which may further affect the effectiveness of CCI testing methods. This method is applicable to specific product packaging that needs to be evaluated and fully proven.

3. Detection capability and effectiveness. Recent techniques using large-scale extraction, HVLD, and vacuum attenuation have proven to reliably detect CCI defects 5-10um or less. These techniques are based on the quantitative determination of certain sample characteristics and can be further related to the presence or to the size of the CCI defect. The superior sensitivity and reliability make them the preferred method of CCI testing over traditional staining or microbial invasion methods.

4. Non-destructive CCI test. Non-destructive methods enable 100% CCI testing. In addition, they allow further analysis of failure modes and root causes, providing valuable feedback for continuous improvement in turn.

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