As discussed in previous technical articles, completing USP 1207 Container Closure Integrity Testing on a package system requires a number of critical steps. This testing must be customized to the specific package system and product and a formal method must be developed and validated. As outlined in the USP 1207 chapter, there are a number of technologies that may be used with the choice of technology being dependent on some key factors. The method choices include:
- Vacuum Decay
- High Voltage Leak Testing
- Laser Based Headspace Analysis
- Helium Leak Testing
For the first critical step in defining the appropriate method is understanding the factors that make up the package system and the type of product it will hold. For example, an white HDPE bottle will not allow penetration of a light laser for laser diffraction testing and a non-conductive liquid product may not work for high voltage testing. Being prepared to share and discuss this information will serve as the first step in defining and prescribing the method that will meet the testing needs for that system. The following outlines what technical items are needed in order to define a USP 1207 method for a specific container.
Technical information on the package system – this includes all the basic information that describes the package system specific to type of package (vial, container, pre-filled syringe, etc.), its materials of construction (glass, plastic, metals, etc.), and size based on volume. In addition, information on the closure type, size of the closure (typically diameter) and method of closure (screw top closure, rubber stopper and crimp seal). Technical drawings of these components, while not necessary during the initial method prescription phase, will be needed for the development of instrument change parts. Thus, it is ideal to have these readily available.
Product information – The product information plays an extremely important role in the selection of an ideal USP 1207 Container Integrity Method. The same package system may be subject to different USP 1207 methods because of the product make-up. A liquid conductive product in a 20ml clear glass vial may be ideal for HVLD while a non-conductive liquid product in the same vial system may not work. The following list of critical product information is needed to help define the correct method:
- Dosage form (solid, liquid, lyophilized, tablet, etc.)
- Fill level(s) of the product in the container. For example, a 5ml vial may have a fill level of 2ml
- Modified headspace once the product fill is completed
- Is the product proteinaceous?
- Is the product aqueous based?
- Is the product sterile?
- Gas (oxygen, etc.) sensitive?
Process Information – The system process information is the final critical information needed to ensure the most effective method is defined for the package system. The key items needed include:
- Storage temperature of the container system and the product. Common choices include room temperature, negative 20C, negative 80C and dry ice.
- Shipment temperature – more applicable to “cold storage” product but understanding that the product will be shipped on dry ice or in cryogenic shippers at negative 15-20C is critical to helping prescribe the best method.
- Assembly process of the package system inclusive of product fill steps.
When initiating a USP 1207 Container Closure Integrity Testing program for your product package system, it is imperative that you are prepared to define and share the critical elements of the system as outlined. This information will be used to define a test method that has proven to be effective and meaningful for that combination of product and package system.
The CS Analytical Team has many years of experience with virtually every type of package system and product combination and can help you define not only the most effective and ideal test methods, but also define a program that will meet all regulatory requirements. The information outlined in this article will help you to be prepared to have the first discussion to meeting this objective.