Container Closure Integrity Test

Container and closure integrity testing

A container and closure integrity test (CCIT) must be performed to ensure that the packaging is leak-proof. As an independent partner, OFI uses sophisticated analytical methods to assess single-use and reusable pharmaceutical containers.

Optimal primary packaging protects the product from contamination (sterile barrier) and prevents changes in product quality due to environmental influences. Container Closure Integrity Testing can be used to determine the functionality of the primary packaging. Using state-of-the-art analytical equipment for CCI testing, OFI offers individual test designs according to GMP, EMA and US guidelines.

Determine the functionality of the primary packaging

Optimal primary packaging protects the product from contamination and prevents changes in product quality due to environmental influences. This applies in particular to the penetration of microorganisms and atmospheric oxygen.

Container Closure Integrity Testing can be used to determine the functionality of the primary packaging. Various test systems can be used for this purpose, as described in detail in USP 1207.2. A fundamental consideration is whether the implementation should be non-destructive. With the help of state-of-the-art analytical equipment, the OFI offers individual test designs for this purpose.

Container Closure Integrity (QM system: GMP)

Tests according to EP 3.2.9, USP <381> and USP <1207>
Dye Immersion Test (e.g. Bluead Test)
Non-destructive Laser Based Headspace CCI Analysis for Vials and Syringes
Method verifications of the CCI tests
Sealing seam strength

Non-destructive testing of glass containers for Container Closure Integrity is possible using laser headspace technology. The prerequisite for this is that the gas compartment of the container is either evacuated or filled with an inert gas. The oxygen content is measured in the gas chamber by means of a laser. An increasing proportion of oxygen indicates the penetration of air. The measurement is used, for example, for lyophilized products, for injectables in vials, or for pre-packaged syringes. Testing can be performed both online, as an in-process control, and offline, i.e. for release testing and stability testing. The only requirement is that the container is made of clear glass and is neither labeled nor printed in the measuring path. Against traces such as fingerprints on the outside, on the other hand, the method is very robust, and thus also very reliable in use. The containers used can thus continue to be used after testing has been completed. The OFI uses it, for example, to perform testing for invisible particles, also using laser-based technology as described in the Ph.Eur. 2.9.19 (Method 1) and USP 787 and 788 is described.

Glass containers can also be tested for leaks by examining the penetration of dye solutions. These tests target the closure. Typically, this involves placing the containers in an aqueous solution of methylene blue. By applying a vacuum over the solution, a vacuum is also created in the containers in the event of leakage, which draws the dye solution into the containers when they are subsequently aerated to normal pressure. Therefore, in the case of staining in the filling material, any leaks can be detected. These tests are also performed at the OFI in combination with quantification of the dye by UV/VIS. As a result, the detection limit can be significantly lowered again compared to visual evaluation, and a quantitative test result is obtained instead of a qualitative test. At the OFI, this method is validated on a product-specific basis. This includes not only the correct measurement of the dye in the product. In addition, the penetration of the dye can also be validated by means of positive and negative controls. For positive control, e.g. microcapillaries between 10 and 20µm are inserted into the rubber stoppers. This simulates a hole of a standard size through which the penetration of the dye can be checked. Another variant is laser cutting, which can be used to create holes down to 2µm. Extensive considerations in this regard are given in USP 1207.1.