Container and closure integrity testing

A container and closure integrity test (CCIT) must be carried out to ensure the tightness of the packaging. As an independent partner, OFI uses highly developed analytical methods to assess disposable and reusable pharmaceutical containers.

 

Patient safety through medical products tested at OFI

Optimum 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. The OFI offers individual test designs according to GMP, EMA and US-Guidelines with the help of state-of-the-art analysis equipment for CCI testing.

 

Determining the functionality of the primary packaging

Optimum primary packaging protects the product from contamination and prevents changes in product quality due to environmental influences. In particular this applies to the ingress of microorganisms and atmospheric oxygen.

Container Closure Integrity Testing can be used to determine the functionality of the primary packaging. Different test systems can be used, as described in detail in USP 1207.2. A fundamental consideration is whether the test should be carried out non-destructively. The OFI offers individual test designs with the aid of state-of-the-art analysis equipment. Two examples show how Container Closure Integrity Testing works and is applied in practice:

 

Non-destructive testing of glass containers

Non-destructive testing of glass containers for container closure integrity is possible using laser headspace technology. The requirement for this is that the gas space of the container is either evacuated or filled with an inert gas. The oxygen content in the gas space is measured 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. The test can be carried out both online, as in-process control, and offline, i.e. for release tests and stability tests. The only requirement is that the container consists of clear glass and is neither labelled nor printed in the measuring path. In contrast to traces such as fingerprints on the outside, the method is very robust and therefore very reliable in use.

The containers can be used after they have been tested. OFI thus carries out e.g. the inspection for invisible particles, also with the aid of a laser-based technology as described in Ph.Eur. 2.9.19 (Method 1) and the USP 787 and 788.

 

Blue bath test

Glass containers can also be tested for leaks by investigating the penetration of dye solutions. These tests are aimed at the closure. Typically, the containers are placed in an aqueous solution of methylene blue. By applying a vacuum above the solution, a negative pressure is also generated in the containers in the event of leakage, which pulls the dye solution into the containers during subsequent ventilation to normal pressure. Therefore, any leaks can be detected in the case of dyeing in the product.

These tests are also carried out at OFI in combination with quantification of the dye using UV/VIS. In this way, the detection limit can be significantly decreased compared to the visual evaluation and a quantitative test result is obtained instead of a qualitative test.

This method is validated product-specifically at OFI. This not only includes 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 20 µm are inserted into the rubber stoppers. This simulates a hole in a standard size through which the penetration of the dye can be checked. A further variant is the laser, with which holes up to 2µm can be produced. The USP 1207.1 provides extensive considerations in this regard.

 

Container Closure Integrity (QM system: GMP)

  • Tests according to EP 3.2.9, USP <381> and USP <1207>
  • Dye Immersion Test (e.g. Blue Bath Test)
  • Non-destructive Laser Based Headspace CCI Analysis for vials and syringes
  • Method verification for CCI tests
  • Seal strength