Container Closure Integrity - Dye and Bacterial Immersion

Container Closure Integrity – Dye Immersion & Bacterial Immersion

Container Closure Integrity (CCI) tests are performed on rigid containers such as vials, screw cap bottles, syringes, and auto injector type devices to check for leaks.

Dye immersion uses a tracer dye with a vacuum to draw the dye through any defects. Bacterial immersion uses a bacterial solution, pressure, and a vacuum.

PDA Technical Report 27 recommends both a physical and microbial test when evaluating the container closure integrity for pharmaceutical packaging. USP <1207> recommends deterministic CCI tests (see Mass Extraction). Both dye immersion and bacterial immersion are probabilistic test methods.

Applicable Standards

USP <1207>
PDA TR 27
FDA Docket 980-0021

Sample Specifications

PKG410 : Number of test containers determined by the sponsor + 9 controls (3 bacteriostasis (included in pricing), 3 negatives and 3 positives)
PKG420 : Number of test containers determined by the sponsor + 5 controls

Testing Locations

Salt Lake City, UT, USA
Fairfield, NJ, USA (Gibraltar Laboratories)
Leuven, Belgium

Study Outline

Dye Immersion: Samples are immersed in a dye solution and a vacuum is applied. The vacuum is released and the containers are washed to remove dye from the outer surfaces. The containers are then analyzed after exposure for the presence of dye using either an ultraviolet-visible (UV/Vis) or visual technique. The UV/Vis method has a higher sensitivity level for detecting the dye than the visual method.

Samples for UV/Vis analysis cannot have viscous or opaque fluids.

Bacterial Immersion: The samples are tested by immersing media-filled containers into a microbial challenge for a specified amount of time using pressure and vacuum. The containers are then removed from the challenge, rinsed, incubated, and examined for growth. A bacteriostasis test is performed concurrent with the test or at the end of the seven-day incubation. Controls are performed with each challenge.

The selection of B. diminuta as the challenge organism is based on its very small size when grown under carefully controlled conditions. Due to its size, B. diminuta represents a most severe bacterial challenge. Other organisms may also be selected. The high concentration in microbiological challenge adds to the worst-case conditions for testing.

Samples must arrive sterile if filled by the sponsor.

B. diminuta is an aerobic organism so it is recommended, when filling test samples, to allow for an air headspace of ≥50% of the total volume of the container, if possible.

If you have additional questions about Dye and Bacterial Immersion testing services, or would like to consult with the experts at Nelson Labs, just send us a request or call us at +1 (801) 290-7500.