Container-closure integrity test

One of a number of physical container-closure integrity tests may be seleeted and validated against the bacterial liquid immersion test. The physieal leak test shall be eorrelated to bacterial ingress. 

The physical container-closure integrity test method shall be chosen after eon-sideration of the container-closure type, the performanee eriteria, and the available validated test methods. 

Container-closure integrity of (product name) USP was performed on the stability batches produced in support of this submission per standard test method no. (specify number), Container/Closure Integrity Testing with Analysis via UV Spectrophotometry, included as (provide reference attachment number). The testing of the (product name) USP vials was performed under static conditions. Vials were immersed in a dye bath. The product in the vials was then tested for the presence of dye. The container/closure integrity testing yielded acceptable results. The final report for the container/ closure integrity test for (product name) is included in (provide reference attachment number). 

Additional container/closure integrity testing is to be performed on the first commercial batch at the end of the expiration date as indicated in the stability protocol. 

Container closure integrity test methodology is per (specify standard test method number). All units for container closure integrity testing are processed using routine production parameters for preparation. Worst-case parameters are used for sterilization. 

Container closure integrity. Test methodology is per ABC Pharmaceutical Industries. The dye ingress challenge test is performed as described in the manufacturing site stability protocol. 

Container closure integrity testing for (product name) USP, batch no. 

Birrer, G.A., Liu, J., Halas, J.M. and Nucera, G.G. (2000) Evaluation of a container closure integrity test model using visual inspection with confirmation by near infrared spectroscopic analysis /. Pharm. Sci. Tech. 54, 373-382. 

The product remains sterile (sterility and container closure integrity testing, including accelerated storage conditions). 

Whenever possible. Container-Closure Integrity Testing should be substituted for Sterility Testing as recommended in the draft FDA Stability Guide. 

The integrity of the container-closure system as a microbial barrier should be assessed using an appropriately sensitive and adequately validated Container-closure Integrity Test. 

One of a number of physical Container-closure Integrity tests may be selected and validated against the Bacterial Liquid Immersion Test. The Physical Leak Test should be correlated to bacterial ingress. 

Container Closure Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products... 

Wolf H, Stauffer T, Chen S, Lee Y, Forster R, Ludzinski M et al (2009) Vacuum decay container/closure integrity testing technology. part 2. comparison to dye ingress tests. PDA J Pharm Sci Technol 63(5) 489-98... 

Abbreviations TAMC = total aerobic count TCYMC = total combined yeasts and molds AET = antimicrobial effectiveness test CCl = container-closure integrity A = water activity. 

Testing must be performed on glass and plastic vials separately. Molded vials and tubing vials must be tested separately. Color of vial (e.g., amber vs. clear) has no impact on container closure integrity. 

The dye ingress challenge test is performed at the end of expiry to show container-closure integrity over the production shelf life. Dye ingress testing is performed on vials having rubber stoppers exposed to the maximum exposure time and temperature during sterilization cycle. 

Guazzo, D.M. Container/closure integrity. In Parenteral Quality Control Sterility, Pyrogen, Particulate, and Package Integrity Testing, 2nd Ed. Akers, M.J., Ed. Marcel Dekker, Inc. New York, 1994 Chapter 4. 

Ophthalmic ointments and solutions Sterility Test, Container-Closure Integrity (CCI) and AET Test all batches on stability with the exception of the first three batches for AE 0, 12, 24, and 36 months... 

Integrity of the microbial barrier should be assessed using an appropriately sensitive and adequately validated container and closure integrity test. The sensitivity of this test should be established and documented to show the amount of leakage necessary to detect a failed barrier in a container and closure system. The number of samples... 

Sterility testing or alternatives (e.g., container and closure integrity testing) should be performed at a minimum initially and at the end of the proposed shelf life. 

Microbiological aspects will need to be discussed, but the amount of information will depend on the type of product. For nonsterile products there will need to be a description of the microbiological attributes of the product and, if appropriate, a rationale for not performing microbial limit tests. For preserved products the selection of the antimicrobial preservatives will need to be discussed and the effectiveness of the selected system demonstrated. For sterile products there will need to be appropriate process validation data and information on the integrity of the container-closure system. 

The integrity of the product container/closure is assessed by physical tests or microbiological challenge tests and long-term product sterility tests. These tests are specific for container size, fill volume, and closure type. All integrity tests are performed after sterilization and are defined in manufacturing site SOPs. 

Evaluating the integrity of the container can be done in several ways. Two of the most common tests are dye penetration and microbial ingress. Container closure systems stored in a dye solution and exposed to pressure and vacuum cycles are examined for dye leakage into the container. The microbial ingress is similar in fashion but determines the microbial contamination of the contents when soaked in a media contaminated with bacteria. Other quantitative tests that can be run are vacuum/pressure decay, helium mass spectrometry, and gas detection. 

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