Closures integrity

D. K. Morton, N. G. Lordi and T. J. Ambrosio. Quantitative and mechanistic measurements of container/closure integrity leakage quantitation. J. Parenter. Sci. Technol., 43, 88 (1989). 

The application should state the rationale for the design of the in-use stability tests performed. The procedures used should be fully validated. One key factor is that the test should simulate the use of the product as far as practicable. This should include any reconstitution or dilution prior to use. Aliquots should be removed in an appropriate manner following, as far as possible, the usage pattern that will be encountered in practice. Physical (color, clarity, closure integrity, particulate matter, and particulates/particle size), chemical (assays for active ingredient, antioxidants and... 

Small-volume parenterals Appearance, color, particulate matter, dispersibility (suspensions), pH, sterility, pyrogenicity, and closure integrity... 

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

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. 

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. 

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. 

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. 

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. 

Container-closure integrity studies also can be conducted to validate the sealing efficiency of the capping equipment. 

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. 

As there were some doubts about the validity of the crack closure integral in the dynamic case, a J-integral expression from Equation (4) was implemented in the FV program. Because it was found that the J-integral is mesh sensitive and requires a very fine mesh, a test case of a center... 

Fracture of polymers, viscoelasticity, crack growth initiation, finite element simulation, crack closure integral, thermomechanical reliability, rate dependence... 

To evaluate erack load in finite element simulations, a virtual crack extension was used Dubois et al. [9]. Xiong et al. [8] applied a modified crack closure integral to analyse viscoelastic effects on interfacid delamination. Both approaches lead to the same equations, whieh ean be generalised for the 3D case ... 

To evaluate G in finite element analyses it is well established to modify the crack closure integral (3) in a way introduced by Rybicki and Kanninen [13]. For 8-noded 2nd order elements a formulation is taken from [14] and extended to the 3D case [19]. 

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

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. 

FDA draft guidance for industry. In Container and Closure Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products, Food and Drug Administration Rockville, MD, 1998. 

Kirsch, L.E. Nguyen, L. Moeckly, C.S. Pharmaceutical container/closure integrity I Mass spectrometry-based helium leak rate detection for rubber-stoppered glass vials, PDA. J. Pharm. Sci. Technol. 1997, 51, 187-195. 

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