Container closure testing

Receipt, identification, storage, and withholding from use of components, dmg product containers, closures, and labeling, pending the appropriate sampling, testing, or examination by the... 

Containers and closures shall be tested for conformance with all appropriate written procedures. In lieu of such testing by the manufacturer, a certificate of testing may be accepted from the supplier, provided that at least a visual identification is conducted on such containers/closures by the manufacturer and provided that the manufacturer establishes the reliability of the supplier s test results through appropriate validation of the supplier s test results at appropriate intervals. 

Testing of the drug product in the same container-closure system as that in which the drug product is marketed ... 

A complete record of all data secured in the course of each test, including all graphs, charts, and spectra from laboratory instrumentation, properly identified to show the specific component, dmg product container, closure, in-process material, or drug product, and lot tested. 

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. 

Primary container-closure system-related data will need to cover storage, transportation, and use. The choice of materials of construction, their description, and the ability of the container-closure system to protect from moisture and/or light will need to be considered. The compatibility of the container-closure and its contents will need to consider sorption, leaching, and safety. The performance of the container-closure system will also need to be considered in terms of dose delivery from any associated device that is to be supplied as part of the product. Container-closure components will require adequate specifications covering description, identification, critical dimensional tolerances, and test methodology (including pharma-copeial and noncompendial methods). More data are likely to be required for liquid or semi-liquid products than for solid dosage forms. In the latter, product stability data and container-closure system specifications may suffice. 

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

The integrity of the container-closure system as a mierobial barrier should be assessed using a sensitive and adequately validated 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. 

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

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. 

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. 

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. 

Areas and surfaces in a controlled environment that are in direct contact with products, containers, or closures and the microbiological status of which can result in potential microbial contamination of the product/container/ closure system should be identified. Once identified, these areas should be tested more frequently than non-product-contact areas or surfaces. Elements that are likely critical product contact points may include compressed air or nitrogen, room air, manufacturing equipment, tools, work surfaces, storage containers, conveyors, gloved hands of personnel, and water. 

In a parenteral vial filling operation, areas of operation would typically include the container-closure supply, paths of opened containers, and other inanimate objects (e.g., fomites) that personnel routinely handle. Examples of non-product-contact elements may include walls, floors, ceilings, doors, benches, chairs, personnel attire, waste containers, and test instruments. 

Process simulation units shall not be required to be inverted at some point during the incubation period. All hlled units shall be sufficiently manipulated to assure the contact of all sterile surfaces by the growth media prior to incubation. Momentary inversion of test units shall be surfaces of the container/closure system. Reconciliation requirements of process simulation units shall be equivalent to the requirement for production. The target will be 100% reconciliation/accountability of all hlled units. Any excursion must be investigated and documented however, a variance is not an automatic invalidation of a process simulation test. Process simulation testing shall simulate normal production as closely as possible because its purpose is to assess the potential of contamination in units representative of normal production. 

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