Packaging/containers, drug product stability testing

After an application for a new drug product is approved, quality control tests must be established to demonstrate that the container closure system and all of its components possess the characteristics established in the original suitability studies. The appropriate packaging system should be included in all applicable stability protocols and observed for instability and drug product leachables. 

Containers, closures and other component parts of drug packages, to be suitable for their intended use, must not be reactive, additive or absorptive to the extent that the identity, strength, quality or purity of the drug will be affected. All drug product containers and closures must be approved by stability testing of the product in the final container in which it is marketed. The stability test includes testing filled containers at room temperature (e.g., 70°F) as well as under accelerated conditions (e.g., 105 and 120°F). 

Stability testing A brief description of the stability study and the test methods used to monitor the stability of the drug product packaged in the proposed container/closure system and storage conditions should be submitted. Preliminary tabular data based on representative material may be submitted. Neither detailed stability data nor the stability protocol need to be submitted. 

Accelerated stability tests provide a means of comparing alternative formulations, packaging materials, and/or manufacturing processes in short-term experiments. As soon as the final formulation and manufacturing process have been established, the manufacturer carries out a series of accelerated stability tests which will enable the stability of the drug product to be predicted and its shelf-life and storage conditions determined. Real-time studies must be started at the same time for confirmation purposes. Suitable measures should be taken to establish the utilization period for preparations in muitidose containers, especially for topical use. 

Consider, as a typical example, the closure systems that are proposed for a given product. To pass the regulatory demands, these systems will need to be tested for extractable and leachable substances that would end up as contaminants in the hnal product. Extractables arise from individual components of the packaging systems under appropriate solvent and temperature conditions. Leachables are compounds that migrate from the container/closure system of the formulated drug product under normal conditions of use or during stability studies. 

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