Container-closure system plastic components

The subject of extractables and leachables in drug products is an area of active discussion in the pharmaceutical industry. Further the regulatory agencies have issued guidances on this subject in recent years. The FDA guidance on container closure systems defines extractables and leachables as follows [124] Extractables are compounds that can be extracted from elastomeric or plastic components of the container closure system when in the presence of a solvent. Leachables are compounds that leach into the formulation from elastomeric or plastic components of... 

A typical container closure system is a plastic (usually HDPE) bottle with a screw-on or snap-off closure and a flexible packaging system, such as a pouch or a blister package. A typical closure consists of a cap — often with a liner — frequently with an inner seal. If used, fillers, desiccants, and other absorbent materials are considered primary packaging components. 

The ability of a container closure system to protect against moisture can be ascertained by performing the USP (661) water vapor permeation test. The USP sets limits on the amount of moisture that can penetrate based upon the size and composition of the plastic components [HDPE, LDPE, or polyethylene terephthal-ate (PET)]. 

Compounds that can leach into the formulation from elastomeric or plastic components of the drug product container closure system. ... 

Removal of extractables from an elastomer or plastic matrix can be accomplished by a variety of techniques, including solvent extraction (e.g., reflux and Soxhlet), supercritical fluid extraction, thermal evolution, etc. Jenke has thoroughly discussed and classified extraction strategies for container closure system components associated with a drug product leachables assessment. His discussion is based on two so-called directives paraphrased as follows ... 

Plastic components (whether container or closure) can be sterilized using steam, ethylene oxide, hydrogen peroxide, or ionizing radiation. The y irradiation is accomplished off-site by a subcontractor with appropriate expertise as these methods are considered the province of specialists because of the extreme health hazards directly related to the sterilization method. Electron beam sterilization may also be done by a contractor, although compact lower energy electron beam systems have been introduced that allow sterilization in-house. Steam sterilization is ordinarily performed in house, though many common components are becoming available presterilized by the supplier. Preparation steps prior to sterilization vary with the component and the methods used to produce the component. Rubber components are washed to reduce particles, while this is less common with plastic materials. 

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