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<1663> ASSESSMENT OF EXTRACTABLES 

 ASSOCIATED WITH PHARMACEUTICAL PACKAGING/DELIVERY SYSTEMS

KEY TERMS


This general chapter uses the following key terms listed below (1, 2; also see Packaging and Storage Requirements <659> ). Note that the terms Packaging System, Packaging Component, Primary Packaging Component, Secondary Packaging Component, and Materials of Construction are also defined in <659> , and the definitions below are intended for clarification purposes within the context of this chapter and are not intended to supersede those provided in <659> .  



  • Packaging Systems are the sum of packaging components that together contain, protect, and in certain cases deliver the dosage form. Packaging systems are also referred to as Container Closure Systems.


  • Packaging Components are single parts of a packaging system. Each individual packaging component has a particular function within the context of containing, protecting, and delivering the dosage form. An individual packaging component can be Primary, meaning that it is or may be in direct contact with the dosage form; or Secondary, meaning that it is not or will not be in direct contact with the dosage form but may provide additional protection. Packaging components are considered to be Tertiary if they are not in direct contact with the dosage form but facilitate handling and transport in order to prevent damage from physical handling and storage conditions to which the dosage form is subjected.  


  • Packaging Materials of Construction are substances used to manufacture packaging components. These are also referred to as Raw Materials.  


  • Extractables are organic and inorganic chemical entities that can be released from a pharmaceutical packaging/delivery system, packaging component, or packaging material of construction under laboratory conditions. Depending on the specific purpose of the extraction study (discussed below), these laboratory conditions (e.g., solvent, temperature, stoichiometry, etc.) may accelerate or exaggerate the normal conditions of storage and use for a packaged dosage form. Extractables themselves, or substances derived from extractables, have the potential to leach into a drug product under normal conditions of storage and use. 


  • Leachables are organic and inorganic chemical entities that migrate from a packaging/delivery system, packaging component, or packaging material of construction into an associated drug product under normal conditions of storage and use or during accelerated drug product stability studies. Leachables are typically a subset of extractables or are derived from extractables. Note that chemical entities can also leach from packaging/delivery systems to patients via direct contact.  


  • Extraction Studies are the overall laboratory processes required in order to create extractables profile(s) of particular pharmaceutical packaging/delivery systems, packaging components, or materials of construction. Extraction studies are also referred to as Controlled Extraction Studies.  


  • Characterization is the discovery, identification, and quantitation of each individual organic and inorganic chemical entity present in an extract above a specified level or threshold. Such thresholds can be based on patient safety considerations, materials considerations, the capabilities of analytical technology, etc.  


  • Scouting is the process of acquiring general chemical information that provides insight into the nature and magnitude of extractables.  


  • Discovery is the process of searching for, and ultimately finding, individual organic and inorganic chemical entities present in an extract.  


  • Identification is the process of assigning a molecular structure to an organic extractable, or assigning constituent elements in the case of an inorganic extractable.  


  • Quantitation is the process of measuring the level, or concentration, of an individual organic or inorganic chemical entity contained in an extract.  


  • Extractables Profiles are qualitative and/or quantitative analytical representations of the extractables content of a particular extracting medium and set of laboratory extraction conditions.  


  • Leachables-Extractables Correlations are established when observed drug product leachables are linked both qualitatively and quantitatively to extractables from associated packaging/delivery systems, packaging components, or materials of construction.  


  • Safety Concern Threshold (SCT) is the threshold below which a leachable has a dose so low that it presents negligible safety concerns from carcinogenic and noncarcinogenic toxic effects.   As noted, additional terminology and associated definitions are available (1, 2, and 659 ).