Identification of Extractables and Leachables

Component name Response Expected RT RT Calculated amount Ion ratio status 

Keywords product safety pharmaceutical product packaging quality control AMDIS deconvolution unknown identification Mass Frontier spectrum interpretation 

Leachables in pharmaceutical products are trace amounts of chemicals originating from containers, medical devices or process equipment that end up as contaminants in medicinal products resulting in exposure to patients (Moffat, 2011). 

The US Food and Drug Administration (FDA) defines extractables as compounds that can be extracted from a container material when in the presence of a solvent, and leachables as those compounds that leach into the drug product formulation as a result of direct contact with the formulation (Lewis, 2011). 

The European Agency for the evaluation of Medical Products Guideline (European Medicines Agency, EMA) states that it should be determined whether any of the extractables are also leachables present in the formulation at the end of the shelf life of the product or to the point equilibrium is reached if sooner . 

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Identification of Extractables and Leachables 647 Table 4.31 Compounds identified by iiquid iPA extraction. 

Identification of Extractables and Leachables 651 Table 433 Compounds identified by liquid DCM extraction and BSTFA derivatization. 

The technical portion of this review has focused on advanced analytical techniques and methods for the identification and quantitation of extractables and leachables. However, analytical techniques/methods are also required for routine use in pharmaceutical manufacturing and quality control. Such methods are used for the following ... 

Process validation involves the identification, monitoring, and control of sources of variation that can contribute to changes in the product. It starts with process characterization studies using scale-down models for optimization, operating range specification, extractables and leachables characterization, and clearance studies. Such work depends on validated assays and representative scale-down models. 

As discussed in an earlier section of this Handbook, additives may eontribute to extraetable and leachable compounds. Other sources include base polymer breakdown produets and/or primary formulation ingredients and flieir breakdown products. These and other extraneous eompounds comprise the basis for the extraction, analysis, and identification methods described in this ehapter. 

As described above, individual packaging components will invariably contain complex mixtures of chemical entities (e.g., additives and oligomers), many if not most of which are at relatively trace levels (i.e., pg/g and lower). The principles of Trace Organic Analysis, as developed in the environmental, geochemical, and bioanalytical fields, can be applied to the problem of identification and quantification of these individual chemical entities, whether as extractables or as leachables.f The general process is as follows ... 

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