COLD CHAIN
Potential Contribution of a Plasticized PVC Packaging Material to the Level of Elemental Impurities in Packaged Drug Products
Dennis Jenke, Barrett E. Rabinow, and Molly Chacko
Medical Products Division Baxter Healthcare Corporation
Submitted: 01/21/2015 Accepted for Publication: 02/25/2015
Jenke D, Rabinow BE, Chacko M. Potential contribution of a plasticized PVC packaging material to the level of elemental impurities in packaged drug products. Pharm Outsourcing. 2015;16(2):26-35.
Abstract
One source of elemental impurities in drug products is substances leached from the product’s packaging system. The maximum amount of elemental entities that can be leached into a packaged drug product is the total pool of the elemental entity in the packaging system; the actual amount that is leached is established by testing the packaged drug product over the course of its clinical shelf life. Either the actual or maximum leachable levels of the elemental impurities can be compared to documented permissible daily exposures (PDEs) to establish the packaging system’s overall impact on the packaged product’s ability to meet elemental impurity requirements. In this study, the total pool of relevant elemental entities in a plasticized poly-vinyl chloride (PVC) material used in aqueous parenteral drug product packaging was established by digesting the material in strong mineral acids (microwave assisted) and analyzing the digesting solution via inductively coupled plasma/mass spectrometry (ICP/MS). The resultant total pools were used to assess a therapeutic situation where six 50-mL PVC packages of a drug solution product would be administered daily. In such a circumstance, zinc is the only elemental entity whose total pool is larger than the associated PDE. However, zinc levels that are measured in packaged drug products are much lower than the total pool and well below the PDE.
Key words
elemental impurities, drug product packaging, plasticized poly-vinyl chloride, permissible daily exposure, total pool
Introduction
Extraneous impurities in a drug product do not provide a therapeutic benefit to the product’s user and could adversely impact the safety and/or efficacy of the drug product. An important set of impurities (known as elemental impurities) are those entities, organic or inorganic, whose chemical formulae include elements from the following series in the periodic table: transition metals, metalloids, other metals, and lanthanides and actinides. As is the case with all impurities, elemental impurities should be managed so that their levels in drug products are known and low. To this end, standards-setting organizations such as the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), the United States Pharmacopeia (USP), and others have developed—or are developing—guidelines and recommendations that address the management of elemental impurities in drug products.1-6
Elemental impurities in drug products can arise from a number of different sources including the active pharmaceutical ingredient, excipients, the vehicle, and the packaging system. Considering the packaging system specifically, it is well known that materials used in packaging contain certain elemental entities and that these entities can leach into drug products (or simulating solvents) under conditions that reflect clinical storage and use.7,8
Despite this circumstance, there are relatively few published studies
that examine the issue of elemental impurities derived from packaging materials in the context of the developed drug product standards for such impurities and which contrast the total pool of elemental entities in packaging materials versus the amount that is readily leached from such materials under clinical conditions of storage and use.
Pharmaceutical Outsourcing | 26 | March/April 2015
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