Abstract
Compendia methods have historically been used to assess heavy metals in both drug products and packaging material extracts. However, these methods have been found to be inadequate for elemental specificity and accurate measurements. The International Council on Harmonization (ICH) has published the Q3D, Guideline for Elemental Impurities to provide a risk-based approach that specifies elements to be considered in a drug product risk assessment and permitted daily exposures (PDEs) depending on toxicological concern and route of administration. Consistent with these efforts, the United States Pharmacopeia (USP) withdrew the <231> Heavy Metals test procedure as of January 2018. The USP has published new methods consistent with ICH Q3D risk-based approaches, <232> Elemental Impurities-Limits, <233> Elemental Impurities-Procedures. These new monographs are intended for evaluation of drug products, which left a gap for assessment of extractable elements in packaging components. This gap prompted the need for a better understanding of the potential for elements of concern to extract from packaging materials and contribute to drug product elemental impurities. The present study investigated multiple extraction conditions coupled with modern analytical techniques to understand the capacity for elements to extract from elastomeric components. All the elements of interest, based on ICH or their potential for occurrence in elastomers, were ultimately recovered at levels below designated thresholds, which allows for correlation to permitted daily exposures (PDEs). These results highlight that while extractable elements from elastomeric components have the potential to contribute elemental impurities to a drug product, the actual contribution to cumulative levels would need to be calculated amongst all other potential sources as part of the process of elemental impurities assessment.
- Elastomer
- Elemental impurities
- Extractables and leachables
- ICH Q3D
- Parenteral packaging materials
- USP <231>/<232>/<233>
- Received January 29, 2018.
- Accepted June 18, 2018.
- Copyright © 2018, Parenteral Drug Association
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