PT  - JOURNAL ARTICLE
AU  - Dennis Jenke
TI  - Materials in Manufacturing and Packaging Systems as Sources of Elemental Impurities in Packaged Drug Products: An Updated Literature Review
AID  - 10.5731/pdajpst.2019.010033
DP  - 2019 Jan 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - pdajpst.2019.010033
4099  - http://journal.pda.org/content/early/2019/12/13/pdajpst.2019.010033.short
4100  - http://journal.pda.org/content/early/2019/12/13/pdajpst.2019.010033.full
AB  - Elemental impurities in drug products arise from different sources and via a number of different means, including leaching of elemental entities (including elements themselves or element-containing compounds) from the drug product′s manufacturing or packaging systems. Thus, knowledge about the presence, level, and likelihood of leaching of elements in manufacturing and packaging systems is relevant to understanding how these systems contribute to a drug product′s total elemental impurity burden. To that end, this manuscript updates a previous review of available literature on elemental entities in pharmaceutically relevant polymers and the presence of these elemental entities in material extracts and/or drug products. This updated review contains the information that has been published subsequent to the publication of the initial review and considers two questions: (1) What elemental entities are present in the relevant polymers and materials and at what levels are they present? (2) To what extent are these elemental entities leached from these materials under conditions relevant to the manufacturing and storage/distribution of solution drug products? This compiled recent data re-affirms the Conclusions drawn from the original review: (1) Elemental entities are present in the materials used to construct packaging and manufacturing systems as these materials either contain these elemental entities as additives or are exposed to elemental entities during their production. (2) Unless the elemental entities are parts of the materials themselves (for example, SiO2 in glass) or intentionally added to the materials (for example, metal stearates in polymers), their incidental amounts in the materials are generally low. (3) When elemental entities are present in materials and systems, generally only a very small fraction of the total available amount of the entity can be leached under conditions that are relevant to packaged drug products. Thus, while sources of certain elemental impurities may be ubiquitous in the natural environment, they are not ubiquitous in materials used in pharmaceutical packaging and manufacturing systems and when they are present, they are not extensively leached under relevant conditions of use for those systems. This conclusion, supported by an ever-increasing body of literature, suggests that in general manufacturing and packaging systems, by themselves, do not contribute sufficiently large quantities of elemental impurities that the impurities pose a meaningful threat to patient safety. Furthermore, this conclusion should be considered when standards are developed for the characterization and qualification of manufacturing systems, packaging systems and their associated materials and components of construction.