IPEC e-newsletter - Excipients Insight April/May 2018 - 15-05-18


Inside this issue


Elemental impurities database: a tool for ICH Q3D risk assessment

by Andrew Teasdale, Chair AstraZeneca  Impurities Advisory Group (IAG)

ICH Q3D is predicated on the need to conduct an holistic risk assessment of all potential sources of elemental impurities (EIs).  Prime among these, at least in terms of perceived risk, are excipients especially those derived from mineral sources. The guideline lays out basic principles for a review including that this should take a risk-based approach, one that is evidence based, pointing to the potential to utilise data, including published data to assess the risk. 

At the onset knowledge was limited, particularly so in terms of data for excipients. In 2015 the results of a study jointly performed by FDA and IPEC Americas was performed. Data from some 200 excipient samples was published. This concluded that the overall risk associated with excipients was relatively low, especially when typical proportions in formulated drug products were taken into account. This important insight led a consortium of pharmaceutical companies to establish a database to collate the results of analytical studies they had performed. This database currently includes the results of over 25000 elemental determinations for over 200 different excipients and represents the largest known, and still rapidly expanding, collection of data of this type.

A soon-to-be-published analysis of the database (which will appear in J Pharm Sci) examined a series of aspects including data coverage as well as impurity levels and variability (across supplier/grade etc.).  Comparison of the excipients studied with those used in drug products showed a very high correlation, there being multiple analytical studies for many of the excipients used by drug product manufacturers. This allowed both excipient supplier and batch-to-batch variability to be examined. The results are compelling.  Critically the data reaffirm the findings of the earlier smaller FDA-IPEC studies providing compelling evidence to support the original conclusion  that elemental impurity levels in excipients, including mined excipients  are generally low and that when used in typical proportions in formulated drug products are unlikely to pose a significant patient safety risk. 

The database is now in active use and provides real evidence in support of holistic ICH Q3D risk assessments.




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