Drug Development Solutions

ICH Q3D elemental impurities testing

As a consequence of the new ICH/USP regulatory guidelines concerning testing of elemental impurities, the way in which pharmaceutical companies and their suppliers are required to test their Drug Product, APIs and excipients has changed dramatically.The guidelines, which aimed to set out a global policy for limiting metal impurities in Drug Products and ingredients puts these impurities in to various categories. In order to comply with the guidelines sponsors need to carry out a detailed risk assessment of their materials in terms of these different categories.

Impact of the changes

USP <231> heavy metals test was replaced with two new chapters, USP <232> elemental impurities (limits) and USP <233> elemental impurities (procedures). As a consequence the use of Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) and Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS) has become the preferred standard approach for the determination of heavy metals in Drug Products, replacing the much out dated and non-specific/non quantitative wet chemical tests. With the added elemental specificity, accuracy and sensitivity (ppb/ppt range) afforded by ICP-OES/ICP-MS, sponsors are able to confirm that their materials meet the new compliance criteria.

Our solution

The new USP directive was implemented in January 2018 and we are already supporting a very significant industry requirement for additional ICP-OES/ICP-MS testing of Drug Products, APIs and excipients. Delivery of large volumes of ICP-OES/ICP-MS testing is not within the typical capability of pharmaceutical QC laboratories. We, however, have extensive experience in delivering high throughput routine ICP testing with short turnaround times.

Our dedicated elemental impurities team is based at our state of the art cGMP facility in Fordham, Cambridgeshire. The techniques routinely utilised for elemental analysis include the following:

Elemental analysis• ICP-OES - Thermo iCAP7600 Duo• ICP-MS - Agilent 7700x and Agilent 7900

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Extraction techniques• Microwave digestion• Fusion• Wet chemical digestion• Accelerated solvent extraction• Sonification

We have in-depth technical knowledge and extensive experience in the quantitation of elemental impurities in pharmaceutical materials by ICP-OES/ICP-MS.

The wide variation in pharmaceutical material composition and the requirement for simultaneous multi-elemental determination across a wide

concentration range can lead to significant analytical challenges. Our scientists are experienced in developing and validating both limit and quantitative test methodologies for a wide range of sample matrices, utilising a variety of specialised sample preparation techniques and digestion regimes.

In addition to the above capabilities, we also have extensive expertise in the related field of metal speciation. We work with sponsors who may have an issue in determining oxidation state (e.g. As III or As IV) such as in trace catalyst residues in pharmaceutical process streams or the presence of metals bound in an organic compound.

For further information on how LGC can assist with ICH Q3D elemental impurities

testing, please contact us:

lgcgroup.com/enquiries

+44(0)1638 720500

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