Elemental impurity analysis in pharmaceuticals

A method to identify the presence of heavy metals in pharmaceuticals was introduced in the United States Pharmacopoeia more than 100 years ago. Today pharmaceutical companies are still using essentially the same method, the USP <231> Heavy Metals Limit Test

A method to identify the presence of heavy metals in pharmaceuticals was introduced in the United States Pharmacopoeia more than 100 years ago. Today pharmaceutical companies are still using essentially the same method, the USP <231> Heavy Metals Limit Test. This paper will give an overview of the current method limitations, considerations for the new methodology and the risk-based assessments being carried out by manufacturers.

The current colorimetric methodology was intended to control metals that form a sulfide precipitate, such as lead and copper, which are potential contaminants from water pipes, manufacturing equipment and processes. However, the risk factors for metal contamination have changed dramatically, for example with the use of metal catalysts, yet the standards for their control have changed little in more than 50 years. The method is no longer fit for purpose and most heavy metal limits currently in place have little basis in toxicology.

To that end whilst IPEC (International Pharmaceutical Excipients Council) Americas, state that they are unaware of any known metal impurity issues impacting patient safety, they, along with pharmaceutical manufacturers and regulators, agree on the need to enhance and harmonise future testing. However, harmonisation of pharmacopoeia methods has a history of making slow progress and it is not surprising that this task has taken as long as it has in coming to what appears to be a conclusion when the Q3D Expert Working Group expects to reach Step 4 later this year following the publication at Step 2 of the ICH Q3D document in June 2013.

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