Apr 05

The new ICH Q3D Elemental Impurities Guideline – nothing to fear if you act now

The ICH Q3D Guideline on Elemental Impurities has been adopted by the European and US Pharmacopoeias, meaning that by the end of 2017 all new and existing products in Europe and the US will need to be assessed.

Initially it was thought that every marketed product would require full testing for trace metals. However, the risk based nature of ICH Q3D means that many elements can be eliminated from consideration if sufficient data are available. Elemental Impurities are rarely seen at levels that require control measures. This means that screening alone may be sufficient to satisfy the ICH Q3D requirements. Screening can fill the knowledge gap and allow an informed risk assessment to be completed prior to committing to full quantitative validation.




What are elemental impurities and how do they get there?

Elemental impurities are traces of metals that can end up in finished drug products. Elemental impurities can come from multiple points in the manufacturing process, such as deliberate addition as reaction catalysts during product synthesis, or from contact with manufacturing equipment and containers. These impurities do not typically contribute to a drugs therapeutic effect, and can cause patients harm if the levels are not monitored and controlled. Therefore, for evaluation, manufacturers need to consider all potential sources of trace metals in the final formulation and product packaging. The permitted daily exposure of each element varies, but overall, no elemental impurity should be present at more than 30% of the Permitted Daily Exposure (PDE) in the final product.


Testing required? Consider this

The wide variation in pharmaceutical material composition and the requirement for simultaneous multi-elemental determination across a wide concentration range can lead to analytical challenges.

The product, 30% PDE level, dosage route and ICH Q3D option selected all affect the sample preparation method, solvent and instrumental detection methods chosen. Each available method has a range in sensitivity and response and these must be aligned carefully with each specific product’s requirements taking into consideration the targeted elements impurities and their documented risk and exposure limits.


Help is at hand!

USP <231> Heavy Metals test is being 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) will become the preferred standard approach for the determination of heavy metals in drug products, replacing wet chemical tests. This means tests with better specificity, accuracy and sensitivity are now available to help sponsors confirm that their materials meet the new compliance criteria.

The implementation deadline for the new USP directive is scheduled for January 2018 and LGC is already prepared for what will be a very significant industry requirement for additional ICP-OES / ICP-MS testing of new products.

To find out more about the new guidelines and LGC’s expertise, please download the fact sheet and view our webinar.



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 View LGC webinar on In Vitro Antimicrobial Efficacy Testing: Potential Pitfalls and Future Methods

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Author: Sarah James, Principal Scientist, CMC Analytical Services, LGC



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