Toxic impurities in pharmaceutical products | Exclusive interview with Abbott

We spoke to Tom van Wijk, Principal Scientist at Abbott, ahead of his presentation at next month's E&L Europe conference in London to get the low down on his presentation covering screening of toxic components in pharmaceutical products, what he feels are the biggest challenges in the E&L industry today and more.

Your presentation will look at the differences in strategies applied for the toxic impurities in pharmaceutical products, can you let us know a bit more about this?

As principal scientist at analytical science and technology, I’m supporting all Abbott globally marketed products for method development, impurity profiling, validation and transfers. Ad hoc support is provided to the regionally and locally manufactured products. As center of excellence support is provided in activities that require specialist knowledge on development of (stability indicating) analytical methods (including ANVISAs RDC166 compliance) and identification by accurate mass. My special interest is in the control of toxic impurities, i.e. extractables & leachables, support implementation of ICHM7 for control of potential mutagenic impurities and ICHQ3D for elemental impurities.

What are the differences in strategies applied for the toxic impurities in pharmaceutical products?

Pharmaceutical product may contain traces of toxic components originating from the active ingredient, excipients or packaging. Being involved in any impurities in pharmaceutical products, I find it especially interesting how the control strategies from differ depending on the origin of the impurity. Control of potential mutagenic impurities (PMI) in pharmaceuticals covered by ICH M7, elemental impurities by ICH Q3D while the guideline for leachables is still evolving. Although all strategies are aiming to cover trace levels of toxic components, remarkable differences in the strategy are observed.  Coverage of elemental impurities is quite straightforward as all compounds of interest are known. The strategy is based on risk control plans supported by limited amount of data of individual constituents. For PMI, the strategy is based on a theoretical assessment of components that are likely to be present, mainly in the active ingredient. Only if assessed as PMI, control is required down to a level of 1.5 µg/day. Analytical screening for PMI is not deemed necessary, and not even considered technically feasible, this the approach applied to monitor leachables. In the strategy applied for leachables, any component detected in comprehensive screening that cannot be identified is considered toxix and should be controlled at the level of a PMI.

What are the key findings you will be presenting?

The presentation will cover the strengths and weaknesses of the current approaches for detecting potential toxic components from the pharmaceutical products as well as the packaging. The potential to come to a more harmonized approach will be discussed.

What do you think are the biggest challenges in the E&L industry today?

Guidelines for E&Ls are evolving e.g. in USP<1663> and USP<1664>. The coverage of the most relevant organic leachables is most challenging. Especially the most reactive leachables, with a likely high toxicity, are most likely to be missed in standard screening approaches. In my role as specialist in mass spectrometry, I’m involved in the analysis of PMI since 2007. In addition to the approaches generally applied, target analysis of PMI, I’ve investigated the potential for screening for PMI in pharmaceuticals, beyond that is requested by the guidelines. A strategy was developed for semi targeted screening for alkyl halides, based on derivatization and subsequent MS/MS detection of reagent related markers. For different classes of PMI semi-targeted approaches with high potential for screening are available that could be applied to improve the coverage of the most reactive leachables. Moreover, making use of prior knowledge can make the approach more effective.


Tom will be presenting as part of the 'Methods to assess the toxicity of E&L compounds' session. Other presentations in the session include:

  • Transformation of toxicology data into specific PDE's - Kim Li, Senior Manager Environment, Health, Safety and Sustainability, Amgen
  • Sensitation risk assessment: Considerations and approaches - Patricia Parris, Project Toxicologist, AstraZeneca
  • Leachables and extractables degradation products: It can always get worse - Thomas Broschard, Associate Director & Head of Chemical Toxicology, Merck
  • The need to identify unknown E&Ls from a risk assessment perspective - Ronald Brown, Toxicologist, former U.S. FDA

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