IPEC e-newsletter - Excipients Insight August 2017 - 11-08-17


Inside this issue


No 'smoking gun' with elemental impurities for excipients

Efforts by a pharma consortium and Lhasa Limited to develop a database of elemental impurities for excipients in response to the ICH Q3D Guideline are now "getting close to critical mass," according to Andy Teasdale of AstraZeneca (pictured), who chairs the company's impurities advisory group and the IPEC Europe Q3D taskforce.

There are around 2,000 data points in the repository, spanning a host of key excipients and multiple suppliers, he told Excipients Insight, while noting that there is still work to be done to identify and fill certain gaps in the database.

"What this resource is showing is that there is really no smoking gun in this area," said Teasdale. "We have not encountered any examples of excipients with high levels of elemental impurities, even among some of the mined excipients like titanium dioxide which at the outset were considered likely to have not only high but also variable levels of metals."

The levels of metals are in fact remarkably consistent – even for mined materials such as iron oxides which are used as colorants for tablet coatings for example – and not high enough to be significant.

"We're not seeing the huge variability that many people feared," said Teasdale. Preparations are underway to publish a peer-review paper on the database and the consortium's findings later this year.

There is also a hope that the resource may be of use in tackling issues raised by the removal of the outdated heavy metals limit test from individual pharmacopoeial monographs in the ICH Q3D guideline, but the retention in many monographs of element-specific tests that are of questionable value.

ICH Q3D was finalised at the end of 2014 and came into force for new products in June 2016, introducing a risk-based approach to the control of elemental impurities in the finished dosage form, taking into account potential sources such as the active pharma ingredient (API), excipients, manufacturing equipment, processing aids such as catalysts or water and container closure systems.

It will be extended to include established products from 31 December 2017 – just a few months away. While it is likely that larger pharma companies will have carried out the large volume of work needed to prepare risk assessments that might be requested by regulatory inspectors, there is speculation that smaller manufacturers and companies in emerging economies may not be ready in time.




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