Dispatches from ChemOutsourcing

ICH elemental impurities guideline expected to be finalized at end of September

By Zachary Brennan

- Last updated on GMT

24 elements will need to be evaluated by manufacturers of finished products
24 elements will need to be evaluated by manufacturers of finished products

Related tags Elemental impurities Pharmacology European union

After much discussion and some confusion, the ICH’s (International Conference on Harmonization) Q3D guideline, which will govern elemental impurities in final drug products, is expected to be finalized at the end of this month.

In the end, 24 elements will need to be evaluated by manufacturers of finished products, which differs from EU guidelines that stipulate limits for 14 elemental impurities, Ulrich Reichert told attendees at the ChemOutsourcing conference on Wednesday.

The parenteral limits, specifically, “are strict, and ICP-MS, [which is one of the techniques used to measure the impurities] will be mandatory​,” Reichert told In-Pharmatechnologist.com.


Under the new ICH guideline, companies will have to create impurity profiles for finished products, which will require testing of reagents and catalysts that are either known to be present or could possibly be present. The limits are based on the maximum daily dose of 10 mg of drug product and will need to be adjusted based on the dosage, Reichert said.

Among the new elements that will need to be evaluated, Reichert pointed out the addition of the so-called ‘Big Four,’ which includes elements classified by the ICH as having the highest potential to be significantly toxic, and includes mercury, lead, cadmium and arsenic.

Manufacturers will likely use one of two methods to detect the impurities: ICP-AES (inductively coupled plasma atomic emission spectroscopy) or ICP-MS (inductively coupled plasma mass spectrometry), the latter of which Reichert said is the “method of choice as it’s very sensitive, but it’s also very expensive​.”

Manufacturers may also have to evaluate the stainless steel equipment and container closure systems used to produce and store their drug products to ensure impurities aren’t later added.

Most of the considerations will be related to excipients​,” Reichert said, noting that manufacturers may need analytical and regulatory support to achieve compliance for pharmaceutical substances as well.

IPEC (International Pharmaceutical Excipients Council) Americas asked pharma companies in April​ to provide more insight on how they plan to deal with ICH Q3D in preparation for the guideline coming out. IPEC noted in a letter to industry that it’s “important to stress that many excipient suppliers may not have information on the presence of many of the elements listed in ICH Q3D​.”

European Regs

Unlike what’s expected to come out of the ICH later this month, the EMA (European Medicines Association) established its own set of elemental impurity regulations in 2008 after eight years of development.

The European regulations are meant to control 14 elements that are intentionally added from catalysts and reagents. And unlike the USP general chapters <232> and <233>​, which apply to the finished drug product and are expected to be applicable in December 2015, the EU regulations apply only to excipients and drug substances and not to the final drug products.

Reichert noted that the European Pharmacopoeia will implement ICH’s Q3D when it’s finalized.

Related news

Show more

Related products

A Guide Through the API Drug Development Pipeline.

A Guide Through the API Drug Development Pipeline.

Content provided by Lonza Small Molecules | 04-Apr-2023 | Insight Guide

With the complexities associated with API and HPAPI drug development, it’s necessary to lean on the experts. With Q&A sections, insights and articles...

Understanding the hidden value of quality

Understanding the hidden value of quality

Content provided by Thermo Fisher Scientific – Production Chemicals and Services | 16-Jan-2023 | White Paper

The raw material supply is too vital to leave to chance, and quality-related supply chain activities are cornerstones to your success.

Related suppliers

Follow us


View more