Elemental impurities

Real Generics’ Regulatory News Digest For Generics – 10 August 2015

Draft ICH Guidelines for Consultation

Mutagenic impurities

ICH has released a draft addendum to ICH Guideline M7 on Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk.

The addendum summarises known mutagenic impurities commonly found or used in drug synthesis (e.g. aniline, dimethyl sulfate, ethyl chloride, hydroxylamine), providing acceptable limits and supporting monographs.

Residual solvents

ICH Residual Solvents Guideline Q3C(R6) introduces a new limit for triethylamine and a revised limit for MIBK. Both solvents are commonly used in the manufacture of drug substances, so the changes may affect many marketing authorisations.

Triethylamine, which was previously unclassified, has now been classified as a Class 3 solvent with a limit of 5000 ppm.

MIBK, which was previously classified as a Class 3 solvent, is now Class 2 with a limit of 4210 ppm.

See the draft ICH guideline with EU deadline for comments on 03 November 2015.


Clinical Trial Master Files

Clinical Trial Master Files held by generic companies (for bioequivalence studies, mostly) may not be enormous, but there are still plenty of pitfalls to be avoided. Here is a very useful blog post on the subject from the UK MHRA.


Mandatory Use of PSURs Repository in the EU from June 2016

On 11 June 2015, the EMA Management Board endorsed the full functionality of the periodic safety update reports (PSURs) repository, based on the positive recommendation of the PRAC and the conclusions of an independent audit report.

Further information on the PSUR repository can be found here.


ICH Q3D on Elemental Impurities

Pharmaceutical companies are preparing for the implementation of ICH Q3D on elemental impurities, effective from June 2016 for new marketing authorisations, and December 2017 for all existing products on the EU market.

The European Pharmacopoeia (EP) is also gearing up for implementation by eliminating heavy metals tests from individual monographs, and revising chapters 5.20 (Metal catalyst or metal reagent residues) and 2.4.20 (Determination of metal catalyst and metal reagent residues).

EP has now clarified that Chapter 5.20 will be applicable to all materials, even products for veterinary use that are outside the scope of ICH Q3D.


Photograph: Periodic Table of Elements by Siyavula Education, CC BY 2.0


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