Europe Updates Elemental Impurities Strategy

On Jan. 11, 2017, the European Directorate for the Quality of Medicines & Healthcare (EDQM)

that, at its 156^th session in November 2016, the European Pharmacopoeia (Ph. Eur.) Commission adopted general texts for the integration of requirements presented in the International Council for Harmonization’s (ICH) Q3D guideline on elemental impurities. ICH Q3D created a shift in EDQM’s focus on elemental impurities, changing from pure substance-based testing to a holistic control strategy in the finished product.

To help integrate this new focus, the agency has outlined a schedule for implementation of the guidelines, and the following chapters will be published on Jan. 1, 2018 in Supplement 9.3 of the Ph. Eur.:

• General chapter 5.20 Elemental impurities: reproduces parts of the Scope and the Introduction sections of the ICH Q3D guideline and refers to the guideline which can be found in full on the ICH website

• General monograph on pharmaceutical preparations (2619): refers to chapter 5.20, rendering it-and by extension the ICH Q3D guideline-legally binding

• General monograph on substances for pharmaceutical use (2034): introduces requirements for the control of elemental impurities intentionally added during production and explains the absence of a test for elemental impurities from individual monographs except for special cases (see paragraph on specific tests below)

• General method 2.4.20 Determination of elemental impurities: provides guidance for aspects of method development such as sample preparation and method validation for the determination of elemental impurities.

The future of specific elemental impurities tests was also discussed at the meeting. The Ph. Eur. Commission plans on keeping the published “specific elemental impurities tests in monographs on substances of natural origin only.” In a press release, EDQM stated, “Given the intrinsic nature of elemental impurities in these substances, they are amongst the major potential sources of elemental contamination in medicinal products. The Ph. Eur. Commission has also recommended keeping in particular the different tests for elements for which no Permitted Daily Exposure limits have been established (i.e., those identified as ‘other elements’ in the ICH Q3D guideline, such as aluminium and iron) in individual monographs.”

Specific elemental impurities tests, however, will be deleted from monographs on substances not from natural original, unless otherwise justified. “In particular,” EDQM states, “the Ph. Eur. Commission decided that, unless otherwise justified, specific tests for elemental contaminants originating from the production process will be deleted. As these elemental impurities are specific to the production process, they will remain the responsibility of the substance manufacturer; this is reflected in the new sentence added to the Production section of the general monograph on Substances for Pharmaceutical Use (2034).”

The Ph. Eur. Commission and groups of experts will continue to clarify, on a case-by-case basis, affected monographs. A list of the impacted monographs will be published for public consultation.

Source: