Pre-Conference Session

24 October 2017


Elemental Impurities and CEPs

– Requirements for new CEP applications,

already existing CEPs and CEP revisions



In this pre-Conference Session you get to know how the requirements of the ICH Q3D Guideline on Elemental Impurities affect the CEP procedure. You will learn:

  • How to deal with these requirements when applying for a new CEP or a revision of an existing CEP
  • What EDQM expects with respect to elemental impurities when you submit a CEP application
  • Which consequences will arise from the comprehensive revision of pharmacopoeial monographs

Furthermore you get examples on how to perform a risk management summary for a CEP application.

This pre-conference session ideally complements the following 20th APIC/CEFIC European Conference on Active Pharmaceutical Ingredients.



In August 2016, the EDQM released a policy document entitled "Implementation of ICH Q3D in the Certification Procedure" (PA/PH/CEP(16)23). The document describes which data on elemental impurities are required for a new CEP application and for the revision/renewal of an existing CEP. An important part of the document is an Annex 1 providing an example of a risk management summary (RMS). Another important document was published in March 2017 by EMA entitled „Implementation strategy of ICH Q3D guideline“ (EMA/CHMP/QWP/115498/2017). This document addresses specific considerations to enable the practical implementation of ICH Q3D in the EU by providing guidance for Appplicants/MAHs. It applies to new applications, as well as variations to existing authorised medicinal products and also reflects dossier expectations and assessment strategy regarding CEPs and ASMFs.


Target Audience

This pre-Conference Session is designed for all persons involved in the compilation of pharmaceutical dossiers for marketing authorisations in the EU especially the documentation of the drug substance quality in a CEP. Furthermore the Session will be of interest to personnel from Regulatory Affairs, Quality Assurance, Quality Control, Production and Project Management of the pharmaceutical and the API industry.


  • The ICH Q3D Guideline – an overview

- Which elements are covered in the guideline
- What is expected from Marketing Authorization Holders
- How to prepare the risk assessment



  • ICH Q3D and the European Pharmacopoeia

- General chapters on elemental impurities
- Impact of ICh Q3D on individual monographs
- Removal of the test 2.4.8 for heavy metals


EDQM Press Release, 11 January 2017 “Update on the Ph. Eur. Policy on Elemental Impurities
“… 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;…”

  • EDQM’s implementation policy of ICH Q3D in the Certification Procedure

- How to implement the principles of ICH Q3D at the level of substances
- Content of the CEP dossier with regards elemental impurities
- Impact on new and granted CEPs

  • ICH Q3D and the global Pharmacopoeial consequences


- Deletion of the heavy metals test for API's
- Consequences for global registration


„Implementation strategy of ICH Q3D guideline“ (EMA/CHMP/QWP/115498/2017).
1. Submission of a summary of a risk assessment/management for elemental impurities by the drug substance manufacturer
Such information would inform the drug product manufacturers overall risk management and would also be assessed by the quality assessor/CEP assessor. The internal reports and the data generated on which the summary risk assessment/management is based on should be available for GMP inspections.

  • Elemental impurities risk assessment of Drug Products

  • Risk evaluation of elemental impurities in Drug Substances – EDQM’s perspective

- Addressing the relevant elemental impurities
- Control strategy for drug substances manufacturers

Implementation of ICH Q3D in the Certification Procedure (PA/PH/CEP (16) 23)
A Risk Management Summary report should be provided in module 3 of the dossier, in the form of a Table, as described in Annex 1 of this document … This summary should detail the rationale used to conduct the study, and include a justification of the control strategy implemented following the risk assessment.

  • Elemental impurities risk Evaluation of Drug Substances – API manufacturer’s perspective

- Sense and nonsense of a risk evaluation for APIs
- How to do- practical implications