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ICH: Q3D(R2) for elemental impurities reaches Step 2

The draft for the ICH Q3D(R2) Guideline for Elemental Impurities has reached Step 2 on September 25, 2020 and thus the consultation phase. The draft guideline includes, amongst others, corrected PDE values for gold, silver and nickel and a new appendix for impurities that are applied cutaneously or transcutaneously.  

What is regulated by the guideline?  

The ICH Q3D guideline is intended to control elemental impurities and establishes PDE (Permitted Daily Exposure) values for 24 elements. These apply to medicinal products that can be ingested orally, parenterally and via inhalation.  

What is new?  

In revision Q3D(R2), the newly added Appendix 5 also defines limits for impurities in medicinal products that are absorbed cutaneously or transdermally. A basic approach based on a modifying factor (Cutaneous PDE) is presented.  

The PDE values for the following elements in Appendix 2 have been corrected:  

  • Gold (Au): The oral and parenteral PDE was increased from 100 µg/day to 300 µg/day and from 1 µg/day to 3 µg/day for inhalation. 
  • Silver (Ag): The parenteral PDE was increased from 10 to 15 µg/day.  
  • Nickel (Ni): The PDE for inhalation has been increased from 5 µg/day to 6 µg/day.  

This also results in new values for the permitted concentration in µg/g for the respective elements. They are to be used when the content of elemental impurities in medicinal products does not exceed the daily dose of 10 grams per day.  

Furthermore, the monographs for gold and silver in Appendix 3 have been adjusted.  

The draft document is now available for public consultation. The ICH has focused on extracts of the passages that have been revised:

  • Part 1 – Appendix 2 extract : Correction of PDEs for gold, silver and nickel  
  • Part 2 – Appendix 3 extract: Correction of gold monograph  
  • Part 3 – Appendix 3 extract: Correction of silver monograph 
  • Part 4 – new Annex 5 for risk assessment of preparations applied cutaneously and transcutaneuosly 

All proposed changes are marked in red letters.  

The ICH has prepared a summarizing presentation for all changes, which provides a good overview. 


Source: 

ICH: ICH Guideline For Elemental Impurities Q3d(R2) Draft Version 

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