New Version of the ICH Q3D Guideline for Impurities published

Since the end of April 2022, the second revision of the "Guideline for Elemental Impurities Q3D(R2)" of the ICH (INTERNATIONAL COUNCIL FOR HARMONISATION OF TECHNICAL REQUIREMENTS FOR PHARMACEUTICALS FOR HUMAN USE) is available on the ICH website under the heading "Quality Guidelines". This version includes revisions and adaptations in Appendices 2 and 3. Appendix 5 has been added.

Appendix 2: Established PDEs for Elemental Impurities

The PDEs (Permitted Daily Exposure) values for the following three substances nickel, gold and silver have been adjusted in Appendix 2.

Appendix 3: Individual Safety Assessments

In the third appendix, the passages on the monographs of the substances gold (pages 41-42 of the guideline) and silver (pages 62-63 of the guideline) were revised.

Appendix 5: Limits for Elemental Impurities by the Cutaneous and Transcutaneous Route

Appendix 5 was added in the second revision of the guideline and contains information on the limits for impurities for cutaneously or transcutaneously applied medicinal products. This appendix comprises the following eight items, with paragraphs 3 and 4 each containing sub-items:

  • 1 Background
  • 2 Scope
  • 3 Principals of Safety Assessment for Cutaneous Products
    - 3.1 Transcutaneous Absorption of Elemental Impurities (EI)
    - 3.2 PDE for Drug Products Directly Applied to the Dermis
  • 4 Establishing the Cutaneous Permitted Daily Exposure (PDE)
    - 4.1 Establishing the Cutaneous Modifying Factor (CMF)
    - 4.2 Cutaneous PDE
    - 4.2.1 Derivation of PDE for EI, other than Arsenic (As) and Thallium (Tl)
    - 4.2.2 Derivation of PDE for arsenic
    - 4.2.3 Derivation of PDE for thallium 
  • 5 Cutaneous Concentration Limits for Ni and Co 
  • 6 Product Risk Assessment
  • 7 Cutaneous PDE Value
  • 8 References

The complete "Guideline for Elemental Impurities Q3D(R2)" as well as all other valid "Quality (Q)-Guidelines" can be found on the ICH website.

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