Main Changes revision ICH Q3D (R2) on elemental impurities guideline

In May , Revision 2 of the ICH Q3D guideline on elemental impurities in medicinal products for human use was published. The new revision has been adopted by the Regulatory Members of the ICH Assembly, although its effective date is set for September this year.

Main changes

1. 1. Correction of PDEs: New PDEs have been established in Appendix 2 for the elemental impurities Nickel, Gold and Silver.

• Nickel (Ni): The PDE by the inhalation route has been updated to 6 µg/day.
• Gold (Au): The PDEs previously established for the oral, parenteral and inhaled routes have been modified to 300, 300 and 3 µg/day, respectively.

• Silver (Ag): The PDE for parenteral route has been updated to 15 µg/day.

2. Addition of a new appendix (Appendix 5): this new appendix establishes the limits for elemental impurities for the cutaneous and transcutaneous routes of administration.

• It is intended to expand the information provided in the main text of the ICH Q3D Guideline and to provide more specific information on the cutaneous and transcutaneous route of administration.

• It is applicable to cutaneous and transcutaneous drug products intended to have local or systemic effect,but does not apply to products intended for mucosal (oral, nasal, vaginal), ophthalmic, rectal or products administered subcutaneously and subdermally. These products should continue to be evaluated as up to now according to the approach in section 3.2 “Other routes of administration”.

• Additionally, a concentration limit for nickel (Ni) and cobalt (Co) is added, in addition to the already established PDE value, to reduce the likelihood of causing skin reactions in already sensitized individuals, which is referred to as the cutaneous and transcutaneous concentration limit (CTCL). For elements with skin PDE and CTCL, both must be met.