The guideline consists of three components: the evaluation of the toxicity data for potential elemental impurities, the establishment of a Permitted Daily Exposure (PDE) for each element of toxicological concern, and development of controls designed to limit the inclusion of elemental impurities in drug products to levels at or below the PDE.
New finished drug products and new drug products employing existing drug substances will have to abide by the newly set limits.
And although the guideline is related to finished products, the guideline’s release also comes as IPEC-Americas (International Pharmaceutical Excipients Council) is seeking more information on the potential impurity levels for excipients used in drug products in preparation for the new ICH guideline and USP chapter.
IPEC notes that suppliers are encouraged to provide information that may assist their customers in meeting these new requirements from the ICH and USP, which are mandatory for finished drug products. “However, users need to recognize that suppliers may not have all of this information readily available,” IPEC notes.
And although the FDA’s release of the guideline comes only two months after the ICH (International Conference on Harmonization) release of Q3D, there have been delays to not only the ICH and FDA work on this subject, but also the USP’s (US Pharmacopeia) work.
The USP delayed its work after industry expressed concerns about compliance.
Some are also warning that the guideline will take time to implement as unknowns about the metal content of APIs (active pharmaceutical ingredients) and excipients could cause products to be reformulated.