The request comes as part of the coalition’s comments on USP’s General Chapter <233> Elemental Impurities, which describes the test procedures companies will use to comply with the Elemental Impurities PDE (permitted daily exposure) limits in USP General Chapter <232>.
The procedures in <233> are also expected to help companies comply with the elemental impurities PDE limits in ICH (International Conference on Harmonisation) guideline Q3D.
In its comments, the coalition calls for the determination of physiologically relevant bioaccessible elemental impurity content “as opposed to requiring total digestion procedures that report the total content of each element.”
The coalition explains some of the issues at hand: “This distinction between the total and bioaccessible amount of an elemental impurity has not been suitably recognized in the context of risk-based control of elemental impurities in drug products and components.
“Permissible Daily Exposure (PDE) limits have been proposed based on toxicology reviews but without apparent consideration as to how analyses of drug products and components should be conducted so that the results are relevant to those reviews.”
USP previously delayed the implementation deadline because of compliance concerns.
David Schoneker, chairman of the coalition, noted in his letter to USP that one of the coalition’s project teams also has developed a PDE Calculator tool and an instruction document to describe how to use the tool.
The coalition seeks feedback from the USP on this tool so that industry can perform various types of risk assessments of their products, as well as for companies who plan to use ICH Q3D Option 2b to determine PDE compliance.
The coalition, known as the Coalition for Rational Implementation of the USP Elemental Impurities Requirements, includes the Consumer Healthcare Products Association, the International Pharmaceutical Excipients Council of the Americas, the NJ Pharmaceutical Quality Control Association, the Society of Chemical Manufacturers and Affiliates’ Bulk Pharmaceutical Task Force and their associated companies.
ICH opened its Q3D guideline for comments on Sept. 30.