FDA Finalizes Elemental Impurities Guidance

From DCAT Value Chain Insights (VCI)

By Regulatory News posted 09-13-2015 15:03


The US Food and Drug Administration (FDA) has issued final guidance, Q3D Elemental Impurities in line with the guideline on elemental impurities adapted by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The ICH guideline was endorsed by the ICH Steering Committee at Step 4 of the ICH process, November 2014, and revised to correct several inconsistencies, December 2014. At Step 4 of the process, the final draft was recommended for adoption to the regulatory bodies of the European Union, Japan, and the United States.

The guidance centers on three main areas: (1) the evaluation of the toxicity data for potential elemental impurities; (2) the establishment of a permitted daily exposure (PDE) for each element of toxicological concern; and application of a risk-based approach to control elemental impurities in drug product. The guidance presents a process to assess and control elemental impurities in the drug product using the principles of risk management as described in ICH Q9. This process provides a platform for developing a risk-based control strategy to limit elemental impurities in the drug product.

The elements included in this guidance have been placed into three classes based on their toxicity (PDE) and likelihood of occurrence in the drug product. The likelihood of occurrence is derived from several factors including: probability of use in pharmaceutical processes, probability of being a co-isolated impurity with other elemental impurities in materials used in pharmaceutical processes, and the observed natural abundance and environmental distribution of the element.

The guidance applies to new finished drug products (as defined in ICH Q6A and Q6B) and new drug products containing existing drug substances. The drug products containing purified proteins and polypeptides (including proteins and polypeptides produced from recombinant or nonrecombinant origins), their derivatives, and products of which they are components (e.g., conjugates) are within the scope of this guidance, as are drug products containing synthetically produced polypeptides, polynucleotides, and oligosaccharides.

This guidance does not apply to herbal products, radiopharmaceuticals, vaccines, cell metabolites, DNA products, allergenic extracts, cells, whole blood, cellular blood components or blood derivatives including plasma and plasma derivatives, dialysate solutions not intended for systemic circulation, and elements that are intentionally included in the drug product for therapeutic benefit.

This guidance does not apply to products based on genes (gene therapy), cells (cell therapy), and tissue (tissue engineering). In some regions, these products are known as advanced therapy medicinal products.

This guidance does not apply to drug products used during clinical research stages of development. As the commercial process is developed, the principles contained in this guidance can be useful in evaluating elemental impurities that may be present in a new drug product. Application of Q3D to existing products is not expected prior to 36 months after publication of the guideline by ICH.

Source FDA


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