The recent challenge for the pharmaceutical industries – ICH Q3D Elemental Impurities

Abstract

The new guidelines relating to elemental impurities from the international council on harmonization (ICH) Q3D guidelines for Elemental impurities have presented the pharmaceutical industry with new challenges. These challenges include the complexity of introducing new analytical technology techniques replacing the wet chemical limit tests like Heavy metals. At present ICH Q3D advocates the use of a risk based approach to assessing the potential aspects of pharmaceutical development, application to elemental impurities in drug products. Specific challenges include determining how to assess or quantify the risks associated with factors such as water, container closure systems and excipients. Defining where in the assessment process data may be required and identifying where risks can be negligible through a through scientific theoretical risk assessment also present significant questions. Elemental impurities in pharmaceutical formulations can come from catalysts, formulation ingredients and process vessels. They can interfere with drug efficacy or elicit a direct toxic effect on the patient. Heavy metal elemental impurities pose serious risks to patients without providing a benefit. Modern methods provide better analytical tests to detect elemental impurities, which in turn, will help protect patients by ensuring that the approved products have safe levels of these impurities.

The ICH guidelines and USP General Chapters <232> Elemental Impurities — Limits are focused on establishing Permitted Daily Exposures (PDEs) for elemental impurities in drug products. USP General Chapter <233> Elemental Impurities—Procedures describes analytical approaches for the detection of elemental impurities. The analytical approaches described in USP General chapter <233> are based on modern analytical capabilities. The outdated tests in the deleted USP General Chapter <231> and allow us to more precisely measure impurities to ensure safe levels. FDA, ICH, USP, and industry experts worked together to develop the new standards that are in alignment and help ensure high quality medicines. Elemental impurities include catalysts and environmental contaminants that may be present in drug substances, excipients, or drug products. These impurities may occur naturally, be added intentionally, or be introduced inadvertently (e.g., by interactions with processing equipment and the container closure system). When elemental impurities are known to be present, have been added, or have the potential for introduction, assurance of compliance to the specified levels is required. A risk-based control strategy may be appropriate when analysts determine how to assure compliance with this standard.