Elemental impurities in drug products may arise from several sources; they may be residual catalysts that were added intentionally in synthesis or they may be present as impurities. Sources can include manufacturing equipment, solvents, water and reagents amongst other things. In the absence of therapeutic benefit to patients, their levels in excipients, drug substances, drug products and dietary supplements should be controlled within acceptable limits. Requirements are clearly outlined within ICH Q3D guidelines which is now harmonized with compendia. Determination procedures are set forth in USP <233> and Ph. Eur. method 2.4.20.
ALS offers GMP compliant elemental impurities analysis of pharmaceutical products, ingredients, APIs and other healthcare products in accordance with compendia requirements. Our facilities are equipped with some of the most sensitive techniques available coupled with decades of experience specifically in metals analysis. Typical limits of quantification reach far below typical PDE requirements; some reaching ppt (parts per trillion) levels with as little as 10mg in sample weight. Our facilities offer a full service range from initial scans to support pre- risk assessment understanding to full and thorough ICH method validation. Our extensive expertise allows for an open, collaborative approach towards managing each product and project.
If purified water in bulk does not meet the requirement for conductivity prescribed for Water for injections in bulk (Ph. Eur. Monograph 0169), a risk assessment according to Ph. Eur. general chapter 5.20 should be carried out. The risk assessment should consider the role of water in the manufacturing process, in particular when water is used in a process but is no longer present in the final product. ALS can quickly and cheaply screen purified water, down to very low limits of quantification, to support these risk assessments.
It is realized many, particularly those manufacturing Active Pharmaceutical Ingredients (API’s), will have their own analytical capability to manage elemental impurity testing. ALS can help to mitigate risk by way of being a partner for independent analytical support and back-up. Contingency planning can be a necessity to help navigate through rare but critical times of need.
Measuring the levels of metals in clinical samples, often referred to as biomonitoring, is required in a variety of fields. Medicine, occupational health studies and therapeutic research, to name but a few, all rely on such information. Due to the high toxicity of some elements, measurements at very low levels are often required. ALS Luleå, Sweden has considerable experience of analyzing human biological matrices using high resolution ICP- MS (ICP-SFMS) and offer accredited analyses of 68 elements in whole blood, plasma, serum and urine. Combined with isotope and elemental speciation capabilities, ALS offers a comprehensive portfolio of elemental analysis for clinical samples.
Yes. Many of our GMP pharmaceutical laboratories still use limit tests, wet chemical techniques and alternative techniques at the direction of our clients. Specific examples include:
Yes, at our global center of excellence in Luleå, Sweden. The site is dedicated to the analysis of elemental impurities supporting testing in whatever capacity is required. The facility regularly handles samples from different sectors including environmental, biological and clinical samples as well as materials and consumer goods. This added offering can be helpful in supporting manufacturing investigations where healthcare materials or product have exceeded permitted elemental impurity levels.
Yes, at our global center of excellence in Luleå, Sweden utilizing GC-ICP-MS and IC-ICP- MS. The toxicity, bioavailability and mobility of an element can be highly dependent on the form in which it is present. Consequently, speciation analysis can provide valuable additional information and insight compared to a traditional measurement of the total elemental concentration. Over the last few years, new legislation and guidelines have been published that introduce threshold values for organotin compounds, inorganic arsenic and methylmercury. Whilst such legislation has more focused on food and environmental samples, ALS is well placed to support the testing should the need arise within the pharmaceutical industry. ALS has the capability to support testing of Methylmercury (as Hg) and Arsenic (inorganic) as required by USP < 223 > Elemental Contaminants in Dietary Supplements.