ICH Q3D Drug Product Elemental Risk Assessment: The Use of An Elemental Impurities Excipients Database.

The purpose of this publication is to show how an elemental impurities excipient database can be used in assisting the execution of a drug product elemental impurities risk assessment as required by the ICH Q3D guidelines. As a result of this exercise, we have demonstrated that the database, used in conjugation with other sources of information, is a credible source of elemental impurity levels in excipients therefore, a valuable source of information in completion of drug product risk assessments. This useful collection of data helps to reduce the burden of analytical testing for elemental impurities in excipients.

An Elemental Impurities Excipient Database: A Viable Tool for ICH Q3D Drug Product Risk Assessment.

To support the practical implementation of the International Council for Harmonisation (ICH) Q3D guideline, which describes a risk-based approach to the control of elemental impurities in drug products, a consortium of pharmaceutical companies has established a database to collate the results of analytical studies of the levels of elemental impurities within pharmaceutical excipients. This database currently includes the results of 26,723 elemental determinations for 201 excipients and represents the largest known, and still rapidly expanding, collection of data of this type. Analysis of the database indicates good coverage of excipients relevant to real-world drug product formulations and tested element profiles consistent with ICH Q3D recommendations.

The use of atomic spectroscopy in the pharmaceutical industry for the determination of trace elements in pharmaceuticals.

The subject of the analysis of various elements, including metals and metalloids, in the pharmaceutical industry has seen increasing importance in the last 10-15 years, as modern analytical instrumentation has afforded analysts with the opportunity to provide element-specific, accurate and meaningful information related to pharmaceutical products. Armed with toxicological data, compendial and regulatory agencies have revisited traditional approaches to the testing of pharmaceuticals for metals and metalloids, and analysts have begun to employ the techniques of atomic spectroscopy, such as flame- and graphite furnace atomic absorption spectroscopy (FAAS, Flame AA or FAA and GFAAS), inductively coupled plasma-atomic emission spectroscopy (ICP-AES) and inductively coupled plasma-mass spectrometry (ICP-MS), to meet their analytical needs. Newer techniques, such as laser-induced breakdown spectroscopy (LIBS) and Laser Ablation ICP-MS (LAICP-MS) are also beginning to see wider applications in the analysis of elements in the pharmaceutical industry.

The use of inductively coupled plasma-atomic emission spectroscopy (ICP-AES) in the determination of lithium in cleaning validation swabs.

The pharmaceutical industry is required to perform cleaning validation studies to verify that equipment used in the manufacture of pharmaceuticals is adequately cleaned from one product or process to the next. Typically, these cleaning validation studies require an analytical method that uses some form of chromatographic technique. In the case of products that may have an inorganic constituent, however, if can often be easier to verify the cleanliness of equipment by using a non-chromatographic technique.

A rapid ICP-MS screen for heavy metals in pharmaceutical compounds.

A robust general inductively coupled plasma-mass spectrometry (ICP-MS) based method was developed as an alternative to the wet chemical heavy metals test prescribed in the United States Pharmacopoeia (USP), British Pharmacopoeia (BP), Japanese Pharmacopoeia (JP) and European Pharmacopoeia (EP). The described method provides specific detection and quantitation for each of the elements expected to give rise to a positive response in the compendial methods: arsenic (As), selenium (Se), cadmium (Cd), indium (In), tin (Sn), antimony (Sb), lead (Pb), bismuth (Bi), silver (Ag), palladium (Pd), platinum (Pt), mercury (Hg), molybdenum (Mo) and ruthenium (Ru). The subjectiveness of the visual based semi-quantitative comparison that is performed in the compendial methods is eliminated through the utilization of the ICP-MS.