24/7 BIOPHARMA - issue 1 / October 2024

ALMAC SCIENCE

Requirements of Pharmaceuticals for Human Use Elemental Impurities – Scientific Guideline, ICH Q3D , Expert Working Group, established Permitted Daily Exposure (PDE) limits for different routes of administration. This categorised the individual elements into different classifications based on their toxicity (PDE) and likelihood of occurrence in the drug product. must be assessed appropriately following the Elemental Impurities monograph <2.66> by analysing with Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES/OES) or Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Therefore, tests such as heavy metals and element specific monographs have become redundant as the Elemental Impurities monograph covers this requirement. This update brings the JP in line with the USP. These new guidelines also require technologies with the capability to reach very low levels in complex matrices with a high degree of accuracy. ICP-MS or ICP-AES are the only permissible detection techniques that can achieve this and comply with the new USP guidance. The EP currently still allows alternative measurement techniques for individual elements, like X-ray fluorescence spectrometry and UV-Vis, as well as ICP-MS or ICP-AES. The British Pharmacopeia (BP) still follows EP even after its departure from the European Union. It is unclear how long that will remain the case. According to the EP Harmonisation status for general texts, elaboration on elemental impurities between the EP and USP is ongoing. It is expected that the EP and BP will soon align themselves with ICH Q3D, the USP and the JP requirements for elemental impurities analysis. The 2024 update includes a new general notice, General Notice 34, which states that drug products

In the meantime, they remain unaligned – causing issues for pharmaceutical companies all over the globe. Until the regulations are harmonised globally, determining all elemental impurities by ICP-MS, a method which has been developed and validated in-line with all the above pharmacopoeias, is the only future-proof solution. ICP-MS allows analysis of multiple elements in one method allowing for a quicker turnaround time, high sample throughput and less preparation time. With ICP-MS all these elements can be detected in a single method with high accuracy and precision, as well as high sensitivity. This allows for complete compliance across all regulations without the need to revalidate. The days of the wet chemistry colorimetric methods are long gone and the onus is on pharmaceutical companies to provide evidence that the drug product is safe from metal impurities.

AMANDA BOLE Senior Analytical Chemist Spectroscopy Team Almac Sciences