Is Your Pharmaceutical Laboratory Ready for the ICH Guideline on 'Control of Elemental Impurities'?

Elemental Impurity Limits in ICH Q3D Step 4 Guidance Titled "Elemental Impurities" and USP <232> Section define permitted daily exposure (PDE) values for oral, parenteral and inhaler drugs. The 24 heavy metals in question are classified into Class-1 (Cd, Pb, As and Hg), Class-2A (V, Co and Ni), Class-2B (Tl, Au, Pd, Ir, Os, Rh, Ru, Se, Ag and Pt) and Class-3 (Li, Sb, Ba, Mo, Cu, Sn and Cr) categories based on their associated risk. The deadline for implementation of the guidance was set as 1 January 2018. In India, which is home to one of the world's largest centres for API manufacturing, most producers have completed their in-house test preparation by establishing ICP-MS systems according to USP <232>. Although ICP-MS technology is an extremely sensitive technique, it has certain disadvantages such as a cumbersome sample preparation phase, high consumable costs and qualified labour expenses. Equipment investment costs are high. Trained chemists are required for sample preparation and analysis. The pharmaceutical industry continuously conducts studies on new products; this means the daily number of samples is increasing day by day, and as the number of samples increases, testing of incoming raw materials, materials used in the production process and new products by ICP-MS becomes more challenging. Due to these challenges, USP has published the X-Ray Fluorescence Spectrometry section (USP <735>) for the analysis of the heavy metals in question. Shimadzu Corporation, a leading supplier of analytical instruments to the pharmaceutical industry, drawing on its experience in pharmaceutical applications, is offering to the sector the EDX-7000 instrument using X-Ray Fluorescence Spectrometry technology, which came into force with USP <735>, in addition to the ICPMS-2030 instrument used for the analysis of elemental impurities. The greatest benefit of this technique is that it enables analysis without, for example, the requirement for chemical pre-preparation.

Key Features of EDX-7000:

EDX-7000 is a desktop instrument that requires no additional equipment. Solid and liquid samples can be placed in the instrument without any sample preparation phase; it is easy to use and up to 12 samples can be loaded simultaneously. After loading the samples into the instrument, the user can attend to other tasks. The instrument cost is lower than ICP-MS. Sensitivity is generally 1 ppm and above. At the same time, Shimadzu has developed a customized calibration package that eliminates matrix effects and provides the best sensitivity and accuracy. XRF has the capacity to measure a wide range of elements from ppm to percentage concentration levels. EDX-7000 can test all elements from Na (11) to U (92). Therefore, it can be used to analyze elements such as Fe, Na, K with high accuracy. The software of the EDX-7000 instrument, Lab-Solution, is 21 CFR compliant. Energy dispersive X-ray fluorescence spectrometers enable qualitative and quantitative analysis of elements present in a sample through the detection of fluorescent X-rays emitted from a sample exposed to X-rays. These instruments have numerous different applications ranging from pharmaceutical raw material analysis to compliance analysis with legal regulations such as the European Union's RoHS Directive, and to material analysis for environmental and research purposes. Zafer Bayram / Senior Chemical Engineer / Pharmaceutical Group Manager / ANT Teknik Cihazlar Ltd. Sti.