Evaluation of Medical Equipment/Implant Materials
Analysis of Metallic Impurities and Residual Catalysts in Medical Products (ICH Q3D Guideline)
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Analysis of medical products for Elemental Impurities Guideline (ICH Q3D).
Analysis of Metallic Impurities of Medical Products
- For analysis of harmful metals in medical products, as of October 2014, the 16th revision of the Japanese Pharmacopoeia provided test methods for arsenic and heavy metals. Because these test methods are visual color tests, there are issues concerning their sensitivity and specificity.
- To address these issues, in the United States, the United States Pharmacopoeia (USP), USP 232 provides object metallic elements for assessment in medical products and their allowable values, and also provides ICP atomic emission spectrometry (ICP-AES) and ICP mass spectrometry (ICP-MS) as analytic methods for those elements.
- The Guideline prepared in the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH; Japan, United States, Europe) has also adopted the provisions of the USP, and it is thought that ICP-AES and ICP-MS will be adopted for analysis of metallic impurities of medical products in the Japanese Pharmacopoeia in the future. (The 16th Revision of the Japanese Pharmacopoeia added ICP-AES and ICP-MS as general test methods in Appendix 1.)
Evaluation Procedure, Object Elements and Allowable Values
- Allowable values (maximum allowable concentration) are calculated by using PDE (Permitted Daily Exposure) values, which are set separately for oral formulations, injections and inhalants.
Evaluation Procedure for Metallic Elements in Pharmaceuticals
- Risk assessment (Selection of object elements for evaluation)
- Selection of evaluation method (Calculation of maximum allowable concentration (µg/g))
- (1)Calculation of allowable concentration for each formulation component
→ Evaluation of formulation components and final product
a) Case of daily intake of 10 g or less
b) Case in which daily intake has been determined. - (2)Calculation of allowable concentration of final product
→ Evaluation of final product - Quantitative analysis by ICP-AES/ICP-MS
- Evaluation by comparison with maximum allowable value
PDE Values of Metallic Impurities
| Class | PDE: Oral formulation | PDE: Injection | PDE: Inhalant | |
|---|---|---|---|---|
| (µg/day) | (µg/day) | (µg/day) | ||
| As | 1 | 15 | 15 | 1.9 |
| Cd | 5.0 | 6 | 3.4 | |
| Hg | 40 | 4 | 1.2 | |
| Pb | 5.0 | 5 | 5.0 | |
| Co | 2A | 50 | 5 | 2.9 |
| Mo | 180 | 180 | 7.6 | |
| Se | 170 | 85 | 140 | |
| V | 120 | 12 | 1.2 | |
| Ag | 2B | 170 | 35 | 6.9 |
| Au | 130 | 130 | 1.3 | |
| Ir | 1000 | 10 | 1.4 | |
| Os | 1000 | 10 | 1.4 | |
| Pd | 100 | 10 | 1.0 | |
| Pt | 1000 | 10 | 1.4 | |
| Rh | 1000 | 10 | 1.4 | |
| Ru | 1000 | 10 | 1.4 | |
| Tl | 8.0 | 8.0 | 69 | |
| Ba | 3 | 13000 | 1300 | 340 |
| Crt | 11000 | 1100 | 2.9 | |
| Cu | 1300 | 130 | 13 | |
| Li | 780 | 390 | 25 | |
| Ni | 600 | 60 | 6.0 | |
| Sb | 1200 | 600 | 22 | |
| Sn | 6400 | 640 | 64 |
