共用施設における異なる医薬 ... - Welcome to ISPE

1 Page 1 / 10 EU-GMP PDE EMA ispe Containment COP ispe (ADE) 2012 12 13 EMA/CHMP/CVMP/SWP/169430/2012 Committee for medicinal products for human use (CHMP) Committee for medicinal products for veterinary use (CVMP) Safety Working Party ( ) 2012 12 CVMP 2012 11 CHMP 2012 12 13 2013 1 8 2013 6 30 Page 2 / 10.

2 3 .. 3 2.. 3 3 .. 4 4 .. 4 .. 6 .. 6 .. 6 .. 7 .. 7 .. 7 .. 8 .. 8 .. 8 Annex .. 9 Page 3 / 10 PDE TTC

3 1/1000 10ppm GMP 3 5 GMP 2. Page 4 / 10 3 EudraLex Volume 4 Good manufacturing practice (GMP) 3 5 GMP 3 5 Dedicated Facilities EMA/INS/GMP/809387/2009 Note for Guidance on Impurities.

4 Residual Solvents (CPMP/ICH/283/95, CPMP/ICH/1507/02, CPMP/ICH/1940/00 corr, CPMP/QWP/450/03, EMEA/CVMP/511/03 and CPMP/QWP/8567/99) VICH GL18 R Impurities Residual solvents in new veterinary medicinal products, active substances and excipients (EMA/CVMP/VICH/502 ) Guideline on the Limits of Genotoxic Impurities EMEA/CHMP/QWP/251344/2006 CPMP/SWP/5199/02 4 ICH Q3C R4 Appendix 3 Impurities: Guideline for Residual Solvents VICH GL 18 Appendix 3 PDE PDE PDE i ii iii NOEL iv ICH Q3C VICH GL 18 Appendix 3 PDE Page 5 / 10 PDE = NOEL x F1 x F2 x F3 x F4 x F5 PDE PDE PDE

5 VICH GL 18 PDE PDE mg/kg 1 1 NOEL in vitro in vivo NOEL(s)

6 NOEL NOEL NOEL PDE NOEL LOEL NOEL 1 mg/kg 50kg mg/kg 1kg Page 6 / 10 PDE NOEL F1 F5 F1 2 12 F2 10 F3 10 F4 1-10 F5 LOEL 10 F1 F4 ICH Q3C (R4)

7 VICH GL 18 Appendix PDE F2 F5 PDE PDE 1 PDE PDE PDE PDE >40% Page 7 / 10 100 PDE / 100% PDE EMA TTC g/ / TTC

8 100,000 1 1 106 g/ / g/ kg PDE PDE PDE GMP

9 Page 8 / 10 PDE NOEL LOEL PDE NOEL NOEL in vitro in vivo PDE NOAEL PDE PDE

10 PDE GMP Annex Page 9 / 10 F GMP Good Manufacturing Practice ICH International Conference on Harmonisation EU LOEL Lowest Observed Effect Level PDE Permitted Daily Exposure NOAEL No Observed Adverse Effect Level NOEL No Observed Effect Level TTC Threshold of Toxicological Concern VICH Veterinary International Conference on Harmonisation EU Annex PDE PDE Page 10 / 10 PDE