EMEA关于金属催化剂或金属试剂残留量限度规定的指导原则

European Medicines Agency

7 Westferry Circus, Canary Wharf, London, E14 4HB, UK London, 21 February 2008

Doc. Ref. EMEA/CHMP/SWP/4446/2000 COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE

(CHMP)

GUIDELINE ON THE SPECIFICATION LIMITS FOR RESIDUES OF METAL

CATALYSTS OR METAL REAGENTS

DRAFT AGREED BY THE SAFETY WORKING PARTY June 1998 -November

2000 ADOPTION BY CHMP FOR RELEASE FOR CONSULTATION January 2001 END OF CONSULTATION (DEADLINE FOR COMMENTS) July 2001 DISCUSSION IN THE SWP October 2001 – June

2002 ADOPTION BY CHMP FOR RE- RELEASE FOR

CONSULTATION

June 2002

DISCUSSION IN THE SWP February 2003 –

December 2006

ADOPTION BY CHMP FOR RE- RELEASE FOR

CONSULTATION

January 2007 END OF CONSULTATION (DEADLINE FOR COMMENTS) 23rd May 2007 DRAFT AGREED BY THE SAFETY WORKING PARTY December 2007 ADOPTION BY CHMP 21 February 2008 DATE FOR COMING INTO EFFECT 01 September 2008

KEYWORDS metal catalysts, classification, concentration limits of metals, drug substance, excipients, PDE, administration routes, testing strategies, reporting levels

GUIDELINE ON THE SPECIFICATION LIMITS FOR RESIDUES OF METAL

CATALYSTS OR METAL REAGENTS

TABLE OF CONTENTS

EXECUTIVE SUMMARY (3)

1.INTRODUCTION (BACKGROUND) (3)

2.DEFINITION AND SCOPE (4)

3.LEGAL BASIS (4)

4.MAIN GUIDELINE TEXT (5)

4.1C LASSIFICATION (5)

4.2E XPOSURE L IMITS (5)

4.3S ETTING C ONCENTRATION L IMITS M ETAL R ESIDUES (6)

4.3.1General (6)

4.3.2Pharmaceutical products applied via the oral, parenteral or inhalation route of

administration (6)

4.3.3Pharmaceutical products applied via other routes of administration (7)

4.3.4Pharmaceutical products used for short-term and for life-saving indications (7)

4.4A NALYTICAL P ROCEDURES (7)

4.5B ATCH R ESULTS, T ESTING F REQUENCY AND D ELETING OF A T EST FROM THE

S PECIFICATION (8)

4.6R EPORTING L EVELS OF M ETALLIC RESIDUES (8)

5.GLOSSARY (9)

6.REFERENCES (SCIENTIFIC AND / OR LEGAL) (11)

APPENDIX 1:RATIONALE FOR PDE SETTING (12)

APPENDIX 2:MONOGRAPHS ON ELEMENTS (14)

PLATINUM (P T) (14)

PALLADIUM (P D) (16)

IRIDIUM (I R) (18)

RHODIUM (R H) (18)

RUTHENIUM (R U) (19)

OSMIUM (O S) (20)

MOLYBDENUM (M O) (20)

NICKEL (N I) (22)

CHROMIUM (C R) (23)

VANADIUM (V) (26)

COPPER (C U) (27)

MANGANESE (M N) (28)

ZINC (Z N) (30)

IRON (F E) (31)

APPENDIX 3:EXAMPLE CALCULATIONS FOR CONCENTRATION LIMITS (33)