Module 3 - Strategic case studies in practice

ICH H ARMONISED G UIDELINE G UIDELINE FOR E LEMENTAL IMPURITIES Q3D(R1) ICH Consensus Guideline T ABLE OF C ONTENTS

1. INTRODUCTION ..................................................................................................................2 2. SCOPE.....................................................................................................................................2 3. SAFETYASSESSMENT OF POTENTIAL ELEMENTAL IMPURITIES......................3 3.1 Principles of the Safety Assessment of Elemental Impurities for Oral, Parenteral and Inhalation Routes of Administration .........................................................................................3 3.2 Other Routes of Administration................................................................................................4 3.3 Justification for Elemental Impurity Levels Higher than an Established PDE.........................4 3.4 Parenteral Products...................................................................................................................5 4. ELEMENT CLASSIFICATION ...........................................................................................5 5. RISK ASSESSMENTAND CONTROL OF ELEMENTAL IMPURITIES .....................6 5.1 General Principles ....................................................................................................................6 5.2 Potential Sources of Elemental Impurities ...............................................................................7 5.3 Identification of Potential Elemental Impurities.......................................................................8 5.4 Recommendations for Elements to be Considered in the Risk Assessment .............................9 5.5 Evaluation...............................................................................................................................10 5.6 Summary of Risk Assessment Process ...................................................................................10 5.7 Special Considerations for Biotechnologically-Derived Products ......................................... 11 6. C ONTROL OF E LEMENTAL I MPURITIES ............................................................................... 11 7. C ONVERTING B ETWEEN PDE S AND C ONCENTRATION L IMITS ..........................................12 8. SPECIATION AND OTHER CONSIDERATIONS..........................................................14 9. ANALYTICAL PROCEDURES .........................................................................................14 10. LIFECYCLE MANAGEMENT..........................................................................................14 GLOSSARY .....................................................................................................................................16 REFERENCES ................................................................................................................................21 APPENDIX 1: METHOD FOR ESTABLISHING EXPOSURE LIMITS.................................22 APPENDIX 2: ESTABLISHED PDES FOR ELEMENTAL IMPURITIES..............................25 APPENDIX 3: INDIVIDUAL SAFETYASSESSMENTS...........................................................27 APPENDIX 4: ILLUSTRATIVE EXAMPLES ............................................................................76

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