preclinical safety evaluation of biotechnology-deriveds6生物技术衍生临床前安全性评价.pdfVIP

PRECLINICALSAFETYEVALUATIONOF

BIOTECHNOLOGY-DERIVEDPHARMACEUTICALS

ICHHarmonisedTripartiteGuideline

HavingreachedStep4oftheICHProcessattheICHSteeringCommitteemeetingon

16July1997,thisguidelineisrecommendedforadoption

tothethreeregulatorypartiestoICH

TABLEOFCONTENTS

1.Introduction1

1.2Objectives1

1.3Scope1

2.Specificationofthetestmaterial2

3.Preclinicalsafetytesting2

3.1Generalpriples2

3.2Biologicalactivity/pharmacodynamics3

3.3Animalspecies/modelselection3

3.4Number/genderofanimals4

3.5Administration/doseselection4

3.6Immunogenicity5

4.Specificconsiderations6

4.1Safetypharmacology6

4.2Exposureassessment6

4.2.1Pharmacokicsandtoxicokics6

4.2.2Assays6

4.2.3Metabolism7

4.3Singledosetoxicitystudies7

4.4Repeateddosetoxicitystudies7

4.5Immunotoxicitystudies7

4.6Reproductiveperformanceanddevelopmentaltoxicitystudies8

4.7Genotoxicitystudies8

4.8Carcinogenicitystudies8

4.9Localtolerancestudies9

Notes9

i

PRECLINICALSAFETYEVALUATIONOF

BIOTECHNOLOGY-DERIVEDPHARMACEUTICALS

1.INTRODUCTION

1.1Background

Biotechnology-derivedpharmaceuticals(biopharmaceuticals)wereinitiallydeveloped

intheearly1980s.Thefirstmarketingauthorisationsweregrantedlaterinthe

decade.Severalguidelinesandpoints-to-consider