USP88生物实验.docx

USP88生物实验.docx

《USP88生物实验.docx》由会员分享，可在线阅读，更多相关《USP88生物实验.docx（12页珍藏版）》请在冰豆网上搜索。

USP88生物实验

88BIOLOGICALREACTIVITYTESTS,INVIVO

Thefollowingtestsaredesignedtodeterminethebiologicalresponseofanimalstoelastomerics,plastics,andotherpolymericmaterialwithdirectorindirectpatientcontact,orbytheinjectionofspecificextractspreparedfromthematerialundertest.Itisessentialtomakeavailablethespecificsurfaceareaforextraction.Whenthesurfaceareaofthespecimencannotbedetermined,use0.1gofelastomeror0.2gofplasticorothermaterialforeverymLofextractionfluid.Also,itisessentialtoexercisecareinthepreparationofthematerialstobeinjectedorinstilledtopreventcontaminationwithmicroorganismsandotherforeignmatter.Threetestsaredescribed.TheSystemicInjectionTestandtheIntracutaneousTestareusedforelastomericmaterials,especiallytoelastomericclosuresforwhichtheappropriateBiologicalReactivityTests,InVitro87haveindicatedsignificantbiologicalreactivity.Thesetwotestsareusedforplasticsandotherpolymers,inadditiontoathirdtest,theImplantationTest,totestthesuitabilityofthesematerialsintendedforuseinfabricatingcontainersandaccessoriesthereto,foruseinparenteralpreparations,andforuseinmedicaldevices,implants,andothersystems.

Thesethreetestsareappliedtomaterialsormedicaldevices,ifthereisaneedforclassificationofplasticsandotherpolymersbasedoninvivobiologicalreactivitytesting.

Forthepurposeofthischapter,thesedefinitionsapply:

theSampleisthespecimenundertestoranextractpreparedfromsuchaspecimen.ABlankconsistsofthesamequantityofthesameextractingmediumthatisusedfortheextractionofthespecimenundertest,treatedinthesamemannerastheextractingmediumcontainingthespecimenundertest.ANegativeControl1isaspecimenthatgivesnoreactionundertheconditionsofthetest.

CLASSIFICATIONOFPLASTICS

SixPlasticClassesaredefined（seeTable1）.Thisclassificationisbasedonresponsestoaseriesofinvivotestsforwhichextracts,materials,androutesofadministrationarespecified.Thesetestsaredirectlyrelatedtotheintendedend-useoftheplasticarticles.Thechoiceofextractantsisrepresentativeofthevehiclesinpreparationswithwhichtheplasticsarelikelytobeincontact.TheTable1classificationfacilitatescommunicationamongsuppliers,users,andmanufacturersofplasticsbysummarizingtheteststobeperformedforcontainersforinjectionsandmedicaldevicesifaneedforclassificationexists.

Table1.ClassificationofPlastics

PlasticClassesa

TeststobeConducted

I

II

III

IV

V

VI

TestMaterial

Animal

Dose

Procedureb

x

x

x

x

x

x

ExtractofSampleinSodiumChlorideInjection

Mouse

50mL/kg

A（IV）

x

x

x

x

x

x

RabbitorGuineaPig

0.2mL/animal

ateachof10or6sites

B（IC）

x

x

x

x

x

ExtractofSamplein1in20SolutionofAlcoholinSodiumChlorideInjection

Mouse

50mL/kg

A（IP）

x

x

x

x

x

RabbitorGuineaPig

0.2mL/animal

ateachof10or6sites

B（IC）

x

x

x

ExtractofSampleinPolyethyleneGlycol400

Mouse

10g/kg

A（IP）

x

x

RabbitorGuineaPig

0.2mL/animal

ateachof10or6sites

B（IC）

x

x

x

x

ExtractofSampleinVegetableOil

Mouse

50mL/kg

A（IP）

x

x

x

RabbitorGuineaPig

0.2mL/animal

ateachof10or6sites

B（IC）

x

x

ImplantstripsofSample

Rabbit

4strips/animal

C

x

x

ImplantSample

Rat

2Samples/animal

C

a Testsrequiredforeachclassareindicatedby“x”inappropriatecolumns.

b Legend:

A（IP）—SystemicInjectionTest（intraperitoneal）;B（IC）—IntracutaneousTest（intracutaneous）;C—ImplantationTest（intramuscularorsubcutaneousimplantation）.

WiththeexceptionoftheImplantationTest,theproceduresarebasedontheuseofextractsthat,dependingontheheatresistanceofthematerial,arepreparedatoneofthreestandardtemperatures:

50,70,and121.Therefore,theclassdesignationofaplasticmustbeaccompaniedbyanindicationofthetemperatureofextraction（e.g.,IV-121,whichrepresentsaclassIVplasticextractedat121,orI-50,whichrepresentsaclassIplasticextractedat50）.

PlasticsmaybeclassifiedasUSPPlasticClassesI–VIonlyonthebasisoftheresponsecriteriaprescribedinTable1.

Thisclassificationdoesnotapplytoplasticsthatareintendedforuseascontainersfororalortopicalproducts,orthatmaybeusedasanintegralpartofadrugformulation.Table1doesnotapplytonaturalelastomers,whicharetobetestedinSodiumChlorideInjectionandvegetableoilsonly.

TheSystemicInjectionTestandtheIntracutaneousTestaredesignedtodeterminethesystemicandlocal,respectively,biologicalresponsesofanimalstoplasticsandotherpolymersbythesingle-doseinj