USP 88 生物实验.docx

USP 88 生物实验.docx

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USP88生物实验

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BIOLOGICALREACTIVITYTESTS,INVIVO

Thefollowingtestsaredesignedtodeterminethebiologicalresponseofanimalstoelastomerics,plastics,andotherpolymericmaterialwithdirectorindirectpatientcontact,orbytheinjectionofspecificextractspreparedfromthematerialundertest.Itisessentialtomakeavailablethespecificsurfaceareaforextraction.Whenthesurfaceareaofthespecimencannotbedetermined,usegofelastomerorgofplasticorothermaterialforeverymLofextractionfluid.Also,itisessentialtoexercisecareinthepreparationofthematerialstobeinjectedorinstilledtopreventcontaminationwithmicroorganismsandotherforeignmatter.Threetestsaredescribed.TheSystemicInjectionTestandtheIntracutaneousTestareusedforelastomericmaterials,especiallytoelastomericclosuresforwhichtheappropriateBiologicalReactivityTests,InVitro

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haveindicatedsignificantbiologicalreactivity.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

mL/animal

ateachof10or6sites

B（IC）

x

x

x

x

x

ExtractofSamplein1in20SolutionofAlcoholinSodiumChlorideInjection

Mouse

50mL/kg

A（IP）

x

x

x

x

x

RabbitorGuineaPig

mL/animal

ateachof10or6sites

B（IC）

x

x

x

ExtractofSampleinPolyethyleneGlycol400

Mouse

10g/kg

A（IP）

x

x

RabbitorGuineaPig

mL/animal

ateachof10or6sites

B（IC）

x

x

x

x

ExtractofSampleinVegetableOil

Mouse

50mL/kg

A（IP）

x

x

x

RabbitorGuineaPig

mL/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.,IV-121

whichrepresentsaclassIVplasticextractedat121

orI-50

whichrepresentsaclassIplasticextractedat50

）.

PlasticsmaybeclassifiedasUSPPlasticClassesI–VIonlyonthebasisoftheresponsecriteriaprescribedinTable1.

Thisclassificationdoesnotapplytoplasticsthatareintendedforuseascontainersfororalortopicalproducts,orthatmaybeusedasanintegralpartofadrugformulation.Table1doesnotapplytonaturalelastomers,whicharetobetestedinSodiumChlorideInjectionandvegetableoilsonly.

TheSystemicInjectionTestandtheIntracutaneousTestaredesignedtodeterminethesystemicandlocal,respectively,biologicalresponsesofanimalstoplasticsandotherpolymersbythesingle-doseinjecti