CACGL 46 2003 Guideline for the Conduct of Food Sa

-1-GUIDELINEFORTHECONDUCTOFFOODSAFETYASSESSMENTOFFOODSPRODUCEDUSINGRECOMBINANT-DNAMICROORGANISMSCAC/GL46-2003SECTION1–SCOPE1.ThisGuidelinesupportsthePrinciplesfortheRiskAnalysisofFoodsDerivedfromModernBiotechnologyandaddressessafetyandnutritionalaspectsoffoodsproducedthroughtheactionsofrecombinant-DNAmicroorganisms.1Therecombinant-DNAmicroorganismsthatareusedtoproducethesefoodsaretypicallyderivedusingthetechniquesofmodernbiotechnologyfromstrainsthathaveahistoryofsafe,purposefuluseinfoodproduction.However,ininstanceswheretherecipientstrainsdonothaveahistoryofsafeusetheirsafetywillhavetobeestablished.2Suchfoodandfoodingredientsmaycontainviableornon-viablerecombinant-DNAmicroorganismsormaybeproducedbyfermentationusingrecombinant-DNAmicroorganismsfromwhichtherecombinant-DNAmicroorganismsmayhavebeenremoved.2.Recognizingthatthefollowingissuesmayhavetobeaddressedbyotherbodiesorotherinstruments,thisdocumentdoesnotaddress:•safetyofmicroorganismsusedinagriculture(forplantprotection,biofertilizers,inanimalfeedorfoodderivedfromanimalsfedthefeedetc.);•risksrelatedtoenvironmentalreleasesofrecombinant-DNAmicroorganismsusedinfoodproduction;•safetyofsubstancesproducedbymicroorganismsthatareusedasadditivesorprocessingaids,includingenzymesforuseinfoodproduction3;•specificpurportedhealthbenefitsorprobioticeffectsthatmaybeattributedtotheuseofmicroorganismsinfood;or•issuesrelatingtothesafetyoffoodproductionworkershandlingrecombinant-DNAmicroorganisms.3.Avarietyofmicroorganismsusedinfoodproductionhavealonghistoryofsafeusethatpredatesscientificassessment.Fewmicroorganismshavebeenassessedscientificallyinamannerthatwouldfullycharacterizeallpotentialrisksassociatedwiththefoodtheyareusedtoproduce,including,insomeinstances,theconsumptionofviablemicroorganisms.Furthermore,theCodexprinciplesofriskanalysis,particularlythoseforriskassessment,areprimarilyintendedtoapplytodiscretechemicalentitiessuchasfoodadditivesandpesticideresidues,orspecificchemicalormicrobialcontaminantsthathaveidentifiablehazardsandrisks;theywerenotoriginallyintendedtoapplytointentionalusesofmicroorganismsinfoodprocessingorinthefoodstransformedbymicrobialfermentations.Thesafetyassessmentsthathavebeenconductedhavefocusedprimarilyontheabsenceofpropertiesassociatedwithpathogenicityinthesemicroorganismsandtheabsenceofreportsofadverseeventsattributedtoingestionofthesemicroorganisms,ratherthanevaluatingtheresultsofprescribedstudies.Further,manyfoodscontainsubstancesthatwouldbeconsideredharmfulifsubjectedtoconventionalapproachestosafetytesting.Thus,amorefocusedapproachisrequiredwherethesafetyofawholefoodisbeingconsidered.4.Informationconsideredindevelopingthisapproachincludes:A)usesoflivingmicroorganismsinfoodproduction;B)considerationofthetypesofgeneticmodificationslikelytohavebeenmadeintheseorganisms;C)thetypesofmethodologiesavailableforperformingasafetyassessment;andD)issuesspecifictotheuseoftherecombinant-DNAmicroorganisminfoodproduction,includingitsgeneticstability,potentialforgenetransfer,colonizationofthegastrointestinaltractandpersistence4therein,1Themicroorganismsincludedintheseapplicationsarebacteria,yeasts,andfilamentousfungi.(Suchusescouldinclude,butarenotlimitedto,productionofyogurt,cheese,fermentedsausages,natto,kimchi,bread,beer,andwine.)2Thecriterionforestablishingthesafetyofmicroorganismsusedintheproductionoffoodswherethereisnohistoryofsafeuseisbeyondthescopeofthecurrentdocument.3TheJointFAO/WHOExpertCommitteeonFoodAdditives(JECFA)isrevisingguidelinesforGeneralSpecificationsandConsiderationsforEnzymePreparationsusedinfoodprocessing.Theseguidelineshavebeenusedtoevaluateenzymepreparationsderivedfromgeneticallymodifiedmicroorganisms.4Persistenceconnotessurvivalofmicroorganismsinthegastrointestinaltractlongerthantwointestinaltransittimes(InternationalLifeScienceInstitute,Thesafetyassessmentofviablegeneticallymodifiedmicroorganismsusedasfood,1999,Brussels;theJointFAO/WHOExpertConsultationonFoodsDerivedfromBiotechnology-Safetyassessmentoffoodsderivedfromgeneticallymodifiedmicroorganisms,24-28September,2001,Geneva,Switzerland).-2-interactionsthattherecombinant-DNAmicroorganismmayhavewiththegastrointestinalfloraorthemammalianhost,andanyimpactoftherecombinant-DNAmicroorganismontheimmunesystem.5.Thisapproachisbasedontheprinciplethatthesafetyoffoodsproducedusingrecombinant-DNAmicroorganismsisassessedrelativetotheconventionalcounterpartsthathaveahistoryofsafeuse,notonlyforthefoodproducedusingarecombinant-DNAmicroorganism,butalsoforthemicroorganismitself.Thisapproachtakesbothintendedandunintendedeffectsintoaccount.Ratherthantryingtoidentifyeveryhazardassociatedwithaparticularfoodorthemicroorganism,theintentionistoidentifyneworalteredhazardsrelativetotheconventionalcounterpart.6.ThissafetyassessmentapproachfallswithintheriskassessmentframeworkasdiscussedinSection3ofthePrinciplesfortheRiskAnalysisofFoodsDerivedfromModernBiotechnology.Ifaneworalteredhazard,nutritionalorotherfoodsafetyconcernisidentifiedbythesafetyassessment,theriskassociatedwithitwouldfirstbeassessedtodeterm