commiss decis septemb guidanc note risk assess outlin annex iii direct eec contain genet modifi micro organ notifi document number text eea relev ec commiss european commun regard treati establish european commun regard council direct eec contain genet modifi micro organ amend council direct ec articl paragraph thereof articl direct user requir carri assess contain genet modifi micro organ gmm minimum principl set annex iii supplement guidanc note annex iii requir guidanc note develop commiss accord procedur set articl measur provid decis accord opinion committe establish articl direct eec adopt decis articl assess contain genet modifi micro organ made articl direct eec annex guidanc note risk assess supplement annex iii direct articl decis address member state brussel septemb commiss margot wallström member commiss oj oj annex guidanc note risk assess outlin annex iii council direct eec contain genet modifi micro organ introduct element risk assess outlin point annex iii requir consider potenti harm effect human health environ potenti harm effect defin effect give rise diseas render prophylaxi treatment ineffect promot establish dissemin environ rise harm effect organ natur popul present harm effect aris gene transfer organ assess requir risk potenti harm effect consid activ alloc class defin articl take account natur scale oper determin final contain facil requir degre risk aris contain genet modifi micro organ gmm construct determin consider sever potenti harm effect human health environ possibl effect occur risk assess consid exposur human environ gmm oper unintend releas contain facil classif level determin risk assess defin contain requir activ involv gmm accord annex iv risk assess full risk assess process consist procedur outlin procedur identifi potenti harm properti hazard gmm alloc gmm initi class class class take account sever potenti harm effect assess possibl harm effect occur consider exposur human environment take account natur scale work contain measur initi class alloc procedur determin final classif contain measur requir activ confirm final classif contain measur adequ revisit procedur procedur identif harm properti hazard gmm risk assess process requir identif potenti harm properti gmm result genet modif alter recipi organ exist properti potenti harm properti gmm determin consider recipi organ donor organ characterist locat insert genet materi vector import genet modif micro organ affect abil harm human health environ genet modif result decreas unchang increas abil harm aspect consid relev recipi organ natur pathogen virul infect allergen toxic vector diseas transmiss natur indigen vector adventiti agent mobilis insert genet materi frequenc mobilis natur stabil disabl mutat prior genet modif host rang relev signific physiolog trait alter final gmm relev stabil natur habitat geograph distribut signific involv environment process nitrogen fixat ph regul interact effect organ environ includ competit pathogen symbiot properti abil form surviv structur spore sclerotia donor organ fusion experi quot shotgun quot experi insert characteris natur pathogen virul infect toxic vector diseas transmiss natur indigen vector sequenc frequenc mobilis specif presenc gene confer resist anti microbi includ antibiot host rang relev physiolog trait insert specif ident function insert gene level express insert genet materi sourc genet materi ident donor organ characterist histori prior genet modif locat insert genet materi possibl insert activ deactiv host gene vector natur sourc vector structur amount vector donor nucleic acid remain final construct modifi micro organ present final gmm frequenc mobilis insert vector capabl transfer genet materi result gmm human health consider expect toxic allergen effect gmm metabol product comparison modifi micro organ recipi parent organ pathogen expect capac colonis micro organ pathogen human immunocompet diseas caus mechan transmiss includ invas virul infect dose alter rout infect tissu specif possibl surviv human host biolog stabil antibiot resist pattern allergen toxigen avail therapi prophylact measur environment consider ecosystem micro organ unintention releas contain expect surviv multipl extent dissemin modifi micro organ identifi ecosystem anticip result interact modifi micro organ organ micro organ expos case unintent releas environ predict effect plant anim pathogen toxic allergen vector pathogen alter antibiot resist pattern alter tropism host specif colonis predict involv biogeochem process initi classif gmm point annex iii stage risk assess process gmm identifi potenti harm properti gmm determin initi classif gmm achiev identif hazard recipi donor organ vector insert process aid take account gener characterist class set point annex iii date nation intern classif scheme includ direct eec amend thereof set contain protect measur annex iv refer set measur determin stringent contain control measur requir control identifi harm effect risk harm aris harm properti gmm obtain consider sever harm biolog properti disabl mutat limit possibl harm occur estim sever harm effect perform independ possibl harm effect occur sever harm determin result occur case instanc pathogen estim diseas assum suscept speci infect alloc gmm initi class includ consider sever classif scheme direct eec sever account scheme base human health environment consider care ensur sever harm effect human health environ gmm fulli consid assess possibl harm effect occur kei factor affect possibl harm event occur level natur exposur human environ gmm exposur case primari import risk assess determin harm effect occur possibl human environ expos gmm depend oper carri scale oper contain measur initi classif determin point appli work point ii iii annex iii requir characterist oper account make final classif select control measur natur scale activ consid order estim possibl exposur human environ affect choic risk manag procedur characterist oper affect risk assess account includ actual activ undertaken work practic scale contain measur appli assess account question dispos wast effluent safeti measur implement order protect human health environ natur activ undertaken degre risk applic control measur reduc risk gmm level influenc natur activ undertaken affect human environment exposur possibl harm occur natur activ determin tabl annex iv contain control measur consid practic laboratori scale work effect standard laboratori procedur exposur detail risk assess individu procedur requir highli hazard organ detail consider routin procedur procedur signific effect degre risk procedur gener aerosol concentr scale densiti cultur lead risk exposur high concentr gmm downstream process oper effect concentr possibl harm event occur consid scale factor account risk assess scale term absolut volum singl oper frequent repetit process give rise increas possibl exposur contain control measur fail affect possibl harm event occur larg scale necessarili high risk increas scale lead increas possibl exposur term number human amount environment exposur occur event contain failur scale influenc tabl annex iv contain control measur consid cultur condit contain activ cultur condit rigor contain protect work natur design growth vessel cultur equip influenc degre risk human health environ highli engin seal ferment vessel significantli reduc exposur risk gmm consider reliabl failur rate equip import failur lead high level exposur harm gmm loss forese addit contain measur requir standard oper procedur individu undertak work cultur gmm centrifug sonic signific impact effect contain measur emploi combin physic cultur condit act contain measur biolog chemic measur emploi protect work contribut significantli contain measur requir exampl biolog contain auxotroph mutant requir specif growth factor suppli grow exampl chemic contain measur disinfect solut maintain drainag system point annex iii requir characterist environ expos sever effect account assess possibl harm effect occur sever number aspect consider environ import extent natur environment exposur biota advers affect gmm area expos factor consid assess characterist receiv environ affect possibl potenti harm effect realis level risk select control measur environ expos environ expos case limit workplac environ area immedi surround facil depend specif characterist contain facil wider environ consid extent environment exposur influenc natur scale activ consider mode transmiss wider environ includ physic mode local drain watercours wast dispos air movement biolog vector movement infect anim insect presenc suscept speci possibl harm occur depend suscept speci includ human anim plant environ expos environ support surviv gmm extent gmm surviv persist environ strong consider risk assess possibl harm occur significantli reduc gmm surviv environ gain access effect physic environ addit direct harm effect gmm indirect harm effect significantli alter physico chemic properti ecolog balanc soil water compon environ consid procedur determin final classif contain measur potenti harm characterist review sever possibl occurr effect contain control measur initi classif recipi consid final classif contain measur gmm determin final classif contain measur initi classif revisit determin correct bear mind activ characterist oper propos comparison initi classif contain measur final class contain requir give rise result harm effect adequ account initi classif adequ contain provision contain consid procedur requir applic addit contain measur possibl revis classif activ initi classif correct attend contain measur adequ prevent minimis harm human health environ initi classif higher activ warrant lower classif attend contain condit confirm adequaci final contain measur propos final classif contain condit determin level human environment exposur reassess procedur confirm possibl harm effect occur take account natur scale work propos contain condit accept low risk assess process complet accord articl direct natur scale work significantli scientif technic knowledg risk assess longer adequ risk assess review light alter contain condit result review risk assess appli forthwith maintain adequ protect human health environ classif contain control measur identifi risk assess requir adequ gmm propos oper lead classif contain activ class contain controlmeasur class contain detail annex iv direct classif contain activ gmm defin administr requir uncertainti final classif contain condit advis contact compet author jo du