direct ec european parliament council novemb commun code relat medicin product human european parliament council european union regard treati establish european commun articl thereof regard propos commiss regard opinion econom social committe act accord procedur laid articl treati council direct eec januari approxim provis laid law regul administr action relat medicin product council direct eec approxim law member state relat analyt pharmaco toxicolog clinic standard protocol respect test proprietari medicin product council direct eec approxim provis laid law regul administr action relat proprietari medicin product council direct eec extend scope direct eec eec lai addit provis immunolog medicin product consist vaccin toxin serum allergen council direct eec extend scope direct eec eec lai addit provis radiopharmaceut council direct eec june extend scope direct eec eec approxim provis laid law regul administr action relat medicin product lai special provis proprietari medicin product deriv human blood human plasma council direct eec march wholesal distribut medicin product human council direct eec march classif suppli medicin product human council direct eec march label medicin product human packag leaflet council direct eec march advertis medicin product human council direct eec septemb widen scope direct eec eec approxim provis laid law regul administr action relat medicin product lai addit provis homeopath medicin product frequent substanti amend interest clariti ration direct codifi assembl singl text essenti aim rule govern product distribut medicin product safeguard public health object attain mean hinder develop pharmaceut industri trade medicin product commun trade medicin product commun hinder dispar nation provis provis relat medicin product exclud substanc combin substanc food anim feed stuff toilet prepar dispar directli affect function intern market hindranc remov entail approxim relev provis order reduc dispar remain rule laid control medicin product duti incumb member state compet author view ensur complianc legal requir concept harm therapeut efficaci examin relat rel signific depend progress scientif knowledg medicin product intend particular document accompani applic market author medicin product demonstr potenti risk outweigh therapeut efficaci product standard protocol perform test trial medicin product effect mean control product protect public health facilit movement product lai uniform rule applic test trial compil dossier examin applic experi shown advis stipul precis case result toxicolog pharmacolog test clinic trial provid view obtain author medicin product essenti similar author product ensur innov firm disadvantag reason public polici conduct repetit test human anim ride adopt standard protocol member state enabl compet author arriv decis basi uniform test refer uniform criteria avoid differ evalu except medicin product subject central commun author procedur establish council regul eec juli lai commun procedur author supervis medicin product human veterinari establish european agenc evalu medicin product market author medicin product grant compet author member state recogn compet author member state ground suppos author medicin product concern present risk public health event disagr member state qualiti safeti efficaci medicin product scientif evalu matter undertaken commun standard lead singl decis area disagr bind member state concern decis adopt rapid procedur ensur close cooper commiss member state purpos committe proprietari medicin product set attach european agenc evalu medicin product establish abovement regul eec direct repres import step achiev object free movement medicin product measur abolish remain barrier free movement proprietari medicin product light experi gain abovement committe proprietari medicin product order protect public health avoid unnecessari duplic effort examin applic market author medicin product member state systemat prepar assess report respect medicin product author exchang report request member state suspend examin applic author place medicin product market activ consider member state view recogn decis reach member state establish intern market specif control guarante qualiti medicin product import countri waiv arrang made commun ensur control carri export countri adopt specif provis immunolog medicin product homeopath medicin product radiopharmaceut medicin product base human blood human plasma rule govern radiopharmaceut account provis council direct euratom septemb lai basic measur radiat protect person undergo medic examin treatment account council direct euratom juli amend direct lai basic safeti standard health protect gener public worker danger ioniz radiat object prevent exposur worker patient excess unnecessarili high level ioniz radiat articl thereof requir prior author addit radioact substanc medicin product import medicin product commun support effort council europ promot voluntari unpaid blood plasma donat attain suffici commun suppli blood product ensur respect ethic principl trade therapeut substanc human origin rule design guarante qualiti safeti efficaci medicin product deriv human blood human plasma appli manner public privat establish blood plasma import countri regard characterist homeopath medicin product low level activ principl difficulti appli convent statist method relat clinic trial desir provid special simplifi registr procedur homeopath medicin product market therapeut indic pharmaceut form dosag present risk patient anthroposoph medicin product offici pharmacopoeia prepar homeopath method treat registr market author homeopath medicin product desir instanc provid user homeopath medicin product clear indic homeopath charact suffici guarante qualiti safeti rule relat manufactur control inspect homeopath medicin product harmon permit circul commun medicin product safe good qualiti usual rule govern author market medicin product appli homeopath medicin product market therapeut indic form present risk balanc desir therapeut effect member state homeopath tradit appli rule evalu result test trial intend establish safeti efficaci medicin product provid notifi commiss order facilit movement medicin product prevent control carri member state repeat minimum requir laid manufactur import come countri grant author relat thereto ensur member state supervis control manufactur medicin product carri person fulfil minimum condit qualif author market immunolog medicin product deriv human blood human plasma grant manufactur demonstr abil attain batch batch consist author market medicin product deriv human blood human plasma grant manufactur demonstr absenc specif viral contamin extent state technolog permit condit govern suppli medicin product public harmon connect person move commun carri reason quantiti medicin product lawfulli obtain person person establish member state receiv member state reason quantiti medicin product intend person addit virtu regul ec medicin product subject commun market author context classif suppli medicin product cover commun market author establish import set criteria basi commun decis initi step harmon basic principl applic classif suppli medicin product commun member state concern take start point principl establish subject council europ work harmon complet framework unit nation narcot psychotrop substanc provis deal classif medicin product purpos suppli infring nation social secur arrang reimburs payment medicin product prescript oper involv wholesal distribut medicin product human cover member state simultan exercis control entir chain distribut medicin product manufactur import commun suppli public guarante product store transport handl suitabl condit requir adopt purpos consider facilit withdraw defect product market effect effort counterfeit product person involv wholesal distribut medicin product possess special author pharmacist person author suppli medicin product public confin activ exempt obtain author order control complet chain distribut medicin product pharmacist person author suppli medicin product public record show transact product receiv author subject essenti condit respons member state concern ensur condit met member state recogn author grant member state member state impos wholesal suppli medicin product pharmacist person author suppli medicin product public public servic oblig member state continu impos oblig wholesal establish territori impos wholesal member state condit impos oblig stringent impos wholesal provid oblig regard warrant ground public health protect proportion relat object protect rule laid label packag leaflet present provis govern inform suppli user provid high degre consum protect order medicin product correctli basi full comprehens inform market medicin product label packag leaflet compli direct prohibit imped ground connect label packag leaflet direct prejudic applic measur adopt pursuant council direct eec septemb relat approxim law regul administr provis member state mislead advertis member state adopt specif measur advertis medicin product dispar measur dispar impact function intern market advertis dissemin member state effect member state council direct eec octob coordin provis laid law regul administr action member state pursuit televis broadcast activ prohibit televis advertis medicin product medic prescript member state jurisdict televis broadcast locat principl made gener applic extend media advertis gener public prescript medicin product affect public health excess ill consid advertis medicin product gener public permit satisfi essenti criteria defin distribut sampl free charg gener public promot end prohibit advertis medicin product person qualifi prescrib suppli contribut inform person advertis subject strict condit effect monitor refer work carri framework council europ advertis medicin product subject effect adequ monitor refer regard made monitor mechan set direct eec medic sale repres import role promot medicin product oblig impos oblig suppli person visit summari product characterist person qualifi prescrib medicin product carri function object influenc direct indirect financi induc restrict condit provid sampl medicin product free charg person qualifi prescrib suppli familiar product acquir experi deal person qualifi prescrib suppli medicin product access neutral object sourc inform product market member state measur end light situat undertak manufactur import medicin product set mechan ensur inform suppli medicin product conform approv condit order ensur continu safeti medicin product ensur pharmacovigil system commun continu adapt account scientif technic progress account aris result intern harmonis definit terminolog technolog develop field pharmacovigil increas electron network commun inform advers reaction medicin product market commun intend compet author share inform time interest commun ensur pharmacovigil system central authoris medicin product authoris procedur consist holder market authoris proactiv respons pharmacovigil medicin product place market measur implement direct adopt accord council decis ec june lai procedur exercis implement power confer commiss commiss empow adopt annex order account scientif technic progress direct prejudic oblig member state time limit transposit direct set annex ii part adopt direct titl definit articl purpos direct term bear mean proprietari medicin product readi prepar medicin product market special special pack medicin product substanc combin substanc present treat prevent diseas human be substanc combin substanc administ human be view make medic diagnosi restor correct modifi physiolog function human be likewis consid medicin product substanc matter irrespect origin human human blood human blood product anim micro organ anim part organ anim secret toxin extract blood product veget micro organ plant part plant veget secret extract chemic element natur occur chemic materi chemic product obtain chemic chang synthesi immunolog medicin product medicin product consist vaccin toxin serum allergen product vaccin toxin serum cover agent produc activ immun cholera vaccin bcg polio vaccin smallpox vaccin ii agent diagnos state immun includ tuberculin tuberculin ppd toxin schick dick test brucellin iii agent produc passiv immun diphtheria antitoxin anti smallpox globulin antilymphocyt globulin quot allergen product quot medicin product intend identifi induc specif acquir alter immunolog respons allerg agent homeopath medicin product medicin product prepar product substanc composit call homeopath stock accord homeopath manufactur procedur european pharmacopoeia absenc thereof pharmacopoeia offici member state homeopath medicin product number principl radiopharmaceut medicin product readi radionuclid radioact isotop includ medicin purpos radionuclid gener system incorpor fix parent radionuclid produc daughter radionuclid obtain elut method radiopharmaceut radionuclid kit prepar reconsititut combin radionuclid final radiopharmaceut prior administr radionuclid precursor radionuclid produc radio label substanc prior administr medicin product deriv human blood human plasma medicin product base blood constitut prepar industri public privat establish medicin product includ albumin coagul factor immunoglobulin human origin advers reaction respons medicin product noxiou unintend occur dose man prophylaxi diagnosi therapi diseas restor correct modif physiolog function advers reaction advers reaction result death life threaten requir inpati hospitalis prolong exist hospitalis result persist signific disabl incapac congenit anomali birth defect unexpect advers reaction advers reaction natur sever outcom consist summari product characterist period safeti updat report period report record refer articl post authoris safeti studi pharmacoepidemiolog studi clinic trial carri accord term market authoris conduct aim identifi quantifi safeti hazard relat authoris medicin product abus medicin product persist sporad intent excess medicin product accompani harm physic psycholog effet wholesal distribut medicin product activ consist procur hold suppli export medicin product suppli medicin product public activ carri manufactur depositori import wholesal distributor pharmacist person author entitl suppli medicin product public member state concern public servic oblig oblig wholesal guarante perman adequ rang medicin product meet requir specif geograph area deliv suppli request short time area question medicin prescript medicin prescript issu profession person qualifi medicin product medicin product invent common scientif trade mark manufactur invent liabl confus common common intern proprietari recommend world health organ exist usual common strength medicin product content activ substanc express quantit dosag unit unit volum weight dosag form packag contain form packag immedi contact medicin product outer packag packag packag label inform outer packag packag leaflet leaflet inform user accompani medicin product agenc european agenc evalu medicin product establish regul eec risk public health risk regard qualiti safeti efficaci medicin product titl ii scope articl provis direct appli industri produc medicin product human intend market member state articl direct appli medicin product prepar pharmaci accord medic prescript individu patient commonli magistr formula medicin product prepar pharmaci accord prescript pharmacopoeia intend suppli directli patient serv pharmaci question commonli offici formula medicin product intend research develop trial intermedi product intend process author manufactur radionuclid form seal sourc blood plasma blood cell human origin articl direct derog commun rule radiat protect person undergo medic examin treatment commun rule lai basic safeti standard health protect gener public worker danger ioniz radiat direct prejudic council decis eec june accept behalf commun european agreement exchang therapeut substanc human origin provis direct affect power member state author set price medicin product inclus scope nation health insur scheme basi health econom social condit direct affect applic nation legisl prohibit restrict sale suppli medicin product contracept abortifaci member state commun nation legisl concern commiss articl member state accord legisl forc fulfil special exclud provis direct medicin product suppli respons bona fide unsolicit order formul accord specif author health care profession individu patient direct person respons titl iii place market chapter market author articl medicin product market member state market author issu compet author member state accord direct author grant accord regul eec authoris refer paragraph requir radionuclid gener radionuclid kit radionuclid precursor radiopharmaceut industri prepar radiopharmaceut articl market author requir radiopharmaceut prepar time person establish author nation legisl medicin product approv health care establish exclus author radionuclid gener radionuclid kit radionuclid precursor accord manufactur instruct articl order obtain author place medicin product market procedur establish regul eec applic made compet author member state concern market author grant applic establish commun applic accompani particular document submit accord annex corpor perman address applic applic manufactur medicin product qualit quantit particular constitu medicin product usual terminolog exclud empir chemic formula mention intern proprietari recommend world health organ exist descript manufactur method therapeut indic contra indic advers reaction posolog pharmaceut form method rout administr expect shelf life applic reason precautionari safeti measur storag medicin product administr patient dispos wast product indic potenti risk present medicin product environ descript control method emploi manufactur qualit quantit analysi constitu finish product special test steril test test presenc pyrogen substanc presenc heavi metal stabil test biolog toxic test control carri intermedi stage manufactur process result physico chemic biolog microbiolog test toxicolog pharmacolog test clinic trial summari accord articl product characterist specimen mock up outer packag packag medicin product packag leaflet document show manufactur authoris countri produc medicin product copi authoris obtain member state countri place medicin product market list member state applic authoris submit accord direct examin copi summari product characterist propos applic accord articl approv compet author member state accord articl copi packag leaflet propos accord articl approv compet author member state accord articl detail decis refus author commun countri reason decis inform updat regular basi articl addit requir set articl applic author market radionuclid gener inform particular gener descript system detail descript compon system affect composit qualiti daughter nucleid prepar qualit quantit particular eluat sublim articl derog articl prejudic law relat protect industri commerci properti applic requir provid result toxicolog pharmacolog test result clinic trial demonstr medicin product essenti similar medicin product author member state concern applic holder market author origin medicin product consent toxicolog pharmacolog clinic refer contain file origin medicin product purpos examin applic question ii constitu constitu medicin product establish medicin recogn efficaci accept level safeti mean detail scientif bibliographi iii medicin product essenti similar medicin product author commun accord commun provis forc year market member state applic made period extend year case high technolog medicin product authoris procedur laid articl council direct eec member state extend period year singl decis cover medicin product market territori consid interest public health member state liberti appli year period date expiri patent protect origin medicin product medicin product intend therapeut medicin product market administ rout dose result toxicolog pharmacolog test clinic trial provid case medicin product constitu hitherto combin therapeut purpos result toxicolog pharmacolog test clinic trial relat combin provid provid refer relat individu constitu annex appli analog pursuant point ii paragraph bibliograph refer publish data submit articl summari product characterist inform medicin product qualit quantit composit term activ substanc constitu excipi knowledg essenti proper administr medicin product usual common chemic descript pharmaceut form pharmacolog properti inform therapeut purpos pharmacokinet particular clinic particular therapeut indic contra indic advers reaction frequenc serious special precaut case immunolog medicin product special precaut person handl product administ patient precaut patient pregnanc lactat interact medica form interact posolog method administr adult children overdos symptom emerg procedur antidot special warn effect abil drive machin pharmaceut particular major incompat shelf life reconstitut medicin product packag open time special precaut storag natur content packag special precaut dispos unus medicin product wast materi deriv medicin product corpor perman address market author holder radiopharmaceut full detail intern radiat dosimetri radiopharmaceut addit detail instruct extemporan prepar qualiti control prepar maximum storag time intermedi prepar eluat readi pharmaceut conform specif articl member state measur ensur document particular list articl articl ii drawn expert technic profession qualif submit compet author document particular sign expert duti expert respect qualif perform task fall respect disciplin analysi pharmacolog similar experiment scienc clinic trial describ object result obtain qualit quantit describ observ accord annex state case analyst medicin product consist declar composit give substanti control method emploi manufactur case pharmacologist specialist similar experiment compet toxic medicin product pharmacolog properti observ case clinician ascertain effect person treat medicin product correspond particular applic accord articl patient toler medicin product posolog clinician advis contra indic advers reaction applic state ground bibliographi mention point ii articl detail report expert form part particular accompani applic applic submit compet author chapter specif provis applic homeopath medicin product articl member state ensur homeopath medicin product manufactur market commun regist author accord articl product cover registr author grant nation law decemb registr author renew date member state due account registr author previous grant member state member state refrain establish special simplifi registr procedur homeopath medicin product refer articl member state inform commiss member state concern territori homeopath medicin product regist member state accord articl articl homeopath medicin product satisfi condit subject special simplifi registr procedur administ oral extern specif therapeut indic appear label medicin product inform relat thereto suffici degre dilut guarante safeti medicin product medicin product part mother tinctur smallest dose allopathi regard activ substanc presenc allopath medicin product result oblig submit doctor prescript time registr member state determin classif dispens medicin product criteria rule procedur provid articl articl articl appli analog special simplifi registr procedur homeopath medicin product except proof therapeut efficaci proof therapeut efficaci requir homeopath medicin product regist accord paragraph articl admit accord articl articl applic special simplifi registr cover seri medicin product deriv homeopath stock stock document includ applic order demonstr pharmaceut qualiti batch batch homogen product concern scientif pharmacopoeia homeopath stock stock statement rout administr pharmaceut form degre dilut regist dossier describ homeopath stock stock obtain control justifi homeopath natur basi adequ bibliographi manufactur control file pharmaceut form descript method dilut potent manufactur author medicin product concern copi registr author obtain medicin product member state specimen mock up outer packag packag medicin product regist data stabil medicin product articl homeopath medicin product refer articl author label accord articl member state introduc retain territori specif rule toxicolog pharmacolog test clinic trial homeopath medicin product refer articl accord principl characterist homeopathi practis member state case member state concern notifi commiss specif rule forc titl ix appli homeopath medicin product except refer articl chapter procedur relev market author articl member state measur ensur procedur grant author place medicin product market complet dai submiss valid applic member state note applic author activ examin member state respect medicin product member state concern decid suspend detail examin applic order await assess report prepar member state accord articl member state concern inform member state applic decis suspend detail examin applic question complet examin applic reach decis member state forward copi assess report member state concern articl member state inform accord articl member state author medicin product subject applic author member state concern member state forthwith request author member state grant author forward assess report refer articl dai receipt assess report member state concern recogn decis member state summari product characterist approv consid ground suppos author medicin product concern present risk public health appli procedur set articl articl order examin applic submit accord articl compet author member state verifi particular submit support applic compli articl examin condit issu author place medicin product market market author compli submit medicin product start materi intermedi product constitu materi test state laboratori laboratori design purpos order ensur control method emploi manufactur particular accompani applic accord articl satisfactori requir applic supplement particular accompani applic respect item list articl compet author avail option time limit laid articl suspend time supplementari inform requir provid likewis time limit suspend time allow applic give oral written explan articl member state measur ensur compet author verifi manufactur import medicin product come countri carri manufactur complianc particular suppli pursuant articl carri control method particular accompani applic accord articl compet author manufactur import medicin product come countri except justifi case stage manufactur control refer carri parti case verif compet author made establish design articl market author issu holder inform compet author member state concern summari product characterist approv compet author measur ensur inform summari conform accept market author issu subsequ compet author forward agenc copi author summari product characterist compet author draw assess report comment dossier result analyt pharmacotoxicolog test clinic trial medicin product concern assess report updat inform import evalu qualiti safeti efficaci medicin product concern articl except circumst consult applic author grant subject specif oblig includ carri studi grant author notif advers reaction medicin product except decis adopt object verifi reason base refer part annex articl author issu author holder respect method manufactur control provid articl account scientif technic progress introduc requir enabl medicin product manufactur check mean gener accept scientif method subject approv compet author member state concern articl author valid year renew year period applic holder month expiri date consider compet author dossier detail data pharmacovigil inform relev monitor medicin product articl author affect civil crimin liabil manufactur applic market author holder articl market authoris refus verif particular document list articl prove medicin product harm normal condit therapeut efficaci lack insuffici substanti applic qualit quantit composit declar authoris likewis refus particular document submit support applic compli articl chapter mutual recognit author articl order facilit adopt common decis member state author medicin product basi scientif criteria qualiti safeti efficaci achiev free movement medicin product commun committe proprietari medicin product hereinaft refer quot committe quot set committe part agenc addit respons confer commun law committe examin question relat grant variat suspens withdraw market author submit accord direct committe draw rule prodecur articl submit applic recognit market author holder author inform member state grant author applic base hereinaft quot refer member state quot applic made accord direct notifi addit origin dossier member state requir applic provid particular document enabl check dossier file ident addit holder author request refer member state prepar assess report respect medicin product concern updat exist assess report member state prepar assess report updat dai receipt request time applic submit accord paragraph refer member state forward assess report member state member state concern applic order obtain recognit procedur laid chapter member state market author issu member state holder author submit applic compet author member state member state concern inform particular refer articl testifi dossier ident accept refer member state identifi addit amend case certifi summari product characterist propos accord articl ident accept refer member state accord articl certifi dossier file part procedur ident holder market author commun applic agenc inform member state concern date submiss applic send copi author grant refer member state send agenc copi author grant member state respect medicin product concern applic author consider member state save except case provid articl member state recogn market author grant refer member state dai receipt applic assess report inform refer member state grant initi author member state concern applic agenc market author holder articl member state consid ground suppos market author medicin product concern present risk public health forthwith inform applic refer member state grant initi author member state concern applic agenc member state state reason detail action correct defect applic member state concern endeavour reach agreement action respect applic provid applic opportun make point view oral write member state reach agreement time limit refer articl forthwith refer matter agenc regard committe refer applic procedur laid articl time limit refer articl member state concern provid committe detail statement matter unabl reach agreement reason disagr applic provid copi inform inform matter refer committe applic forthwith forward committe copi inform particular refer articl articl applic submit accord articl articl made market author medicin product member state adopt diverg decis author medicin product suspens withdraw member state commiss market author holder refer matter committe applic procedur laid articl member state concern market author holder commiss identifi question refer committe consider inform holder member state market author holder forward committe inform relat matter question articl member state commiss applic holder market author specif case interest commun involv refer matter committe applic procedur laid articl reach decis request market author suspens withdraw author variat term market author appear account inform collect accord titl ix member state concern commiss identifi question refer committe consider inform market author holder member state market author holder forward committe inform relat matter question articl refer made procedur articl committe matter concern issu reason opinion dai date matter refer case submit committe accord articl period extend dai case urgenc propos chairman committe agre shorter deadlin order matter committe appoint member act rapporteur committe appoint individu expert advis specif question appoint expert committe defin task time limit complet task case refer articl issu opinion committe provid market author holder opportun present written oral explan case refer articl market author holder ask explain oral write consid committe invit person provid inform relat matter committe suspend time limit refer paragraph order market author holder prepar explan agenc forthwith inform market author holder opinion committe applic satisfi criteria author summari product characterist propos applic accord articl amend author grant subject condit regard condit consid essenti safe effect medicin product includ pharmacovigil market author suspend vari withdrawn dai receipt opinion market author holder notifi agenc write intent appeal case forward detail ground appeal agenc dai receipt opinion dai receipt ground appeal committe opinion revis conclus reach appeal annex assess report refer paragraph dai adopt agenc forward final opinion committe member state commiss market author holder report describ assess medicin product state reason conclus event opinion favour grant maintain author place medicin product concern market document annex opinion draft summari product characterist refer articl condit affect author mean paragraph articl dai receipt opinion commiss prepar draft decis respect applic take account commun law event draft decis envisag grant market author document refer articl annex exception draft decis accord opinion agenc commiss annex detail explan reason differ draft decis forward member state applic articl final decis applic adopt accord procedur refer articl rule procedur stand committe establish articl adjust account task incumb accord chapter adjust involv case refer paragraph articl opinion stand committe obtain write member state allow dai forward written observ draft decis commiss member state requir write draft decis discuss stand committe give reason detail opinion commiss written observ member state rais import question scientif technic natur address opinion agenc chairman suspend procedur refer applic back agenc consider provis implement paragraph adopt commiss accord procedur refer articl decis refer paragraph address member state concern matter report market author holder member state grant withdraw market author vari term market author compli decis dai notif inform commiss agenc thereof articl applic market author holder vari market author grant accord provis chapter submit member state previous author medicin product concern commiss consult agenc adopt arrang examin variat term market author arrang includ notif system administr procedur minor variat defin precis concept quot minor variat quot arrang adopt commiss form implement regul accord procedur refer articl case arbitr submit commiss procedur laid articl appli analog variat made market author articl member state consid variat market author grant accord provis chapter suspens withdraw protect public health member state concern forthwith refer matter agenc applic procedur laid articl prejudic provis articl except case urgent action essenti protect public health definit decis adopt member state suspend market medicin product concern territori inform commiss member state work dai reason action articl articl appli analog medicin product author member state opinion committe accord articl direct eec januari articl agenc publish annual report oper procedur laid chapter forward report european parliament council inform januari commiss publish detail review oper procedur laid chapter propos amend improv procedur council decid condit provid treati commiss propos year submiss articl provis refer articl appli homeopath medicin product refer articl titl iv manufactur import articl member state measur ensur manufactur medicin product territori subject hold author manufactur author requir nothwithstand medicin product manufactur intend export author refer paragraph requir total partial manufactur process divid packag present author requir prepar divid packag present process carri sole retail suppli pharmacist dispens pharmaci person legal author member state carri process author refer paragraph requir import come countri member state titl articl applic import manufactur articl order obtain manufactur author applic meet requir medicin product pharmaceut form manufactur import place manufactur control dispos manufactur import suitabl suffici premis technic equip control facil compli legal requir member state concern lai manufactur control storag medicin product accord articl dispos servic qualifi person mean articl applic provid particular support applic articl compet author member state issu manufactur author made accuraci particular suppli pursuant articl mean inquiri carri agent order ensur requir refer articl compli author made condit carri oblig impos author grant date author appli premis applic medicin product pharmaceut form applic articl member state measur ensur time procedur grant manufactur author exce dai dai compet author receiv applic articl holder manufactur author request chang particular refer point paragraph articl time procedur relat request exce dai except case period time extend dai articl compet author member state requir applic inform particular suppli pursuant articl qualifi person refer articl compet author concern exercis applic time limit refer articl suspend addit data requir suppli articl holder manufactur author oblig dispos servic staff compli legal requir exist member state concern manufactur control dispos author medicin product accord legisl member state concern give prior notic compet author make particular suppli pursuant articl compet author event immedi inform qualifi person refer articl replac unexpectedli agent compet author member state concern access premis time enabl qualifi person refer articl carri duti place dispos facil compli principl guidelin good manufactur practic medicin product laid commun law articl principl guidelin good manufactur practic medicin product refer articl adopt form direct accord procedur refer articl detail guidelin line principl publish commiss revis account technic scientif progress articl member state measur ensur holder manufactur author perman continu dispos servic qualifi person accord condit laid articl respons carri duti articl person fulfil condit laid articl holder author assum respons refer paragraph articl member state ensur qualifi person refer articl fulfil minimum condit qualif set paragraph qualifi person possess diploma certif evid formal qualif award complet univers studi recogn equival member state concern extend period year theoret practic studi scientif disciplin pharmaci medicin veterinari medicin chemistri pharmaceut chemistri technolog biologi minimum durat univers half year period theoret practic train minimum durat year includ train period month pharmaci open public corrobor examin univers level univers cours cours recogn state equival exist member state extend year year year lead diploma certif evid formal qualif award complet univers recogn equival consid fulfil condit durat refer subparagraph diploma certif evid formal qualif award complet cours recogn equival state question includ theoret practic studi bear basic subject appli physic gener inorgan chemistri organ chemistri analyt chemistri pharmaceut chemistri includ analysi medicin product gener appli biochemistri medic physiolog microbiolog pharmacolog pharmaceut technolog toxicolog pharmacognosi studi composit effect natur activ substanc plant anim origin studi subject balanc enabl person concern fulfil oblig articl diploma certif evid formal qualif mention subparagraph fulfil criteria laid paragraph compet author member state ensur person concern evid adequ knowledg subject involv qualifi person acquir practic experi year undertak author manufactur medicin product activ qualit analysi medicin product quantit analysi activ substanc test check ensur qualiti medicin product durat practic experi reduc year univers last year year half last year articl person engag activ person refer articl time applic direct eec member state compli provis articl elig continu engag activ state concern holder diploma certif evid formal qualif award complet univers recogn equival member state concern scientif disciplin allow engag activ person refer articl accord law state began prior consid qualifi carri state duti person refer articl provid previous engag activ year notif direct undertak author manufactur product supervis qualit quantit analysi activ substanc test check direct author person refer articl ensur qualiti medicin product person concern acquir practic experi refer subparagraph year practic experi accord condit refer subparagraph requir complet immedi engag activ articl member state measur ensur qualifi person refer articl prejudic relationship holder manufactur author respons context procedur refer articl secur case medicin product manufactur member state concern batch medicin product manufactur check complianc law forc member state accord requir market author case medicin product come countri product batch undergon import member state full qualit analysi quantit analysi activ constitu test check ensur qualiti medicin product accord requir market author batch medicin product undergon control member state exempt control market member state accompani control report sign qualifi person case medicin product import countri arrang made commun export countri ensur manufactur medicin product appli standard good manufactur practic equival laid commun ensur control refer point subparagraph paragraph carri export countri qualifi person reliev respons carri control case medicin product releas sale qualifi person certifi regist equival document provid purpos product batch satisfi provis articl regist equival document date oper carri remain dispos agent compet author period provis member state concern event year articl member state ensur duti qualifi person refer articl fulfil mean administr measur make person subject profession code conduct member state provid temporari suspens person commenc administr disciplinari procedur failur fulfil oblig articl provis titl appli homeopath medicin product titl label packag leaflet articl particular outer packag medicin product outer packag packag medicin product common product activ substanc invent medicin product pharmaceut form strength pharmaceut form strength babi child adult includ medicin product statement activ substanc express qualit quantit dosag unit form administr volum weight common name pharmaceut form content weight volum number dose product list excipi recogn action effect includ guidelin publish pursuant articl product inject topic ey prepar excipi state method rout administr special warn medicin product store reach children special warn medicin product expiri date clear term month year special storag precaut special precaut dispos unus medicin product wast materi medicin product address holder author place medicin product market number author place medicin product market manufactur batch number case medic instruct medicin product articl particular laid articl packag refer paragraph particular packag form blister pack outer packag compli requir laid articl medicin product laid articl holder author place product market expiri date batch number particular small packag unit particular laid articl displai medicin product strength rout administr method administr expiri date batch number content weight volum unit articl particular refer articl easili legibl comprehens indel articl notwithstand articl member state requir form label medicin product make ascertain price medicin product reimburs condit social secur organ legal statu suppli patient accord titl vi identif authent articl inclus packag medicin product packag leaflet obligatori inform requir articl directli convei outer packag packag articl packag leaflet drawn accord summari product characterist includ order identif medicin product medicin product common product activ substanc invent medicin product pharmaceut form strength pharmaceut form strength babi child adult includ medicin product full statement activ substanc excipi express qualit statement activ substanc express quantit common name case present medicin product pharmaceut form content weight volum number dose product case present product pharmaco therapeut group type activ term easili comprehens patient address holder author place medicin product market manufactur therapeut indic list inform take medicin product contra indic precaut form interact medicin product form interact alcohol tobacco foodstuff affect action medicin product special warn list account condit categori user children pregnant breastfeed women elderli person specif patholog condit mention potenti effect abil drive vehicl oper machineri detail excipi knowledg import safe effect medicin product includ guidelin publish pursuant articl usual instruct proper dosag method rout administr frequenc administr time medicin product administ depend natur product durat treatment limit action case overdos symptom emerg procedur action dose indic risk withdraw effect descript undesir effect occur normal medicin product action case patient expressli invit commun undesir effect mention leaflet doctor pharmacist refer expiri date label warn product date special storag precaut warn visibl sign deterior date packag leaflet revis notwithstand paragraph author compet decid therapeut indic mention packag leaflet dissemin inform disadvantag patient articl member state prohibit imped place market medicin product territori ground connect label packag leaflet compli requir titl articl specimen mock up outer packag packag medicin product draft packag leaflet submit author compet author market market author request compet author refus market author label packag leaflet compli provis titl accord particular list summari product characterist propos aspect label packag leaflet cover titl connect summari product characterist submit author compet author market compet author oppos propos chang dai introduct request applic put chang effect fact compet author refus market author pursuant paragraph chang label packag leaflet pursuant paragraph alter gener legal liabil manufactur market author holder articl outer packag packag leaflet includ symbol pictogram design clarifi inform mention articl inform compat summari product characterist health educ exclus element promot natur articl particular label list articl offici languag languag member state product market subparagraph prevent particular languag provid particular languag packag leaflet written clear understand term user legibl offici languag languag member state medicin product market subparagraph prevent packag leaflet print languag provid inform languag compet author exempt label packag leaflet specif medicin product oblig particular leaflet offici languag languag member state product market product intend deliv patient administr articl provis titl compli notic serv person concern remain effect compet author member state suspend market author label packag leaflet medicin product question made compli requir titl articl commiss publish guidelin formul special warn categori medicin product inform relat medic legibl particular label packag leaflet method identif authent medicin product list excipi featur label medicin product excipi guidelin adopt form direct accord procedur refer articl articl outer carton contain medicin product radionuclid label accord regul safe transport radioact materi laid intern atom energi agenc label compli provis set paragraph label shield includ particular mention articl addit label shield explain full code vial time date amount radioact dose vial number capsul liquid number millilitr contain vial label inform code medicin product includ chemic symbol radionuclid batch identif expiri date intern symbol radioact manufactur amount radioact paragraph articl compet author ensur detail instruct leaflet enclos packag radiopharmaceut radionuclid gener radionuclid kit radionuclid precursor text leaflet establish accord provis articl addit leaflet includ precaut user patient prepar administr medicin product special precaut dispos packag unus content articl prejudic provis articl homeopath medicin product label accord provis titl identifi refer label clear legibl form homeopath natur articl addit clear mention word quot homeopath medicin product quot label packag insert medicin product refer articl bear inform scientif stock stock degre dilut make symbol pharmacopoeia accord articl address registr holder manufactur method administr rout expiri date clear term month year pharmaceut form content sale present special storag precaut special warn medicin product manufactur batch number registr number quot homeopath medicin product approv therapeut indic quot warn advis user consult doctor symptom persist medicin product notwithstand paragraph member state requir type label order show price medicin product condit refund social secur bodi titl vi classif medicin product articl market author grant compet author classif medicin product medicin product subject medic prescript medicin product subject medic prescript end criteria laid articl appli compet author fix categori medicin product medic prescript case refer classif medicin product renew renew medic prescript medicin product subject special medic prescript medicin product restrict medic prescript reserv special area articl medicin product subject medic prescript present danger directli indirectli correctli util medic supervis frequent wide extent incorrectli result present direct indirect danger human health substanc prepar thereof activ advers reaction requir investig prescrib doctor administ parenter member state provid categori medicin product subject special medic prescript account factor medicin product exempt quantiti substanc classifi narcot psychotrop substanc mean intern convent forc unit nation convent medicin product incorrectli present substanti risk medicin abus lead addict misus illeg purpos medicin product substanc reason novelti properti consid belong group envisag indent precautionari measur member state provid categori medicin product subject restrict prescript account factor medicin product pharmaceut characterist novelti interest public health reserv treatment hospit environ medicin product treatment condit diagnos hospit environ institut adequ diagnost facil administr follow carri medicin product intend outpati produc advers reaction requir prescript drawn requir specialist special supervis treatment compet author waiv applic paragraph regard maximum singl dose maximum daili dose strength pharmaceut form type packag circumst compet author design medicin product categori refer articl account criteria refer paragraph articl determin medicin product classifi prescript medicin articl medicin product subject prescript meet criteria list articl articl compet author draw list medicin product subject territori medic prescript categori classif updat list annual articl occas yearli renew market author fact brought notic compet author examin amend classif medicin product appli criteria list articl articl year member state commun commiss member state made list refer articl titl vii wholesal distribut medicin product articl prejudic articl member state action ensur medicin product respect market author grant accord commun law distribut territori articl member state measur ensur wholesal distribut medicin product subject possess author engag activ wholesal medicin product state place valid person author entitl suppli medicin product public nation law engag wholesal busi person subject author provid paragraph possess manufactur author includ author distribut wholesal medicin product cover author possess author engag activ wholesal medicin product give dispens oblig possess manufactur author compli condit set respect manufactur import busi secondari request commiss member state member state suppli inform individu author grant paragraph check person author engag activ wholesal medicin product inspect premis carri respons member state grant author member state grant author refer paragraph suspend revok author condit author ceas met forthwith inform member state commiss thereof member state respect person hold author grant member state term paragraph condit author longer met forthwith inform commiss member state involv measur inform commiss member state decis reason decis articl member state ensur time procedur examin applic distribut author exce dai dai compet author member state concern receiv applic compet author requir applic suppli inform condit author author exercis option period laid paragraph suspend requisit addit data suppli articl order obtain distribut author applic fulfil minimum requir suitabl adequ premis instal equip ensur proper conserv distribut medicin product staff qualifi person design respons meet condit provid legisl member state concern undertak fulfil oblig incumb term articl articl holder distribut author fulfil minimum requir make premis instal equip refer articl access time person respons inspect obtain suppli medicin product person possess distribut author exempt obtain author term articl suppli medicin product person possess distribut author author entitl suppli medicin product public member state concern emerg plan ensur effect implement recal market order compet author carri cooper manufactur market author holder medicin product concern record form purchas sale invoic comput form give transact medicin product receiv dispatch inform date medicin product quantiti receiv suppli address supplier consigne record refer compet author inspect purpos period year compli principl guidelin good distribut practic medicin product laid articl articl regard suppli medicin product pharmacist person author entitl suppli medicin product public member state impos holder distribut author grant member state oblig public servic oblig stringent impos person author engag equival activ oblig justifi keep treati ground public health protect proportion relat object protect articl suppli medicin product person author entitl suppli medicin product public member state concern author wholesal enclos document make ascertain date pharmaceut form medicin product quantiti suppli address supplier consignor member state measur ensur person author entitl suppli medicin product public provid inform make trace distribut path medicin product articl provis titl prevent applic stringent requir laid member state respect wholesal distribut narcot psychotrop substanc territori medicin product deriv blood immunolog medicin product radiopharmaceut articl commiss publish guidelin good distribut practic end consult committe proprietari medicin product pharmaceut committe establish council decis eec articl provis titl appli homeopath medicin product except refer articl titl viii advertis articl purpos titl quot advertis medicin product quot includ form door door inform canvass activ induc design promot prescript suppli sale consumpt medicin product includ advertis medicin product gener public advertis medicin product person qualifi prescrib suppli visit medic sale repres person qualifi prescrib medicin product suppli sampl provis induc prescrib suppli medicin product gift offer promis benefit bonu monei kind intrins minim sponsorship promot meet attend person qualifi prescrib suppli medicin product sponsorship scientif congress attend person qualifi prescrib suppli medicin product payment travel accommod expens connect therewith cover titl label accompani packag leaflet subject provis titl correspond possibl accompani materi promot natur need answer specif question medicin product factual inform announc refer materi relat pack advers reaction warn part gener drug precaut trade catalogu price list provid includ product claim statement relat human health diseas provid refer indirect medicin product articl member state prohibit advertis medicin product respect market author grant accord commun law part advertis medicin product compli particular list summari product characterist advertis medicin product encourag ration medicin product present object exagger properti mislead articl member state prohibit advertis gener public medicin product medic prescript accord titl vi psychotrop narcot substanc unit nation convent advertis gener public accord subparagraph paragraph medicin product advertis gener public virtu composit purpos intend design intervent medic practition diagnost purpos prescript monitor treatment advic pharmacist member state prohibit mention advertis gener public therapeut indic tuberculosi sexual transmit diseas infecti diseas cancer tumor diseas chronic insomnia diabet metabol ill member state ban territori advertis gener public medicin product cost reimburs prohibit refer paragraph appli vaccin campaign carri industri approv compet author member state prohibit refer paragraph appli prejudic articl direct eec member state prohibit direct distribut medicin product public industri promot purpos author distribut special case purpos articl prejudic articl advertis gener public medicin product set clear messag advertis product identifi medicin product includ minimum inform medicin product common medicin product activ substanc inform correct medicin product express legibl invit read carefulli instruct packag leaflet outer packag case member state decid advertis medicin product gener public notwithstand paragraph includ medicin product intend sole remind articl advertis medicin product gener public materi impress medic consult surgic oper unnecessari offer diagnosi suggest treatment mail suggest effect take medicin guarante unaccompani advers reaction equival treatment medicin product suggest health subject enhanc take medicin suggest health subject affect take medicin prohibit appli vaccin campaign refer articl direct exclus princip children refer recommend scientist health profession person forego celebr encourag consumpt medicin product suggest medicin product foodstuff cosmet consum product suggest safeti efficaci medicin product due fact natur descript detail represent case histori lead erron diagnosi refer improp alarm mislead term claim recoveri improp alarm mislead term pictori represent human bodi caus diseas injuri action medicin product human bodi part thereof mention medicin product grant market author articl advertis medicin product person qualifi prescrib suppli product includ essenti inform compat summari product characterist suppli classif medicin product member state requir advertis includ sell price indic price present condit reimburs social secur bodi member state decid advertis medicin product person qualifi prescrib suppli product notwithstand paragraph includ medicin product intend sole remind articl document relat medicin product transmit part promot product person qualifi prescrib suppli includ minimum particular list articl state date drawn revis inform contain document refer paragraph accur date verifi suffici complet enabl recipi form opinion therapeut medicin product concern quotat tabl illustr matter medic journal scientif work document refer paragraph faithfulli reproduc precis sourc articl medic sale repres adequ train firm emploi suffici scientif knowledg provid inform precis complet medicin product promot visit medic sale repres give person visit summari product characterist medicin product present legisl member state permit detail price condit reimburs refer articl medic sale repres transmit scientif servic refer articl inform medicin product advertis refer advers reaction report person visit articl medicin product promot person qualifi prescrib suppli gift pecuniari advantag benefit kind suppli offer promis person inexpens relev practic medicin pharmaci hospit sale promot reason level secondari main purpos meet extend health profession person qualifi prescrib suppli medicin product solicit accept induc prohibit paragraph contrari paragraph exist measur trade practic member state relat price margin discount affect paragraph articl provis articl prevent hospit offer directli indirectli event pure profession scientif purpos hospit reason level remain subordin main scientif object meet extend person health profession articl free sampl provid except basi person qualifi prescrib condit number sampl medicin product year prescript limit suppli sampl respons written request sign date prescrib agent suppli sampl maintain adequ system control account sampl ident smallest present market sampl mark quot free medic sampl sale quot show word mean sampl accompani copi summari product characterist sampl medicin product psychotrop narcot substanc mean intern convent unit nation convent suppli member state place restrict distribut sampl medicin product articl member state ensur adequ effect method monitor advertis medicin product method base system prior vet event includ legal provis person organ regard nation law legitim interest prohibit advertis inconsist titl legal action advertis bring advertis administr author compet decid complaint initi legal proceed legal provis refer paragraph member state confer court administr author power enabl case deem measur take account interest involv public interest order cessat institut legal proceed order cessat mislead advertis mislead advertis publish public immin order prohibit institut legal proceed order prohibit public proof actual loss damag intent neglig part advertis member state make provis measur refer subparagraph acceler procedur interim effect definit effect member state decid option set subparagraph select member state confer court administr author power enabl view elimin continu effect mislead advertis cessat order final decis requir public decis full part form deem adequ requir addit public correct statement paragraph exclud voluntari control advertis medicin product regulatori bodi recours bodi proceed bodi addit judici administr proceed refer paragraph articl market author holder establish undertak scientif servic charg inform medicin product place market market author holder commun author bodi respons monitor advertis medicin product sampl advertis eman undertak statement indic person address method dissemin date dissemin ensur advertis medicin product undertak conform requir titl verifi medic sale repres emploi undertak adequ train fulfil oblig impos articl suppli author bodi respons monitor advertis medicin product inform assist requir carri respons ensur decis author bodi respons monitor advertis medicin product immedi fulli compli articl member state measur ensur provis titl appli determin penalti impos provis adopt execut titl infring articl advertis homeopath medicin product refer articl articl subject provis titl except articl inform articl advertis medicin product member state prohibit territori advertis homeopath medicin product refer articl articl titl ix pharmacovigil articl member state measur encourag doctor health care profession report suspect advers reaction compet author member state impos specif requir doctor health care profession respect report suspect unexpect advers reaction report condit market author articl order ensur adopt regulatori decis medicin product author commun regard inform obtain advers reaction medicin product normal condit member state establish pharmacovigil system system collect inform surveil medicin product refer advers reaction human be evalu inform scientif inform collat data consumpt medicin product system account inform misus abus medicin product impact evalu benefit risk articl market author holder perman continu dispos appropri qualifi person respons pharmacovigil qualifi person respons establish mainten system ensur inform suspect advers reaction report personnel compani medic repres collect collat order access point commun prepar compet author report refer articl form laid author accord guidanc refer articl ensur request compet author provis addit inform evalu benefit risk afford medicin product answer fulli promptli includ provis inform volum sale prescript medicin product concern provis compet author inform relev evalu benefit risk afford medicin product includ inform post author safeti studi articl market author holder requir maintain detail record suspect advers reaction occur commun countri market author holder requir record report suspect advers reaction brought attent health care profession immedi compet author member state territori incid occur case calendar dai receipt inform market author holder requir record report suspect advers reaction meet report criteria accord guidanc refer articl expect knowledg immedi compet author member state territori incid occur case calendar dai receipt inform market author holder ensur suspect unexpect advers reaction occur territori countri brought attent health care profession report immedi accord guidanc refer articl agenc compet author member state medicin product authoris case calendar dai receipt inform case medicin product consid scope direct eec benefit procedur mutual recognit foreseen articl direct articl direct medicin product referr procedur foreseen articl direct market authoris holder addition ensur suspect advers reaction occur commun report format interv agre refer member state compet author act refer member state access refer member state requir laid condit grant authoris subsequ guidanc refer articl record advers reaction submit compet author form period safeti updat report immedi request period monthli year authoris annual subsequ year time renew period safeti updat report submit yearli interv applic renew authoris period safeti updat report includ scientif evalu benefit risk afford medicin product grant market authoris market authoris holder request amend period refer articl procedur laid commiss regul ec articl agenc collabor member state commiss set data process network facilit exchang pharmacovigil inform medicin product market commun intend compet author share inform time make network foreseen paragraph member state ensur report suspect advers reaction place territori immedi made agenc member state case calendar dai notif latest member state ensur report suspect advers reaction place territori immedi made market authoris holder case calendar dai notif latest articl order facilit exchang inform pharmacovigil commun commiss consult agenc member state interest parti draw guidanc collect verif present advers reaction report includ technic requir electron exchang pharmacovigil inform accord internation agre format publish refer internation agre medic terminolog guidanc publish volum rule govern medicin product european commun account intern harmonis work carri field pharmacovigil interpret definit refer articl point principl outlin titl market authoris holder compet author refer guidanc refer paragraph articl result evalu pharmacovigil data member state consid market authoris suspend withdrawn vari accord guidanc refer articl forthwith inform agenc member state market authoris holder case urgenc member state concern suspend market authoris medicin product provid agenc commiss member state inform latest work dai articl amend updat provis articl account scientif technic progress adopt accord procedur refer articl titl special provis medicin product deriv human blood plasma articl respect human blood human plasma start materi manufactur medicin product member state measur prevent transmiss infecti diseas cover amend refer articl applic monograph european pharmacopoeia blood plasma measur compris recommend council europ world health organ refer select test blood plasma donor member state measur ensur human blood human plasma donor donat centr identifi safeti guarante refer paragraph import human blood human plasma countri articl member state measur promot commun suffici human blood human plasma purpos encourag voluntari unpaid donat blood plasma measur develop product product deriv human blood human plasma come voluntari unpaid donat notifi commiss measur titl xi supervis sanction articl compet author member state concern ensur mean repeat inspect legal requir govern medicin product compli inspect carri offici repres compet author empow inspect manufactur commerci establish laboratori entrust holder manufactur author task carri check pursuant articl sampl examin document relat object inspect subject provis forc member state place restrict power regard descript method prepar member state step ensur manufactur process manufactur immunolog product properli valid attain batch batch consist inspect refer paragraph offici repres compet author report manufactur compli principl guidelin good manufactur practic laid articl content report commun manufactur undergo inspect articl member state measur ensur holder market author medicin product holder manufactur author furnish proof control carri medicin product ingredi control carri intermedi stage manufactur process accord method laid articl articl purpos implement articl member state requir manufactur immunolog product submit compet author copi control report sign qualifi person accord articl articl consid interest public health member state requir holder author market live vaccin immunolog medicin product primari immun infant group risk immunolog medicin product public health immun programm immunolog medicin product immunolog medicin product manufactur alter kind technolog manufactur transit period market author submit sampl batch bulk medicin product examin state laboratori laboratori design purpos releas market case batch manufactur member state compet author member state previous examin batch question declar conform approv specif member state ensur examin complet dai receipt sampl interest public health law member state provid compet author requir market author holder medicin product deriv human blood human plasma submit sampl batch bulk medicin product test state laboratori laboratori design purpos releas free circul compet author member state previous examin batch question declar conform approv specif member state ensur examin complet dai receipt sampl articl member state measur ensur manufactur purifi process prepar medicin product deriv human blood human plasma properli valid attain batch batch consist guarante state technolog permit absenc specif viral contamin end manufactur notifi compet author method reduc elimin pathogen virus liabl transmit medicin product deriv human blood human plasma compet author submit sampl bulk medicin product test state laboratori laboratori design purpos examin applic pursuant articl market author grant articl compet author member state suspend revok author place medicin product market product prove harm normal condit therapeut efficaci lack qualit quantit composit declar therapeut efficaci lack establish therapeut result obtain medicin product author suspend revok particular support applic provid articl incorrect amend accord articl control refer articl carri articl notwithstand measur provid articl member state measur ensur suppli medicin product prohibit medicin product withdrawn market medicin product prove harm normal condit lack therapeut efficaci qualit quantit composit declar control medicin product ingredi control intermedi stage manufactur process carri requir oblig relat grant manufactur author fulfil compet author limit prohibit suppli product withdraw market batch subject disput articl compet author suspend revok market author categori prepar prepar requir laid articl longer met addit measur articl compet author suspend manufactur import medicin product come countri suspend revok manufactur author categori prepar prepar articl compli articl provis titl appli homeopath medicin product subject provis articl titl xii stand committe articl order adapt annex account scientif technic progress adopt accord procedur refer articl articl commiss assist stand committe medicin product human adapt technic progress direct remov technic barrier trade medicin product sector hereinaft refer quot stand committe quot refer made paragraph articl decis ec appli regard articl thereof period provid articl decis ec set month stand committe adopt rule procedur titl xiii gener provis articl member state measur ensur compet author concern commun inform guarante requir manufactur author market author fulfil reason request member state forthwith commun report refer articl compet author member state report member state receiv report consid accept conclus reach compet author member state report establish inform compet author concern reason request inform member state concern endeavour reach agreement case differ opinion commiss inform member state concern articl member state measur ensur decis author market refus revok market author cancel decis refus revok market author prohibit suppli withdraw product market reason decis base brought attent agenc forthwith market author holder oblig notifi member state concern forthwith action suspend market medicin product withdraw medicin product market reason action concern efficaci medicin product protect public health member state ensur inform brought attent agenc member state ensur inform action pursuant paragraph affect protect public health countri forthwith brought attent world health organ copi agenc commiss publish annual list medicin product prohibit commun articl member state commun inform guarante qualiti safeti homeopath medicin product manufactur market commun inform refer articl articl decis refer direct compet author member state state detail reason base decis notifi parti concern inform redress law forc time limit allow access redress market author decis revok author publish member state offici public articl author market medicin product refus suspend revok ground set direct decis suspens manufactur import medicin product come countri prohibit suppli withdraw market medicin product ground set articl articl request manufactur export author import countri member state certifi manufactur medicin product possess manufactur author issu certif member state compli condit regard prevail administr arrang world health organ medicin product intend export author territori suppli summari product characterist approv accord articl manufactur possess market author provid author respons establish certif refer paragraph declar explain market author titl xiv final provis articl direct eec eec eec eec eec eec eec eec eec eec eec amend direct refer annex ii part repeal prejudic oblig member state time limit implement set annex ii part refer repeal direct constru refer direct read accord correl tabl annex iii articl direct enter forc twentieth dai public offici journal european commun articl direct address member state brussel novemb european parliament presid fontain council presid reynder oj opinion european parliament juli publish offici journal council decis septemb oj direct amend direct eec oj oj direct amend commiss direct ec oj oj direct amend commiss direct ec oj oj oj oj oj oj oj oj oj oj regul amend commiss regul ec oj oj direct repeal effect direct euratom oj oj direct amend direct euratom oj repeal effect direct euratom oj oj direct amend direct ec oj oj direct amend direct ec oj oj oj oj direct repeal direct eec oj oj oj regul amend regul ec oj annex analyt pharmacotoxicolog clinic standard protocol respect test medicin product introduct particular document accompani applic market author pursuant articl present part accord requir set annex take account guidanc publish commiss rule govern medicin product european commun volum ii notic applic market author medicin product human member state european commun assembl dossier applic market author applic account commun guidelin relat qualiti safeti efficaci medicin product publish commiss rule govern medicin product european commun volum iii supplement guidelin qualiti safeti efficaci medicin product human inform relev evalu medicin product concern includ applic favour unfavour product relev detail incomplet abandon pharmacotoxicolog clinic test trial relat medicin product order monitor benefit risk assess market author grant chang data dossier inform origin applic pharmacovigil report submit compet author gener section annex give requir categori medicin product supplement section addit special requir radiopharmaceut biolog medicin product immunolog medicin product deriv human blood plasma addit special requir biolog medicin product applic medicin product obtain process mention part indent part annex regul eec member state ensur test anim conduct accord council direct eec novemb approxim law regul administr provis member state protect anim experiment scientif purpos part summari dossier administr data medicin product subject applic identifi activ substanc pharmaceut form method administr strength final present includ packag address applic address manufactur site involv stage manufactur includ manufactur finish product manufactur activ substanc relev address import applic identifi number volum document submit support applic sampl provid annex administr data copi manufactur author defin articl list countri author grant copi summari product characterist accord articl approv member state list countri applic submit summari product characterist applic propos summari product characterist accord articl addit applic provid sampl mock up packag label packag leaflet medicin product concern expert report accord articl expert report provid chemic pharmaceut biolog document pharmacotoxicolog document clinic document expert report consist critic evalu qualiti medicin product investig carri anim human be bring data relev evalu word enabl reader obtain good understand properti qualiti propos specif control method safeti efficaci advantag disadvantag medicin product import data summar appendix expert report includ report format tabular graphic form expert report summari precis cross refer inform contain main document expert report prepar suitabl qualifi experienc person sign date expert attach report inform educ background train profession experi expert profession relationship expert applic declar part chemic pharmaceut biolog test medicin product test procedur correspond state scientif progress time valid procedur result valid studi provid test procedur suffici precis detail reproduc control test carri request compet author special apparatu equip adequ detail possibl accompani diagram formula laboratori reagent supplement manufactur method case test procedur includ european pharmacopoeia pharmacopoeia member state descript replac detail refer pharmacopoeia question qualit quantit particular constitu particular document accompani applic market author pursuant point articl submit accord requir qualit particular quot qualit particular quot constitu medicin product design descript activ substanc constitu excipi natur quantiti includ colour matter preserv adjuv stabil thicken emulsifi flavour aromat substanc constitu intend ingest administ patient outer cover medicin product capsul gelatin capsul rectal capsul particular supplement relev data contain manner closur detail devic medicin product administ deliv medicin product context radiopharmaceut kit radiolabel suppli manufactur activ substanc consid part formul intend carri bind radionuclid detail sourc radionuclid state addit compound essenti radiolabel state gener mother daughter radionuclid consid activ substanc quot usual terminolog quot describ constitu medicin product notwithstand applic provis articl respect substanc european pharmacopoeia fail nation pharmacopoeia member state main titl head monograph question refer pharmacopoeia concern respect substanc intern proprietari recommend world health organ accompani proprietari fail exact scientif design substanc intern proprietari exact scientif design statement prepar supplement relev detail respect colour matter design quot quot code assign council direct eec decemb approxim rule member state colour matter author medicin product quantit particular order give quot quantit particular quot activ substanc medicin product depend pharmaceut form concern mass number unit biolog activ dosag unit unit mass volum activ substanc unit biolog activ substanc defin chemic intern unit biolog activ defin world health organ intern unit defin unit biolog activ express provid unambigu inform activ substanc biolog activ unit mass inform supplement respect inject prepar mass unit biolog activ activ substanc unit contain take account usabl volum product reconstitut respect medicin product administ drop mass unit biolog activ activ substanc contain number drop ml prepar respect syrup emuls granular prepar pharmaceut form administ measur quantiti mass unit biolog activ activ substanc measur quantiti activ substanc present form compound deriv design quantit total mass relev mass activ entiti entiti molecul medicin product activ substanc subject applic market author member state time quantit statement activ substanc salt hydrat systemat express term mass activ entiti entiti molecul subsequ author medicin product member state quantit composit state activ substanc allergen product quantit particular express unit biolog activ defin allergen product concentr express mass unit volum requir express content activ substanc term mass activ entiti point appli radiopharmaceut radionuclid radioact express becquerel date time refer time zone type radiat develop pharmaceut explan provid regard choic composit constitu contain intend function excipi finish product explan support scientif data develop pharmaceut overag manufactur justif thereof state radiopharmaceut includ consider chemic radiochem puriti relationship biodistribut descript manufactur method descript manufactur method accompani applic market author pursuant articl draft give adequ synopsi natur oper emploi purpos includ mention stage manufactur assess made process emploi produc pharmaceut form produc advers chang constitu case continu manufactur full detail precaut ensur homogen finish product actual manufactur formula quantit particular substanc quantiti excipi approxim term pharmaceut form make mention made substanc disappear manufactur overag justifi statement stage manufactur sampl carri process control test data document support applic show test qualiti control finish product experiment studi valid manufactur process standard method manufactur critic product steril medicin product detail steril process asept procedur radiopharmaceut kit descript manufactur method includ detail manufactur kit detail recommend final process produc radioact medicin product radionuclid nuclear reaction involv discuss control start materi purpos section quot start materi quot constitu medicin product contain refer section point case activ substanc european pharmacopoeia pharmacopoeia member state activ substanc european pharmacopoeia pharmacopoeia member state prepar method liabl leav impur mention pharmacopoei monograph monograph inappropri adequ control qualiti manufactur person applic arrang detail descript manufactur method qualiti control manufactur process valid suppli directli compet author manufactur activ substanc case manufactur provid applic data respons medicin product manufactur confirm write applic ensur batch batch consist modifi manufactur process specif inform applic document particular support applic chang suppli compet author particular document accompani applic market author pursuant articl includ result test includ batch analys activ substanc relat qualiti control constitu submit accord provis start materi list pharmacopoeia monograph european pharmacopoeia applic substanc appear respect substanc member state requir observ nation pharmacopoeia regard product manufactur territori constitu fulfil requir european pharmacopoeia pharmacopoeia member state deem compli suffici articl case descript analyt method replac detail refer pharmacopoeia question start materi european pharmacopoeia pharmacopoeia member state prepar method liabl leav impur control pharmacopoeia monograph impur maximum toler limit declar suitabl test procedur colour matter case satisfi requir direct eec routin test carri batch start materi state applic market author test mention pharmacopoeia proof suppli start materi meet qualiti requir pharmacopoeia case specif contain monograph european pharmacopoeia nation pharmacopoeia member state insuffici ensur qualiti substanc compet author request specif market author holder compet author inform author respons pharmacopoeia question market author holder provid author pharmacopoeia detail alleg insuffici addit specif appli case start materi european pharmacopoeia pharmacopoeia member state complianc monograph countri pharmacopoeia accept case applic submit copi monograph accompani valid test procedur contain monograph translat start materi pharmacopoeia constitu pharmacopoeia form monograph head substanc meet requir section point supplement trade scientif synonym definit substanc set form similar european pharmacopoeia accompani explanatori evid molecular structur accompani descript method synthesi substanc manufactur method descript suffici detail character substanc constant composit effect method identif form complet techniqu product substanc form test carri routin matter puriti test relat sum total predict impur harm effect regard combin substanc applic refer advers affect stabil medicin product distort analyt result regard complex substanc plant anim human origin distinct made case multipl pharmacolog effect render chemic physic biolog control princip constitu case substanc group principl similar activ respect method assai accept materi anim human origin measur ensur freedom potenti pathogen agent radionuclid natur radionuclid ident isotop impur carrier specif activ special precaut storag start materi maximum period storag retest physico chemic characterist liabl effect bio avail item inform activ substanc list pharmacopoeia provid part gener descript activ substanc bio avail medicin product depend crystallin form solubl coeffici particl size pulver state solvat oil water coeffici partit indent applic substanc sole solut biolog medicin product immunolog medicin product medicin product deriv human blood plasma requir paragraph appli purpos paragraph start materi substanc manufactur medicin product includ constitu medicin product contain refer paragraph point sourc materi microorgan tissu plant anim origin cell fluid includ blood human anim origin biotechnolog cell construct origin histori start materi document descript start materi includ manufactur strategi purif inactiv procedur valid process control procedur design ensur qualiti safeti batch batch consist finish product cell bank cell characterist shown remain unchang passag level product seed materi cell bank pool serum plasma materi biolog origin sourc materi deriv test adventiti agent presenc potenti pathogen adventiti agent inevit correspond materi process ensur elimin inactiv valid vaccin product base seed lot system establish cell bank serum defin pool start materi bacteri viral vaccin characterist infecti agent demonstr seed addit live vaccin stabil attenu characterist demonstr seed proof suffici attenu characterist demonstr product stage allergen product specif control method sourc materi detail descript includ particular collect pretreat storag medicin product deriv human blood plasma origin criteria procedur collect transport storag sourc materi document defin pool sourc materi radiopharmaceut start materi includ irradi target materi specif measur prevent transmiss anim spongiform encephalopathi applic demonstr medicin product manufactur accord note guidanc minimis risk transmit anim spongiform encephalopathi agent medicin product updat publish commiss volum public rule govern medicin product european commun control test carri intermedi stage manufactur process particular document accompani applic market author pursuant articl articl paragraph direct includ particular relat product control test carri intermedi stage manufactur process view ensur consist technic characterist product process test essenti check conform medicin product formula exception applic propos analyt method test finish product includ assai activ substanc excipi constitu subject requir activ substanc appli qualiti control finish product depend process control test medicin product essenti defin method prepar biolog medicin product immunolog medicin product medicin product deriv human blood plasma procedur criteria accept publish recommend requir biolog substanc serv guidelin control product stage european pharmacopoeia fall nation pharmacopoeia member state inactiv detoxifi vaccin effect inactiv detoxif verifi product run control depend test avail suscept anim limit case test carri consist product correl process control establish compens process control modifi adsorb allergen product product qualit quantit character intermedi stage late manufactur process control test finish product control finish product batch medicin product compris unit pharmaceut form made initi quantiti materi undergon seri manufactur steril oper case continu product process unit manufactur period time applic market author list test carri routin batch finish product frequenc test carri routin state releas limit particular document accompani applic market author pursuant articl articl direct includ particular relat control test finish product releas submit accord requir provis monograph pharmaceut form immunosera vaccin radiopharmaceut prepar european pharmacopoeia fail member state applic product defin control biolog medicin product immunolog medicin product medicin product deriv human blood plasma european pharmacopoeia fail pharmacopoeia member state procedur criteria accept publish recommend requir biolog substanc serv guidelin test procedur limit mention monograph european pharmacopoeia fail nation pharmacopoeia member state proof suppli finish product test accord monograph meet qualiti requir pharmacopoeia pharmaceut form concern gener characterist finish product test gener characterist product includ test finish product test applic relat control averag mass maximum deviat mechan physic microbiolog test organolept characterist physic characterist densiti ph refract index characterist standard toler limit applic case condit test equip apparatu emploi standard precis detail european pharmacopoeia pharmacopoeia member state appli case method prescrib pharmacopoeia applic solid pharmaceut form administ oral subject vitro studi liber dissolut rate activ substanc substanc studi carri administr mean compet author member state concern identif assai activ substanc identif assai activ substanc carri averag repres sampl product batch number dosag unit analys individu justif maximum accept deviat activ substanc content finish product exce time manufactur basi stabil test manufactur propos justifi maximum accept toler limit activ substanc content finish product end propos shelf life except case complex mixtur assai activ substanc numer present low amount necessit intric investig difficult carri respect product batch assai activ substanc finish product omit express condit assai made intermedi stage product process relax extend character substanc concern simplifi techniqu supplement method quantit evalu enabl compet author conform medicin product specif verifi market vivo vitro biolog assai obligatori physico chemic method provid adequ inform qualiti product assai includ refer materi statist analysi allow calcul confid limit test carri finish product perform intermedi stage late manufactur process particular section show signific overag activ substanc emploi manufactur medicin product descript control test finish product includ chemic toxico pharmacolog investig substanc undergon possibl character assai degrad product identif assai excipi constitu excipi subject identif test test procedur propos identifi colour matter enabl verif made matter list annex direct eec upper lower limit test obligatori respect preserv agent upper limit test excipi constitu liabl affect advers organ function upper lower limit test obligatori respect excipi liabl affect bio avail activ substanc bio avail guarante test safeti test pharmacotoxicolog test submit applic market author particular safeti test steril bacteri endotoxin pyrogen local toler anim includ analyt particular test undertaken matter routin order verifi qualiti product control biolog medicin product immunolog medicin product medicin product deriv human blood plasma european pharmacopoeia fail nation pharmacopoeia member state procedur criteria accept publish recommend world health organ requir biolog substanc serv guidelin radiopharmaceut radionuclid puriti radiochem puriti specif activ content radioact deviat state label exce gener detail test mother daughter radionuclid requir gener eluat test mother radionuclid compon gener system provid kit specif finish product includ test perform product radiolabel control radiochem radionuclid puriti radiolabel compound includ materi essenti radiolabel identifi assai stabil test particular document accompani applic market author pursuant articl submit accord requir descript investig shelf life recommend storag condit specif end shelf life propos applic determin finish product liabl give rise degrad product applic declar character method test procedur conclus result analys justifi propos shelf life recommend storag condit specif finish product end shelf life recommend storag condit maximum accept level degrad product end shelf life studi interact product contain submit risk interact regard inject prepar aerosol intern concern biolog medicin product immunolog medicin product medicin product deriv human blood plasma stabil test carri finish product accept carri stabil indic test intermedi stage product late manufactur process addit evalu stabil finish product secondari test radiopharmaceut inform stabil radionuclid gener radionuclid kit radiolabel product stabil radiopharmaceut multi dose vial document part toxicolog pharmacolog test introduct particular document accompani applic market author pursuant articl accord requir member state ensur safeti test carri conform provis relat good laboratori practic laid council direct eec eec toxicolog pharmacolog test show potenti toxic product danger undesir toxic effect occur propos condit human be evalu relat patholog condit concern pharmacolog properti product qualit quantit relationship propos human be result reliabl gener applic mathemat statist procedur design experiment method evalu result addition clinician inform therapeut potenti product medicin product intend topic system absorpt investig due account product broken skin absorpt relev surfac prove system absorpt condit neglig repeat dose system toxic test foetal toxic test studi reproduct function omit system absorpt demonstr therapeut experiment toxic test carri anim includ foetal toxic test case test local toler repeat applic carri care includ histolog examin possibl sensit investig carcinogen potenti investig case refer section ii part biolog medicin product immunolog medicin product medicin product deriv human blood plasma requir part adapt individu product test programm carri justifi applic establish test programm consider test requir repeat administr product design account induct interfer antibodi examin reproduct function embryo foetal perinat toxic mutagen potenti carcinogen potenti consid compon activ substanc incrimin valid remov replac studi radiopharmaceut appreci toxic radiat dose diagnosi consequ radiopharmaceut therapi want properti evalu safeti efficaci radiopharmaceut address requir medicin product radiat dosimetri aspect organ tissu exposur radiat document absorb radiat dose estim calcul internation recogn system rout administr toxicolog pharmacokinet excipi time pharmaceut field investig possibl signific degrad storag medicin product toxicolog degrad product consid ii perform test toxic singl dose toxic acut test qualit quantit studi toxic reaction result singl administr activ substanc substanc contain medicin product proport physico chemic state present actual product acut toxic test carri mammalian speci strain singl speci justifi rout administr ident similar propos human be ensur system exposur substanc studi cover sign observ includ local reaction period test anim observ fix investig adequ reveal tissu organ damag recoveri period dai dai expos anim prolong suffer anim dy observ period subject autopsi anim surviv end observ period histopatholog examin consid organ show macroscop autopsi maximum amount inform obtain anim studi singl dose toxic test conduct sign acut toxic reveal mode death assess suitabl speci quantit evalu approxim lethal dose inform dose effect relationship obtain high level precis requir studi give indic effect acut overdosag man design toxic studi requir repeat dose suitabl anim speci case activ substanc combin studi carri check enhanc toxic toxic effect occur repeat dose toxic acut chronic toxic repeat dose toxic test intend reveal physiolog anatomo patholog induc repeat administr activ substanc combin activ substanc examin determin relat dosag gener desir test perform short term last week long term durat depend condit clinic purpos determin experi toxic dose rang product month respect medicin product administ human singl test last week perform regard propos durat human be investig see fit carri experi greater lesser durat give adequ reason reason dosag chosen repeat dose toxic test carri speci mammal rodent choic rout administr emploi depend intend therapeut possibl system absorpt method frequenc dosag state maximum dose chosen bring harm effect light lower dose enabl anim toler product determin experi small rodent design experi control procedur suit scale problem tackl enabl fiduci limit determin evalu toxic effect base observ behaviour growth haematolog biochem test relat excretori mechan autopsi report accompani histolog data choic rang group test depend speci anim state scientif knowledg time case combin substanc investig accord provis direct chronic long term test acut acut toxic test demonstr potenti toxic effect suitabl modifi investig submit reason modif examin reproduct function result test reveal suggest harm effect progeni impair male femal reproduct function investig test embryo foetal perinat toxic investig compris demonstr toxic teratogen effect observ issu concept medicin product investig administ femal pregnanc present test limit predict regard applic result human be thought provid import inform result show effect resorpt anomali omiss test medicin product women capabl child bear reason adequ justifi embryo foetal toxic studi conduct mammalian speci rodent peri postnat studi conduct speci metabol medicin product speci similar man desir includ speci desir speci repeat dose toxic studi detail test number anim amount administ time administr criteria evalu result depend state scientif knowledg time applic lodg level statist signific result attain mutagen potenti purpos studi mutagen potenti reveal substanc genet materi individu cell effect make successor perman hereditarili predecessor studi obligatori substanc number type result criteria evalu depend state scientif knowledg time applic lodg carcinogen potenti test reveal carcinogen effect requir respect substanc close chemic analog carcinogen cocarcinogen compound respect substanc rise suspici long term toxicolog test respect substanc rise suspici result mutagen potenti test short term carcinogen test test requir respect substanc includ medicin product administ regularli prolong period patient life state scientif knowledg time applic lodg account determin detail test pharmacodynam head cover variat caus medicin product function physiolog system function normal experiment modifi studi follow distinct line approach firstli action recommend applic therapeut practic base adequ result express quantit term dose effect curv time effect curv compar data relat substanc activ higher therapeut potenc claim substanc differ demonstr shown statist signific investig provid gener pharmacolog character substanc special refer advers reaction gener main function physiolog system investig depth investig increas dose liabl produc advers reaction approach produc main effect substanc propos experiment techniqu standard procedur detail reproduc investig establish valid experiment result set relev test statist signific quot good reason contrari quantit modif respons result repeat administr substanc investig test combin activ substanc prompt pharmacolog premiss indic therapeut effect case pharmacodynam studi demonstr interact make combin therapeut case scientif justif combin sought therapeut experiment investig determin effect expect combin demonstr anim import collater effect investig combin includ activ substanc previous studi depth pharmacokinet pharmacokinet mean studi fate activ substanc organ cover studi absorpt distribut biotransform excret substanc studi phase carri mean physic chemic biolog method observ actual pharmacodynam activ substanc inform distribut elimin biotransform excret case data indispens determin dosag human respect chemotherapeut substanc antibiot substanc depend pharmacodynam effect numer diagnost agent pharmacokinet investig pharmacolog activ substanc case combin substanc investig accord provis direct pharmacokinet studi requir toxic test therapeut experiment justifi omiss local toler purpos local toler studi ascertain medicin product activ substanc excipi toler site bodi contact medicin product result administr clinic test strategi mechan effect administr pure physico chemic action product distinguish toxicolog pharmacodynam establish medicin purpos demonstr pursuant articl ii compon medicin product establish accept level safeti specif rule appli factor account order establish quot establish medicin quot compon medicin product time substanc quantit aspect substanc degre scientif interest substanc reflect publish scientif literatur coher scientif assess period time establish quot establish quot substanc case period time requir establish quot establish medicin quot compon medicin product decad systemat document substanc medicin product commun document submit applic cover aspect safeti assess includ refer review relev literatur take account pre postmarket studi publish scientif literatur experi form epidemiolog studi compar epidemiolog studi document favour unfavour commun attent paid miss inform justif demonstr accept level safeti support studi lack expert report explain relev data submit concern product product intend market judgment made product studi consid similar product grant market authoris spite exist differ post market experi product compon import applic put special emphasi issu part clinic document particular document accompani applic market author pursuant articl direct submit accord provis clinic trial systemat studi medicin product human subject patient patient volunt order discov verifi effect identifi advers reaction investig product studi absorpt distribut metabol excret order ascertain efficaci safeti product evalu applic market author base clinic trial includ clinic pharmacolog trial design determin efficaci safeti product normal condit regard therapeut indic human be therapeut advantag outweigh potenti risk gener requir clinic particular provid pursuant articl enabl suffici found scientif valid opinion form medicin product satisfi criteria govern grant market author essenti requir result clinic trial commun favour unfavour clinic trial preced adequ pharmacolog toxicolog test carri anim accord requir part annex investig acquaint conclus drawn pharmacolog toxicolog studi applic provid investig brochur consist relev inform prior onset clinic trial includ chemic pharmaceut biolog data toxicolog pharmacokinet pharmacodynam data anim result earlier clinic trial adequ data justifi natur scale durat propos trial complet pharmacolog toxicolog report provid request materi human anim origin mean emploi ensur safeti transmiss infecti agent prior commenc trial conduct trial good clinic practic phase clinic investig includ bioavail bioequival studi design implement report accord good clinic practic clinic trial carri accord ethic principl laid current revis declar helsinki principl freeli inform consent trial subject obtain document trial protocol includ statist design technic applic document submit sponsor investig opinion relev ethic committe trial begin opinion committe receiv write pre establish systemat written procedur organ conduct data collect document verif clinic trial requir case radiopharmaceut clinic trial carri respons medic doctor author radionuclid medic purpos archiv market author holder make arrang archiv document investig arrang retent patient identif code year complet discontinu trial patient file sourc data maximum period time permit hospit institut privat practic sponsor owner data retain document pertain trial long product author procedur includ protocol includ rational object statist design methodolog trial condit perform manag detail investig product refer medicin product placebo standard oper procedur written opinion protocol procedur investig brochur case report form trial subject final report audit certif final report retain sponsor subsequ owner year medicin product longer author chang ownership data document data document made request relev author present result particular clinic trial suffici detail object judgement made protocol includ rational object statist design methodolog trial condit perform manag detail investig medicin product audit certif list investig investig give address appoint qualif clinic duti state trial carri assembl inform respect patient individu includ case report form trial subject final report sign investig multicentr trial investig coordin princip investig particular clinic trial refer forward compet author agreement compet author applic omit part inform complet document provid forthwith request clinic observ summar trial indic number sex patient treat select ag distribut group patient investig compar test number patient withdrawn prematur trial reason withdraw control trial carri condit control group receiv treatment receiv placebo receiv medicin product effect receiv treatment therapi medicin product frequenc observ advers reaction detail patient increas risk elderli peopl children women pregnanc menstruat physiolog patholog condit requir special consider paramet evalu criteria efficaci result term paramet statist evalu result call design trial variabl factor involv investig conclus experiment evid express opinion safeti product normal condit toler efficaci inform relat indic contra indic dosag averag durat treatment special precaut treatment clinic symptom overdosag report result multi centr studi princip investig conclus express opinion safeti efficaci investig medicin product behalf centr addit investig observ sign habitu addict difficulti wean patient medicin product interact observ medicin product administ concomitantli criteria determin exclus patient trial death occur trial follow period particular combin medicin substanc ident requir medicin product substanti safeti efficaci combin total partial omiss data explain unexpect result occur trial preclin toxicolog pharmacolog test undertaken review medicin product intend long term administr particular modif pharmacolog action repeat administr establish long term dosag clinic pharmacolog pharmacodynam pharmacodynam action correl efficaci demonstr includ dose respons relationship time justif dosag condit administr mode action pharmacodynam action relat efficaci demonstr pharmacodynam effect human be suffici justifi conclus potenti therapeut effect pharmacokinet pharmacokinet characterist absorpt rate extent distribut metabol excret clinic signific featur includ implic kinet data dosag regimen patient risk differ man anim speci preclin studi interact medicin product administ concomitantli medicin product particular joint administr test perform demonstr modif pharmacolog action pharmacodynam pharmacokinet interact exist substanc medic product substanc alcohol caffein tobacco nicotin simultan interact discuss point view clinic relev relationship statement interact summari product characterist present accord articl point bioavail bioequival assess bioavail undertaken case therapeut dose toxic dose previou test reveal anomali relat pharmacodynam properti variabl absorpt addit assess bioavail undertaken demonstr bioequival medicin product refer articl clinic efficaci safeti gener clinic trial quot control clinic trial quot random design justifi treatment control group vari case case depend ethic consider instanc pertin compar efficaci medicin product establish medicin product proven therapeut effect placebo trial effect product object measur step avoid bia includ method random blind protocol trial includ descript statist method emploi number reason inclus patient includ calcul power trial level signific descript statist unit measur avoid bia method random document inclus larg number subject trial regard adequ substitut properli control trial clinic statement efficaci safeti medicin product normal condit scientif substanti accept valid evid data efficaci safeti medicin product normal condit greatli enhanc data compet investig work independ vaccin serum immunolog statu ag trial popul local epidemiolog critic import monitor trial fulli live attenu vaccin clinic trial design reveal potenti transmiss immun agent vaccin vaccin subject transmiss genotyp phenotyp stabil immun agent studi vaccin allergen product follow studi includ immunolog test applic antibodi assai pertin trial assess safeti valid method evalu discuss expert report advers event includ abnorm laboratori valu present individu discuss term advers experi function natur serious causal effect critic assess rel safeti take account advers reaction made relat diseas treat therapeut approach characterist group patient preclin data toxicolog pharmacolog recommend made condit intent reduc incid advers reaction document applic except circumst respect therapeut indic applic show unabl provid comprehens data efficaci safeti normal condit indic product question intend encount rare applic expect provid comprehens evid present state scientif knowledg comprehens inform provid contrari gener accept principl medic ethic collect inform market author grant condit applic complet identifi programm studi time period compet author result form basi reassess benefit risk profil medicin product question suppli medic prescript case administ strict medic supervis possibl hospit radiopharmaceut author person packag leaflet medic inform draw attent medic practition fact particular medicin product question inadequ respect post market experi medicin product author countri inform respect advers drug reaction medicin product concern medicin product activ substanc relat usag rate inform worldwid studi relev safeti medicin product includ purpos advers drug reaction reaction noxiou unintend occur dose man prophylaxi diagnosi therapi diseas modif physiolog function case vaccin author countri inform monitor vaccin subject evalu preval diseas question compar nonvaccin subject submit allergen product respons period increas antigen exposur identifi establish medicin purpos demonstr pursuant articl ii compon medicin product establish recognis efficaci specif rule appli factor account order establish quot establish medicin quot compon medicin product time substanc quantit aspect substanc degre scientif interest substanc reflect publish scientif literatur coher scientif assess period time establish quot establish quot substanc case period time requir establish quot establish medicin quot compon medicin product decad systemat document substanc medicin product commun document submit applic cover aspect efficaci assess includ refer review relev literatur take account pre postmarket studi publish scientif literatur experi form epidemiolog studi compar epidemiolog studi document favour unfavour commun attent paid miss inform justif demonstr efficaci support studi lack expert report explain relev data submit concern product product intend market judgment made product studi consid similar product grant market authoris spite exist differ post market experi product compon import applic put special emphasi issu oj oj direct amend act access compet author request pk ph valu inform essenti oj oj direct amend direct eec oj annex ii part repeal direct success amend refer articl council direct eec oj council direct eec oj council direct eec oj council direct eec oj council direct eec oj council direct eec oj council direct eec oj council direct eec oj council direct eec oj council direct eec council direct eec oj council direct eec commiss direct eec oj council direct eec commiss direct ec oj commiss direct ec oj council direct eec council direct eec oj council direct eec council direct eec council direct eec council direct eec commiss direct ec oj council direct eec oj council direct eec oj council direct eec oj council direct eec oj council direct eec oj council direct eec council direct eec oj council direct eec oj part time limit transposit nation law refer articl gt tabl gt annex iii correl tabl gt tabl gt