direct ec european parliament council april approxim law regul administr provis member state relat implement good clinic practic conduct clinic trial 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 requir applic authoris place medicin product market accompani dossier particular document relat result test clinic trial carri product council direct eec approxim law member state relat analyt pharmaco toxicolog clinic standard protocol respect test medicin product lai uniform rule compil dossier includ present accept basi conduct clinic trial human found protect human right digniti human regard applic biologi medicin instanc reflect version helsinki declar clinic trial subject protect safeguard risk assess base result toxicolog experi prior clinic trial screen ethic committe member state compet author rule protect person data person incap give legal consent clinic trial special protect incumb member state lai rule effect person includ clinic trial result obtain person capabl give consent person includ clinic trial ground expect administ medicin product direct benefit patient outweigh risk clinic trial involv children improv treatment children repres vulner popul development physiolog psycholog differ adult make ag develop relat research import benefit medicin product includ vaccin children test scientif widespread achiev ensur medicin product signific clinic children fulli studi clinic trial requir purpos carri condit afford protect subject criteria protect children clinic trial laid case person incap give consent person dementia psychiatr patient inclus clinic trial case restrict basi medicin product trial administ individu ground assum direct benefit patient outweigh risk case written consent patient legal repres cooper treat doctor particip clinic trial notion legal repres refer back exist nation law includ natur legal person author bodi provid nation law order achiev optimum protect health obsolet repetit test carri commun countri harmonis technic requir develop medicin product pursu fora intern confer harmonis medicin product fall scope part annex council regul eec juli lai commun procedur authoris supervis medicin product human veterinari establish european agenc evalu medicin product includ product intend gene therapi cell therapi prior scientif evalu european agenc evalu medicin product hereinaft refer quot agenc quot assist committe proprietari medicin product mandatori commiss grant market authoris evalu committe request full detail result clinic trial applic market authoris base manner trial conduct committe requir applic authoris conduct clinic trial provis made agenc full inform conduct clinic trial medicin product singl opinion member state concern reduc delai commenc trial jeopardis peopl particip trial exclud possibl reject specif site inform content commenc termin clinic trial member state trial take place member state access inform european databas bring inform set due regard rule confidenti clinic trial complex oper gener last year involv numer particip trial site member state member state current practic diverg consider rule commenc conduct clinic trial requir carri vari wide result delai complic detriment effect conduct trial commun simplifi harmonis administr provis govern trial establish clear transpar procedur creat condit conduc effect coordin clinic trial commun author concern rule authoris implicit vote favour ethic committe compet author object period begin clinic trial except case rais complex problem explicit written authoris requir principl good manufactur practic appli investig medicin product special provis laid label product commerci clinic trial conduct research particip pharmaceut industri great benefit patient concern direct account special posit trial plan requir manufactur packag process trial carri medicin product market authoris mean direct eec manufactur import accord provis direct eec eec patient characterist cover indic market authoris label investig medicin product intend trial natur subject simplifi provis laid good manufactur practic guidelin investig product direct eec verif complianc standard good clinic practic subject data inform document inspect order confirm properli gener record report essenti order justifi involv human subject clinic trial person particip trial consent scrutini person inform inspect compet author properli authoris person provid person inform treat strictli confidenti made publicli direct appli prejudic direct eec european parliament council octob protect individu regard process person data free movement data make provis monitor advers reaction occur clinic trial commun surveil pharmacovigil procedur order ensur cessat clinic trial unaccept level risk measur implement direct adopt accord council decis ec june lai procedur exercis implement power confer commiss adopt direct articl scope direct establish specif provis conduct clinic trial includ multi centr trial human subject involv medicin product defin articl direct eec relat implement good clinic practic direct appli intervent trial good clinic practic set internation recognis ethic scientif qualiti requir observ design conduct record report clinic trial involv particip human subject complianc good practic assur right safeti trial subject protect result clinic trial credibl principl good clinic practic detail guidelin line principl adopt revis account technic scientif progress accord procedur refer articl detail guidelin publish commiss clinic trial includ bioavail bioequival studi design conduct report accord principl good clinic practic articl definit purpos direct definit appli quot clinic trial quot investig human subject intend discov verifi clinic pharmacolog pharmacodynam effect investig medicin product identifi advers reaction investig medicin product studi absorpt distribut metabol excret investig medicin product object ascertain safeti efficaci includ clinic trial carri site multipl site member state quot multi centr clinic trial quot clinic trial conduct singl protocol site investig trial site locat singl member state number member state member state countri quot intervent trial quot studi medicin product prescrib usual manner accord term market authoris assign patient therapeut strategi decid advanc trial protocol fall current practic prescript medicin separ decis includ patient studi addit diagnost monitor procedur appli patient epidemiolog method analysi collect data quot investig medicin product quot pharmaceut form activ substanc placebo test refer clinic trial includ product market authoris assembl formul packag authoris form unauthoris indic gain inform authoris form quot sponsor quot individu compani institut organis take respons initi manag financ clinic trial quot investig quot doctor person profess agre member state investig scientif background experi patient care requir investig respons conduct clinic trial trial site trial conduct team individu trial site investig leader respons team call princip investig quot investig brochur quot compil clinic clinic data investig medicin product product relev studi product product human subject quot protocol quot document describ object design methodolog statist consider organis trial term protocol refer protocol success version protocol protocol amend quot subject quot individu particip clinic trial recipi investig medicin product control quot inform consent quot decis written date sign part clinic trial freeli duli inform natur signific implic risk appropri document person capabl give consent person capabl give consent legal repres person concern unabl write oral consent presenc wit except case provid nation legisl quot ethic committe quot independ bodi member state consist healthcar profession medic member respons protect right safeti wellb human subject involv trial provid public assur protect thing express opinion trial protocol suitabl investig adequaci facil method document inform trial subject obtain inform consent quot inspect quot act compet author conduct offici review document facil record qualiti assur arrang resourc deem compet author relat clinic trial locat site trial sponsor contract research organis facil establish compet author see fit inspect quot advers event quot untoward medic occurr patient clinic trial subject administ medicin product necessarili causal relationship treatment quot advers reaction quot untoward unintend respons investig medicin product relat dose administ quot advers event advers reaction quot untoward medic occurr effect dose result death life threaten requir hospitalis prolong exist hospitalis result persist signific disabl incapac congenit anomali birth defect quot unexpect advers reaction quot advers reaction natur sever consist applic product inform investig brochur unauthoris investig product summari product characterist authoris product articl protect clinic trial subject direct appli prejudic nation provis protect clinic trial subject comprehens provis direct consist procedur time scale member state adopt detail rule protect abus individu incap give inform consent clinic trial undertaken forese risk inconveni weigh anticip benefit individu trial subject present futur patient clinic trial initi ethic committe compet author conclus anticip therapeut public health benefit justifi risk continu complianc requir perman monitor trial subject person give inform consent legal repres opportun prior interview investig member investig team understand object risk inconveni trial condit conduct inform withdraw trial time right subject physic mental integr privaci protect data accord direct ec safeguard trial subject person give inform consent legal repres written consent inform natur signific implic risk clinic trial individu unabl write oral consent presenc wit except case provid nation legisl subject result detriment withdraw clinic trial time revok inform consent provis made insur indemn cover liabil investig sponsor medic care medic decis made behalf subject respons appropri qualifi doctor qualifi dentist subject provid contact point obtain inform articl clinic trial minor addit relev restrict clinic trial minor undertaken inform consent parent legal repres obtain consent repres minor presum revok time detriment minor minor receiv inform capac understand staff experi minor trial risk benefit explicit minor capabl form opinion assess inform refus particip withdrawn clinic trial time consid investig princip investig incent financi induc compens direct benefit group patient obtain clinic trial research essenti valid data obtain clinic trial person give inform consent research method addition research relat directli clinic condit minor concern suffer natur carri minor scientif guidelin agenc clinic trial design minimis pain discomfort fear forese risk relat diseas development stage risk threshold degre distress special defin constantli monitor ethic committe paediatr expertis take advic clinic ethic psychosoci problem field paediatr endors protocol interest patient prevail scienc societi articl clinic trial incapacit adult give inform legal consent case person incap give inform legal consent relev requir list person capabl give consent appli addit requir inclus clinic trial incapacit adult refus inform consent onset incapac allow inform consent legal repres obtain consent repres subject presum revok time detriment subject person give inform legal consent receiv inform capac understand trial risk benefit explicit subject capabl form opinion assess inform refus particip withdrawn clinic trial time consid investig princip investig incent financi induc compens research essenti valid data obtain clinic trial person give inform consent research method relat directli life threaten debilit clinic condit incapacit adult concern suffer clinic trial design minimis pain discomfort fear forese risk relat diseas development stage risk threshold degre distress special defin constantli monitor ethic committe expertis relev diseas patient popul concern take advic clinic ethic psychosoci question field relev diseas patient popul concern endors protocol interest patient prevail scienc societi ground expect administ medicin product test produc benefit patient outweigh risk produc risk articl ethic committe purpos implement clinic trial member state measur establish oper ethic committe ethic committe give opinion clinic trial commenc issu request prepar opinion ethic committe relev clinic trial trial design evalu anticip benefit risk requir articl satisfactori conclus justifi protocol suitabl investig support staff investig brochur qualiti facil adequaci complet written inform procedur purpos obtain inform consent justif research person incap give inform consent specif restrict laid articl provis indemn compens event injuri death attribut clinic trial insur indemn cover liabil investig sponsor amount arrang reward compens investig trial subject relev aspect agreement sponsor site arrang recruit subject notwithstand provis articl member state decid compet author design purpos articl respons consider give opinion matter refer paragraph articl member state avail provis notifi commiss member state agenc ethic committe maximum dai date receipt valid applic give reason opinion applic compet author member state concern period examin applic opinion ethic committe send singl request inform supplementari suppli applic period laid paragraph suspend receipt supplementari inform extens dai period refer paragraph permiss case trial involv medicin product gene therapi somat cell therapi medicin product genet modifi organ case extens maximum dai permit product dai period extend dai event consult group committe accord regul procedur member state concern case xenogen cell therapi time limit authoris period articl singl opinion multi centr clinic trial limit territori singl member state member state establish procedur provid notwithstand number ethic committe adopt singl opinion member state case multi centr clinic trial carri member state simultan singl opinion member state concern clinic trial articl detail guidanc commiss consult member state interest parti draw publish detail guidanc applic format document submit applic ethic committe opinion inform subject safeguard protect person data articl commenc clinic trial member state measur ensur procedur articl commenc clinic trial sponsor start clinic trial ethic committe issu favour opinion compet author member state concern inform sponsor ground accept procedur reach decis run parallel depend sponsor commenc clinic trial sponsor requir submit valid request authoris compet author member state sponsor plan conduct clinic trial compet author member state notifi sponsor ground accept sponsor occas amend content request refer paragraph order due account ground sponsor fail amend request request consid reject clinic trial commenc consider valid request authoris compet author state paragraph carri rapidli exce dai member state lai shorter period dai area respons complianc current practic compet author notifi sponsor end period ground accept extens period refer subparagraph permiss case trial involv medicin product list paragraph extens maximum dai permit product dai period extend dai event consult group committe accord regul procedur member state concern case xenogen cell therapi time limit authoris period prejudic paragraph written authoris requir commenc clinic trial trial medicin product market authoris mean direct eec refer part annex regul eec medicin product special characterist medicin product activ ingredi activ ingredi biolog product biolog product human anim origin biolog compon human anim origin manufactur requir compon written authoris requir commenc clinic trial involv medicin product gene therapi somat cell therapi includ xenogen cell therapi medicin product genet modifi organ gene therapi trial carri result modif subject germ line genet ident authoris issu prejudic applic council direct eec april contain genet modifi micro organ eec april deliber releas environ genet modifi organ consult member state commiss draw publish detail guidanc format content request refer paragraph document submit support request qualiti manufactur investig medicin product toxicolog pharmacolog test protocol clinic inform investig medicin product includ investig brochur present content propos amend refer point articl substanti amend made protocol declar end clinic trial articl conduct clinic trial amend made conduct clinic trial procedur hereinaft commenc clinic trial sponsor make amend protocol amend substanti impact safeti trial subject chang interpret scientif document support conduct trial signific sponsor notifi compet author member state member state concern reason content amend inform ethic committe committe concern accord articl basi detail refer articl accord articl ethic committe give opinion maximum dai date receipt propos amend good due form opinion unfavour sponsor implement amend protocol opinion ethic committe favour compet author member state rais ground accept abovement substanti amend sponsor proce conduct clinic trial amend protocol case sponsor account ground accept adapt propos amend protocol withdraw propos amend prejudic point light circumst notabl occurr event relat conduct trial develop investig medicin product event affect safeti subject sponsor investig urgent safeti measur protect subject hazard sponsor forthwith inform compet author event measur ensur ethic committe notifi time dai end clinic trial sponsor notifi compet author member state member state concern ethic committe clinic trial end trial termin earli period reduc dai reason explain articl exchang inform member state territori clinic trial take place enter european databas access compet author member state agenc commiss extract request authoris refer articl amend made request provid articl amend made protocol provid point articl favour opinion ethic committe declar end clinic trial refer inspect carri conform good clinic practic substanti request member state agenc commiss compet author request authoris submit suppli inform clinic trial question data european databas consult member state commiss draw publish detail guidanc relev data includ european databas oper assist agenc method electron commun data detail guidanc drawn ensur confidenti data strictli observ articl suspens trial infring member state object ground condit request authoris refer articl longer met inform rais doubt safeti scientif valid clinic trial suspend prohibit clinic trial notifi sponsor thereof member state reach decis immin risk sponsor investig opinion deliv week case compet author concern forthwith inform compet author ethic committe concern agenc commiss decis suspend prohibit trial reason decis compet author object ground sponsor investig person involv conduct trial longer meet oblig laid forthwith inform thereof indic action remedi state affair compet author concern forthwith inform ethic committe compet author commiss action articl manufactur import investig medicin product member state measur ensur manufactur import investig medicin product subject hold authoris order obtain authoris applic subsequ holder authoris meet requir defin accord procedur refer articl member state measur ensur holder authoris refer paragraph perman continu dispos servic qualifi person accord condit laid articl council direct eec approxim provis laid law regul administr action relat proprietari medicin product respons carri duti paragraph articl member state measur ensur qualifi person refer articl direct eec prejudic relationship manufactur import respons context procedur refer articl direct ensur case investig medicin product manufactur member state concern batch medicin product manufactur check complianc requir commiss direct eec june lai principl guidelin good manufactur practic medicin product human product specif file inform notifi pursuant articl direct case investig medicin product manufactur countri product batch manufactur check accord standard good manufactur practic equival laid commiss direct eec accord product specif file product batch check accord inform notifi pursuant articl direct case investig medicin product compar product countri market authoris document certifi product batch manufactur condit equival standard good manufactur practic refer obtain product batch undergon relev analys test check confirm qualiti accord inform notifi pursuant articl direct detail guidanc element account evalu product object releas batch commun drawn pursuant good manufactur practic guidelin annex guidelin guidelin adopt accord procedur refer articl direct publish accord articl direct eec provis laid compli investig medicin product undergo check import member state batch releas certif sign qualifi person case qualifi person certifi regist equival document product batch satisfi provis articl regist equival document date oper carri remain dispos agent compet author period provis member state concern period event year person engag activ qualifi person refer articl direct eec investig medicin product time direct appli member state person compli condit laid articl direct authoris continu activ member state concern articl label particular offici languag member state outer packag investig medicin product outer packag packag publish commiss good manufactur practic guidelin investig medicin product adopt accord articl direct eec addit guidelin lai adapt provis relat label investig medicin product intend clinic trial characterist plan trial requir manufactur packag process trial conduct medicin product member state concern studi market authoris mean direct eec manufactur import accord provis direct eec patient particip trial characterist cover indic abovement authoris articl verif complianc investig medicin product good clinic manufactur practic verifi complianc provis good clinic manufactur practic member state appoint inspector inspect site concern clinic trial conduct trial site site manufactur site investig medicin product laboratori analys clinic trial sponsor premis inspect conduct compet author member state concern inform agenc carri behalf commun result recognis member state inspect coordin agenc framework power provid regul eec member state request assist member state matter inspect inspect report prepar made sponsor safeguard confidenti aspect made member state ethic committe agenc reason request request agenc framework power provid regul eec member state concern consult member state concern commiss request inspect verif complianc direct reveal differ member state subject arrang conclud commun countri commiss receipt reason request member state initi member state propos trial site sponsor premis manufactur establish countri undergo inspect inspect carri duli qualifi commun inspector detail guidelin document relat clinic trial constitut master file trial archiv qualif inspector inspect procedur verifi complianc clinic trial question direct adopt revis accord procedur refer articl articl notif advers event investig report advers event immedi sponsor protocol investig brochur identifi requir report report detail written report follow report identifi subject uniqu code number assign advers event laboratori abnorm identifi protocol critic safeti evalu report sponsor report requir time period protocol report death subject investig suppli sponsor ethic committe addit inform request sponsor detail record advers event report investig investig record submit member state territori clinic trial conduct request articl notif advers reaction sponsor ensur relev inform suspect unexpect advers reaction fatal life threaten record report compet author member state concern ethic committe case dai knowledg sponsor case relev follow inform subsequ commun addit dai suspect unexpect advers reaction report compet author concern ethic committe concern maximum fifteen dai knowledg sponsor member state ensur suspect unexpect advers reaction investig medicin product brought attent record sponsor inform investig year clinic trial sponsor provid member state territori clinic trial conduct ethic committe list suspect advers reaction occur period report subject safeti member state suspect unexpect advers reaction investig medicin product brought attent immedi enter european databas accord articl compet author member state agenc commiss access agenc make inform notifi sponsor compet author member state articl guidanc report commiss consult agenc member state interest parti draw publish detail guidanc collect verif present advers event reaction report decod procedur unexpect advers reaction articl gener provis direct prejudic civil crimin liabil sponsor investig end sponsor legal repres sponsor establish commun member state establish precis condit except circumst investig medicin product case devic administr made free charg sponsor member state inform commiss condit articl adapt scientif technic progress direct adapt account scientif technic progress accord procedur refer articl articl committe procedur commiss assist stand committe medicin product human set articl direct eec hereinaft refer committe refer made paragraph articl decis ec appli regard provis articl thereof period refer articl decis ec set month committe adopt rule procedur articl applic member state adopt publish law regul administr provis compli direct forthwith inform commiss thereof appli provis latest effect member state adopt provis refer direct accompani refer occas offici public method make refer laid member state member state commun commiss text provis nation law adopt field govern direct articl entri forc direct enter forc dai public offici journal european commun articl addresse direct address member state luxembourg april european parliament presid fontain council presid rosengren oj oj oj opinion european parliament novemb oj council common posit juli oj decis european parliament decemb council decis februari oj direct amend council direct eec oj oj direct amend commiss direct ec oj oj regul amend commiss regul ec oj oj oj oj direct amend direct ec oj oj direct amend commiss direct ec oj oj direct amend council direct ec oj oj