目標(biāo)產(chǎn)品概述

GuidanceforIndustryandReviewStaff

TargetProductProfile—AStrategicDevelopmentProcessToolDRAFTGUIDANCE行業(yè)與評(píng)審員指南目標(biāo)產(chǎn)品概述——戰(zhàn)略研發(fā)過程的工具草案Thisguidancedocumentisbeingdistributedforcommentpurposesonly.本指南文件的發(fā)布僅供征求意見之用。Commentsandsuggestionsregardingthisdraftdocumentshouldbesubmittedwithin60daysofpublicationintheFederalRegisterofthenoticeannouncingtheavailabilityofthedraftguidance.

SubmitcommentstotheDivisionofDocketsManagement(HFA-305),FoodandDrugAdministration,5630FishersLane,rm.1061,Rockville,MD

有關(guān)本草案文件的意見和建議應(yīng)在聯(lián)邦注冊(cè)公布本草案生效之日起60天內(nèi)遞交。將意見遞交至食品藥品監(jiān)督管理局檔案管理部（HFA-305），地址為：5630FishersLane,rm.1061,Rockville,MD20852。所有意見應(yīng)用聯(lián)邦注冊(cè)ForquestionsregardingthisdraftdocumentcontactJeanneM.Delaskoat301-796-0900.如對(duì)本草案文件有任何問題，請(qǐng)致電301-796-0900，JeanneM.Delasko將為您解答疑問。

U.S.DepartmentofHealthandHumanServices

FoodandDrugMarch2007

Procedural美國(guó)衛(wèi)生和人類服務(wù)部食品藥品管理局藥品評(píng)估和研究中心（CDER）2007年3月程序性的GuidanceforIndustryandReviewStaff

TargetProductProfile—AStrategicDevelopmentProcessTool行業(yè)與評(píng)審員指南 目標(biāo)產(chǎn)品概述——戰(zhàn)略研發(fā)過程的工具 Additionalcopiesareavailablefrom:可從下述地址獲得副本：OfficeofTrainingandCommunications

DivisionofDrugInformation,HFD-240

CenterforDrugEvaluationandResearch

FoodandDrugAdministration

5600FishersLane

Rockville,MD

20857

(Tel)301-827-4573藥品信息部的培訓(xùn)和通信辦公室，HFD-240藥品研究和評(píng)價(jià)中心食品和藥品管理局5600FishersLane

Rockville,MD

20857

(電話)301-827-4573/cder/guidance/index.htmU.S.DepartmentofHealthandHumanServices

FoodandDrugAdministrationMarch2007

Procedural美國(guó)衛(wèi)生和人類服務(wù)部食品和藥品管理局藥品研究和評(píng)價(jià)中心（CDER）2007年3月程序化文件

TABLEOFCONTENTS目錄INTRODUCTION引言BACKGROUND背景DESCRIPTIONANDBENEFITSOFATPPTPP的介紹及其優(yōu)點(diǎn)PurposeofaTPPTPP的目的AttributesofaTPPTPP的特點(diǎn)AdvantagesofaTPPTPP的優(yōu)點(diǎn)WhataTPPisNotTPP不具備的屬性UsingaTPPasPartofaBriefingDocument使TPP成為摘要文件的組成部分COMPLETINGATPP完成一份TPPLabelingConcepts標(biāo)簽內(nèi)容ProposedPromotionalClaims需要改進(jìn)的內(nèi)容的建議LINKAGESWITHOTHERINITIATIVES與其它主動(dòng)努力的關(guān)系CONCLUSION結(jié)論

APPENDIXA:CASESTUDIES附錄A：案例研究

A.

AdvantagesofUsingaTPPDuringDevelopmentofanAntibacterialDrug使用TPP在研發(fā)抗菌藥物時(shí)表現(xiàn)出來(lái)的優(yōu)勢(shì)

B.

AdvantagesofUsingaTPPDuringDevelopmentofaNewTherapyforOsteoporosis使用TPP在研發(fā)骨質(zhì)疏松質(zhì)的新療法時(shí)表現(xiàn)出來(lái)的優(yōu)勢(shì)

C.

DisadvantagesofNotUsingaTPPforanEOP2MeetingEOP2會(huì)審時(shí)未使用TPP所造成的不利之處

D.

DisadvantagesofNotUsingaTPPEarlyinDevelopment在研發(fā)早期不使用TPP所造成的不利之處

APPENDIXB:SAMPLESECTIONOFATPP附錄B：TPP的樣品部分

APPENDIXC:TARGETPRODUCTPROFILETEMPLATE附錄C：目標(biāo)產(chǎn)品概述的模板

GuidanceforIndustryandReviewStaff1\o""

TargetProductProfile—AStrategic

DevelopmentProcessTool行業(yè)與評(píng)審員指南1 目標(biāo)產(chǎn)品概述——戰(zhàn)略研發(fā)過程的工具Thisdraftguidance,whenfinalized,willrepresenttheFoodandDrugAdministration’s(FDA’s)currentthinkingonthistopic.

ItdoesnotcreateorconferanyrightsfororonanypersonanddoesnotoperatetobindFDAorthepublic.

Youcanuseanalternativeapproachiftheapproachsatisfiestherequirementsoftheapplicablestatutesandregulations.

Ifyouwanttodiscussanalternativeapproach,contacttheFDAstaffresponsibleforimplementingthisguidance.

IfyoucannotidentifytheappropriateFDAstaff,calltheappropriatenumberlistedonthetitlepageofthisguidance.本指南草案代表了截至完稿時(shí)FDA對(duì)本議題目前的想法。不授予任何人任何權(quán)利，也不對(duì)FDA或公眾造成任何約束。如果有其它方法能夠滿足當(dāng)前適用的條例和法規(guī)，也可以采用。如果您想同F(xiàn)DA討論其它替代方法，請(qǐng)與負(fù)責(zé)執(zhí)行本指南的FDA管理人員聯(lián)系。如果您不能確定應(yīng)和哪位FDA管理人員聯(lián)系，請(qǐng)按本指南標(biāo)題頁(yè)上的電話號(hào)碼查詢。

INTRODUCTION引言ThepurposeofthisguidanceistoprovidesponsorsandthereviewstaffintheCenterforDrugEvaluationandResearch(CDER)attheFoodandDrugAdministration(FDA)withinformationregardingtargetproductprofiles(TPPs).

ATPPisaformatforasummaryofadrugdevelopmentprogram2\o""describedintermsoflabelingconcepts.

ATPPcanbepreparedbyasponsorandthensharedwiththeappropriateFDAreviewstafftofacilitatecommunicationregardingaparticulardrugdevelopmentprogram.

SubmissionofaTPPisvoluntary.本指南旨在向主辦者和食品和藥品監(jiān)督管理局下屬的藥品研究和評(píng)價(jià)中心（CDER）的評(píng)審人員提供有關(guān)目標(biāo)產(chǎn)品概況（TPP）的信息。TPP即標(biāo)簽概念項(xiàng)下所描述的藥品研發(fā)項(xiàng)目2的摘要格式?？捎芍鬓k者起草某一特定藥品研發(fā)項(xiàng)目的TPP，然后與FDA的評(píng)審員共享，促進(jìn)溝通與交流。TPP文件的遞交是一種自愿行為。ThisguidancedescribesthepurposeofaTPP,itsadvantages,anditsoptimaluse.

ItalsoprovidesguidanceonhowtocompleteaTPPandrelatescasestudiesthatdemonstrateaTPP’susefulness.本指南闡述了TPP的目的、優(yōu)點(diǎn)和最佳使用方法；同時(shí)也給出指導(dǎo)如何完成TPP及能夠證明TPP有效性的相關(guān)案例研究。FDA’sguidancedocuments,includingthisguidance,donotestablishlegallyenforceableresponsibilities.

Instead,guidancesdescribetheAgency’scurrentthinkingonatopicandshouldbeviewedonlyasrecommendations,unlessspecificregulatoryorstatutoryrequirementsarecited.

TheuseofthewordshouldinAgencyguidancesmeansthatsomethingissuggestedorrecommended,butnotrequired.

AlthoughguidancedocumentsdonotlegallybindFDA,reviewstaffmaydepartfromguidancedocumentsonlywithappropriatejustificationandsupervisoryconcurrence.包括本指南在內(nèi)的

FDA指南文件并沒有產(chǎn)生法律上的強(qiáng)制實(shí)施責(zé)任。相反，這些指南描述了FDA對(duì)某一主題的現(xiàn)行思想，除非引用了特定的法律法規(guī)要求，否則僅作為建議來(lái)采用。FDA指南中的‘應(yīng)該’一詞表示建議或推薦某事，而不是要求。雖然這些指南文件在法律上對(duì)FDA沒有約束作用，但只有在同時(shí)具備適當(dāng)?shù)睦碛珊吞幱诒O(jiān)督的情況下，評(píng)審員方可偏離這些指南文件的要求。BACKGROUND背景In1997,aClinicalDevelopmentWorkingGroupcomposedofrepresentativesfromtheFDAandpharmaceuticalsponsorsbegandiscussionsonwaystoimprovesponsorandFDAinteractionsinthedrugdevelopmentprocess.

TheworkinggrouprecommendeduseofatemplatethatprovidesasummaryofdruglabelingconceptstofocusdiscussionsandaidintheunderstandingbetweensponsorsandtheFDA.

Thenamegiventothistemplatewasthetargetproductprofile.1977年，一個(gè)由FDA和藥品主辦者的代表組成的臨床研發(fā)工作小組展開了關(guān)于促進(jìn)主辦者和FDA之間在藥品研發(fā)過程中相互作用的方式的討論。該工作小組建議使用一種模板來(lái)提供藥品標(biāo)簽概念的摘要，用于集中討論和增進(jìn)主辦者與FDA之間的理解。這個(gè)模板被命名為目標(biāo)產(chǎn)品概況。ExperiencewithTPP-focusedmeetingswithsponsorsattheFDAhasindicatedthatsuchdocumentscanbeuseful(seeAppendixA).

AnefficientdialoguebetweenasponsorandtheFDAduringthedrugdevelopmentprocesscanminimizetheriskoflate-stagedrugdevelopmentfailures,increasetheprobabilitythatoptimalsafetyandefficacydataareavailableinatimelymanner,improvelabelingcontent,andpossiblydecreasethetotaltimeinvolvedwithdrugdevelopment.根據(jù)FDA召開的主辦者參以重點(diǎn)討論TPP的會(huì)議可以看出，這些文件是相當(dāng)有用的（見附錄A）。在藥品研發(fā)過程中主辦者和FDA之間的有效對(duì)話可以使藥品研發(fā)后期出現(xiàn)失敗的風(fēng)險(xiǎn)最小化；提高及時(shí)提供最佳安全性和功效數(shù)據(jù)的可能性；改進(jìn)標(biāo)簽內(nèi)容并有可能縮短藥品研發(fā)的整體時(shí)間。III.

DESCRIPTIONANDBENEFITSOFATPPTPP的說明及其優(yōu)點(diǎn) A.

PurposeofaTPPTPP的目的ThepurposeofaTPPistoprovideaformatfordiscussionsbetweenasponsorandtheFDAthatcanbeusedthroughoutthedrugdevelopmentprocess,frompre-investigationalnewdrugapplication(pre-IND)orinvestigationalnewdrugapplication(IND)phasesofdrugdevelopmentthroughpostmarketingprogramstopursuenewindicationsorothersubstantialchangesinlabeling.

TheTPPembodiesthenotionofbeginningwiththegoalinmind.

Thatis,thesponsorspecifiesthelabelingconceptsthatarethegoalsofthedrugdevelopmentprogram,documentsthespecificstudiesintendedtosupportthelabelingconcepts,andthenusestheTPPtoassistinaconstructivedialoguewiththeFDA.

Theidealversionofwhatthesponsorwouldliketoclaiminlabelingguidesthedesign,conduct,andanalysisofclinicaltrialstomaximizetheefficiencyofthedevelopmentprogram.

Ideally,thefinalversionoftheTPPwillbesimilartotheannotateddraftlabelingsubmittedwithanewdrugapplication(NDA)orbiologicslicenseapplication(BLA).

TPP的目的在于給主辦者和FDA提供一個(gè)貫穿整個(gè)藥品研發(fā)過程的討論形式，這個(gè)過程是指從藥品研發(fā)的新藥臨床研究前申請(qǐng)（pre-IND）或新藥臨床研究申請(qǐng)階段到上市后的項(xiàng)目直至完成新的適應(yīng)癥或標(biāo)簽的其它實(shí)際性變更的整個(gè)過程。TPP體現(xiàn)了這樣一種概念，即從心中的目標(biāo)開始。也就是說，主辦者在標(biāo)簽概念里列出藥品研發(fā)項(xiàng)目的目標(biāo)并將用于支持標(biāo)簽概念的具體研究記錄下來(lái)，然后使用TPP來(lái)協(xié)助開展與FDA之間的建設(shè)性對(duì)話。主辦者希望在標(biāo)簽中主張的理想版本指導(dǎo)著臨床試驗(yàn)的設(shè)計(jì)、實(shí)施和分析，從而最大限度的提高研發(fā)項(xiàng)目的效率。從理想的角度來(lái)說，TPP的最終版本應(yīng)與新藥申請(qǐng)（NDA）或生物制劑許可申請(qǐng)（BLA）時(shí)所遞交的有注解的標(biāo)簽草稿相似。AttributesofaTPPTPP的特點(diǎn)Ideally,theTPPprovidesastatementoftheoverallintentofthedrugdevelopmentprogram,andgivesinformationaboutthedrugataparticulartimeindevelopment.

Usually,theTPPisorganizedaccordingtothekeysectionsinthedruglabelingandlinksdrugdevelopmentactivitiestospecificconceptsintendedforinclusioninthedruglabeling.

Thesponsorcandraftandupdatepertinentsectionsofthetemplatethatareintendedtosupportthespecificstatementsinlabeling.

ThesponsorcanalsousetheseupdatedversionsoftheTPPinpreparationfordiscussionswithFDAreviewstafftoidentifythemostimportantdevelopmentgoalsforthedrug.

TheTPPisadynamicsummarythatchangesasknowledgeofthedrugincreases.

Foroptimaluse,werecommendthattheTPPbeupdatedregularlytoreflectnewinformationaboutthedrugandchangesintheclinicaldevelopmentprogram.一份完美的TPP需要說明藥品研發(fā)項(xiàng)目的總體目的，并提供研發(fā)過程某一特定時(shí)間內(nèi)藥品的信息。一般來(lái)說，TPP是根據(jù)藥品標(biāo)簽中的關(guān)鍵部分來(lái)組織的，并且將藥品研發(fā)活動(dòng)和藥品標(biāo)簽中計(jì)劃包含的特定概念連接起來(lái)。主辦者可以起草和更新模板中用來(lái)支持標(biāo)簽中的特定聲明的有關(guān)章節(jié)。主辦者還可以使用更新后的TPP版本來(lái)準(zhǔn)備與FDA評(píng)審人員之間討論，說明藥品研發(fā)的最主要目標(biāo)。TPP是一份動(dòng)態(tài)摘要，隨著對(duì)藥品認(rèn)識(shí)的增加，它也會(huì)發(fā)生相應(yīng)的變化。為了最好的利用TPP，我們建議定期更新TPP，從而反映出藥品的新信息和臨床研究中出現(xiàn)的變化。Generally,thefinalTPPisshorterthantheultimateannotateddraftlabelingsinceitcapturesonlyasummaryofthedrugdevelopmentactivitiesandconcepts.

EarlyTPPscanbebriefdependingonthestatusofthesponsor’sdevelopmentprocess.由于最終的TPP僅包含了藥品研發(fā)活動(dòng)及其概念摘要，所以它通常要比有注解的標(biāo)簽最終草稿要簡(jiǎn)短。可以根據(jù)主辦者的研發(fā)過程的情況對(duì)早期的TPP進(jìn)行精簡(jiǎn)。C.

AdvantagesofaTPPTPP的優(yōu)點(diǎn) Awell-organizedTPPcansavemeetingtimefordiscussionofissuesbyeliminatingtheneedforasponsor’sintroductiontothehistoryofthedrugdevelopmentprogram.

SponsorscanalsouseaTPPtostreamlinetheirinteractionswithFDAreviewstaffbydistinguishingTPPentriesandsectionsthathavebeenpreviouslydiscussedfromentriesthatarethecurrentorfuturefocusofadiscussion.

Thisprocesscaneliminatetheneedtorevisittheestablishedentries,unlessthedevelopmentgoalschangeornewscientificissuesemerge.

TheuseofaTPPisespeciallyimportantatpre-newdrugapplication(pre-NDA)andpre-biologicslicenseapplication(pre-BLA)meetings,whenitcanhelpthereviewstafffocusonasponsor’sgoalsandmakesurepreviouslydiscusseditemshavenotchangedwhenthesponsorsubmitsanNDAorBLA.

InaBriefingDocument,asponsorcanuseaTPPtoquicklyupdatenewFDAorsponsorpersonnelwhojointheprogram.

一份組織良好的TPP能夠使主辦者省去介紹藥品研發(fā)項(xiàng)目歷史的必要，從而節(jié)省在會(huì)議上討論問題的時(shí)間。主辦者還可以使用TPP將之前討論過的TPP條目和章節(jié)與現(xiàn)在或?qū)?lái)需要討論的條目和章節(jié)區(qū)分開來(lái)，使之與FDA評(píng)審人員之間的互動(dòng)簡(jiǎn)單化。這種方法能夠消除對(duì)已建立的條目進(jìn)行第二次訪問的必要，除非研發(fā)目標(biāo)發(fā)生變化或者出現(xiàn)新的科學(xué)問題。TPP的使用對(duì)新藥申請(qǐng)前（pre-NDA）和生物制劑許可申請(qǐng)前（pre-BLA）的會(huì)議尤其重要，因?yàn)樗兄贔DA評(píng)審員將重心放在主辦者的目標(biāo)上，并且確保主辦者在遞交NDA或BLA時(shí)，先前討論過的問題都沒有發(fā)生變化。在一份簡(jiǎn)要文件中，主辦者可運(yùn)用TPP迅速更新參加該項(xiàng)目的FDA官員和主辦者人員的名單。ATPPenablesasponsortopursuethedesiredoutcome(i.e.,approvalandoptimallabelingofasafeandeffectivedrug)inthemostefficientmannerwithrespecttoFDAinteractionbecauseallsuchinteractionisfocusedontheexplicitlystatedgoalsofthedevelopmentprogram.TPP能夠使主辦者以最有效的方式在與FDA的相互溝通上獲得他希望的結(jié)果（也即是使一種安全的和有效的藥品獲得批準(zhǔn)并采用最佳標(biāo)識(shí)），因?yàn)樗兄T如此類的溝通均集中在詳細(xì)說明的研發(fā)項(xiàng)目目標(biāo)上。TheTPPispartoftheproprietaryINDfile.TPP是IND文件的一部分WhataTPPisNotTPP所不具備的SubmissionofaTPPisvoluntaryandisnotrequiredforgrantinganend-of-phase2(EOP2)orothermeetingwithsponsors.TPP的遞交是一種自愿行為；第2期臨床試驗(yàn)結(jié)束（EOP2）或其他與主辦者之間的會(huì)議不要求遞交TPP。ATPPdoesnotrepresentanimplicitorexplicitobligationonthesponsor’sparttopursueallstatedgoals.

ProvidingaTPPsummarydoesnotconstrainthesponsortosubmitdraftlabelinginanNDAorBLAthatisidenticaltotheTPP.

就主辦者而言，TPP并不代表其實(shí)現(xiàn)全部既定目標(biāo)的暗含或明確義務(wù)。提供一份TPP摘要并沒有強(qiáng)制主辦者在遞交NDA和BLA申請(qǐng)時(shí)遞交一份與TPP相同的標(biāo)簽草稿。TheTPPdoesnotrepresentacommitmentoranobligationontheFDA’sparttoconsidertheresultantevidenceasadequatetoattainapproval.

FDAconcordancewithpartoralloftheTPPdoesnotrepresentacommitmenttoapprovetheidenticallanguageinthefinallabel.就FDA而言，TPP不是獲得批準(zhǔn)的充分條件，它并不代表FDA的承諾或者義務(wù)。FDA對(duì)部分或整個(gè)TPP表示認(rèn)可，也不表示FDA承諾批準(zhǔn)最終標(biāo)簽中的相同語(yǔ)言。UsingaTPPasPartofaBriefingDocument將TPP作為摘要文件的一個(gè)組成部分RegulatoryproceduresandAgencyrecommendationsintroducedinrecentyearsprovidesponsorswithstandardizedmechanismstopreparesounddrugdevelopmentproposals,submitthemtotheFDAforreview,andengageinastructureddialoguetoreachanunderstandingoftheFDA’sthinkingonvariousaspectsofadrugdevelopmentprogram.

Specifically,regulationsrelatedtoEOP2meetings(21CFR312.47(b)),theguidanceforindustryFormalMeetingsWithSponsorsandApplicantsforPDUFAProducts,3\o""andtheguidanceforindustrySpecialProtocolAssessmentallcontributetofosteringanenvironmentthatencouragesproactivedialoguebetweensponsorsandFDAreviewstaffondrugdevelopmentprograms.

FDAregulationsandguidancessuchasthoserelatingtodrugsandbiologicswithafasttrackdesignation,4\o""drugsforseverelydebilitatingorlife-threateningdiseases(21CFR312.82),anddrugsandbiologicspursuingacceleratedapproval(21CFRpart314,subpartH)furtherrecognizeandreinforcestructured,proactivedialogue.

TheTPPsummarygoesastepfurtherintherecognitionofthevalueofproactivedialogue.

TheTPPenhancesasponsor’seffortinpreparingaBriefingDocumentthatwillprovidethebasisforaconstructivemilestonemeetingwithreviewstaff.最近幾年，所引用的法規(guī)程序和FDA建議在許多方面為主辦者提供了標(biāo)準(zhǔn)化的機(jī)制，如準(zhǔn)備合理的藥品研發(fā)方案、遞交方案給FDA進(jìn)行評(píng)審并與FDA進(jìn)行交流，了解FDA對(duì)藥品研發(fā)項(xiàng)目的各個(gè)方面的想法等。特別是，與EOP2會(huì)議有關(guān)的法規(guī)（21CFR312.47（b））、行業(yè)指南《與申請(qǐng)人和主辦者之間關(guān)于PDUFA產(chǎn)品的的正式會(huì)議》，3和行業(yè)指南《特別方案評(píng)估》均為鼓勵(lì)主辦者與FDA評(píng)審人員就藥品研發(fā)項(xiàng)目展開積極對(duì)話創(chuàng)造了環(huán)境。FDA法規(guī)和指南，例如那些與具有快速追蹤指定的藥物和生物制品、用于治療嚴(yán)重衰弱或危及生命的疾病的藥物(21CFR312.82)，和希望獲得加速批準(zhǔn)的藥物和生物制品(21CFRpart314,subpartH)等相關(guān)的法規(guī)和指南進(jìn)一步認(rèn)可和鞏固了有組織的積極對(duì)話。TPP摘要是在認(rèn)可積極對(duì)話的價(jià)值之后的進(jìn)一步行動(dòng)。TPP加強(qiáng)了主辦者準(zhǔn)備摘要文件的效果，這份摘要文件將成為與評(píng)審員之間的具有建議性的里程碑會(huì)議的基礎(chǔ)。Withrespecttomeetingsbetweenasponsorandthereviewstaff,theguidanceforindustryFormalMeetingsWithSponsorsandApplicantsforPDUFAProductsstatesthefollowingkeypoints:關(guān)于主辦者和評(píng)審員之間的會(huì)議，行業(yè)指南《申請(qǐng)人和主辦者之間關(guān)于PDUFA產(chǎn)品的正式會(huì)議》闡述了以下關(guān)鍵要點(diǎn)：ThesponsorshouldprepareandsubmitaBriefingDocument(alsoreferredtoasaninformationpackage),includingspecificinformationonthesponsor’sclinicaldevelopmentplanandspecificquestionsfromthesponsorposedtothereviewstaffforfeedback.主辦者應(yīng)準(zhǔn)備和遞交一份摘要文件（也稱為信息包），包括關(guān)于主辦者的臨床開發(fā)計(jì)劃的詳細(xì)資料和主辦者向評(píng)審員提出的具體問題。Thereviewstaffwillreviewanddiscussthebackgroundinformation,aswellasthesponsor’squestions,inadvanceofthemeeting.在召開會(huì)議之前，評(píng)審員將審查和討論這些背景資料和主辦者提出的問題。Themeeting’sdialoguewillfocusonthequestionsposedtothereviewstaff,therebyprovidingconstructivefeedback.會(huì)議談話將集中在主辦者向?qū)彶槿藛T提出的問題上，并提供建議性的反饋信息。ATPPcanprovidethestructuretosuchaBriefingDocumentandhelpensurethesponsorpresentsallrelevantmedicalandscientificinformationinthecontextoftheoveralldrugdevelopmentgoals.

TPP能夠提供組織結(jié)構(gòu)給這類摘要文件，而且有助于保證主辦者在總體藥品研發(fā)目標(biāo)中展示所有相關(guān)的醫(yī)藥和科學(xué)方面的信息。TheTPPitselfcanassistintheachievementandmaintenanceofconstructivefeedbackandunderstandingbetweentheFDAandsponsor,whichiscriticalforsuccessfuldrugdevelopment.TPP本身有助于實(shí)現(xiàn)和維持建設(shè)性的反饋，并有助于FDA和主辦者之間的相互理解，這對(duì)于藥品研發(fā)的成功是非常關(guān)鍵的。TheFDAofficialmeetingminutesshouldreflectwhenthesponsorsubmittedaTPPandthereviewstaffandthesponsordiscusseditscontents.

Forthemeetings,theTPPshouldbeattachedasanappendixtotheofficialmeetingminutes.FDA的正式會(huì)議備忘錄中應(yīng)反映出主辦者何時(shí)遞交了TPP，而且評(píng)審員和主辦者何時(shí)對(duì)TPP的內(nèi)容進(jìn)行了討論。TPP應(yīng)作為正式會(huì)議備忘錄的附件附在其后。IV.

COMPLETINGATPP完成一份TPPA.

LabelingConcepts標(biāo)簽的概念TheTPPcanincludeinformationfromeachdiscipline.

Usually,theTPPbrieflysummarizesthespecificstudies(bothplannedandcompleted)thatwillsupplytheevidenceforeachconclusionthatisalabelingconcept.

TheTPPshouldbeorganizedaccordingtokeysectionsinthedrug’slabeling.

Typicalkeysectionsfromwhichasponsorcanchoose,dependingonthenatureofthemeeting,include:TPP可以包含各方面的信息。一般來(lái)講，TPP對(duì)具體（計(jì)劃和完成）的研究進(jìn)行簡(jiǎn)要的總結(jié)，為每項(xiàng)結(jié)論提供依據(jù)，這就是標(biāo)簽的概念。應(yīng)根據(jù)藥品標(biāo)簽中的關(guān)鍵部分來(lái)組織TPP。主辦者可根據(jù)會(huì)議的性質(zhì)來(lái)選擇典型的關(guān)鍵部分，包括：IndicationsandUsage適應(yīng)癥和應(yīng)用DosageandAdministration用量和用法DosageFormsandStrengths劑型和濃度Contraindications禁忌癥WarningsandPrecautions警告和注意事項(xiàng)AdverseReactions不良反應(yīng)DrugInteractions藥物相互作用UseinSpecificPopulations特定人群的使用DrugAbuseandDependence藥物濫用和依賴性O(shè)verdosage過量給藥Description性狀 ClinicalPharmacology臨床藥理學(xué)NonclinicalToxicology非臨床毒理學(xué)ClinicalStudies臨床研究References參考文獻(xiàn)HowSupplied/StorageandHandling包裝/貯存和處理辦法PatientCounselingInformation患者咨詢信息TheTargetProductProfileTemplate,showninAppendixC,detailstheinformation(initalics)thatwesuggestsponsorsincludeineachsection.5\o""

Ingeneral,werecommendsponsorsusethefollowingstepstocompleteaTPP:附錄C是目標(biāo)產(chǎn)品概況模板，模板中提供了詳細(xì)的信息5（斜體字），這些是我們建議主辦者在每個(gè)部分中提供的信息。一般而言，我們建議主辦者按照下列步驟來(lái)完成TPP：Sponsorsshouldcompletetheappropriatesections(seeAppendixBforanexampleofacompletedsectionofaTPP)dependingonthedrug,stageofdevelopment,andthequestionsandissuestheywishtodiscusswiththereviewstaff.

Sponsorscandeletenonrelevantsectionsoraddadditionalsubsections.

Eachsectioncontainsthefollowingareas:主辦者應(yīng)根據(jù)藥物、研發(fā)階段以及他希望與評(píng)審員進(jìn)行討論的問題和事項(xiàng)來(lái)完成相應(yīng)部分（附錄B給出了已完成部分內(nèi)容的TPP范例）。主辦者可刪去無(wú)關(guān)的部分或者增加另外的小節(jié)。每個(gè)部分包含以下內(nèi)容：Target.

Thisareashouldincludelabelinglanguagesponsorshopetoachievebasedontheoutcomeoftheindicatedstudies.目標(biāo)。這個(gè)部分應(yīng)包含主辦者根據(jù)研究的結(jié)果希望表達(dá)的標(biāo)簽語(yǔ)言。Annotations.

Thisareashouldincludesummaryinformationregardingcompletedorplannedstudiestosupportthetarget.

Sponsorsshouldalsoincludetheprotocolnumber,serialnumber,andsubmissiondatethatwillhelpguidediscussionabouttheoveralldevelopmentprogram,thenumberofstudies,andhowsponsorswillconductthestudies.

Sponsorscanincludeadditionalinformationaboutthestudies,buttheyshouldavoidrepeatingdetailcontainedelsewhereintheBriefingDocument.注解。本部分內(nèi)容應(yīng)包含關(guān)于已完成或計(jì)劃好的研究信息總結(jié)，用來(lái)支持目標(biāo)。主辦者還應(yīng)提供方案編號(hào)、序列號(hào)和遞交日期，這些信息有助于指導(dǎo)討論總體研發(fā)項(xiàng)目、研究的數(shù)量、以及主辦者將如何開展研究等。主辦者可以包含研究的其他信息，但應(yīng)避免重復(fù)摘要文件中所涵蓋的內(nèi)容。Comments.

Thisareashouldincludeadditionalinformationthatcanaidcommunicationandunderstanding(e.g.,dateofdiscussionswithFDAreviewstaff,progresstowardtarget,keypointsduringdiscussions,keyissuesfordiscussions,questions).

Sponsorsareencouragedtousethisareatoprovideclarity.評(píng)論。本部分應(yīng)包含有助于交流和理解的附加說明（如，與FDA評(píng)審員進(jìn)行討論的日期、目標(biāo)進(jìn)展情況、討論過程的關(guān)鍵要點(diǎn)、討論的關(guān)鍵內(nèi)容、問題等）。鼓勵(lì)主辦者利用這個(gè)部分的內(nèi)容使一切清晰化。ToavoidrevisitingportionsoftheTPPasthedocumentevolves,sponsorsshouldindicateitemstheyhavepreviouslydiscussedwiththereviewstaffbyanotation(e.g.,previouslydiscussedon)andareferencetotheinteractionwiththereviewstaff(e.g.,previouslydiscussedon05MAY2004,duringEOP2meeting).

SponsorscanincludethisnotationintheTarget,Annotations,orCommentsareaoftheTPP,asapplicable.

為了避免重復(fù)閱讀TPP的部分內(nèi)容，對(duì)于已經(jīng)與評(píng)審員討論過的項(xiàng)目，主辦者應(yīng)使用注釋來(lái)說明（如已討論），而且指明參考文件（如已在2004年5月5日的EOP2會(huì)議上討論）。若適合，主辦者可以將這些注釋列入TTP的目標(biāo)、注解或評(píng)論部分。Sponsorsshouldupdatethemilestoneboxasneeded.

(ThemilestoneboxappearsatthetopoftheTPP,regardlessofthesectionsofthetemplatecompleted.)

Sponsorsshouldindicateaversiondateeachtimetheysubmitanupdatedtemplate.主辦者應(yīng)根據(jù)需要更新重要事件表。（無(wú)論模板各個(gè)部分是否已完成，重要事件表通常位于TPP的頂部。）主辦者每次遞交更新后的模板時(shí)，應(yīng)注明版本日期。Sponsorsshouldupdatethetemplateatappropriatemilestones.

Sponsorscanhighlightnewinformation.

AfterimplementationoftheTPP,sponsorscancontinuetousetheTPPtohelpwithfinallabelingdiscussionsrelatedtobothinitialapprovalsandlabelingsupplements.主辦者應(yīng)在相應(yīng)的轉(zhuǎn)折點(diǎn)更新模板。主辦者可以突出強(qiáng)調(diào)新的信息。在執(zhí)行TPP之后，主辦者可以繼續(xù)使用TPP對(duì)標(biāo)簽進(jìn)行最后的討論，主要針對(duì)最初的批準(zhǔn)和標(biāo)簽的補(bǔ)充說明。B.

ProposedPromotionalClaims 建議的促銷主張ATPPcanassistinaconstructivedialoguewithFDAreviewstaffregardingproposedpromotionalclaimsand/orpresentationsforuseinproductpromotionalmaterialsandthedocumentationofspecificstudiesintendedtosupporttheseclaims.

TheTPPcanlinkdrugdevelopmentactivitiestospecificconceptsintendedforproposedpromotionalclaims.TPP有助于開展與FDA評(píng)審員之間的建設(shè)性對(duì)話—關(guān)于產(chǎn)品促銷材料中使用的建議促銷主張和介紹以及用于支持這些主張的具體研究的證明文件。TPP能夠?qū)⑺幤费邪l(fā)活動(dòng)和計(jì)算用于所建議的促銷主張的具體概念聯(lián)系起來(lái)。Ingeneral,werecommendsponsorsusethefollowingstepstocompletetheTarget,Annotations,andCommentsareasofaTPPforproposedpromotionalclaims:一般而言，我們建議主辦者按照以下步驟來(lái)完成TPP的目標(biāo)、注解和意見部分中的建議促銷主張。Target.

ThisareashouldprominentlystateProposedPromotionalClaim(s)andshouldincludetheproposedclaimsand/orpresentationsforuseintheproduct’spromotionalmaterials.目標(biāo)。本部分內(nèi)容應(yīng)重點(diǎn)闡述所建議的促銷主張，而且應(yīng)包含產(chǎn)品的促銷材料中使用的建議內(nèi)容和/或介紹。Annotations.

Thisareashouldincludesummaryinformationregardingcompletedorplannedstudiestosupporttheproposedpromotionalclaimsand/orpresentations.

Sponsorsshouldincludetheprotocolnumber,serialnumber,andsubmissiondatethatwillhelpguidediscussionabouttheoveralldevelopmentprogram,thenumberofstudies,andhowsponsorswillconductthestudies.注解。本部分應(yīng)包含用于支持所建議的促銷主張和/或介紹的已完成或已計(jì)劃的研究信息總結(jié)。主辦者應(yīng)提供方案編號(hào)、序列號(hào)和遞交日期，這些信息有助于為總體研發(fā)項(xiàng)目、研究的數(shù)量、以及主辦者將如何開展研究的討論提供指導(dǎo)。Comments.

Thisareashouldincludeadditionalinformationaboutthestudiesthatcanaidincommunicationandunderstanding.意見。本部分應(yīng)包含有助于溝通和理解的研究附加說明。LINKAGESWITHOTHERINITIATIVES與其它創(chuàng)始活動(dòng)的關(guān)系TheTPPinitiativecomplementsotherinitiativesinwhichtheFDAandpharmaceuticalsponsorsareparticipating.

TheFDAissponsoringtheCriticalPathInitiativefollowingtheMarch16,2004,releaseofthereportentitled“Innovation/Stagnation:

ChallengeandOpportunityontheCriticalPathtoNewMedicalProducts.”6\o""

Inthisreport,theFDAsuggeststhatthereisasubstantialopportunitytoincreasethepaceofdiscoveryanddevelopmentofnewmedicalproducts.

Thereportstressestheneedfornewtoolsfromdiscoveryorthepre-INDphasethroughapprovalofthemedicalproduct.

SinceaTPPcanfacilitateconstructivediscussionandunderstandingbetweenasponsorandtheFDA,theTPPrepresentsapotentialcriticalpathtool.TPP的開創(chuàng)是FDA和藥品主辦者正在參與的其他創(chuàng)始活動(dòng)的補(bǔ)充。FDA于2004年3月16日起動(dòng)了關(guān)鍵途徑創(chuàng)始行動(dòng)，并做了題為“革新/停滯：新藥產(chǎn)品的關(guān)鍵途徑帶來(lái)的挑戰(zhàn)和機(jī)遇”6的報(bào)告。在這份報(bào)告中，F(xiàn)DA認(rèn)為有大量的機(jī)會(huì)來(lái)加快新藥產(chǎn)品的發(fā)現(xiàn)和研究的步伐。該報(bào)告強(qiáng)調(diào)了新工具在發(fā)現(xiàn)新藥或開始臨床試驗(yàn)前到藥品獲得批準(zhǔn)的過程中的重要性。因?yàn)門PP能促進(jìn)主辦者和FDA之間的建設(shè)性討論和理解，所以TPP代表著一種潛在的關(guān)鍵途徑工具。CONCLUSION結(jié)論BoththeFDAandsponsorshaveseentheadvantagesofusingaTPPatmeetingsearlyinthedrugdevelopmentprocess.

UseofaTPPcanfacilitatetheefficiencyofsponsor-FDAinteractionsandcommunications.

ATPPhelpsfocusasponsor’sdrugdevelopmentteamandFDAreviewstaffonthedrugdevelopmentgoalsintermsofdruglabeling.

Ifusedproperly,aTPPcanhelpaddressissuesearlyoninthedrugdevelopmentprocesstherebypreventinglate-stagedrugdevelopmentfailuresanddecreasingthetotaltimeinvolvedwithdrugdevelopment.FDA和主辦者都已經(jīng)看到在藥品研發(fā)早期的會(huì)議時(shí)使用TPP的優(yōu)點(diǎn)。使用TPP能夠促進(jìn)主辦者-FDA之間的相互作用和交流的效率。就藥品標(biāo)簽來(lái)講，TPP有助于使主辦者的藥品研發(fā)隊(duì)伍和FDA評(píng)審人員將重點(diǎn)集中在藥品的研發(fā)目標(biāo)上。如果使用得當(dāng)，TPP有助于在藥品研發(fā)早期提出問題，從而預(yù)防藥品研發(fā)晚期出現(xiàn)失敗，并且減少藥品研發(fā)所需的總體時(shí)間。AppendixA:附錄A：

CaseStudies案例研究A.

AdvantagesofUsingaTPPDuringDevelopmentofanAntibacterialDrug在抗菌藥物的研發(fā)過程中使用TPP的優(yōu)點(diǎn)From1999-2001,theDivisionofAnti-InfectiveDrugProducts(DAIDP)pilotedtheuseofaTPPwithasponsorduringphase2andphase3inthedevelopmentprogramofanantibacterialdrug.

Thedrugproductwasanewmolecularentityforwhichthesponsorwasseekingmultipleindicationsandforwhichthesponsorwishedtodevelopthreeformulationssimultaneously.

Thisgoalcreatedadditionalchallengesinthedrugdevelopmentprocess,butwasconsideredbybothpartiestobeagoodtestcaseforusingaTPP.

TheDAIDPsuggestedholdingaface-to-facemeetingwiththesponsorbeforetheEOP2meetingsolelytodiscusstheTPP.

1999年至2001年，抗感染藥品處（DAIDP）指導(dǎo)一位主辦者在抗菌藥物研發(fā)項(xiàng)目的第2和第3期中使用TPP。這是一種主辦者正在探索多種適應(yīng)癥，而且希望同時(shí)開發(fā)出三種配方的新分子實(shí)體。這個(gè)目標(biāo)給藥品研發(fā)過程帶來(lái)了額外的挑戰(zhàn)，但雙方都認(rèn)為這是一次嘗試運(yùn)用TPP的好機(jī)會(huì)?？垢腥舅幤诽幗ㄗh在EOP2會(huì)議之前召開一次與主辦者面對(duì)面討論TPP的會(huì)議。TheTPPfacilitatedFDA-sponsordiscussionsregardingthedevelopmentoftheantimicrobialproductandtheappropriatenessoftargetedlabelingstatementsresultingfromtheproposeddevelopmentprogram.

TheTPPmeetinghelpedtoclarifyforthesponsorthedatacurrentlythoughttobesupportiveofitsproposedindications.

TheproposedstatementswithintheTPPwereusedtoidentifyanddiscusscriticalelementsofthedevelopmentprogram.

TheTPPmeetingwiththeDAIDPwashelpfulinlightoftheevolvingscientificandregulatoryissues.

ThesediscussionsgavethesponsortheopportunitytoclearlydelineatedesiredlabelingconceptsandensuredtheFDAwassatisfiedthattheproposedclinicaldevelopmentprogramcouldsupportlabelingconceptsthatwereproposedintheTPP.

TPP促進(jìn)FDA-主辦者之間展開討論，討論的主題是關(guān)于抗菌制劑的研發(fā)和根據(jù)研發(fā)項(xiàng)目得到的目標(biāo)標(biāo)簽內(nèi)容的適宜性。TPP會(huì)議有助于申請(qǐng)人說明當(dāng)前獲得的數(shù)據(jù)可以支持所建議的適應(yīng)癥。TPP中所建議的聲明用于確定和討論研發(fā)計(jì)劃中的關(guān)鍵元素。與DAIDP之間的TPP會(huì)議對(duì)于展開科學(xué)和法規(guī)問題是很有幫助的。這些討論為主辦者提供了描述所希望的標(biāo)簽概念的機(jī)會(huì)，并且保證FDA對(duì)所提議的臨床開發(fā)項(xiàng)目能夠支持TPP中提出的標(biāo)簽概念感到非常滿意。Throughoutproductdevelopment,theTPPwasupdatedasnewinformationbecameavailable,withthesponsorseekinga