优化快速监管途径加快上市时间 更快地为患者提供创新疗法的监管策略

Optimizingexpeditedregulatory

pathwaystospeedtimetomarketRegulatorystrategiestodeliverinnovativetherapiestopatientsfaster204

Pursueexpeditedregulatorypathways.05FocusontheUnitedStates08

FocusontheEuropeanUnion10

FocusonJapan13

Leveragerelianceprocedures.17

Submit

tomultiplemarkets

via

consortia

agreements.19

Investinregulatoryintelligencetoolstodesign

amultifacetedglobalregulatorystrategy.23

References.ContentsCompaniesfacethedualchallengeofrapiddevelopmentwhilefulfillingregulatoryobligations.However,withtherightstrategy,

thisbalance

canbecomeacompetitiveadvantagerather

thanaconstraint,especiallywhen

developing

therapiesthataddressunmetpatientneedsandnichepatientpopulations.Thisebookexaminesinitiatives

andcollaborative

programsthatempowerorganizations

tobuild

smarter,fasterregulatorystrategieswithoutcompromising

safetyorquality.

Theseprogramsincludeexpeditedregulatorypathways,relianceproceduresandconsortiaagreements.

WhencombinedwithrobustregulatoryandCMC

intelligence,these

strategies

canstreamlinemarketaccessglobally.Bysecuringspecialregulatorydesignations

andmaintainingtransparentcommunication

withagenciesatevery

stage,

innovatorscanstrengthentrust

andreduceuncertainty,

ensuringthat

therapiesaredelivered

tothepatientswhoneedthem

faster.Intoday'sfast-pacedlifesciencesandpharmaceuticallandscape,acceleratingthetimetomarketforinnovative

therapiesismorecriticalthanever.3Forlifesciencescompaniesseekingtoacceleratepatientaccesstotransformativetherapies,expeditedregulatorypathways,alsoknownasfacilitatedregulatorypathways(FRPs),providealternativestostandardregulatoryreviewroutes.Theyenablefasterreview,approvalandavailabilityoftherapies,particularlyfortherapiesaddressingmajorpublic

healthneeds,throughseveralmechanisms:•Greaterregulatorysupporttominimizeissuesuponsubmission•

Compressingthereviewtimeline

togettherapiestopatientsfaster•

Allowingapprovalbasedonpreliminarydatawithpostmarketingfollow-uprequiredInthe

U.S.,the

E.U.andJapan,atleastone-thirdoftheapprovalsofnoveldrugsfrom2020through2024benefitedfromatleastone

FRP(Figure

1)accordingtoanalysisfromTheCentreforInnovationinRegulatoryScience(CIRS),a

neutral,independent

U.K.-based

subsidiaryofClarivate(Laraetal,2025).PursueexpeditedregulatorypathwaysFigure1:ProportionofapprovalsofanoveldrugbenefitingfromatleastoneFRP(2020-2024)JapanPharmaceuticalsand

Medical

DevicesAgency(PMDA)U.S.FoodandDrugAdministration(FDA)EuropeanMedicinesAgency(EMA)195of260approvals67of180approvals73of198approvals37%37%75%Source:Lara

et

al,20254

approvalduration.Acceleratedapprovalallowsmarketauthorizationbasedonsurrogateorintermediateclinicalendpoints,breakthroughtherapydesignationprovides

intensiveFDAinteractionandguidancethroughoutdevelopment,fasttrackdesignationfacilitatesdevelopmentofdrugsforseriousconditionswithpreliminaryclinicalevidenceofefficacy,andpriorityreviewdesignationcompressesthereviewtimeline(Table1).Theacceleratedapprovalpathwayandbreakthroughandpriorityreviewdesignationseachhad112-dayshorterapprovaltimelinesthanthemedian

356-daytimeframefornewdrugsapprovedintheU.S.in2024,whilethefasttrackdesignationshaved

63daysofftheapprovalduration(Laraetal,2025).FocusontheUnited

StatesTheU.S.FDAmaintainsarobustportfolioofexpedited

regulatorypathwaysthatsupportthemajorityofnew

drugapprovals(Figures1and2),aproportionthatremainsthehighestofthesixmajorregulatory

authoritiesevaluatedbyCIRS(Laraetal,2025). Accelerated

approval

Breakthrough

therapy

designation

(BTD) Fast

track

designation

Priority

reviewSources:CenterforDrugEvaluationandResearch,NewDrug

TherapyApprovals2021,2022,2023,2024,2025Thefasttrackdesignation

shaved63daysofftheFigure2:Proportionofnewdrugapprovalsoverthepastfiveyears

(2021-2025)usingexpeditedpathwaysintheU.S.100%90%80%70%60%50%40%30%20%10%020212022202320242025Proprotion

ofnew

drug

approvals5ProgramnameCorepurposeBenefit(s)AcceleratedapprovalForseriousconditionswithunmetneed,allowingapprovalbasedon

a

surrogateor

intermediateendpointreasonablylikely

topredictclinical

benefit,withrequiredpost-marketingconfirmatory

trialsCanbringproductstomarketyearsearlierbynotwaitingforlong-termclinicaloutcomeswhilemaintainingobligations

toverifybenefitpost-approvalBreakthroughtherapydesignation(BTD)Forseriousconditionswherepreliminaryclinicalevidence

indicates

substantial

improvementoverexisting

therapiesProvides

intensiveguidance,organizationalcommitmentandeligibilityforfasttrackdesignationfeatures;canmarkedlycompressdevelopment

timelines

andsupportuseof

innovative

trialdesignsFast

track

designationForseriousconditionswithunmetmedicalneed,offeringmorefrequentFDAmeetings,writtencommunicationsandrollingreviewFacilitatesearlier,iterativefeedbackand

allows

sectionsof

theNDA/BLA

tobereviewedastheyareready,whichcanshorten

overalldevelopment

andreview

timePriorityreviewFordrugs

that,

ifapproved,wouldprovidesignificant

improvement

insafetyoreffectiveness

for

seriousconditionsShortensFDAIsgoalreviewtimeforanapplication

to6monthsSource:CortellisRegulatoryIntelligenceBeyondthesefoundationalpathways,theFDA'sspecializedacceleratedprogramsforspecifictherapeuticareasormodalitiesincludeReal-TimeOncologyReview(RTOR),whichstreamlinesdatasubmissionforoncologydrugsbypermittingsubmission

ofdatamodulespriortothecompleteapplicationfiling.TheRegenerativeMedicineAdvancedTherapy(RMAT)designationprovidesintensive

FDAguidancetoexpeditedevelopmentandreviewexclusivelyforregenerativemedicine

andcellandgenetherapyproducts.Table1:OverviewofexpeditedregulatorypathwaysintheUnitedStates6ProgramnameCorepurposeBenefit(s)Chemistry,Manufacturing,and

ControlsDevelopment

andReadinessPilot(CDRP)Pilotprogram

to

facilitate

theexpeditedCMCdevelopment

ofproductsunder

an

IND

application

with

acceleratedclinicaldevelopment

timelines,basedon

theanticipatedclinicalbenefit

of

earlierpatient

access

toprogramsFacilitatesenhancedFDAcommunication

with

additional,

focused

FDA

interactions

for

specificCMC

issues

and

alignsmanufacturing

development

acceleratedclinical

timelines,reducingpotentialapprovalbottlenecks;particularlybeneficial

forproducts

with

complexmanufacturingchallengeslikecell

and

gene

therapiesCommissioner'sNational

PriorityVoucher

(CNPV)Pilotprogram

forproducts

that

advancedefinedU.S.nationalhealthpriorities(public

healthcrises,largeunmetneed,

innovativecures,domesticmanufacturingor

affordability)Cutsreview

time

for

the

specificNDA/BLA(orkey

supplement)from

the

usual~10-12months

to

a

target

decision

in~1-2months,withenhancedcommunication,rollingreview

and'tumor-board-style'

multidisciplinaryreview;

vouchers

areproduct-specific

andnon-transferableRareDiseaseEvidencePrinciples(RDEP)Fordrugs/biologics

targeting

very

small,

serious,genetically

definedrare

diseasepopulations(generally<1,000U.S.patients)

withno

adequate

therapiesAllows

approvalbasedon

a

single(possibly

single-arm)pivotal

study

plus

strongmechanistic/biomarker,non-clinical,PK/PD,real-world,

case-reportornatural-historydata,

which

can

increase

feasibilitywhen

traditionalmulti-trialprograms

are

impracticalReal-TimeOncologyReview(RTOR)Fornewdrug

applications

(NDAs)

andbiologicslicenseapplications

(BLAs)with

selected

oncology

indicationsAllows

the

submissionofkeyeCTDmodule

sections

from

an

oncology

drug

application

independentlyof

theentiremodule,

whichenables

thereviewprocess

tobe

initiatedbefore

acomplete

application

isreceivedaswell

as

earlier

identification

ofpotential

data

quality

and

review

issues

foramore

streamlinedand

efficientreviewprocessRegenerativeMedicine

Advanced

Therapy(RMAT)Forregenerativemedicine

therapies

to

treatseriousconditions

wherepreliminaryevidence

showspotential

toaddressunmetneedProvides

intensiveguidanceand

thepotential

for

accelerated

approval

andpriorityreview

tailored

to

cell

andgene/regenerativeproductsSplitReal

TimeApplicationReview

(STAR)Pilotprogram

fornovelusesofexistingtherapiesfor

a

seriouscondition

withunmetmedicalneedsInvolves

applicationsbeing

submitted

in

a'split'

two-part

fashion,with

thecomponents

submitted

approximately

twomonths

apart

and

datareviewbeginningwith

thepart1

submissionandPDUFAreview

clockstarting

with

thepart2

submissionNewinitiativesannouncedin2025includetheCommissioner'sNationalPriorityVoucher

(CNPV)pilotprogram(June2025),whichaims

todramaticallycompressreviewtimelinesfromthestandard10-12monthstoatargetof

1-2monthsforapplicationsaddressingfivecriticalnationalpriorities(Table2).AsofApril

2026,18vouchershavebeenissued,

andtwo

drugshaveachievedapprovalunderCNPV:•USAntibiotics'AugmentinXR(amoxicillin-clavulanatepotassium)onDecember

10,2025•BoehringerIngelheim'sHernexeos(zongertinib)

on

February26,2026,just44daysafteritsapplicationwasfiledonJanuary13,2026The

Rare

Disease

Expedited

Program(RDEP),introducedinSeptember2025,addressestheuniquechallengesofraregeneticdiseasesbypermittingapprovalbasedonasingleadequate

andwell-controlledstudyplusrobustconfirmatory

evidenceincludingmechanisticdata,biomarkers,

non-clinicalmodelsorexpandedaccessdata.Table2:OverviewofotherexpeditedregulatorymechanismsintheUnitedStatesSource:CortellisRegulatoryIntelligence7ProgramnameCorepurposeBenefit(s)Accelerated

assessmentForproductsofmajorpublichealth

interest,particularly

therapeuticinnovation,requiring

the

sponsor

to

justifyunmetneed

andexpectedbenefitReducesCHMPevaluation

time

forcentralizedmarketing

authorization

fromup

to210days

toaslittle

as150daysAdaptivepathwaysFor

areasofhighmedicalneed

where

it

isdifficult

to

collect

data

via

traditional

routesandlargeclinical

trials

wouldunnecessarily

exposepatients

who

areunlikely

tobenefit

from

themedicineAllowsearlyandprogressivepatientaccess

to

a

medicine,

by

building

on

regulatory

processesalready

inplacewithin

theexisting

framework

such

as

scientific

advice,

compassionateuse

and

theconditional

approvalmechanism(formedicinesaddressinglife-threateningconditions)ConditionalmarketingFormedicinesaddressingunmetmedicalneedswherebenefit–risk

ispositivebutAllowsearliermarketaccesswith

specificpost-authorization

obligations;

can

laterauthorisation

(CMA)dataarelesscompleteat

approval

(e.g.,

for

serious,

rare

or

emergency

conditions)convert

to

standardmarketing

authorizationonce

additionaldata

areprovidedExceptionalcircumstancesFor

situations

whencomprehensive

safety/efficacydatacannotbe

generated

undernormalconditionsofuse

(e.g.,

extremelyrare

disease,

current

science

cannot

yetdeliver

fulldata,unethical

to

collect

data)Grants

authorization

withongoing,legallybinding'specificobligations'(e.g.,enhancedpharmacovigilance,restricteduse,annualbenefit–riskreassessment);

parallelacceleratedassessment

canberequested

to

shorten

thereview

clockPRIMEFormedicinesoffering

amajor

therapeutic

advantageorbenefitingpatients

with

unmetneed;

focusesonearlydialogue

and

support,particularly

for

complex

or

orphanproductsor

advanced

therapymedicinalproducts(ATMPs)Early,

iterative

scientific

advice

andrapporteur

appointment;morelikely

to

secure

accelerated

assessment,reducingoverall

time

tomarketing

authorizationFocusontheEuropeanUnionTheEMA'sFRPshaveevolvedconsiderablyas

theEMAseeks

tobalanceearlyaccesswithrobustevidence.Acceleratedassessmentreduces

timelines

to150days,CMApermitsapprovalon

incompletedatasetswithbinding

post-market

obligations,exceptional

circumstances

authorization

serves

ultra-rare

conditions

wherecomprehensivedatacollection

is

infeasible,andPRIMEoffersearlycoordinationandscientificguidance(Table3).Table3:OverviewofexpeditedregulatoryinitiativesinEuropeSource:CortellisRegulatoryIntelligence8TheCMApathwayhasbeen

usedconsistently

overthepastfiveyears,includingforfourCOVID-19vaccinesin2021(Figure3).Theprogramoffersapragmaticbalancebetweenearlypatientaccessandregulatoryrigor,allowing

approvalbasedonlesscomprehensivedatawhen

thebenefit-riskbalanceispositive,anunmetmedicalneedexistsandimmediateavailability

outweighstherisksofremainingdatagaps.InDecember2025,theEuropean

ParliamentandtheCounciloftheEuropeanUnionagreedonanoverhaulofE.U.pharmaceuticallegislation,consideredtobethemostcomprehensivepackageofreformsinovertwodecades(European

MedicinesAgency,2025).Thecommitmentaims

tofurtherstreamlineregulatoryprocedures,enhanceincentivesformedicinesaddressing

criticalneedsandstrengthenmechanismstoensurefasterpatientaccesstoinnovative

treatmentsacrossthe

E.U.

Furtherdetailsand

implementationareexpectedin2026.

Accelerated

assessmentConditionalmarketing

authorisation

(CMA) Exceptional

circumstances

PRIMESources:EMA,Humanmedicines[in/highlights]2021,2022,2023,2024,2025Theprogram

offers

apragmaticbalance

between

earlypatientFigure3:Recommendationsandapprovalsoverthepastfiveyears(2021-2025)usingexpeditedpathwaysintheE.U.

access

andregulatoryrigor.

2021202220232024202514121086420Number

of

drugs9Onceconsideredtohaveasignificantly

slowerregulatorysystemthanitsWestern

counterparts,Japannowranksamong

thefastestamongmajorauthorities.Focuson

JapanOnceconsideredtohaveasignificantlyslowerregulatorysystemthanitsWesterncounterparts,

Japannowranksamongthefastestamongmajor

authorities.Althoughthemediantotalreviewtime

inJapanexceeded600daysin2005andremained

at333days

as

recently

as

2023

(Kohno

et

al,

2025),

by2024,thePMDAachievedtheshortestmedian

approvaltimeforallnewdrugapprovalsamongsixmajorregulatoryauthoritiesatamedianof

290days,comparedwiththe

FDA's356daysand

EMA's430days(Laraetal,2025).

Inaddition,medianpriorityreviewtimessatat245daysin2024,

onparwiththeFDA's244daysforpriority

review.ThisdramaticimprovementreflectsJapan'sstrategiccommitmenttoacceleratingpatientaccess

toinnovativemedicineswhilemaintainingrigorous

safetystandards,includingarangeofinitiativessuchasconditionalearlyapprovalandthePioneer

drugprogram(Sakigakedesignation;Table4).10ProgramnameCorepurposeBenefit(s)Conditional

early

approvalFordrugsandregenerativeproductsforseriousdiseaseswherefullconfirmatory

dataarenotyetavailablebutearlydatasupportapositivebenefitrisk

profileEnablesearliermarketaccesswithobligationsforpost-marketingstudiesand

riskmanagement,significantlyspeedingavailabilityversusstandardapprovalDrugs

withhighnecessity

in

infectious

disease

controlFordrugsorothermedicalproductsthatareapprovedinothercountriesand

areessentialforaddressingpriorityinfectiousdiseasesandotherinfectiousdiseasecountermeasuresforwhichconductingcomparativeefficacytrialsin

JapanischallengingEnablesapprovalwithoutclinicaltrialsconductedinJapanDrugs

with

supply

shortagesFordrugsthataredeemedtohavethesameactiveingredients,quantity,

usage,dosage,efficacyandeffectsasalreadyapproveddrugsinothercountriesandforwhichdemandisdeemedtobesignificantlyunmet,andthereisnootherappropriatemedicaltreatmentotherthanitsuseShortensthetypicalreviewtargetfrom~12monthsto~9monthsviapriority

reviewHIVmedicineshavingbeen

approvedoutside

JapanToexpeditetheapprovalofHIVdrugsdevelopedintheU.S.orEurope,whichhavelargerpatientpopulationstoparticipateinclinicaltrialsthaninJapanShortensthetypicalreviewtargetfrom~12monthsto~4months;involvesadedicatedcommitteetoreviewmedicinaldrugsforHIVandpriorityinspectionsofanti-infectivedrugsforHIV(consideredasmedicinaldrugsforraredisorders)KOUCHI

ShinseiApprovalofanexpansionofadrug'sindicationwithoutconductingclinicaltrialsShortensthetypicalreviewtargetfrom~12monthsto~1month;isbasedonthepremiseof'well-recognized'safetyandefficacyofdrugsalreadyapproved

outsideJapan;involvessubmittingdataonreal-worlduseinothercountriesor

regionsMedicinalproducts

subject

toemergency

approvalFortherapiesorvaccinesaddressinganurgentneedtopreventthespreadof

diseaseorotherhealthhazardsthatmayhaveaseriousimpactonthe

livesand

healthofthegeneralpublicandforwhichnopropermethodisavailableother

thantheuseofthedrugEnablesapprovalwithoutclinicaltrialsconductedinJapanwhenclearresults

havebeenobtainedinothercountries;allowsconfirmatoryclinicalstudiesto

beconductedinparallelwiththeapprovalrevieworusingreal-worlddata(RWD)whenrecruitingasufficientsamplesizeisn'tfeasibleNew

drugs

thatmeet

all

therequirementsFordrugsthat,fromamedicalpointofview,providesignificantefficacyorsafetybenefitoverexistingdrugsforseriousdiseasesShortensthetypicalreviewtargetfrom~12monthsto~9monthsviapriority

review;includesproductsthatcannotbeclassifiedintoanyoftheotherpriorityreviewcategoriesbutareconsideredtoextremelysuperiorinterms

ofefficacyand/orsafetytoexistingdrugsortreatmentsforseriousdiseasesTable4:OverviewofexpeditedregulatoryinitiativesinJapan11ProgramnameCorepurposeBenefit(s)Orphandrug

designationForseriousdiseases,includingdifficult-to-treatdiseasesforwhichtherearehigh

medicalneeds,affecting<50,000peopleinJapanexcept'designatedintractable

diseases'Shortensthetypicalreviewtargetfrom~12monthsto~9monthsviapriorityreview;providesguidanceandconsultationfordevelopmentPioneer

drugs

(Sakigake

designation)Forfirst-in-Japaninnovativetherapiesforseriousconditionswithprominentearlyefficacy,requiringinitialdevelopmentinJapanornear-simultaneousglobal

filingsShortensthetypicalreviewtargetfrom~12monthsto~6months;providespriorityconsultations,adedicatedPMDA'concierge'andextendedpost-marketingre-examinationPriorityreviewFordrugsmeetingcriteriasuchashighmedicalneed,includingmanyorphanand

other

priority

productsShortensthetypicalreviewtargetfrom~12monthsto~9monthsSpecified-purposedrugsFordrugsintendedforthediagnosis,treatmentorpreventionofpediatricdiseasesortargetingdrug-resistantpathogensforwhichthereisanunmetneedShortensthetypicalreviewtargetfrom~12monthsto~9monthsviapriority

reviewTokureiShonin

(Extraordinary

Approval)ForseriousdiseasetherapiesthathavenotyetbeenapprovedinJapanbut

havebeenapprovedintheU.S.,theU.

K.,Canada,Germanyor

FranceShortensthetypicalreviewtargetfrom~12monthsto~9monthsviapriority

review;involvesrequirementsforpost-approvalstudiestomonitoradversereactions;detectorconfirminformationonproductquality,efficacyandsafety;andreviewresearchreportsobtainedaftermarketingauthorizationregardingindications/effectsandsafetySource:CortellisRegulatoryIntelligence12Regulatoryrelianceenablesanauthoritytoleveragethescientificassessmentsanddecisions

ofareferenceregulator(e.g.,

FDA,

EMA,

PMDA)

ratherthanconductingafull,standalonereview.

Thisapproachservestwostrategicpurposes:•Generalapprovals:

agenciescanissuefull

marketingauthorizationsfarmorerapidlyby

acceptingun-redactedassessmentreports

andkeydossiersalreadyreviewedelsewhere•Expeditedpathways:sponsorscanfirstsecureanacceleratedorconditional

approval

inamajormarketandthen

triggera

verification

orabridgedprocedure

inothercountries

usingthesame

expedited

timelineReliancemechanismscancuttypicalreviewtimesfortheseorganizationsfrom

ayearormoredowntomonthsorweeks.Althoughreliance,bydefinition,mustwaitforthereferencedecision,itoftenremainsthefastestroutetomarketinjurisdictionsthathavelimitedefficacyandsafetyassessmentcapabilities,

whichincludesmorethan70%oftheworld'smedicinesregulatoryauthorities,accordingtoaWorldHealthOrganization

assessmentin2022(World

HealthOrganization,2022).Reliancemechanisms

cancuttypicalreviewtimesfortheseorganizationsfromayearormoredown

tomonthsorweeks.Leveragerelianceprocedures13Country/regionReliance

modelReference

authorityReview

timelineNotesEgyptVerificationor

abridgedAustrian

Medicines&Medical

Devices

Agency,Belgian

Federal

Agency

for

MedicinesandHealthProducts,DanishHealth

&Medicines

Authority,FDA,FinnishMedicinesAgency,FrenchNational

Agency

for

the

Safety

ofMedicines

andHealthProducts(ANSM),

GermanFederal

institute

for

drugs

andmedical

devices,Health

Canada,IcelandicMedicines

Agency,IrishHealthProductsRegulatory

Authority

(HPRA),ItalianMedicines

Agency,Luxembourg

Agency

for

Medicines

and

Health

Products

(ALMPS),MHRA,Ministry

ofFood

andDrug

Safety

of

theRepublic

ofKorea

(MFDS),NetherlandsMedicinesEvaluationBoard,New

ZealandMedicines

&MedicalDevices

safety

authority(Medsafe),NorwegianMedicalProducts

Agency,PMDA,PortugueseINFARMED,Spanish

Agency

forMedicines

andHealthProducts

(AEMPS),

SwedishMedicalProductsAgency,

SingaporeHealth

Sciences

Authority

(HSA),

SwissmedicVerification:30

daysAbridged:60

days•

Verification:Must

be

approved

by

at

least

two

reference

authorities

or

one

referenceauthority

and

have

WHO

prequalification•

Abridged:Must

be

approved

by

at

least

one

reference

authority

and

haveWHO

prequalification•

Full

sameness

ofproduct•

Launch

within

one

year

of

reference

approval•

Exemption

from

local

clinical/non-clinical

data

submissionMexicoFast-trackrelianceEMA,FDA,HealthCanada,Swissmedic~4-6months•

'Fast-track'

status

issuedwhendossiermatchesreferenceauthority's

submission•

Also

includes

WHOprequalificationNew

ZealandVerificationorabbreviatedapplicationEMA,E.U.memberstates(abbreviatedapplicationonly),FDA,HealthCanada,MHRA,SingaporeHSA,Swissmedic,

TGAVerification:~30daysAbbreviatedapplication:~100daysfor

theinitialreviewVerification:•

Fullmarketing

authorization

grantedby

≥2recognized

authorities

Abbreviated

application:•

Submitted

within10

years

of

approvalby

areference

authority

Bothpathways:•

Supplied

medicine

identical

in

all

material

respects

to

the

authorized

medicine•

Noprior

withdrawal,rejection

or

suspensionby

anyregulator•

Same

formulation,

dosage

and

indications

asthereference

authority

approval•

No

independent

assessmentneeded

to

contextualize

thebenefit-riskprofile

forlocaldisease

epidemiology,publichealth

considerations

or

specificlocalhealthris