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10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency

Regulatory Perspective for an Application of New Drug Development Tools

Yoshiaki Yoshiaki UyamaUyamaPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency


Reasons for Attrition of Drug Developments

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Kola I et al, Nature Rev Drug Discov, 3: 711Kola I et al, Nature Rev Drug Discov, 3: 711--715, 2004715, 2004 Frank R et al, Nature Rev Drug Discov, 2: 566Frank R et al, Nature Rev Drug Discov, 2: 566--580, 2003580, 2003


Quick Decision Strategy

Traditional

Quick Process

Phase II/IIIPhase II/IIIProof of Proof of ConceptConcept

NonNon--ClinicalClinical

CandidatesCandidates

Quick Go, Quick KillQuick Go, Quick Kill

Phase IIIPhase IIIPhase IIPhase IIPhase IPhase INonNon--ClincialClincial

CandidatesCandidates

Many Trials for a productMany Trials for a product

Early Decision MakingEarly Decision Making


To design a confirmatory trials appropriately and make clinical drug development successful,

Importance of Data in Exploratory Trials

Highly reliable data in the exploratory trials are critical Reliable tools should be available

Biomarker Modeling & Simulation etc.


PMDA Omics Projects (POP)

日本ヒトプロテオーム機構第8回大会・第6回日本臨床プロテオーム研究会連合大会

Pharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency

PMDA Omics Project (POP) Team

2525 members (October 2010) members (October 2010) (Office of New Drug, Office of Biologics, Office of (Office of New Drug, Office of Biologics, Office of Safety, Office of Medical Devices, Office of Safety, Office of Medical Devices, Office of Conformity Audit, Office of Review Management, Conformity Audit, Office of Review Management, Office of OTC/Generic Drug) Office of OTC/Generic Drug)

-Mission-In any In any omicsomics such as such as PGxPGx, proteomics and , proteomics and metabonomicsmetabonomics for the personalized medicine of for the personalized medicine of drugs/medical devices,drugs/medical devices,

SharingSharing experiences and scientific knowledgeexperiences and scientific knowledge Discuss Discuss related regulationsrelated regulations Establish Establish general principlesgeneral principles Evaluate Evaluate PGxPGx/biomarker data/biomarker data



PSTC Kidney Biomarker

http://www.c-path.org/News/PSTCPMDANews62010.pdf



PSTC Kidney Biomarker

http://www.c-path.org/pdf/PMDAReportPSTCtranslation.pdf

Renal Tubular Injury Glomerular Injury


Summary of PMDA Conclusion (1)

It is an important to confirm the It is an important to confirm the qualificationqualification of novel of novel biomarkers (BMs) for the biomarkers (BMs) for the objectiveobjective and and context of use context of use at at the stage the stage before wide use before wide use of novel BMs in drug of novel BMs in drug developmentdevelopment

The The PSTC data PSTC data about 7 BMs (Kimabout 7 BMs (Kim--1, 1, clusterinclusterin, albumin, , albumin, TFF3, TFF3, cystatincystatin C, C, β2β2--microglobulinmicroglobulin and total protein) will and total protein) will be be a useful information a useful information for new drug developmentfor new drug development


The The use of 7 BMs are acceptable use of 7 BMs are acceptable for the purpose to detect for the purpose to detect drugdrug--induced acute urinary tubular changes induced acute urinary tubular changes or or acute acute glomerularglomerular changes/injurychanges/injury in in ratrat GLP studies when they are GLP studies when they are used used in combination with existent BMs in combination with existent BMs ((sCrsCr and BUN).and BUN).

Sufficient qualificationSufficient qualification has has notnot been been performedperformed for general for general wide usewide use of these 7 novel BMs for detection of drugof these 7 novel BMs for detection of drug--induced induced acute kidney injury acute kidney injury in early clinical studies in early clinical studies (Phase I study, (Phase I study, etc.), and that utility of these BMs should be etc.), and that utility of these BMs should be individually individually judged judged on the basis of results obtained in the courses of on the basis of results obtained in the courses of future clinical developments of drugs or a future biomarker future clinical developments of drugs or a future biomarker qualification.qualification.

Summary of PMDA Conclusion (2)


International Harmonization

PMDA’s opinion is similar to the FDA/EMA opinionsPMDA’s opinion is similar to the FDA/EMA opinions

Therefore, these 7 BMs are now qualified by all Therefore, these 7 BMs are now qualified by all ICH regulatory agencies at same levelICH regulatory agencies at same level

Internationally Qualified Biomarkers are necessary and important in Global Drug Development

http://www.emea.europa.eu/htms/human/mes/biomarkers.htm


PMDA activities for PMDA activities for Modeling & Simulation Modeling & Simulation


Modeling & Simulation

It is common to review simulation data (mainly It is common to review simulation data (mainly PK) in the scientific consultation and NDAPK) in the scientific consultation and NDA review review

A learning stage for other simulation data A learning stage for other simulation data (PK(PK--PD modeling, Disease model etc.)PD modeling, Disease model etc.) Resource & raw data are necessary for Resource & raw data are necessary for

conducting analysis by ourselves conducting analysis by ourselves


Develpoment Phase & Pharmacometrix

Stone JA et al., J Clin Pharmacol, 50: 20S-30S, 2010


Current Consideration

Recognize an importance of Modeling Recognize an importance of Modeling Simulation (M&S) in drug developmentsSimulation (M&S) in drug developments

A use of M&S in A use of M&S in exploratory trials exploratory trials may may provide a useful information for provide a useful information for planning a planning a later stagelater stage of clinical trials (confirmatory of clinical trials (confirmatory trials) trials) more appropriatelymore appropriately..

M&S is M&S is notnot a tool to a tool to excuse data excuse data in a failed in a failed trialtrial

Discussions about new tools are welcome Discussions about new tools are welcome


Expectation for New Tools

Decrease of an Decrease of an attrition rate attrition rate of clinical of clinical developmentsdevelopments

Clear understanding of the impacts of Clear understanding of the impacts of ethnic ethnic factorsfactors in drug responsein drug response More accurate estimation More accurate estimation

PKPK--PD relationshipsPD relationshipsDoseDose--response relationshipsresponse relationshipsRisk factor for serious adverse eventsRisk factor for serious adverse events

Accelerate drug developments


New Division for Regulatory ScienceNew Division for Regulatory Science


On October 1On October 1stst, 2010, PMDA established the new , 2010, PMDA established the new division division specialized for a research in regulatory specialized for a research in regulatory sciencescience Division of Regulatory Science Research Division of Regulatory Science Research

(DRSR)(DRSR)

Mission of DRSR is to Mission of DRSR is to advance regulatory scienceadvance regulatory science

Advancing Regulatory Science


Regulatory Science & New Tools

New tools for drug development should be useful New tools for drug development should be useful for for regulatory decision makingregulatory decision making

Advancing regulatory science Advancing regulatory science will promote a will promote a proper implementation proper implementation of the new tools in drug of the new tools in drug developmentsdevelopments

The new division (DRSR) will contribute to The new division (DRSR) will contribute to promote an promote an appropriate use of the new toolsappropriate use of the new tools in in drug developments drug developments


Information

PMDA HOMEPAGEhttp://www.pmda.go.jp/

PMDA DRUG Information Searchhttp://www.info.pmda.go.jp/info/search.html

E-mail:[email protected]

Thank you for your attention

Documents

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