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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
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
Reasons for Attrition of Drug Developments
% o
f Pro
ject
failin
g%
of P
roje
ct fa
iling
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
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
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
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
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.
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
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
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
PSTC Kidney Biomarker
http://www.c-path.org/News/PSTCPMDANews62010.pdf
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
PSTC Kidney Biomarker
http://www.c-path.org/pdf/PMDAReportPSTCtranslation.pdf
Renal Tubular Injury Glomerular Injury
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
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
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
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)
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
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
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
PMDA activities for PMDA activities for Modeling & Simulation Modeling & Simulation
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
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
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
Develpoment Phase & Pharmacometrix
Stone JA et al., J Clin Pharmacol, 50: 20S-30S, 2010
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
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
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
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
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
New Division for Regulatory ScienceNew Division for Regulatory Science
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
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
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
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
10th Kitasato-Harvard Symposium, October 2010, TokyoPharmaceuticals & Medical Devices AgencyPharmaceuticals & Medical Devices Agency
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