jan. 26, 2011 meir-chyun tzou, ph.d. director, division of drugs & new
DESCRIPTION
Sharing Assessment of Regulatory Approval or Assessment Reports – Could This be an Effective Way for Agencies in Asia Pacific to Use Regulatory Resources?. Jan. 26, 2011 Meir-Chyun Tzou, Ph.D. Director, Division of Drugs & New Biotechnology Products, Taiwan FDA. Outline. - PowerPoint PPT PresentationTRANSCRIPT
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Sharing Assessment of Regulatory Sharing Assessment of Regulatory Approval or Assessment Reports – Approval or Assessment Reports – Could This be an Effective Way for Could This be an Effective Way for
Agencies in Asia Pacific to Use Agencies in Asia Pacific to Use Regulatory Resources?Regulatory Resources?
Jan. 26, 2011
Meir-Chyun Tzou, Ph.D.Director, Division of Drugs & NewBiotechnology Products, Taiwan FDA
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OutlineOutline Organization and regulation of TFDA Challenge for regulatory agency Advantage of sharing assessment report APEC “Best Regulatory Practice Project”
A pilot case report Action Plan for Taiwan APEC Project
Conclusion/ Future Perspectives
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Establishment of Taiwan FDA (TFDA)Establishment of Taiwan FDA (TFDA) TFDA was inaugurated on Jan. 1, 2010 TFDA supersedes the following 4 bureaus
of Department of Health Bureau of Food Safety Bureau of Pharmaceutical Affairs Bureau of Food and Drug Analysis Bureau of Controlled Drugs
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TFDA Organization ChartTFDA Organization Chart
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DeputyDirector
Director
Generic Drugs
Biologics and New Biotechnology
Products
New Drugs
Drug Safety and Evaluation
Clinical Trial Management
Pharmaceutical Management
Center for Drug Evaluation, CDE
Division of Drugs and New Biotechnology ProductsDivision of Drugs and New Biotechnology Products
Medical and Pharmaceutical Industry
Technology and Development Center,
PITDC
Taiwan Drug Relief Foundation, TDRF
Cooperation Institute
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Pharmaceuticals Regulation in TaiwanPharmaceuticals Regulation in TaiwanPost-Market Management
Quality
Drug InjuryRelief
Research & Discovery
PreclinicalTesting
NDA/PMA
GLP
ADR/AE ★ Reporting
Insurance
cGMP
Market
GPvP
ADR/AE Reporting
IRB/GCP
IND/IDE
Pre-Market Approval
GTP
★ADR/AE: adverse drug reaction/adverse event
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Review Process for INDReview Process for IND Implement Fast TrackImplement Fast Track
Hospitals 、 Sponsors 、 CRO Application
Archives
Assessment Report
Consultation with AC Experts if neededAdvisory
Committee
Hospitals 、 sponsors 、 CRO
Technical and AdministrativeDocument
TFDAReview Team
First-in Human、
Ethnic and Ethical concern
etc.
TFDA TFDA DecisionDecision
IRB/J-IRB
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Review Process for NDAReview Process for NDASponsor Application
Technical and administrative document,
GMP/PMF
TFDA Review Team (TFDA Staff+ CDE)
Assessment report
Consult with AC experts for special concern Advisory
Committee
Sponsor
Decision★ GMP: Good manufacturing practice PMF: Plant master file
Global New,Botanical product,
Biosimilar product, etc.
GMP/PMF
Archives
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Challenge for Regulatory AgencyChallenge for Regulatory Agency
Limited regulatory resources with overwhelming workload and increasing complexity and expectation from all stakeholders
Build-in uncertainty for drug safety – “Drug Lag” vs “Drug Withdrawal”
Safety beyond the boarder – global drug development, supply chain, ethnicity, safety signal
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Potential Solution to Avoid Duplicate Potential Solution to Avoid Duplicate AssessmentAssessment Standardization: ICH, GHTF, PIC/S Mutual recognition: EMA, ASEAN Bilateral agreement among countries Partnership in Harmonization: APEC, Tripartite, ICH
GCG Administration requirement: CPP
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Current NDA Review Strategy in TaiwanCurrent NDA Review Strategy in Taiwan
Non-CPP 1-CPP 2-CPP
1. Pivotal clinical trials
in Taiwan
2. REMS/RMP if necessary
1. Early phase
clinical trials
in Taiwan
2. REMS/RMP
1. REMS/RMP if necessary
★CPP: Certificate for Pharmaceutical Product from 10 advanced countries ★REMS/RMP: Risk Evaluation and Mitigation Strategy/ Risk management plan★expected review time does not include the time for document supplementation and bridging study
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To EstablishTo Establish Accelerated NDA Review MechanismAccelerated NDA Review Mechanism
Fast-track reviewInnovative domesticProducts aiming at
International markets
Streamlined reviewApproved by
FDA + EMANo ethnic sensitivity
Review verification Future with MOU
Priority review Unmet medical needs:1.Severe diseases2.Urgent medical needs
Priority review:Full documents
Partial review,focused on bridging data, REMS, PSUR, etc.
Verification based on reference agencies’assessment reports
Accelerated Review:Full documents
MOU: Memorandum of Understanding MOU: Memorandum of Understanding
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Why not Sharing Assessment Report?Why not Sharing Assessment Report? Confidentiality data of company esp. CMC data Different review approach, template and regulatory
consideration “Lack of confidence” or “Strong ego” in assessment
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Why not Just use FDA/EMA/PMDA Why not Just use FDA/EMA/PMDA Assessment Report on the Web Site?Assessment Report on the Web Site?
Good reference but can be better – Ethnic sensitivity, accumulated safety data, different indication approved, life cycle management of drug
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Advantage of Sharing Assessment ReportAdvantage of Sharing Assessment Report
Transparency, Efficiency, Predictability, Consistence Improve Good Review Practice – Review quality,
template, process, peer group interactions “Compare and Contrast” from different agenies,
spot check the concerns risk/benefit decision Share responsibility and liability via public private
partnership
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APEC “Best Regulatory Practice Project” APEC “Best Regulatory Practice Project” (I)(I) A 2-year APEC project leaded by Taiwan
cosponsored by Canada, China, Indonesia, Korea, Malaysia, Mexico, Peru, Philippine, Thailand and US
“Partnership in Harmonization” is the key Build up capacity of regulatory science via GRP
workshop on drug and medical device targeting on regulators
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APEC “Best Regulatory Practice Project” APEC “Best Regulatory Practice Project” (II)(II) APEC PER (Pharmaceutical Evaluation Report)
Scheme for sharing of regulatory assessment report – follow the successful example of PER Scheme (1979-2000) and the EMA centralized procedure
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A Model in the Past: PER Scheme 1979-2000A Model in the Past: PER Scheme 1979-2000 - - EFTA as secretariat EFTA as secretariat
ItalyItaly
SwedenSwedenAustriaAustria
NetherlandNetherland
UKUK
GermanyGermanyHungaryHungary
FinlandFinland
IrelandIreland
NorwayNorway EUEU
CanadaCanada
AustraliaAustraliaSouth AfricaSouth Africa
New ZealandNew Zealand SwitzerlandSwitzerland
IcelandIceland
Czech RepublicCzech Republic
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Current Status for Sharing ReportsCurrent Status for Sharing Reports
X company agreed that Taiwan can share CDE’s assessment report of Y drug to regulators in the GRP workshop for drug in Nov. 2010
Concept endorsed by PhRMA & EFPIA and presented in many regional conferences
Taiwan – China Cross-Strait Medical and Health Care Cooperation Agreement
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Pilot Study for APEC PER SchemePilot Study for APEC PER Scheme Select a few marketed products approved by several
regulatory agencies to exchange NDA assessment reports with the permission from the license holders
Evaluate the experience of these “case studies” in GRP, review template and administrative requirement
Preliminary interest from PhRMA SGD Committee, EFPIA ICH GCG Regulatory Forum, some RA (Health Canada, TGA, etc.) and Individual companies (Eli Lilly, Novartis, etc.)
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A Pilot Case Study of APEC PER SchemeA Pilot Case Study of APEC PER Scheme Y drug (X company), NDA approved in 2006 A selective norepinephrine reuptake inhibitor Indicated for the treatment of Z disease Letter from X company: CDE/TFDA’s regulatory
information (except CMC) can share with DRAs in this workshop
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TFDA/CDE Review TeamTFDA/CDE Review Team Project manager CMC Pharmacology/Toxicology Pharmacokinetic/Pharmacodynamic Clinical Statistical Primary reviewer plus secondary reviewer in
each section Supervisor
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Review Process Review Process (continue)(continue)
Supp*Supp* Review meeting*Review meeting* Report* Report* DOH
letterDOHletterU.S.U.S.
Germany, U.K., Canada,Australia
Germany, U.K., Canada,Australia
NDA submission*
NDA submission*
Filingmeeting*Filingmeeting*
ACMeeting#
ACMeeting#
11.26.200211.26.2002 20042004
ApprovalApproval
07.25.200507.25.2005
08.15.2005 08.15.2005
10.15.200510.15.2005
10.17.200510.17.2005
01.11.200601.11.2006
02.15.200602.15.2006
03.29.200603.29.2006
ApprovalNot
recommended
ApprovalNot
recommendedApprovableApprovable
transparent review process for sponsor *: searchable from CDE website #: searchable from DOH website
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Review Process Review Process (continue)(continue)
DOHletterDOHletterReport*Report*
ACmeeting #ACmeeting #
NDA supp.submission*NDA supp.submission*
Sponsor prepare dossier*
Sponsor prepare dossier*
06.12.200606.12.2006
07.12.2006 07.12.2006
09.04.200609.04.2006
05.15.200605.15.2006
3.29 ~ 5.152006
3.29 ~ 5.152006
LicensedLicensed
Total time: 406 calendar days (licensed)
1st submission: CDE review time: 106 days: sponsor time: 62 daysSupp submission: CDE review time: 28 days sponsor time: 0 days
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Request for More Data Request for More Data
PSURs – FDA approved in 2002, EMA in 2004 Trial report conducted in Taiwan – IND in Taiwan in
2002: placebo controlled, DB, RCT for 6 wks in 106 children and Adolescence in 2 hospitals Result statistic significant for superiority
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Any Special Issue or Local ConcernAny Special Issue or Local ConcernPK/PD Y drug metabolized by CYP2D6 Difference in the proportion of population with
CYP2D6 PM status: 5-10% in Caucasians and 0-2% in Asians, but Asian have 24% IM (Intermediate Metabolizer)
The AUC of PM was 10-fold higher than EM No dose adjustment for IM and PM in terms of
safety from clinical trial
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Any Special Issue or Local Concern?Any Special Issue or Local Concern?Clinical 1. Severe liver toxicity noted after drug approval in the US 2. Warning issued for severe liver toxicity (2008) 3. Black box warning issued for suicide ideation (2006) 4. QT prolongation side effect noted after drug approval
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More Data SubmittedMore Data Submitted Liver toxicity: 373 reports received in 3,710,000
patients. Mostly mild abnormality with severe toxicity very rare.
Suicidal ideation: 669 reports from Nov 2002 to Nov 2005. The rate of 0.013% was not higher than the rate of suicidal attempt and self injury in general population.
QT prolongation: 27 cases from Nov 2002 to Nov 2004. No TDP case found.
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Decision Made By ACDecision Made By AC Approval recommended with warnings and data
added to drug label on liver toxicity, suicide ideation, CYP2D6
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Sharing Assessment of Regulatory Approval or Sharing Assessment of Regulatory Approval or Assessment Reports – Could This be an Effective Way Assessment Reports – Could This be an Effective Way for Agencies in Asia Pacific to Use Regulatory for Agencies in Asia Pacific to Use Regulatory Resources?Resources?
Sharing Assessment report is Save resource better review quality early approval Win-win solution for all parties
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Action Plan for Taiwan APEC Project 2011-Action Plan for Taiwan APEC Project 2011-2012 (cosponsored by 10 countries)2012 (cosponsored by 10 countries) Survey the current status of bilateral agreement Conduct pilot study for sharing assessment report Involving more agencies and companies Coordinate the procedure for sharing and set up the
secretariat
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Future Perspectives on Pharmaceutical Future Perspectives on Pharmaceutical Regulatory IssuesRegulatory Issues Sharing review experience
exchange review reports of IND/NDA/IDE/PMA/BLA ethnic issue study by retrospective data surveillance establish bridging study review consensus. Fast tract review for IND/NDA, Joint IRB
Enhance pharmaceutical regulatory networking joint training program, e.g., GRP, GCP inspections communication and information sharing, e.g. ADR report potentially harmonize the review process, report format,
data requirement Establish reviewer exchange program
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Thank You for Your AttentionThank You for Your Attention
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