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Regulation on Clinical Trialsin JapanHBD East 2017 Think Tank MeetingAt National Institute of Global Health and MedicineTokyo, Japan: December 7, 20171
Introducing Innovative MDsPreviously CT is conducted in EU Introduced in US/JapanFutureNovel, Innovative MDsare developed in US/Japan Need for EFS2
Acceleration measures for Innovative MDsTypeAreaDesignation is not neededNeeded to expedite the reviewExpedited reviewPriority reviewAny productcategoriesSAKIGAKE(Forerunner designation)DrugsConditional EarlyApprovalMedical DevicesConditional and Timelimited AuthorizationDesignation requirementRegenerativeMedical ProductsDesignation is needed1. Orphan2. Apparent improvement of medicalcare and for severe diseasesDesignation is needed Innovative medical products For serious diseases Development & NDA in Japan ・beingworld’s first or simultaneous with othercountries Prominent effectiveness expected onnon-clinical and early phase clinicalstudiesDesignation is not neededEarly application through confirmation ofa certain degree of efficacy and safetythrough clinical trials other thanconfirmatory clinical trials.Designation is not needed- MDs in high clinical needs- Balancing the pre- and post-marketrequirementsDesignation is not needed3
Strategy of SakigakeAn innovative MD/IVD for patients in urgent need of innovative therapy may bedesignated as a Sakigake Product if;1) its premarket application will be filed in Japan firstly or simultaneously insome countries including Japan, AND2) prominent effectiveness can be expected.Once an MD/IVD is designated, its developer can enjoy such benefits as:A) Prioritized Consultation by PMDAB) Pre-application substantive reviewC) Prioritized Review (12 months 6 months [MD])D) Review Concierge assigned by PMDA4
Fast Break Scheme(Conditional Early Approval for Innovative MDs) Implemented on 31 July 2017 Accelerate approval of MDs in high clinical needs by balancing thepre- and post-market requirements, based on the lifecyclemanagement of the MDs. PresentLong periodReviewCollection of clinical dataApprovalMarket - Use Conditional Early Approval for Innovative MDsCollection of clinical dataCooperationwith academiaPlanning Post-marketRisk ManagementReviewPost-marketRiskManagementPlan (draft)ApprovalMarket - UseCooperationwith academiaPartial changeapplication (e.g.expandedindication, etc.)- Implementation of Post-market Risk Management Measures- Data collection to confirm use results, long-term performance5
Categorisation of Clinical Research in JapanClinical Research on Human SubjectsClinical Trial (CT)ClinicalResearchprospective interventional studyCT for MarketingAuthorization6
Research on Human SubjectsClinical ResearchClinical Trial (CT)prospective interventional studyStudy purpose is other than MarketingAuthorization (academic purpose)Ethical Guidelines for Medical and HealthResearch Involving Human SubjectsThe studies are conducted as a part ofdaily medical practice. In addition tomutual trust between patient and doctor,requirement of ethical consideration isstipulated by ministerial announcement.CT for MarketingAuthorizationStudy purpose is to file for MAGood Clinical Practice (GCP)The study sponsors conduct trials for profit(product development). Therefore operatingprocedures and system are stipulated byministerial ordinance (GCP) in order to protectstudy subjects and ensure data reliability.7
Ethical Guidelines for Medical and HealthResearch Involving Human SubjectsThe Ministry of Education, Culture, Sports, Science and Technology andthe Ministry of Health, Labour and Welfare established joint committeefor reviewing 2 guidelines on 2013 Feb.Ethical guidelines forepidemiology research2002 in force(revise in 2007)Ethical Guidelines forClinical Research2003 in force (revise in 2008)Ethical Guidelines for Medical and Health ResearchInvolving Human Subjects2015 April 1st in force8
Recent scandal in the field of clinical trial Diovan (Valsartan)–––––Kyoto Heart StudyJikei Heart StudySMART (the Shiga Micro albuminuria Reduction Trial)VART (The Valsartan Amlodipine Randomized Trial)Nagoya Heart Study Tasigna (Nilotinib)– SIGN Trial Bropress (Candesartan)– CASE-J9
Movement to new regulationReview Committee for clinical trials ofhypertension Drug (Diovan)（2013.Aug. 2014.Mar.）Review of EthicalGuidelines for ClinicalResearch（2014.Dec.）Committee for clinical trialregulation（2014.Spr. 2014.Dec.）Clinical Trial Act10
Summary of the report on the Committee forclinical trial regulation①１．Necessity of establishing new act Overviewing based on the globalization of drug andmedical device development over the 5 years, 10 years Current guideline is not enough to recover theconfidence Establishing excess regulation leads to shrink the studyactivity. Balance is needed between the self regulation and legalframework. New regulation is expected for the clinical trial to somedegree.11
Summary of the report on the Committee forclinical trial regulation②2．Main target of the act Clinical trial intending to evaluate Non-Approved drugsand medical devices etc. Clinical trial planned to use the data for advertising thedrugs and medical devices etc.3．Summary content of the act Ethical Review Committee Requirement of the membership Guarantee of the quality of the committee12
Summary of the report on the Committee forclinical trial regulation③ Information disclosure related to the clinical trial Guarantee of transparency by the informationdisclosure Considering the intellectual property Practice standards of clinical research Corresponding at the time of adverse events Monitoring and guidance by government authorities Penalty to the investigator Ensure transparency, such as pharmaceutical companies13
Regulation on Clinical ResearchClinical Research of Medical ProductsCT TypeCT for Marketing Designated ClinicalAuthorizationResearchOther ClinicalResearch Clinical Research of unapprovedproducts or Off-label use Clinical Research with fundingfrom companyRegulationPMD ActGCP OrdinanceClinical Research Act (CRA)CRA OrdinanceEthical Guidelines forMedical and HealthResearch InvolvingHuman Subjects14
Content of Clinical Trial ActChapter 1 general provisionarticle 1 , article 2Chapter 2 conducting clinical trialsarticle 3 article 22Chapter 3 accredited clinical research review committeearticle 23 article 31Chapter 4 providing the funds for clinical trialsarticle 32 article 34Chapter 5 Miscellaneous provisionarticle 35 article 38Chapter 6 Penal provisionarticle HBD39 article43 Tank MeetingEast2017 ThinkAtNational Institute ofprovisionGlobal Health and MedicineSupplementaryTokyo, Japan: December 7, 201715
Major issue of ministry order of Clinical Trial Act平成29 年8 月2 日Article第1回 臨床研究部会 参考資料6よりTitle of the articleChapter 1Article 2DefinitionChapter 2Article 3Clinical trial implementation standardsArticle 5Submission of clinical trial planArticle 9Informed ConsentArticle 12Record of specific clinical trialsArticle 13Article 14Adverse event report to the accredited clinical research reviewcommittee and MHLWArticle 17Article 18Annual Report to the accredited clinical research review committeeand MHLWChapter 3Article 23Accreditation of clinical research review committee by MHLWChapter 4Article 32Conclusion of the contractArticle 33Publication of information related to the provision for the specificclinical trialsArticle 38Delegation to ministry orderChapter 3372.pdf
Early Feasibility Study Necessary for Early Access ofInnovative MDs Need for Protection of Patients Improving Environment for PatientProtection would encourage EFS,Innovative MD development, andEarly access for Innovative MDs!17
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clinical trial regulation② 2．Main target of the act Clinical trial intending to evaluate Non-Approved drugs and medical devices etc. Clinical trial planned to use the data for advertising the drugs and medical devices etc. 3．Summary content of the act Ethical Review Committee Requirement of the membership
