Regulatory Framework in Japan - Past and Future - Building a Regulatory Framework Essential Elements of Compliance / Surveillance Nobuo UEMURA Director Office of Medical Devices III Pharmaceuticals and Medical Devices Agency (PMDA)
Disclaimer The views and opinions expressed in the following Power Point slides and the presentation are those of the individual presenter, and do not necessarily represent the formal position of PMDA and MHLW. The amendment law has just been passed last month by the Parliament, and the precise and detailed regulations will be announced from now on. 2
Agenda 1. Current Regulatory Framework in Japan 2. History of medical device regulation in Japan 3. Major Topics in the next revision of PAL 1 Third party certification system 2 Quality Management System (QMS) 3 Other revisions related to medical devices 4 Regenerative and Cellular Therapy Products, and Gene Therapy Products 4. Final message 3
Ministry of Health Labor & Welfare (MHLW) & Pharmaceuticals & Medical Devices Agency (PMDA) Imperial palace Kasumigaseki Ministry H. L. W. PMDA 10 min. by walk 4 4
Role of MHLW and PMDA MHLW Ultimate Responsibilities in policies & administrative measures PMDA ex. Final judgment on approval Product withdrawal from market Actual review, examination, data analysis, etc. to assist MHLW s measures ex. Approval Review of MDs QMS/GLP/GCP inspection Collection and analysis of Adverse Event Reports 5
Outline of approval review process (Brand-new medical device) Consultation Applicant Application PAFSC: Pharmaceutical Affairs and Food Sanitation Council PMDA Conformity Audits ( GLP/GCP/QMS etc. ) + External Experts MHLW Advisory body PAFSC Scientific Review Review Consultation Advice Inquiry Answer Report Minister Approval 6
Overview of Medical Device Regulation in Japan Classification (According to the GHTF classification) Class I Class II Class III Class IV Extremely low risk Low risk Medium risk High risk Example X-Ray film MRI Dialyzer, Artificial bone Pacemaker, Artificial heart valve Category General MDs Controlled MDs Specially controlled MDs Review regulation Self-declaration Third party certification QMS inspection No requirement Registered notification body Post-market safety vigilance/surveillance PMDA and MHLW Minister s approval (PMDA s review) PMDA or Prefecture Gov. 7
Medical Devices Regulation EU Japan US Pre-market review Notified body certification (requirements depend on device classification) Class IV: Minister s approval Class III: Minister s approval Class II: Notified body certification Class III: PMA Approval Class II: 510(k) clearance, Class I: Self-declaration Class I: exemption Self declaration Notified body review/certification Governmental approval/license 8
Agenda 1. Current Regulatory Framework in Japan 2. History of medical device regulation in Japan 3. Major Topics in the next revision of PAL 1 Third party certification system 2 Quality Management System (QMS) 3 Other revisions related to medical devices 4 Regenerative and Cellular Therapy Products, and Gene Therapy Products 4. Final message 9
History of Review System Transition in Japan 1994 1995 1997 1999 2001 2004 2013 Commissioned new activities to OPSR MHW Commissioned new activities to JAAME Establishment of PMDEC at NIHS PMDEC/NIHS Introduction of Team Review Establishment of PMDA MHLW GHTF 1992 OPSR (KIKO) Drug Equivalency Review JAAME Device Equivalency Review OPSR (KIKO) Clinical Trial Consultation Compliance Audit GCP Inspection PMDA Device:Ca140 Transition of Number of Review Resources (incl. MHW, JAAME,OPSR,PMDEC,MHLW,PMDA) 89 (1994) 99(1995) 121(1996) 241(1999) 311(2004) > 650 Note) Numbers indicated here stand for sum of the officials of Drugs and Medical Devices Review and Vigilance (including administrators & reviewers) 10
Quantitative Increase and Background of Medical Device Reviewers 90 reviewers As of Sep. 2013 Total 98 reviewers M:13, V: 2, B:12, P:34, E:35, O: 2 11
Japan s Medical Device regulations and international guidance documents Revision of Pharmaceutical Affairs Law (PAL) in 2002 (enforced in 2005 ) GHTF classification rule (SG1-N15) GMDN 2003 JMDN Essential Principles (EPs) + Check lists STED (GHTF-based) GCP/GLP OECD-GLP, ICH-GCP/ISO14155:2011 12
Regulations on medical device, based on risk GHTF Classification PAL classification Category Pre-market regulation Japanese MD Nomenclature Class A extremely low risk X-Ray film General MDs ( Class I ) Self Declaration 1,195 Class B low risk MRI, Digestive catheters Controlled MDs ( Class II ) Third party Certification 1,799 (1,367 for 3 rd Party) Class C Class D medium risk Artificial bones, Dialyzer high risk Pacemaker, Artificial heart valves Specially Controlled MDs ( Class III & IV ) Minister s Approval (Review by PMDA) 756 342 As of July, 2013 13
1. Classification of Medical Devices Former Regulation Current Regulation (From April 2005) GHTF Classification Approval is not necessarily General MDs ( Class I ) Self declaration Class A extremely low risk X-Ray film Controlled MDs ( Class II ) Third party Certification (in principle) Class B low risk MRI, Digestive catheters Minister s Approval is needed Specially Controlled MDs ( Class III & IV ) Minister s Approval Class C medium risk Artificial bones, Dialyzer Class D high risk Pacemaker, Artificial heart values 14
2. Japanese Medical Devices Nomenclature (JMDN) and MD classification Each MD has to fall under generic nomenclature (JMDN). JMDN is based on 2003 version of GMDN. Ministerial Notification #298 (July 20, 2004) shows lists of JMDN and their classification. Classification rule is based on GHTF document (SG1-N15). 15
3. The Essential Principles (EPs) (benefit) EPs provide clear requirements for MDs. (barrier) EPs were new requirements and big challenges especially for SMEs. Two step approach for introducing. - Until April 2008, the General Requirements only - Then, the Design and Manufacturing Requirements Industry has drafted ; - around 400 checklists for conformity to EPs for class II (GHTF class B) MDs, product by product. - 38 checklists for class III, IV (GHTF class C, D) MDs 16
Structure of Product Standards Contents of certification standard (MHLW Ministerial Notification) 1. Scope Applicable medical devices are defined by Japanese Medical Device Nomenclature (JMDN). 2. Technical standard Japan Industrial Standards (JIS) 3. Intended use and indications Most of JIS are harmonized with ISO/IEC The intended use and indications for a medical device are determined based on its definition given in the JMDN. Conformity to Essential Principles (MHLW-PFSB, Notification) The Essential Principles conformity checklist is also provided for confirming the conformity to the Essential Principles. (The Essential Principles are designated by MHLW Ministerial Notification.) 17
3. Essential Principles and 4. STED - Application Dossier - Application Form (Form22-3 of Ministerial Ordinance on PAL) STED + + Data set Declaration of Conformity with EP Essential Principles from GHTF were introduced in Japanese regulation (PAL Art.41(3)) and any device shall be in conformity with the EPs. GHTF-based STED is required. Since 2002 : STED(PD) a trial basis for new or improved MDs. Since 2005 : STED(PD) mandatory for application. 18
5. GLP/GCP Good Laboratory Practice (GLP) for MD J-GLP Ministerial Ordinance incorporated OECD-GLP in 2005 Good Clinical Practice (GCP) for MD J-GCP Ministerial Ordinance incorporated ICH-GCP(ICH E6 guideline) in 2005 and ISO14155:2011 in 2013 19
Agenda 1. Current Regulatory Framework in Japan 2. History of medical device regulation in Japan 3. Major Topics in the next revision of PAL 1 Third party certification system 2 Quality Management System (QMS) 3 Other revisions related to medical devices 4 Regenerative and Cellular Therapy Products, and Gene Therapy Products 4. Final message 20
The Japan Revitalization Strategy June 2013 [Three Policies] Aggressive monetary policy (first arrow) New Growth Strategy (third arrow) Flexible fiscal policy (second arrow) [Three Plans] Plan for the Revitalization of Japanese Industry Strategic Market Creation Plan Strategy of Global outreach Extend healthy life expectancy Expand the markets for pharmaceuticals, medical devices, and regenerative medicine-related industries 21
Brief overview of revision of PAL Points of this amendment are to; 1. Strengthen safety measures regarding drugs and medical devices 2. Revise medical device regulations based on its characteristics 3. Introduce Regenerative and Cellular Therapy Products (RCTP) & Gene Therapy Products (GTP) regulations based on their characteristics Name of PAL will be changed to Act on Securing Quality, Efficacy and Safety of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics. The chapter for Medical Device will be prepared. 22
Scope of Third Party Certification will be expanded GHTF Classification Category PAL classification Pre-market regulation Japanese MD Nomenclature Class A extremely low risk X-Ray film General MDs (Class I) Self declaration 1,195 Class B low risk MRI, digestive catheters Controlled MDs (class II) Third party Certification 1,799 (1,367 for 3 rd Party) Class C Class D medium risk artificial bones, dialyzer high risk pacemaker, artificial heart valves Specially Controlled MDs (class III & IV) Minister s Approval (Review by PMDA) 756 342 23
Framework of Approval Review and QMS Inspection Pre-approval Post-approval Application Form Partial Change Application Submission of Application Form Review by Review Divisions Market Approval Minor Change Notification 軽微変更届出 Design transfer to manufacturing site QMS inspection before approval Actual production Market Release QMS inspection every 5 years after approval 24
QMS regulation change under the revision of PAL QMS inspection applied to Market Authorization Holder(MAH) Foreign manufacturer s Accreditation to Registration QMS inspection per product family
QMS inspection will be applied to MAH, not each manufacturer [Current QMS] [Future QMS] Marketing Authorization Holder (MAH) GQP QMS Marketing Authorization Holder (MAH) Plant A in USA QMS Plant B in Tokyo QMS PMDA Tokyo Plant A in USA Plant B in Tokyo PMDA or Third Party Plant C in Osaka Plant C in Osaka QMS Osaka 26
Registration of Foreign Manufacturer Foreign manufacturer need to register until the QMS inspection is conducted. Accreditation of foreign manufacturer would change to Registration. Accreditation Registration Manufacturing License would change to Registration. License for inland manufacturing Registration
QMS inspection per product family Now Ex) Product A, B,C are Product family XXX QMS Inspection per Product A, B and C After the revision of PAL QMS Inspection per Product family XXX QMS inspection per product family manufactured by the same establishments.
Standalone Medical Device Software (SMDS) will be regulated by the revised PAL Current PAL Image Diagnostic Apparatus It processes, stores and displays image data from CT, MRI etc. Future SMDS Hardware Software (program) Software (program) Only combination of hardware and software is regulated. Standalone Software will also be regulated. 29
Outcome examination system, instead of re-examination system, will be introduced Outcome examination system Outcomes (efficacy and safety) of a designated medical device under a postmarketing surveillance for an appropriate period will be examined. Current [Scope] All brand-new medical devices Future Review [Scope] Designated medical devices ex) Implantable medical devices like stent Approval Annual report Annual report Re-examination period Orphan 7 years New structure 4 years Others 3 years Post-marketing surveillance Outcome examination period Designated Period Not necessary to start the period just after approval Application for re-examination Application for outcome examination 30
Regulations on Package Insert will become more reasonable 1. Contents of package insert of class IV medical device should be notified to MHLW in advance. 2. Package insert notified will be uploaded on web-site. 3. Draft of package insert will be required as a material in a new medical device application. 4. Paper package insert of any medical devices can be omitted under certain conditions. 31
Regenerative and Cellular Therapy Products(RCTP), and Gene Therapy Products(GTP) will be newly categorized [Current] [Future] Drug RCTP GTP Drug Medical Device RCTP GTP Medical Device Regenerative and Cellular Therapy Products (RCTP) & Gene Therapy Products (GTP) 32
Agenda 1. Current Regulatory Framework in Japan 2. History of medical device regulation in Japan 3. Major Topics in the next revision of PAL 1 Third party certification system 2 Quality Management System (QMS) 3 Other revisions related to medical devices 4 Regenerative and Cellular Therapy Products, and Gene Therapy Products 4. Final message 33
Ideal Picture of Medical Device Regulation Collaboration among Industry, Regulatory Authorities(Government), Academia, and People in public with recognition of each parties obligations and responsibilities Industry Academia People Regulatory Authorities 34
Thank you MHLW PMDA