Idea Transcript
“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
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4
Role of MHLW and PMDA
MHLW Ultimate Responsibilities in policies & administrative measures ex. Final judgment on approval Product withdrawal from market
PMDA 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) Applicant Consultation
PAFSC: Pharmaceutical Affairs and Food Sanitation Council
Application
PMDA
MHLW
Conformity Audits
Advisory body
( GLP/GCP/QMS etc. ) +
PAFSC
Scientific Review Inquiry
Answer
External Experts
Review Report
Consultation
Advice
Minister
Approval 6
Overview of Medical Device Regulation in Japan Classification (According to the GHTF classification)
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
Minister’s approval (PMDA’s review)
QMS inspection
No requirement
Registered notification body
PMDA or Prefecture Gov.
Post-market safety vigilance/surveillance
Class I
Class II
Class III
Class IV
PMDA and MHLW 7
Medical Devices Regulation EU
Japan
US
Pre-market review Class IV: Minister’s approval
Class III: PMA Approval
Class III: Minister’s approval Notified body certification (requirements depend on device classification)
Class II: Notified body certification
Class I: Self-declaration
Self declaration
Notified body review/certification
Class II: 510(k) clearance,
Class I: exemption
Governmental approval/license
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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 Commissioned new activities to
OPSR
1995 Commissioned new activities to JAAME
2001
1999
1997
Establishment of PMDEC at NIHS
2004
2013
Establishment of
PMDA
☆MHLW
☆MHW ☆PMDEC／NIHS ･Introduction of Team Review ☆OPSR (KIKO)
☆OPSR (KIKO)
・Drug Equivalency Review
GHTF 1992
・Clinical Trial Consultation
ＰＭＤＡ
・Compliance Audit ・GCP Inspection ☆JAAME ・Device Equivalency Review 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)
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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
Class A extremely low risk X-Ray film
Class B low risk MRI, Digestive catheters
PAL classification Category
Pre-market regulation
Japanese MD Nomenclature
General MDs ( Class I )
Self Declaration
1,195
Controlled MDs ( Class II )
Third party Certification
1,799
Specially Controlled MDs ( Class III & IV )
Minister’s Approval (Review by PMDA)
Class C medium risk Artificial bones, Dialyzer
Class D high risk Pacemaker, Artificial heart valves
(1,367 for 3rd Party)
756
342
As of July, 2013
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1. Classification of Medical Devices Former Regulation
Approval is not necessarily
Minister’s Approval is needed
Current Regulation (From April 2005)
GHTF Classification
“General MDs” ( Class I )
Self declaration
Class A
extremely low risk X-Ray film
“Controlled MDs” ( Class II )
Third party Certification
Class B
low risk MRI, Digestive catheters
Class C
medium risk Artificial bones, Dialyzer
Class D
high risk Pacemaker, Artificial heart values
“Specially Controlled MDs” ( Class III & IV )
(in principle)
Minister’s Approval
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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).
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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). Most of JIS are 2. Technical standard harmonized with Japan Industrial Standards (JIS) ISO/IEC 3. Intended use and indications 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)
Strategic Market Creation Plan
Strategy of Global outreach
[Three Plans] Plan for the Revitalization of Japanese Industry
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
Class A extremely low risk X-Ray film
Class B low risk MRI, digestive catheters
PAL classification Category
Pre-market regulation
Japanese MD Nomenclature
General MDs (Class I)
Self declaration
1,195
Controlled MDs (class II)
Third party Certification
1,799 (1,367 for 3rd Party)
Class C medium risk artificial bones, dialyzer
Class D high risk pacemaker, artificial heart valves
Specially Controlled MDs (class III & IV)
756 Minister’s Approval (Review by PMDA)
342 23
Framework of Approval Review and QMS Inspection Pre-approval
Post-approval
Application Form
Partial Change Application Minor Change 軽微変更届出
Submission of Application Form
Review by Review Divisions
Market Approval
Notification
Market Release Design transfer to manufacturing site
Actual production
QMS inspection before approval
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 A in USA PMDA
Plant B in Tokyo QMS
Plant B in Tokyo Tokyo
Planｔ C in Osaka QMS
PMDA or Third Party
Planｔ C in Osaka 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 Ex) Product A, B ,C are Product family XXX
Now 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 Future
Current PAL
Image Diagnostic Apparatus It processes, stores and displays image data from CT, MRI etc.
Hardware
Software (program)
Only combination of hardware and software is regulated.
SMDS
Software (program) 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
Re-examination period
[Scope] All brand-new medical devices
Review
Approval
Future [Scope] Designated medical devices ex) Implantable medical devices like stent
Annual report
Orphan ・・・・・・・・・・・・ 7 years New structure ・・・・・・4 years Others ・・・・・・ ・・・・・・ 3 years Application for re-examination
Post-marketing surveillance Application for outcome examination
Annual report
Outcome examination period Designated Period Not necessary to start the period just after approval
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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.
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Regenerative and Cellular Therapy Products（RCTP), and Gene Therapy Products（GTP) will be newly categorized [Current]
Drug
Medical Device
[Future]
RCTP GTP
RCTP GTP
Drug
Medical Device Regenerative and Cellular Therapy Products (RCTP) & Gene Therapy Products (GTP)
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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