Japan Medical Device Regulatory Approval Process
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Transcript of Japan Medical Device Regulatory Approval Process
Japan Medical Device Registration
Ann Marie BoullieVice President, Business Development
Telephone:+1 512 327 9997
EmergoGroup.com
Topics• Foreign Special Approval System
• MAH and DMAH
• Device Application • Classification and JMDN Codes
• Clinical Data
• PMDA Meeting Modules
• Registration Routes
• Foreign Manufacturer Registration• Warehouse Manufacturer
• QMS Application & Audit• Importation Process and Release Judgment
Introduction
Elements of Registration
Foreign Special Approval System
Foreign Manufacturer Registration
QMS Application &
Audit
Regulatory Approval
Warehouse Manufacturer
Device Application
MHLW / PMDA
The PMDA is a division of the Ministry of Health Labor and Welfare (MHLW)
Medical devices are approved by the Pharmaceuticals and Medical Devices Agency (PMDA)
Pharmaceutical and Medical Device Act (PMD Act) –main medical device regulation
Foreign Special
Approval System
Foreign Manufacturer Registration
QMS Application &
Audit
Regulatory Approval
Warehouse Manufacturer
Device Application
Foreign Special Approval System
•Concept introduced in 2005 oForeign Manufacturer can submit and “own” their device registration
•If companies do not submit under the FSAS:oThe Japanese entity becomes the “owner” / legal manufacturer of the device
•Class I devices not eligible for FSAS
MAH versus DMAH
What is a Marketing Authorization Holder (MAH)?
• Owner of the device registration, like a local legal manufacturer
• Assumes all QMS and vigilance responsibilities
What is a Designated Marketing Authorization Holder (DMAH)?
• No difference in the type of license; the difference is in level of responsibilities, based on who is the owner/legal manufacturer
• Foreign manufacturer maintains control of registration
• Designated MAH appointed for certain activities that must be handled in Japan (e.g., product release judgement; vigilance)
MAH License Requirements
Must be licensed - by classification; some licenses are only for specific classificationsIVD and Medical Devices require separate MAH licensesMinimum staffing criteria based on license category
•Highly Controlled, Controlled and General Medical Devices
•General Manager is allowed to double as Quality Manager only
Category I
MAH License
•Controlled and General Medical Devices
•General Manager is allowed to double as Quality or Safety Manager
Category II
MAH License
•General Medical Devices only
•General Manager is allowed to triple as all roles for MAH
•Only one qualified employee is needed to obtain this license
Category III
MAH License
Foreign Special
Approval System
Foreign Manufacturer Registration
QMS Application &
Audit
Regulatory Approval
Warehouse Manufacturer
Device Application
Device Application:
• Classification and JMDN Codes
• Clinical Data
• (PMDA Meeting Modules)
• Registration Routes
Classification System
•Regulatory route determined by JMDN Code (predicate device) and Classification
•If no JMDN code is available, classification determined by risk to the human body
Japan classification rules based on Global Harmonization Task Force (GHTF) guidance
Japan Medical Device Nomenclature (JMDN) Codes
•Broadly based on Global Medical Device Nomenclature (GMDN)
•JMDN codes are regulated
•List maintained by Japan Association for the Advancement of Medical Equipment (JAAME)
•Used to determine pathway
GMDN ≠ JMDN
JMDN Code Information (translated)JMDN: Passer, suture, single-use (Code: 37839002)
CLASSIFICATION: Class II
DEFINITION: A surgical instrument for passing sutures and suture needles through tissue. Typical passers may be flexible or rigid rods with handles that have hooks, catches or clasps to hold the material being passed through the tissue. Passers may also be ring handled instruments with extended, straight or slightly curved blades. The device is single use.
CERTIFICATION STANDARD: No. 425: Certification Standard for Single use products to which JIS T0993-1 is applied
APPLICABLE JIS: JIS T0993-1
INTENDED USE: To be used for puncturing a hole through tissues to pass sutures or suture needles
IVD Classification
•IVDs technically drugs; however:oRegulatory requirements closely align with medical devices
•IVDs require a Market Authorization Holder (MAH) with an IVD license
•Classes I, II, III
Confirming Borderline Classification
Schedule a Meeting with Local Metropolitan Government
(e.g. Tokyo Metropolitan Government)
If unable to determine, request is escalated
MHLW
Device Determination Classification
PMDA not involved in this process
Unsure of JMDN Code? Classification?
Medical Device?
Device Application:
• Classification and JMDN Codes
• Clinical Data
• PMDA Meeting Modules
• Registration Routes
When is clinical data required?
•Clinical Data is required for:New devices (e.g., no JMDN code)Improved devices, where the safety and efficacy cannot be verified by non-clinical data alone
•Clinical Data is not required for:Pre-Market Submission (PMS) filesGeneric (me-too) devicesImproved devices where safety and efficacy can be verified through non-clinical data
Is your clinical data sufficient?
• The clinical trial protocol is typically “pre-reviewed” by the PMDA and is therefore more likely deemed sufficient
Clinical Trial Conducted in Japan (to Japan Good Clinical Practices - GCPs)
• Yes, if the study includes a sufficient Asian patient population (if applicable for the device)
• Can provide scientific rationale why the data can be extrapolated for the Japanese market
Foreign study conducted to ICH Good Clinical Practices or ISO 14155
Is your clinical data sufficient?
• Officially possible, but difficult for manufacturers to verify objective results
Clinical Evaluation based on non-clinical data and scientific literature?
• Japanese Ministries advocate for the product approval due to an urgent need
• The device has significant clinical worth, allowing physicians to address an unmet clinical need
Higher likelihood of acceptance when the product has an acceptable low risk and:
X
What is considered insufficient clinical data?
Voluntarily gathered data via post-market surveillance (Good Post-marketing Study Practice, GPSP) as it typically:
• Lacks appropriate protocol for study and surveillance
• Lacks adequate documentation
• The data is not statistically valid to support the results
The sales record in markets outside of Japan, even if the data is from long-term post-market surveillance
Comparison to similar products
Clinical Data Consultations
Unsure if clinical data is required
and/or sufficient?
Device Application:
• Classification and JMDN Codes
• Clinical Data
• PMDA Meeting Modules
• Registration Routes
PMDA Pre-Submission Meetings
•Voluntary
•Conducted entirely in JapaneseoStrongly recommended for novel and some high-risk devices
•Some meetings require extensive preparation
•Associated feeoBetween ~JPY 40,000 (US$400/ €350) and JPY 2,325,000 (US$22,850/20,500)
Pre-Submission Meeting
=Typically a series of meetings, ending with the formal
meeting
Meetings Prior to PMDA Pre-Sub Consultation
Meeting Type Intended Purpose PMDA Fee
General Introduction Consultation“ZenpanSodan”
• Introduce applicable MHLW guidance notifications, regulations
• Consultation to select appropriate pre-sub consultation program
Free of charge
Pre-meeting for Pre-Sub Consultation“JunbiSodan”
• Receive PMDA feedbackbefore moving to formal Pre-Sub Consultation
JPY 29,400(~US $252 / € 255)
Pre-Development Consultation“KaihatsumaeSodan”
Meeting Type Intended Purpose PMDA Fee
Pre-Development Consultation
Consultation for anticipated data package, including needed testing and necessity of clinical data
JPY 264,700(~US $2,560 / € 2,315)
Clinical Trial Necessity Consultation“RinshoYohiSodan”
Meeting Type Intended Purpose PMDA Fee
Non-Clinical Data Route
Confirm necessity of another clinical trial based on manufacturer’s non-clinical data and/or results of data based on actual clinical use
JPY 950,500(~US $9,200 / € 8,315)
Clinical Data Route
Confirm necessity of another clinical trial based on the above items plus:• Clinical data (from foreign clinical trial)
and its protocol, if trial conducted• Literature
JPY 1,931,500(~US $18,680 / € 16,895)
Clinical Trial Consultations“ProtocolSodan”
Confirm validity of clinical trial protocol (e.g., study design, number of patients, necessity of controlled study, endpoints, etc.) JPY 2,323,700 (~US $22,500 / € 20,325)
Only applicable if conducting clinical study inside Japan
PMDA Meeting Module Timeframes
Including:
General Introduction Consultation Pre-meeting Formal meeting module
PMDA availability may affect timeframe
Excluding:
x Prep time for the meeting
x PMDA timeframe to finalize assessment and respond after meeting
Three to Four Months
Device Application:
• Classification and JMDN Codes
• Clinical Data
• PMDA Meeting Modules
• Registration Routes
Determining Regulatory Routes
*JMDN code primarily determines regulatory route
Class I Class II Class III Class IV
Pre-MarketSubmission
Pre-Market Certification
Pre-Market Approval
Class I: Pre-market Submissions (PMS)
•Similar to EU Class I self-declaration
•Once PMS application is provided to PMDA, free to selloApplication must still be compiled and submitted
oNo technical review
•Usually no QMS audit
•Not eligible for Foreign Special Approval System; MAH “owns” the registration
Class II Specified Controlled: Pre-Market Certification (PMC)
•Devices with an associated certification standard are eligible to Pre-market Certification
•Review by a Registered Certification Body (RCB)oSimilar to EU CE Marking Process
oUsually onsite QMS audit, subject to RCB
oMust meet Certification Standard
•Some Class III products eligible PMCs, e.g., insulin pen injector
Unable to meet the PMC criteria
PMA application
JMDN Code Information (translated)JMDN: Passer, suture, single-use (Code: 37839002)
CLASSIFICATION: Class II
DEFINITION: A surgical instrument for passing sutures and suture needles through tissue. Typical passers may be flexible or rigid rods with handles that have hooks, catches or clasps to hold the material being passed through the tissue. Passers may also be ring handled instruments with extended, straight or slightly curved blades. The device is single use.
CERTIFICATION STANDARD: No. 425: Certification Standard for Single use products to which JIS T0993-1 is applied
APPLICABLE JIS: JIS T0993-1
INTENDED USE: To be used for puncturing a hole through tissues to pass sutures or suture needles
List of Licensed Japanese RCBs
BSI Japan K.K. SGS Japan
Cosmos Corporation TÜV Rheinland Japan Ltd.
Fuji Pharma Co. Ltd. TÜV SÜD Japan Ltd.
Japan Association for the Advancement of Medical Equipment (JAAME)
DQS Japan
Japan Quality Assurance Organization (JQA)
DEKRA Certification Japan K.K.
Japan Electrical Safety & Environment Technology Laboratories (JET)
Japan Chemical Quality Assurance Ltd.
Nanotec Spindler Co. Ltd. BVQI Japan
Class III and Class IV: Pre-Market Approval (PMA)
•Reviewed directly by the PMDA
•Class I & II devices without a JMDN code (or cannot meet the Certification Standard) are subject to PMA
•QMS Conformity Assessment could be either on-or-offsite, depending on the device and/or condition of the Certificate of QMS Conformance (Kijuntekigosho)
PMA Application Types: Generic, Improved, New
Generic or “me-too”
Existing JMDN code with submission based on a registered technical file
ImprovedExisting JMDN Code with submission based on new technical file including comparison table
New No existing applicable JMDN code
PMA Application Types: Generic, Improved, New
Class IV: Generic device (with approval standard, without clinical data)
Class IV: Generic device (without approval standard or clinical data)
Class II or III: Generic device (with approval standard , without clinical data)
Class IV: Improved device (with clinical data)
Class IV: Improved device (without approval standard or clinical data)
Class II or III: Improved device (with clinical data)
Class II or III: Improved device and Generic device (without approval standard or
clinical data)
Class IV: New device
Class II or III: New device
PMA Application Review Times
Foreign Special
Approval System
Foreign Manufacturer Registration
QMS Application &
Audit
Regulatory Approval
Warehouse Manufacturer
Device Application
Foreign Manufacturer Registration (FMR)
•Registration of a foreign manufacturing facilityoFormally Foreign Manufacturer Accreditation - now registration under the PMD Act
•Fairly simple process, mostly administrative
Which Medical Device Sites Require FMR?
Registration Category MD Class I MD Software MDRecording
Medium of Software MD
Design
Key Manufacturing Process
Sterilization
Entity which stores final product in Japan before the release judgement
Which IVD Sites Require FMR?
Device Category IVD Radioactive IVD Class I IVD
Design
Fulfilling Process
Warehouse of final product in Japan
FMR Submission
•FMR must be obtained before the product registration is submitted (e.g., PMA Application) oThe FMR Number must be included in the application
•FMR submitted by MAH
PMDA Review Timeframe: One Month
FMR Fee: Tax of JPY 90,000 (~US$870/€ 785)
FMR Renewal
•The FMR is valid for five years
•Any product imported after the FMR expires technically needs to be recalled
Monitor the expiration date!
Foreign Special
Approval System
Foreign Manufacturer Registration
Warehouse Manufacturer
Regulatory Approval
QMS Application &
Audit
Device Application
• A registered entity that receives incoming shipments
What is a Warehouse Manufacturer (WM)?
• Must be named in the device registration application
• Can be a distributor (if licensed as a WM) or an independent company
• Doesn’t have to perform the incoming inspection; however, typically assigned
What’s the role of a WM?
Foreign Special
Approval System
Foreign Manufacturer Registration
QMS Application &
Audit
Regulatory Approval
Warehouse Manufacturer
Device Application
PMDA QMS Overview
•Comprised of two main elements:
1. QMS Conformity Assessment application
E.g., document provision
2. QMS Assessment
Audit to Ministry Ordinance #169
QMS Conformity Assessment Application
Includes documents such as:
Quality Manual
ISO 13485 Cert (if available)
Product list
Manufacturing Flowchart
Floor plan
Etc.
The QMS application must be submitted within 10 days of the device registration
QMS Audits
• The application is not the audit
• PMDA will review the application and decide whether to conduct an on-or-off-site audit
Typically an off-site audit, unless the device (not inclusive):
QMS Conformity Assessment may be avoided when:
• The device is in the same product category as a previously approved deviceo Same MAHo Same manufacturing facility
• Is a New product• Has improved with clinical data• Is high risk (e.g., absorbable; biological origin)
Validity of QMS
•QMS Maintenance Requirements:
oPMA: 5 year QMS assessments
oPMC: Annual surveillance by the RCB + 5 year QMS assessment
QMS Requirements
•Ministry Ordinance (MO) #169 ≈ ISO 13485:2003
oMinor differences, e.g., retention time for obsolete documents and records, and MAH related
•ISO 13485:2016?oMHLW Administrative Circular “Handling of the Revision of ISO 13485 in QMS Surveillance”
ISO 13485:2016 compliant system accepted
MHLW has no current plans to modify MO #169 to meet 13485:2016
•ISO 13485:2003/2016 certification does not exempt companies from proving compliance to Japan Conformity Assessment requirements
Foreign Special
Approval System
Foreign Manufacturer Registration
QMS Application &
Audit
Regulatory Approval
Warehouse Manufacturer
Device Application
DMAH and the Importation Process
DMAH: Standard distribution channel for Imported Medical Devices
Clinical site
Thank you. Questions?
http://www.emergogroup.com/services/japan
Ways Emergo can assist:Device and IVD Registration
Foreign Manufacturer RegistrationQMS Ordinance 169 Compliance
Clinical Data EvaluationD-MAH Representation
United StatesAustin, Texas+1 512 327 9997
NetherlandsThe Hague+31 (0)70 345 8570
GermanyHamburg+49 (0) 40 6094 4360
UKSheffield+44 114 307 2338
JapanShinjuku-ku, Tokyo+81 3 3513 6641
All offices: http://www.emergogroup.com/contact