Watch the recorded webinar: https://www.emergogroup.com/resources/video-webinar-japan-registration-process
Japan's medical device market is one of the most robust markets in Asia, but its regulatory system can be confusing. Before deciding to sell your device in the Japanese market, it is important to understand how the regulations apply to your device, which steps to take, and what resources are required to complete the process. In this presentation, Ann Marie Boullie, Vice President of Business Development for EMERGO, will discuss some of the most complex aspects of the Japanese registration process, including:
JMDN codes: device classification and predicates
Clinical data requirements and PMDA pre-submission meetings
Registration routes (Todokede, Ninsho, Shonin)
QMS (Ordinance 169) requirements
Role of the Marketing Authorization Holder (MAH)
Plus more ...
4. Elements of Registration
Foreign Special
Approval
System
Foreign
Manufacturer
Registration
QMS
Application &
Audit
Regulatory Approval
Warehouse
Manufacturer
Device
Application
5. 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
8. 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
9. 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)
10. MAH License Requirements
Must be licensed - by classification; some licenses are only
for specific classifications
IVD and Medical Devices require separate MAH licenses
Minimum 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
13. 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
14. 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
15. 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
16. 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
17. 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?
19. 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) files
Generic (me-too) devices
Improved devices where safety and
efficacy can be verified through non-
clinical data
20. 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
21. 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
22. 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
26. PMDA Pre-Submission Meetings
•Voluntary
•Conducted entirely in Japanese
oStrongly recommended for novel and some
high-risk devices
•Some meetings require extensive
preparation
•Associated fee
oBetween ~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
27. 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 feedback
before moving to formal
Pre-Sub Consultation
JPY 29,400
(~US $252 / € 255)
28. 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)
29. 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)
30. 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
31. 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
33. Determining Regulatory Routes
*JMDN code primarily determines regulatory route
Class I Class II Class III Class IV
Pre-Market
Submission
Pre-Market
Certification
Pre-Market
Approval
34. Class I: Pre-market Submissions (PMS)
•Similar to EU Class I self-declaration
•Once PMS application is provided to
PMDA, free to sell
oApplication must still be compiled and
submitted
oNo technical review
•Usually no QMS audit
•Not eligible for Foreign Special
Approval System; MAH “owns” the
registration
35. 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
36. 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
37. 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
38. 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)
39. PMA Application Types: Generic,
Improved, New
Generic or
“me-too”
Existing JMDN code with submission based on
a registered technical file
Improved
Existing JMDN Code with submission based on
new technical file including comparison table
New No existing applicable JMDN code
40. 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
43. Foreign Manufacturer Registration (FMR)
•Registration of a foreign manufacturing facility
oFormally Foreign Manufacturer Accreditation - now
registration under the PMD Act
•Fairly simple process, mostly administrative
44. Which Medical Device Sites Require FMR?
Registration Category MD Class I MD Software MD
Recording
Medium of
Software MD
Design
Key Manufacturing
Process
Sterilization
Entity which stores final
product in Japan before
the release judgement
45. Which IVD Sites Require FMR?
Device Category IVD Radioactive IVD Class I IVD
Design
Fulfilling Process
Warehouse of final
product in Japan
46. 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)
47. 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!
49. • 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?
51. 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
52. 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
53. 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
device
o Same MAH
o Same manufacturing facility
• Is a New product
• Has improved with clinical data
• Is high risk (e.g., absorbable; biological origin)
54. Validity of QMS
•QMS Maintenance Requirements:
oPMA: 5 year QMS assessments
oPMC: Annual surveillance by the RCB + 5 year QMS
assessment
55. 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
59. Thank you. Questions?
http://www.emergogroup.com/services/japan
Ways Emergo can assist:
Device and IVD Registration
Foreign Manufacturer Registration
QMS Ordinance 169 Compliance
Clinical Data Evaluation
D-MAH Representation
United States
Austin, Texas
+1 512 327 9997
Netherlands
The Hague
+31 (0)70 345 8570
Germany
Hamburg
+49 (0) 40 6094 4360
UK
Sheffield
+44 114 307 2338
Japan
Shinjuku-ku, Tokyo
+81 3 3513 6641
All offices: http://www.emergogroup.com/contact
Editor's Notes
A licensed entity that receives incoming shipments, post-approval
Must be named in the device registration application
Can be a distributor, if they’re licensed as a WM, or an independent company
WM doesn’t have to do the incoming inspection; however, WM typically assigned this activity