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