Japan PMDA Medical Device Regulatory Approval Process
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The document provides a comprehensive overview of the medical device registration process in Japan, detailing the roles of the Pharmaceuticals and Medical Devices Agency (PMDA) and the Ministry of Health, Labour and Welfare (MHLW). Key topics include the Foreign Special Approval System, the requirements for Marketing Authorization Holders (MAH), clinical data requisites, and various registration routes based on classification. Additionally, it outlines the Quality Management System (QMS) audit process, timelines, and necessary consultations for successful device registration.
Japan PMDA Medical Device Regulatory Approval Process
- 1. Japan Medical Device Registration Ann Marie Boullie Vice President, Business Development Telephone:+1 512 327 9997 EmergoGroup.com
- 2. 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
- 3. Introduction
- 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
- 12. Device Application: • Classification and JMDN Codes • Clinical Data • (PMDA Meeting Modules) • Registration Routes
- 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?
- 18. Device Application: • Classification and JMDN Codes • Clinical Data • PMDA Meeting Modules • Registration Routes
- 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
- 23. Comparison to similar products
- 24. Clinical Data Consultations Unsure if clinical data is required and/or sufficient?
- 25. Device Application: • Classification and JMDN Codes • Clinical Data • PMDA Meeting Modules • Registration Routes
- 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
- 32. Device Application: • Classification and JMDN Codes • Clinical Data • PMDA Meeting Modules • Registration Routes
- 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
- 41. PMA Application Review Times
- 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
- 57. DMAH and the Importation Process
- 58. DMAH: Standard distribution channel for Imported Medical Devices Clinical site
- 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
- #50: 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