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Comparing Medical Device Law & Regulations of Japan, EU and US
April ２００8．Medical Device Consulting Japan
Japan EU US
Population: 127 million Population: 493 million, 27 countries Population: 303 million
Competent Ministry of Health, Labor and Welfare( MHLW), EC unit F3：Medical Device & Cosmetic FDA (Food & Drug Administration)
Authority, -Pharmaceutical and Food Safety Bureau, Competent Authority of each Member States CDRH (Center for Devices and Radiological Health)
Related - Office of Medical Device Control : about 1,000 reviewers and specialists
Organization - Office of Compliance Notified Body (NB) : About 70 (BSI, TUV/RH,
- Pharmaceutical Affairs office of each Government Prefectures TUV/SUD, KEMA, etc) Review of 510(k) by Third Party Accredited Bodies
- Review and Audit by Pharmaceutical and Medical Device such as UL、TUV America, TUV/RH, BSI etc
Agency （PMDA）: about 30 specialists Notified Body (NB) in Japan: BSI, TUV/RH,
Registered Certification Body (RCB) :14 (JQA, TUV/RH ， TUV/SUD, SGS ,etc.
TUV/SUD, BSI, UL, SGS etc)
Pharmaceutical Affairs Law (PAL) 90/385/EEC Active Implantable Medical Food, Drug and Cosmetic Act of 1938
Laws New PAL promulgated in July 2002, enforced as of April 1, 2005 Devices Directive（AIMDD） 1976 Medical Device Amendments (MDA)
and to harmonize with GHTF and adopt Quality Management 93/42/EEC Medical Devices Directive（MDD） 1990 Safe Medical Device Act
Regulations System (QMS), and Essential Principles. 98/79/EEC In Vitro Medical Devices Directive 1997 FDA Modernization Act
PAL Enforcement Ordinance, PAL Enforcement Regulation, GQP （IVDD） 2002 Medical Device User Fee and
(Good Quality Practice)，GVP (Good Vigilance Practice)，QMS Essential Requirements of each Directives FDA Modernization
(Quality Management System) and GCP (Good Clinical Practice) Harmonized Standards (EN,IEC,ISO) 21CFR: Code of Federal Regulation, Food and
promulgated in July 2004 – July 2005. MEDDEV Guidance Documents Drugs
Many Ordinances and Notices issued up till now. : Vigilance Guidance MEDDEV 2.12-1 Rev 5 §801 Labeling
Transfer of Certification or Approval (KISAI-SEIBI: June 8, 2007) (effective from Jan..1, 2008) §807 Establishment registration and device listing
for medical devices approved or notified under Old PAL must be for manufacturers and initial importers of devices
done until the next renewal of license of MAH (2006 – March 98/47/EEC Revised Medical Devices Directive §814 Pre-Marketing Approval (PMA)
2010) (revised in September 2007) §820 Quality System Regulation (QSR)
Technical Standards (JIS) for Certification (396) , Approval (35) The following contents are mainly mentioned on Many Guidelines related to CFR
and IVD Reagent Certification (8 groups, 366) MDD. Recognized Consensus Standards
License The following Licenses are required for MD business, Registration of Representative Authority (Initial Initial Registration of Device Establishment ：
and/or 1. License for Manufacturer (4,269 as of 2007) Distributor in EU) Manufacturer including Foreign Manufacturer and
Registration 2. Accreditation of Foreign Manufacturers (about 1,000) Registration of Manufacturer and List of Device Initial Importer shall be registered into FDA File.
of each type 3. License for Marketing Authorization Holder (MAH: 2,676) who Category and Products Annual Device Listing of the manufacturer shall be
of Business is responsible for marketing medical devices and was provided to FDA/CDRH
Manufacturer or Importer of MDs under Old PAL. Number of Japanese manufacturers registered
3 controllers are required, Marketing Supervisor, Safety Control manager, is about 350 – 400. Number of Japanese manufacturers registered
Quality Assurance manager (quite unique compared with US, EU) is 605 as of Oct. 2007.
4. License for Retail and Rental Business of ClassⅡ- Class Ⅳ
MDs and Registration for sales of ClassⅠ
5. License for Repair Business of each Technical Support Office
MDC Japan 1
Japan EU US
IVD is included in the category of Medical Device. Although Annex 8 Medical Device Classification §862 – 892 Medical Device Classification : Class
Classification of 2000 MDs were classified under Old PAL, 4000 MDs have been Class Ⅰ, Ⅱa,Ⅱb, Ⅲ Ⅰ,Ⅱ,Ⅲ
MDs and defined based on GMDN and classified. into 4 classes under General Controls: Common controls for all medical
Requirements New PAL, so many devices are newly included as MD and devices, such as Initial Registration of Device
for Marketing about 200 MDs were changed from Class Ⅰto higher classes, Establishment and Initial Importers, Device listing,
Clearance so called Class-Up MDs. GMP/QSR etc
Class Ⅰ（General Medical Device ：Malfunction causes only Class Ⅰ: Annex 7 ClassⅠ: X-ray tubes, Vacuum Tubes, etc 510(k)
minor effect on human body） Technical File of the MD, Declaration of (Pre-market Notification) is not required except
: X-ray film, surgical steel knife etc are required Notification Conformity by the manufacturer and CE specific devices.
only. Marking.
Serialized MD and measuring MD must be
certified by NB
ClassⅡ（Controlled Medical Device：Malfunction raises low ClassⅡａ : Annex 7 + Annex 2 or (Annex 4 or 5 or ClassⅡ: Substantial equivalence to other products
possibility of life threatening effect or serious injury） 6) (Predicate Device) in commercial distribution, such
: About 400 MDs with Certification Standard (JIS) : X-ray, CT, 1. Certification for Full Quality System (ISO as Diagnostic X-ray system, Ultrasound, CT, MRI,
Ultrasound, EKG, Endo-scope etc 13485) of the manufacturer by NB EKG etc
shall comply with the applicable standard and Essential 2. Technical File of the MD to show compliance 510(k) submission needs the device name, the
Principles which are same to Essential Principles of GHTF and with Essential Requirements and inspection establishment registration number, the class, action
be applied to Registered Certification Body (RCB) . by NB taken to comply with the requirements of the act for
MDs without JIS shall comply with Essential Principles and be 3. Declaration of Conformity by the performance standard, proposed labels, labeling and
applied to PMDA manufacturer documents indicating the device is substantially
4. CE Marking equivalent to predicate devices .
For medical device contained Software,
manufacturers must submit the documents of the
Software including Risk Analysis and Verification &
Validation Data.
Class Ⅲ (Highly Controlled Medical Device : Malfunction Class Ⅱｂ :Diagnostic X-ray, CT, etc.: Annex 7 +
cause substantial effect on subjects) Annex 2 or (Annex 3 + 4 or 5 or 6)
: Dialyzer, Radio-therapy system, Respirator, etc 1. Certification for Full Quality System (ISO
MDs shall comply with Essential Principles and be applied to 13485) of the manufacturer by NB
PMDA. 2. Technical File of MD to show compliance with
MDs with Approval Standard (35 Std.) shall comply with the Essential Requirements and inspection by NB
standard and Essential Principles 3. Declaration of Conformity of the MD by the
Depending on the intended use and materials Bio-compatibility manufacturer with Technical File
test, Sterilization Validation and/or Clinical Study are required. 4. CE Marking
MDC Japan 2
Japan ＥＵ US
Classification Class Ⅳ (Highly Controlled Medical Device : Invasive Device Class Ⅲ : Implantable MDs in heart or Central Class Ⅲ (Implantable MDs, Vascular Stent,
and of which malfunction may cause life threatening effects): Nerve etc. Annex 2 including Sec. 4 or (Annex 3 + Artificial Heart and New MD etc)
Requirements Implantable pace maker, stent etc. shall comply with Annex 4 or 5) : is required to meet General Controls, approval of
for Marketing Essential Principles and be applied to PMDA. 1. Clinical Investigation approved by Competent IDE(Investigational Device Exemption for
Clearance Authority of Member State Clinical Study) and PMA (Pre-market
2. Certification for Full Quality System of the Approval) with submission of documents for
New MDs are required GLP (Good Laboratory Practice, manufacturer by NB each of 4 modules
Pre-Clinical tests) and Clinical Study based on GCP 3. Type Test of the MD for Essential
Requirements by NB
Notice “Remark points on Application for Marketing Approval 4. Review Design Dossier of the product and
for Medical Devices” (No. 0216001, dated Feb. 16. 2005) Pre-market inspection by NB, then Approval of
Attachment 1 shows the list of example of Medical Devices CE Marking
required Clinical Study
Time scale to Class Ⅱ: Class Ⅱ：
get Marketing MDs with Certification Standard (JIS) shall be reviewed and Class Ⅱａ, Ⅱｂ After submitting documents for 510(k), it takes 2 – 6
Clearance QMS of the manufacturer shall be audited by Third Party Audit of ISO 13485 and inspection of compliance months to get clearance depending on the quality of
Certification Body. of MDD by NB; the documents and response to questions from FDA
Certification time is 1 –3 months depending on quality of Audit of NB takes 3 –5 days depending on the size or Third Party.
documents and QMS. of manufacturer and quality of Technical File etc
Certification Fee is less than 1 million yen depending on RCB of the MDs
and numbers of application per year
Class Ⅲ:
MDs with and without Approval Standard shall be reviewed
by PMDA and the QMS shall be audited by Inspectors of each
Government Prefecture.
Approval Time is 6 to 18 months.
Review fee without JIS of PMDA is 1,232.8 kyen.
Review fee with JIS of PMDA is 351.4 kyen.
Class Ⅳ: shall be reviewed by PMDA, review time depends Class Ⅲ, depending on period of Clinical Class Ⅲ：
on the quality of application documents and QMS. The Investigation and Type Test by NB IDE + Clinical Study takes 6 months – 2 years
review fee for approval is 3,741 kyen excluding consultation After submitting application documents of 4
fee by PMDA. Clinical Investigation (MDD Article 15) is modules for PMA to FDA, it takes min. 6 months
New MD: Period for Clinical Study is 1 – 3 years required for Class Ⅲ and Implantable/ invasive and average 8 months to get approval depending on
depending on the intended use and number of applicable Class Ⅱａ orⅡｂ the report of Clinical Study, quality of documents
patients. and response to FDA. and the result of PMA
Review fee of GLP & Clinical Study of PMDA is 2,697.7 kyen. MEDDEV 2.7.1 : Talks about evaluation of Inspection for manufacturer
Cost of Clinical Study is 10 million – 100 million yen. medical device clinical data
MDC Japan 3
Japan ＥＵ US
Manufacturer must establish QMS based on New QMS Quality Management System (ISO13485) 21 CFR 820 QSR（Quality System Regulation）
Quality Regulation (almost equivalent to ISO 13485) : Audit for manufacturer and Certification by NB : Almost same to ISO 13485
Management Marketing Authorization Holder must establish QMS based Audit for manufacturer by FDA takes normally 3 –
System/GMP on GQP and Post Marketing Vigilance System based on GVP. 5 days depending on the size and quality of
Manufacturer of Class ⅡMD with Certification Standard manufacturer
(JIS) is audited by RCB. FDA audit focuses to Management Responsibility,
Manufacturers of ClassⅡMD without JIS or Class Ⅲ or Ⅳ Design Control including Risk Analysis, Process
is audited by inspectors of Government Prefecture Validation, Complaint Handling and Corrective and
Manufacturers of New MD is audited by PMDA Preventive Actions (CAPA)
The QMS of Foreign Manufacturer will be audited by PMDA
or RCB based on QMS regulation.
At every application for Certification or Approval for MD
QMS audit is done for the manufacturer of MD.
It is quite unique and too much cost.
Adverse Event or Incident Report: Chapter 10 of PAL Incident Report and Recall (Article 10 of MDD) MDR (Medical Device Reporting) : CFR 803
Adverse Event or Enforcement Regulation and Vigilance Guideline MEDDEV 2.12-1 Rev.5 Manufacturers are required to report an
Incident When Marketing Authorization Holder notices any of the 1. Old MEDDEV requires reporting Incidents individual adverse event (MDR) to FDA from
Report to following cases, they shall inform the Minister and PMDA within 10 or 30 days., now replaced by
becoming aware of an event as follows,
Competent within the period specified in each item, “immediately”
Authority (1) 15 days report of death, which are suspected to be due to
2. Incident and Event Reporting to relevant 1) 5 day reports on events that require remedial
faults of the medical device or the medical device used in Competent Authority (CA) action to prevent an unreasonable risk of
foreign country, or the occurrence of cases attributable to1) Serious public health threat : Report substantial harm to the public health and other
infection diseases suspected to be associated with the use of
immediately (without any delay that could not be types of events designated by FDA
the medical device, etc. justified) but not later than 2 calendar days after
(2) 30 days report of the occurrence cases such as Disabling,
awareness by the manufacturer of the threat. 2) 30 day reports of deaths, serious injuries that is
potential leading to death or disabling etc. (See Chapter 2) Death or Unanticipated serious deterioration in life threatening, even if temporary in nature and
10, Article 253 about detail) state of health : Report immediately (without any malfunctions
delay that could not be justified) after the
The number of the report is increasing, because penalty for manufacturer established a link between the MDR in 2005 17,000
violation was enforced strongly device and the event but not later than 10 elapsed
In 2002 5,252 reports calendar days following the date of awareness of MDR in 2006 20,000
In 2004 16,000 reports the event
3) Others : Report immediately (without any
delay that could not be justified) after the
manufacturer established a link between the
device and the event but not later than 30 elapsed
calendar days following the date of awareness of
the event
3. Reporting of use errors to relevant CA
MDC Japan 4
Japan US
EU
Marketing Authorization Holder must report to Government Field safety Corrective Action (FSCA) and Field Recall to FDA （Ｃｏｒｒｅｃｔｉｏｎｓ ａｎｄ Ｒｅｍｏｖａｌｓ）
Recall and Prefecture and PMDA in case of Recall and Removal Safety Notices (FSN) Classification of Recall : Ⅰ(most urgent and
Removal Class Ⅰ (most urgent and important) →Ⅱ→Ⅲ 1) Recall Notice now replaced by FSCA ,but covers important) →Ⅱ→Ⅲ
recall as well Number of Recall in 2005 was 571
In 2005 number of Recall was 322 2) FSCA should be notified to relevant CA and NB In 2006 was 630
In 2006 was 365 via FSN
3) If recall is ordered outside EU but product sold
in EU, FSCA must be notified to relevant CA
MDC Japan 5
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