Global Regulatory Partners GK Current Capabilities in Japan Company - - PowerPoint PPT Presentation

Global Regulatory Partners GK Current Capabilities in Japan

Company Profile

▪ Global Regulatory Partners GK (GRP Japan) is the Japanese affiliate of Global Regulatory Partners US (GRP US) ▪ GRP US was established in 2010 and is headquartered in Massachusetts (Boston area) USA. ▪ GRP Japan was established in 2016 and is based in Tokyo, Japan ▪ GRP Japan is licensed as MAH category I for medical devices & drugs and MAH for IVDs. ▪ Total staff is 64 = 26 senior management (4 in Japan) ▪ Key personnel have Ph.D. or Master degrees and more than 15 years’ experience in the pharmaceutical and biotechnology industries

Vision & Strategy

Focus on early stage and medium size life science companies

01

Be a one (1) stop shop for Regulatory Affairs, Safety, Quality Services

02

Offer tailored services that meet companies’ need.

03

Cover the whole products lifecycle, from concept till commercialization.

04

GRP GK MAH/DMAH Services

▪ GRP Japan provides the following services:  Foreign Manufacturing site Accreditation (FMA)  Pharmacovigilance  Regulatory affairs services  Reimbursement  Quality Services  ICC (In Country Care-taker) ▪ GRP GK is licensed by local authorities as MAH/DMAH category 1 and can represent

any foreign medical device/IVD and drug company in Japan.

▪ As MAH/DMAH, GRP GK complies with all Japanese requirements outlined in Act No.

145, Article 23-2-1/Article23-2-17.

MAH/DMAH Responsibilities

In Japan, GRP is licensed as Category I MAH. MAH/DMAH services:

▪ Importation of products ▪ Product registration ▪ Product quality and safety assurance ▪ Product storage in an establishment with MAH licensing ▪ Product release to distributors or other sales groups ▪ Post-market vigilance

Registration Flow Chart for MD

Step 1 • FMA/FMR : Foreign Manufacturing Registration Step 2 • PMDA Meeting (if necessary) Step 3

• Clinical Trial (if necessary)

Step 4 • Registration Dossier Submission and QMS Application* Step 5 • Approval/Certification/Notification Step 6 • Application for Reimbursement

* It is not necessary for most of Class I product

Foreign Manufacturing Sites Accreditation: FMA

▪ Foreign Manufacturers need to register their manufacturing sites before importing their devices to Japan according to the requirements of Act No. 145, Article 23-2- 4. ▪ Sites to be registered : Design Facility, Main Assembling Plant, Sterilizing Facility. ▪ Required documents for registration:

• Form No. 63(5) (related to MHLW Ordinance No. 1 in 1961 Article 114-15)
• Personal History of Responsible Person
• Self-Declaration
• Document of buildings and facilities
• ISO13485 certificate (preferable)

Regulatory Affairs Services

⮚ Regulatory Strategy ⮚ Preparation of meeting with PMDA ⮚ Device registration in compliance with the

requirements of Act No. 145, Article 23-2-5)

⮚ Device registration process

• Device classification
• Registration of device Class I
• Registration of devices Class II, Class III and Class IV

Classification of Medical Device in Japan

Class Definition Class I : General medical devices The risk to customers in the event of malfunction is regarded as almost negligible. Registration category: Notification Self Declaration (submission to PMDA) Class II : Controlled medical devices The risk to customers in the event of malfunction is regarded as relatively low. Registration category: Certification or Approval Certified by Registered Certification Body or Approved by PMDA Class III: Specially controlled medical device The risk to customers in the event of malfunction is regarded as relatively high. Registration category: Approval or Certification Approved by PMDA or Certified by Registered Certification Body Class IV: Specially controlled medical device The device is high invasive with potential fatal risk to customers. Registration category: Approval Approved by PMDA

Registration of Class I Devices

The content of the notification for Class I devices is as follows:

• Classification
• General name
• Sales name
• Purpose of usage and effect
• Figure, machinery and principle
• Raw materials
• Standards concerning performance and safety
• Usage
• Storage conditions and Expiry
• Manufacturing process
• Manufacturing site
• Package inserts
• Photograph of product appearance
• Suitability rational for definition of

general name

• 9. Storage condition and expiry
• 10. Manufacturing process
• 11. Manufacturing site (name of the place and

registered number)

• 12. Package inserts
• 13. QMS compatibility confirmation
• 14. STED*

Registration Dossier for Class II-IV

Content of registration dossier for Class II, Class III and Class IV devices

• 1. Classification
• 2. General name
• 3. Sales name
• 4. Purpose of usage and effect
• 5. Figure, machinery and principle
• 6. Raw materials
• 7. Standards concerning performance and safety
• 8. Usage

Content of the Registration Dossier of STED*

List of requirements List of requirements

• 1. Summary of Product

1.1 Overview of Product 1.2 Origin or History of Discovery and History of Development 1.3 Usage Conditions in Foreign Countries 4.2.1.2 Electrical Safety and Electromagnetic Compatibility 4.2.1.3 Biological Safety 4.2.1.4 Radiation Safety 4.2.1.5 Mechanical Safety 4.2.1.6 Stability and Durability 4.2.2 Tests to Support Performance 4.2.3 Tests to Support Efficacy 4.2.4 Tests to Support Usage Method 4.3 Clinical Evidence 4.3.1 Clinical Trial Results 4.3.2 Conclusion of Clinical Trial Results 4.3.3 Miscellaneous

• 2. Essential Principles and Conformity to the Essential Principles

2.1 List of Referenced Standards 2.2 Essential Principles and Evidence of Conformity

• 5. Labeling

5.1 Instructions for Use (Draft) and Basis for Establishing Its Content 5.2 Label (Draft)

• 3. Device Description

3.1 General Information 3.2 Raw Materials 3.3 Product Specifications 3.4 Storage Method and Expiration Period 3.5 Comparison with Similar Medical Devices

• 6. Risk Analysis

6.1 Risk Analysis System 6.2 Important Hazards

• 4. Summary of Pre-clinical Design Verification and Validation

Documents 4.1 General Information 4.2 Summary of Medical Device Design Validation 4.2.1 Tests to Support Safety 4.2.1.1 Physical and Chemical Properties

• 7. Manufacturing Information

7.1 Information on Manufacturing Process and Manufacturing Site 7.2 Sterilization Method 7.3 Quality Control

Quality Services

⮚ Quality Audits of manufacturers, suppliers and distributors in Japan according to MHLW ordinance 169 in 2004, FDA 21 CFR 820 or ISO 13485. ⮚ Preparation for PMDA pre-approval inspection and FDA inspection (gap analysis, mock inspection, training) and response to FDA after inspection. ⮚ Creating Quality Manual and SOPs ⮚ Implementation of Quality system ⮚ Products release in Japan

Content of QMS Application

▪ QMS (MHLW Ordinance No. 169 in 2004, MHLW Ordinance No. 94, 2014) ▪ QMS compliance inspection can be performed either on desktop/document or

• n-site

▪ Content of QMS application includes :

• Product application document (photocopy) for manufacturing and sales approval
• ISO13485 certification or Inspection report issued by registered certification bodies in Japan or

by recognized foreign health authorities under within 3 years.

• Manufacturing process flow
• Outline of contents of MAH/RMS (Registered Manufacturing Site) activities and documents

which can identify mutual relations of QMS between MAH and RMS

• Summary of Plant
• Child Products List

QMS Inspection (Pre-, Post-)

R&D Application for Approval Regulatory Review

Approval

Marketing Every 5 years Post-approval inspection Pre-approval inspection Post-approval inspection One of the requirements for marketing Approval of medical device Conducted every 5 years after Marketing approval Based on application Conducted per Product Family

PRE-MARKETING SAFETY

▪ Receipt, data entry, review, analysis, coding and follow up on serious adverse events (SAEs) and ▪ (SUSARs) from clinical studies. ▪ Provide safety input to protocols, clinical study reports and investigator brochures. ▪ Safety data reporting to competent authorities, ethics committees and investigators.

POST-MARKETING SAFETY

▪ Collection, evaluation and review of complaints. ▪ Medical Safety Assessment of individual Case Reports. ▪ Adverse events reporting PSUR preparation and submission. ▪ Health Authorities PV databases monitoring. ▪ Products Safety profile building and continuous update.

Safety/Pharmacovigilance Services

Pharmacovigilance

GVP Reporting activities in Japan

ICSR (individuals case safety report for domestic and foreign issues)

Two categories in ICSR

• 1. Medical device defect
• 2. Infection (equal to contamination)

Two types of information are required in ICSR for Medical device. (different from drugs) *AER and Device defects

• 1. Devise defects with no AERs should also be reported if the defect has possibility to develop serious adverse

events

• 2. Difference in timelines of ICSR between foreign and domestic (Japanese) cases.

Research Report

There is another expedited report (Research Report) other than ICSRs Source of Research Report are:

• 1. Scientific literatures and presentations at scientific meetings (Japan and foreign)
• 2. Actions taken for safety measures (recall, disposal, stop manufacturing ) in foreign countries

Annual Reports

• 1. Unexpected non-serious individual cases are reported annually as periodical report.

▪ There are three categories (A, B & C) of MD A1: Comprehensive

The technical fee comprises the cost of MD (e.g., sutures, gauzes)

A2: Specifically comprehensive

Items that are evaluated comprehensively in specific categories (e.g., PET, CT, MRI)

B: Individual evaluation (reimbursable MD)

Device prices that are individually determined and evaluated. It is usually called as Special Treatment Medical Device (STM). (e.g., pacemakers, artificial joints)

C1: New-function products

Products that need a new function classification and have already been evaluated for technical fee (e.g., drug eluting coronary stents)

C2: New-function/technology products

Products that need a new function classification and have not yet been evaluated for technical fee (e.g., implantable artificial hearts)

F: Material and products not suitable for reimbursement for health insurance

Reimbursement of Medical Devices

▪ Time-line of Reimbursement A1: Comprehensive 20 days after submission of the application A2: Specifically comprehensive & B: Individual evaluation First day of the next month for applications submitted by the10th day of each month

• automatically determined using current fees-

C1: New-function products & C2: New-function/technology products It takes 4 months for C1 and 5 months for C2 from submission to approval by Chuikyo*, respectively except objection raised case. Listing will be done 4 times a year (March, June, September, December)

• determined by the Chuikyo* through medical device special committee -

* Central Social Insurance Medical Council of MHLW

Reimbursement of Medical Devices

+Note: These timelines do not include the time lines needed for the preparation of the submission

Procedure for Medical Device Reimbursement

Submission for a “request for health insurance reimbursement*”

Objection Raised No Objection Approval by the Chuikyo (Central Social Insurance Medical Council of MHLW) Medical Device Specialist Committee

• 1. Presentation needs to be made to Medical

Economics Division

• 2. Meeting with Medical Economics Division
• 3. Submission of confirmation note of the findings
• 4. Presentation needs to be made to the Medical

Device Specialist Committee

Examination of Applications

Notification of the draft decision C1/C2 Listing in the National Health Insurance Reimbursement A1/A2/B Submission of complaint form Medical Device Specialist Committee the 2nd Non- applicable

• r F

4-5 months 1-3 months 20-50 days

▪ GRP Service Contents:

1) Make an Application form of Drug Master File 2) Apply for and maintain DMF 3) FMA application and maintenance 4) Communicate with foreign manufacturer and represent

• f the foreign manufacturer in Japan

5) Communicate with PMDA and respond to the inquiries 6) Communicate with MAH or distributors in Japan 7) Perform ICC maintenance work

ICC (In Country Care-taker)

Thank You

• Dr. Suzan Davis

Global Regulatory Partners Inc. & GK

info@globalregulatorypartners.com (USA) +1 781-672- 4200 (JP) +81 3 4360 9287

ありがとうございました