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 01 02 03 04 Focus on early Be a one (1) stop Offer tailored Cover the whole stage and medium shop for services that meet products lifecycle, size life science Regulatory Affairs, companies’ need. from concept till companies Safety, Quality commercialization. Services

GRP GK MAH/DMAH Services ▪ GRP Japan provides the following services:  Foreign Manufacturing site  Pharmacovigilance Accreditation (FMA)  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) • Clinical Trial (if necessary) Step 3 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 The risk to customers in the event of malfunction is regarded as almost Class I : General medical negligible. devices Registration category: Notification Self Declaration (submission to PMDA) The risk to customers in the event of malfunction is regarded as relatively low. Class II : Controlled Registration category: Certification or Approval medical devices Certified by Registered Certification Body or Approved by PMDA The risk to customers in the event of malfunction is regarded as relatively high. Class III: Specially Registration category: Approval or Certification controlled medical device Approved by PMDA or Certified by Registered Certification Body Class IV: Specially The device is high invasive with potential fatal risk to customers. controlled medical device Registration category: Approval Approved by PMDA

Registration of Class I Devices The content of the notification for Class I devices is as follows:  Classification  Storage conditions and Expiry  General name  Manufacturing process  Sales name  Manufacturing site  Purpose of usage and effect  Package inserts  Figure, machinery and principle Photograph of product appearance   Raw materials  Suitability rational for definition of general name  Standards concerning performance and safety Usage 

Registration Dossier for Class II-IV Content of registration dossier for Class II, Class III and Class IV devices 1. Classification 9. Storage condition and expiry 2. General name 10. Manufacturing process 11. Manufacturing site (name of the place and 3. Sales name registered number) 4. Purpose of usage and effect 12. Package inserts 5. Figure, machinery and principle 13. QMS compatibility confirmation 6. Raw materials 14. STED* 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 4.2.1.2 Electrical Safety and Electromagnetic Compatibility 1.1 Overview of Product 4.2.1.3 Biological Safety 1.2 Origin or History of Discovery and History of Development 4.2.1.4 Radiation Safety 4.2.1.5 Mechanical Safety 1.3 Usage Conditions in Foreign Countries 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 5. Labeling 2.1 List of Referenced Standards 5.1 Instructions for Use (Draft) and Basis for Establishing Its Content 2.2 Essential Principles and Evidence of Conformity 5.2 Label (Draft) 3. Device Description 6. Risk Analysis 3.1 General Information 6.1 Risk Analysis System 3.2 Raw Materials 6.2 Important Hazards 3.3 Product Specifications 3.4 Storage Method and Expiration Period 3.5 Comparison with Similar Medical Devices 4. Summary of Pre-clinical Design Verification and Validation 7. Manufacturing Information Documents 7.1 Information on Manufacturing Process and Manufacturing Site 4.1 General Information 7.2 Sterilization Method 4.2 Summary of Medical Device Design Validation 7.3 Quality Control 4.2.1 Tests to Support Safety 4.2.1.1 Physical and Chemical Properties

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 on-site ▪ Content of QMS application includes : o Product application document (photocopy) for manufacturing and sales approval o ISO13485 certification or Inspection report issued by registered certification bodies in Japan or by recognized foreign health authorities under within 3 years. o Manufacturing process flow o Outline of contents of MAH/RMS (Registered Manufacturing Site) activities and documents which can identify mutual relations of QMS between MAH and RMS o Summary of Plant o Child Products List

QMS Inspection (Pre-, Post-) Application Approval for Approval Regulatory R&D Marketing Review Every 5 years Pre-approval Post-approval Post-approval inspection inspection inspection One of the requirements for marketing Conducted every 5 years after Marketing approval Approval of medical device Based on application Conducted per Product Family

Safety/Pharmacovigilance Services PRE-MARKETING SAFETY POST-MARKETING SAFETY ▪ Receipt, data entry, review, analysis, coding ▪ Collection, evaluation and review of and follow up on serious adverse events complaints. (SAEs) and ▪ Medical Safety Assessment of individual ▪ (SUSARs) from clinical studies. Case Reports. ▪ Provide safety input to protocols, clinical ▪ Adverse events reporting PSUR preparation study reports and investigator brochures. and submission. ▪ Safety data reporting to competent ▪ Health Authorities PV databases monitoring. authorities, ethics committees and ▪ Products Safety profile building and investigators. continuous update.

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.