Pharmaceutical Administration and Regulations in Japan

1 Japan Pharmaceutical Manufacturers Association 2017 INFORMATION ON JAPANESE REGULATORY AFFAIRS Regulatory Information Task Force Japan Pharmaceutical Manufacturers Association Pharmaceutical Administration and Regulations in Japan Pharmaceutical Regulations in Japan : 2 0 1 7 (Japanese) (English) Pharmaceutical Administration and Regulations in Japan This file contains information concerning Pharmaceutical Administration , Regulations , and new drug development in Japan updated annually by the English RA Information Task Force, International Affairs Committee, Japan Pharmaceutical Manufacturers Association (JPMA). The contents are not abstracts of governmental rules or Regulations but concise descriptions of most current practices by regulatory agencies and the industry that the working group complies. The file does not contain anything related to forecasts.

2 The file is available also at the homepage of National Institute of Health Sciences ( ). Japan Pharmaceutical Manufacturers Association Pharmaceutical Regulations in Japan : i Table of Contents CHAPTER 1 .. 1 ORGANIZATION AND FUNCTION OF THE MINISTRY OF HEALTH, LABOUR AND WELFARE .. 1 1. Pharmaceutical SAFETY AND ENVIRONMENTAL HEALTH BUREAU (PSEHB) .. 2 General Affairs Division .. 2 Pharmaceutical Evaluation Division .. 2 Medical Device Evaluation Division .. 2 Safety 3 Compliance and Narcotics Division .. 3 Blood and Blood Products Division .. 3 2. HEALTH POLICY BUREAU .. 4 Economic Affairs Division .. 4 Research and Development Division .. 4 3. NATIONAL INSTITUTE OF HEALTH SCIENCES .. 5 4. PHARMACEUTICALS AND MEDICAL DEVICES AGENCY (PMDA), AN INDEPENDENT ADMINISTRATIVE ORGANIZATION .. 5 Office of Review Administration .. 6 Office of Review Management .. 6 Office of Standards and Guidelines Development.

3 6 Office of New Drug I .. 6 Office of New Drug II .. 6 Office of New Drug III .. 6 Office of New Drug 7 Office of New Drug 7 Office of Cellular and Tissue-based Products .. 7 Office of Vaccines and Blood Products .. 7 Office of OTC and Generics .. 7 Office of Generics .. 7 Office of Medical Devices I .. 7 Office of Medical Devices II .. 7 Office of Medical Devices III .. 7 Office of Compliance and Standards .. 7 Office of Safety I .. 8 Office of Safety II .. 8 Office of Manufacturing/Quality and Compliance .. 8 Office of International Programs .. 8 Advanced Review with Electronic Data Promotion Gruop .. 8 Kansai Branch .. 8 Hokuriku Branch .. 8 5. NATIONAL INSTITUTE OF BIOMEDICAL INNOVATION, HEALTH AND NUTRITION (NIBIOHN) .. 8 6. Japan AGENCY FOR MEDICAL RESEARCH AND DEVELOPMENT (AMED) .. 9 7. Pharmaceutical AFFAIRS AND FOOD SANITATION COUNCIL (PAFSC) .. 9 8.

4 NATIONAL INSTITUTE OF INFECTIOUS DISEASES .. 9 CHAPTER 2 .. 15 Pharmaceutical LAWS AND Regulations .. 15 1. Pharmaceutical LAWS .. 15 2. Pharmaceutical AND MEDICAL DEVICE ACT .. 15 3. OUTLINE OF Pharmaceutical Regulations .. 17 Definition of Drugs .. 17 Definition of Drugs .. 17 License for Manufacturing/Marketing Businesses .. 19 License for Manufacturing Business and Accreditation of Overseas Pharmaceutical Regulations in Japan : ii Manufacturers .. 20 Manufacturing/Marketing Approvals 22 Good Manufacturing Practice (GMP) .. 22 Drug Master File (MF) .. 23 Drug Retail Seller Licensing .. 23 Labeling and Package Inserts .. 24 Proper Advertisement .. 25 Good Laboratory Practice (GLP) .. 25 Good Clinical Practice (GCP) .. 25 Trial Conducted from a Compassionate Viewpoint (expanded trial) .. 26 Patient-requested Therapy System . 27 Good Post-marketing Study Practice (GPSP).

5 27 Reexamination and Reevaluation .. 27 Adverse Drug Reaction (ADR) and Infection Reporting .. 28 Risk Management Plan .. 28 Dissemination of Information .. 29 Measures related to the Law Concerning Access to Information Held by Administrative Organizations .. 29 Patent System .. 29 Drug Abuse Control .. 30 4. MARKETING APPROVALS .. 31 Drug Marketing Approvals .. 31 Marketing Approval Reviews .. 31 Manufacturing/Marketing Approval Application with Electronic Data .. 33 Priority Review System and Designation of Drug Products for Priority 34 Restrictive Approval System .. 35 Orphan Drugs .. 35 Drugs for Pediatric Use .. 35 Unapproved Drugs and Drugs of Off-label Use .. 36 Packaging Strategy for World-first Products .. 37 Regulatory Strategy Consultations for Regenerative Medicine Products 38 Approval System Implemented to Promote the Application of Regenerative Medicine Including Cellular and Tissue-Based Products for Commercialization (Approval with Conditions and Time Limit).

6 38 Biosimilar Products .. 38 Combination Products .. 39 Codevelopment .. 39 Transfer of Marketing Approvals .. 40 Approval Applications for Drugs Manufactured Overseas .. 40 Issuing of Certificates for Exported Drugs by MHLW .. 40 5. JAPANESE PHARMACOPOEIA AND OTHER STANDARDS .. 41 Japanese Pharmacopoeia (JP) .. 41 Standards Based on Article 42 of the Pharmaceutical Affairs Law .. 42 Standards for Biological Materials .. 43 Quality Standards Based on Notifications .. 44 Government Batch Test .. 44 6. Pharmaceutical SUPERVISION .. 44 Pharmaceutical Supervision .. 44 Product Recalls .. 44 Prevention of Medical Accidents Caused by Drugs, etc.. 45 Safety Measures against Bovine Spongiform Encephalitis (BSE) .. 45 CHAPTER 3 .. 53 DRUG DEVELOPMENT .. 53 1. PROCESS FROM DEVELOPMENT TO APPROVAL .. 53 Development of New Drugs .. 53 Procedures for Clinical Trials .. 53 Safety information on Adverse Pharmaceutical Regulations in Japan : iii Reactions and Infections during the Study.

7 56 Interview advice meetings .. 57 Approval review .. 59 Compliance review .. 61 GMP compliance inspection .. 62 2. DATA REQUIRED FOR APPROVAL APPLICATIONS .. 64 Data to be Attached to Approval Application of Drugs .. 67 3. GUIDELINES CONCERNING DRUG APPROVAL APPLICATIONS .. 68 Nonclinical Studies .. 69 Clinical Studies .. 77 4. OTHER .. 88 Biotechnological Products .. 88 Drugs Using Materials of Human or Animal Origin as Ingredients (Biological Products) .. 89 Biosimilar Products .. 90 Public Disclosure of Information on New Drug Development .. 90 ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) .. 91 CHAPTER 4 .. 106 POST-MARKETING SURVEILLANCE OF DRUGS .. 106 1. GVP .. 108 2. GPSP .. 115 3. PAPER COMPLIANCE REVIEW AND ON-SITE GPSP SURVEYS OF DATA FOR REEXAMINATION AND REEVALUATION .. 118 4. ADVERSE DRUG REACTIONS AND INFECTIONS REPORTING SYSTEM.

8 119 Adverse Drug Reaction and Infectious Disease Reporting System by Pharmaceutical 119 Drug and Medical Device Safety Information Reporting System by Medical Personnel .. 122 WHO International Drug Monitoring Program .. 122 5. PERIODIC INFECTION REPORTS FOR BIOLOGICAL PRODUCTS (ARTICLE 68-14 AND 68-24 IN THE LAW) .. 122 6. REEXAMINATION SYSTEM (ARTICLE 14-4 AND 23-29 OF THE Pharmaceutical AFFAIRS LAW) .. 123 Designation for Reexamination of Drugs .. 123 Periodic Safety Reports (Article 63 of the Enforcement Regulations of the Law) .. 124 Data Required for Reexamination Applications and Reexamination Procedures .. 124 7. REEVALUATION SYSTEM (ARTICLES 14-6 AND 23-31 OF THE LAW) .. 125 CHAPTER 5 .. 132 SUPPLY AND DISSEMINATION OF DRUG SAFETY MANAGEMENT INFORMATION .. 132 1. PACKAGE INSERTS .. 132 Guidance on the Style and Format of Package Inserts .. 134 Headings and Their Sequence in Package Inserts.

9 135 Precautions .. 136 Labeling of Excipients .. 137 Entries for Biological Products .. 138 Brand Names of Prescriptions Drugs .. 138 Information on Package Inserts in English .. 139 2. INFORMATION TO SUPPLEMENT PACKAGE INSERTS .. 139 Outline of Prescription Pharmaceutical Regulations in Japan : iv Pharmaceutical Product Information .. 139 Pharmaceutical Interview Forms (IF) .. 140 3. SUPPLY AND DISSEMINATION OF SAFETY MANAGEMENT INFORMATION .. 140 Distribution of Emergency Safety Information (Yellow Letters).. 141 Safety Flash Report (Blue Letters) 142 Distribution of Information by 'Notices of Revision of Precautions'143 Dissemination of Information for Drugs That Have Completed Reexamination or Reevaluation .. 144 Dissemination of ADR Information by the Pharmaceuticals and Medical Devices Safety Information (Information on Adverse Reactions to Drugs) .. 144 Dissemination of Information by Drug Safety Update.

10 144 Commentaries on "Precautions" in Package Inserts of New Drugs .. 145 4. ELECTRONIC INFORMATION DISSEMINATION .. 145 5. PACKAGE INSERTS OF NON-PRESCRIPTION DRUGS .. 145 6. PACKAGE INSERTS OF GUIDANCE-MANDATORY DRUGS .. 146 CHAPTER 6 .. 150 HEALTH INSURANCE PROGRAMS AND DRUG PRICING IN Japan .. 150 1. HISTORY OF HEALTH INSURANCE PROGRAMS .. 150 2. MEDICAL BENEFITS OFFERED UNDER HEALTH INSURANCE PROGRAMS .. 151 3. REIMBURSEMENT OF MEDICAL FEES 151 4. NATIONAL HEALTH INSURANCE PRICE LIST .. 152 5. PRICING FORMULA FOR REIMBURSEMENT PRICE REVISIONS OF DRUGS LISTED IN THE NHI PRICE LIST .. 152 6. RECENT REVISIONS OF THE NHI PRICE LIST .. 154 7. DETERMINATION OF REIMBURSEMENT PRICES FOR NEW DRUGS .. 155 8. ENTRY OF GENERIC DRUGS IN THE NHI PRICE LIST .. 156 9. ISSUES RELATED TO THE USE OF DETERMINATION OF UNAPPROVED DRUGS AND OFF-LABEL 156 Fig. 1 Organization of Ministry of Health, Labour, and Welfare (Health-related organizations only).