1. Link between legal framework of VMP regulation and VICH GLs in Japan Takashi Kozasa DVM Ministry of Agriculture, Forestry and Fisheries Government of Japan

2. 1.Legal Framework of VMP Regulation in Japan 2.Implementation of VICH GLs in Japan Topics

3. 1.Legal Framework of VMP Regulation in Japan 2.Implementation of VICH GLs in Japan Topics

4. Pharmaceutical Affairs Act (Act No.145 of 1960) Purpose of the Act is - to regulate matters pertaining to drugs, quasi-drugs, cosmetics and medical devices. - to ensure their quality, efficacy and safety. - to regulate each stage of development, manufacturing (importing), marketing, retailing and usage. The same Act regulates medicinal products for human use (MPs) and veterinary medicinal products (VMPs)

5. Marketing Approval of Medicinal Products [Article 14]  The approval shall not be granted when the drug; does not possess effects indicated in the dossier, has harmful action outweighing its effects, does not have appropriate quality.  Before providing an approval, the Minister shall seek the opinion of the Pharmaceutical Affairs and Food Sanitation Council (PAFSC). A person intending to market a pharmaceutical product (including biological), quasi-drug, cosmetic or medical device shall, for each product, obtain marketing approval of the Minister with respect to its marketing.

6. Ministers in charge of Medicinal-Products administration Minister of Agriculture, Forestry and Fisheries (MAFF) Medicinal products exclusively used for animals (VMPs) Minister of Health, Labor and Welfare (MHLW) Medicinal products for human use (MPs)

7. Legal Cascade for VMPs in Japan Biological products standard National-Assay standard, etc. Regulatory rules specific to VMPs (GLP, GCP, GMP, etc.) Legally-binding Top legislation for medicinal products in Japan Applicable for both MPs and VMPs PHARMACEUTICAL AFFIARS ACT (No.145, 1960) MAFF Ministerial Ordinances MAFF Ministerial Announcements from MAFF-HQ Director General or Director from NVAL Director General (including GUIDELINEs) non-binding Notice

8. 1.Legal Framework of VMP Regulation in Japan 2.Implementation of VICH GLs in Japan Topics

9. Guidelines contribute faster approval of new VMPs Issues on new drug developmentGuidelines Specification of quality and stability is unknown due to physical /chemical properties of VMP Method for establishing specification and stability study Evaluation method is unknown due to new mechanism of action Difficult to assess the efficacy due to mild or slow action Efficacy parameter setting and study design For User: Increase options for veterinary service, improve animal health and secure food safety For Applicant: Encourage new research & development in lower cost For RA: Shorten reviewing period of time

10. Use guidelines at each stage Dossier prep Applicant Submission Review Seek opinion Regulatory Authority Pharmaceutical Affairs and Food Sanitation Council Report Approval from dossier preparation to approval, if the study design in the dossier is scientifically relevant

11. Application for marketing approval of VMPs =Application Form= 1. Name and Address of Manufacturer 2. License No. & Address of Manufacturer 3. Type of License 4. Name of VMP 5. Name, quantities, acceptance criteria of active ingredients and excipients 6. Manufacturing Method 7. Dosage and Administration 8. Properties of the VMP 9. Condition for storage 10. Period of validity 11. Acceptance criteria and Test Procedures 12. References With sets of examination data GUIDELINEs

12. Implementation of VICH GLs VICH GLs are implemented in Japan as notices (legally non-binding). In addition, we amended ministerial ordinances and/or ministerial announcements for the smooth implementation of some GLs.

13. Implementation of TABST GL (1) GL50 (Waiver for TABST) after translated into Japanese was implemented in Japan as notice in February, 2014. Issued explanation notice of the Director of the National Veterinary Assay Laboratory. Amended the Ministerial Announcement (Biological products standard) to implement the GL smoothly.

14. Implementation of TABST GL (2) “Test procedures” of batch release (including TABST) are approved under the Pharmaceutical Affairs Act. To waive the TABST, MAHs have to apply for the approval of the MAFF. Detailed explanation to the Industry is in the notice of the Director of the NVAL. For more detail on the content of this guideline, please refer to Dr. Endo’s presentation tomorrow (Session2; agenda item #10.3).

15. VICH GLs JMAFF regards VICH GLs as important tools to accelerate the approval of VMPs RA and Industry work together throughout the creation steps as an equal partner –A mutual agreement between RA and industry –Maximum study design Published as Notice –Legally non-binding (recommendation) –In Japanese, with critical translation check by the Experts Lead both applicant and reviewer to the goal –Faster approval –Benefit also to veterinarians & users

16. BeforeAfter Chapter for Medicinal Products and Medical Devices -Pharmaceuticals -Biologicals -Diagnostics -Surgical devices -Imaging devices etc. -Artificial tissues (skin, cartilage) Chapter for Medicinal Products -Pharmaceuticals -Biologicals, etc. Chapter for Medical Devices -Surgical devices -Imaging devices -Diagnostics, etc. Chapter for Regenerative Medicinal Products -Stem cells -Immune cells -Artificial tissues, etc. (Ref) Revision of Pharmaceutical Affairs Act (effective since Nov. 2014)