Outline of Regulation System of Veterinary …

1 1 Outline of Regulation System of Veterinary medicinal Products (VMPs) in Japan To ensure quality, efficacy and safety of VMPs based on the Pharmaceutical Affairs Law - Animal Products Safety Division, Food Safety and Consumer Affairs Bureau Ministry of Agriculture, Forestry and Fisheries 1-2-1, Kasumigaseki, Chiyoda-ku, Tokyo, 100-8950 Japan National Veterinary Assay Laboratory NVAL Ministry of Agriculture, Forestry and Fisheries 1-15-1 Tokura, Kokubunji, Tokyo, 185-8511 Japan Contents List of Abbreviation ---------------------------------------- ---------------------------------------- ---- 1. Organization and Functions of Veterinary Pharmaceutical Administration ------ 2. Outline of the Pharmaceutical Affairs Law to ensure quality, efficacy and safety of VMPs ---------------------------------------- ---------------------------------------- ------- 3. License System for Marketing Authorization Holders of VMPs ----------------------- 4.

2 License System for Manufacturer of VMPs ---------------------------------------- ---------- 5. Accreditation System for Foreign Manufacturers of VMPs ----------------------------- 6. Marketing Approval System of VMPs ---------------------------------------- ----------------- 7. Drug Master File Registration System of VMPs ---------------------------------------- --- 8. National Assay and National Test System of VMPs -------------------------------------- 9. Retailing Control System of VMPs ---------------------------------------- --------------------- 10. Proper Application System of VMPs ---------------------------------------- ------------------- 11. Post-marketing Surveillance System of VMPs ---------------------------------------- ----- Reference ---------------------------------------- ---------------------------------------- --------------- 2 3 4 7 7 8 8 14 14 15 16 16 17 2 List of Abbreviations ADI APSD FSCAB GCP GLP GMP GPSP GQP GVP LMOs MAFF MAH MHLW Minister MRL NVAL OECD OIE PAFSC PASC VICH VMPs Acceptable Daily Intake Animal Products Safety Division Food Safety and Consumer Affairs Bureau Good Clinical Practice Good Laboratory Practice Good Manufacturing Practice Good Post-marketing Study Practice Good Quality Practice Good Vigilance Practice Living Modified Organisms Ministry of Agriculture, Forestry and Fisheries Marketing Authorization Holder Ministry of Health, Labor and Welfare Minister of Agriculture.

3 Forestry and Fisheries Maximum Residue Limit National Veterinary Assay Laboratory Organization for Economic Co-operation and Development International Epizootic Office: World Organization for Animal Health Pharmaceutical Affairs and Food Sanitation Council Pharmaceutical Affairs Sub-council, International Cooperation on Harmonization of Technical Requirements for Veterinary medicinal Products Veterinary medicinal Products (Drugs for animal use) 3 1. Organization and Functions of Veterinary Pharmaceutical Administration The Ministry of Agriculture, Forestry and Fisheries (MAFF) controls Veterinary medicinal products (VMPs) exclusively used for animals under the Pharmaceutical Affairs Law (Law No. 145, Series of 1960). The Ministry of Health, Labor and Welfare (MHLW) controls pharmaceuticals for human use. National administrative authorities and their functions for VMPs are as follows. 1) Animal Products Safety Division (APSD), Food Safety and Consumer Affairs Bureau (FSCAB), Ministry of Agriculture, Forestry and Fisheries (MAFF): Legislative authority for VMPs Planning of Regulation and administration for risk management of VMPs Management of marketing approval Licensing of marketing authorization holder (MAH), manufacturer Accreditation of foreign manufactures Pharmaceutical supervision, guidance, etc.

4 2) Fish and Fishery Products Safety Office, APSD, FSCAB, MAFF Examination of VMPs for fishery use Guidance for proper application of VMPs for fishery use 3) National Veterinary Assay Laboratory (NVAL), MAFF: Technical service for VMPs Examination of application for marketing approval, reexamination and reevaluation GMP inspection GLP/GCP inspection National assay and testing Distribution of standard materials for test Technical guidance Research for regulatory science International technical cooperation ( action for OIE collaborating center, action for expert working groups of VICH, etc.) 4) Committee on Veterinary Products, PASC, PAFSC: Council for VMPs Investigation important items for VMPs. For example, Approval of new VMPs, Reexamination or reevaluation of approved VMPs Establishment of standards for VMPs Establishment of withdrawal period of VMPs for food producing animal use 5) Other authorities related of VMPs a.

5 Animal Health Division, FSCAB, MAFF Control and prevention of animal diseases b. Plant products Safety Division Regulation on the use of living modified organisms (LMOs) for VMPs c. Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau, MHLW 4 Services concerning the Japanese Pharmacopoeia including VMPs d. Standard and Evaluation Division, and Inspection and Safety Division, Department of Food Safety, Pharmaceutical and Food Safety Bureau, MHLW Regulation concerning residue of feed additives, VMPs etc. in foods e. Risk assessment Division, Food Safety Commission Secretariat, Cabinet Office Assessment of the effect of food on health (Risk assessment of food in relation to VMPs) 2. Outline of the Pharmaceutical Affairs Law to ensure quality, efficacy and safety of VMPs VMPs are controlled directly by the Pharmaceutical Affairs Law, the Pharmaceutical Affairs Law Enforcement Ordinance (Government Ordinance No.)

6 11, Series of 1961), The Control regulations of Veterinary Medical Products (MAFF Ministerial Ordinance , Series of 2004), etc. The Outline of the Pharmaceutical Affairs Law related to VMPs is described as follows. 1) Alternative reading for VMPs In this law, as far as drugs, which are intended for exclusive use with animals (VMPs), "the Minister of Health, Labor and Welfare" shall be replaced as "the Minister of Agriculture, Forestry and Fisheries; "MHLW ordinance" shall be replaced as "MAFF ordinance". (Article 83) 2) Objectives This law is intended to provide regulations required to ensure the quality, efficacy and safety of drugs, quasi-drugs, cosmetics (out of scopes for animal use) and medical devices and to improve the public health and hygiene. 3) License for Marketing Approval Holder or Manufacturer, Marketing Approval, etc. A person intending to market release of a VMP shall obtain the license for MAH. The Minister of Agriculture, Forestry and Fisheries (the Minister) issues the license and approval.

7 (Article 12) Without the license for manufacturing VMPs, no one shall engage in business to manufacture VMPs. The license shall be granted by the Minister for each manufacturing facilities, according to the category specified by MAFF ordinance. (Article 13) A person intending to manufacture an overseas VMP which will be imported to Japan from the country may be accredited by the Minister as a foreign manufacturer. The accreditation shall be granted for each manufacturing facilities according to the category specified by MAFF ordinance. (Article 13-3) A person intending to market each VMP shall be obtained formal approval from the Minister. (Article 14) A person obtaining the marketing approval of a new VMP shall apply for the reexamination of such product after six years from the new approval (Article 14-4). Other VMPs, that already approved, shall apply for reevaluation based on designation of the Minister. (Article 14-6) A person who manufactures active pharmaceutical ingredients of VMPs may register the 5 name, ingredients, manufacturing methods, properties, quality or storage of the active pharmaceutical ingredient in a drug master file.

8 (Article 14-11) 4) Pharmacy or Retailing Business Any person intending to establish a pharmacy or to retail VMPs shall obtain a license from the governor of the prefecture where his or her office is located. (Article and 24) 5) Standards and Tests The MHLW shall establish and publish the Japanese Pharmacopoeia (Article 41) The Minister may establish the standard of VMPs. (Article 42) 6) Handling, Advertising, Supervision, etc. Distribution of VMPs with poor quality, improperly labeled, unapproved, not yet performed national assay as well as extravagant advertising shall be prohibited. (Article 55, 56 and 66) Proper supply of VMPs are secured by means of national assay, spot inspections, national test etc. (Article 43, 69, 71 etc.) No proprietor of a pharmacy and no retailer of VMPs shall retail VMPs so designated by the Minister to persons other than those who have received a prescription or direction from a veterinarian.

9 (Article 49) 7) Report of adverse reactions When marketing authorization holders of VMPs are informed of any adverse reaction, etc. as specified by MAFF ordinance for their marketed products, they must report it to the Minister. (Article 77-4-2) 8) Handling of Clinical Trials Provisions concerning clinical trials are enacted, including requirements for the sponcer of clinical trials. 9) Handling of VMPs Prohibition of Manufacturing and Import of VMPs without license: No person shall manufacture VMPs without license of a manufacturer, and import VMPs without license for a marketing approval holder in principle. (Article 83-2) Prohibition of Use of unapproved VMPs: No person shall provide unapproved VMPs which will be provided animals for food production in principle. (Article 83-3) Restriction on Use of VMPs : The Minister shall be able to enact restriction on the use of VMPs which will be provided food producing animals. (Article 83- , 83-5) regulations of VMPs under the Law from the stage of their development to post-marketing evaluation are shown in Fig.

10 1. 6 Fig. 1 Regulation of Veterinary medicinal Products (VMPs) in Japan I Examination for Marketing Approval II Marketing Authorization Holder, Manufacturing and Quality Control III Distribution Control VMPs Marketing approval GLP GCP GMP Drug master file IV Evaluation Control Nat l assay Regulation for proper labeling, advertising, etc. Inspection, spot sampling test, national test (Nat l order for test) VMPs Inspection System Reevaluation GPSP Reexamination GPSP Report of adverse reactions GXP: Ministerial ordinance GLP Good Laboratory Practice GCP Good Clinical Practice GMP Good Manufacturing Practice GMP (structure & facility): Regulation of GMP hardware GQP Good Quality Practice GVP Good Vigilance Practice GPSP Good Post-marketing Study Practice License for manufacturer GMP (structure & facility) Accreditation for foreign manufacturer GMP (structure & facility) License for marketing authorization holder GQP & GVP License for pharmacy or retailing VMPs regulations for management, buildings and facilities Prescription of direction for retailing of vaccine, antibiotics, etc.