Regulatory process to register Veterinary
Description: Regulatory process to register Veterinary Biological Products in Japan Shoko IWAMOTO, Ph.D., D.V.M. National Veterinary Assay Laboratory, JMAFF Law Hierarchy of Pharmaceutical Affairs in Japan Act on Securing Quality, Efficacy and Safety of
Related Topics
Download Presentation
"Regulatory process to register Veterinary" is the property of its rightful owner. Permission is granted to download and print the materials on this website for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Presentation Transcript
slide1. Regulatory process to register Veterinary Biological Products in Japan Shoko IWAMOTO, Ph.D., D.V.M.
National Veterinary Assay Laboratory, JMAFF<br>
slide2. Law Hierarchy of Pharmaceutical Affairs in Japan Act on Securing Quality, Efficacy and Safety of Products including Pharmaceuticals and Medical Devices (Law No.145, Series of 1960) Enforcement ordinance (No.11, Series of 1961 )
Regulatory rules for Veterinary Products
( Law No. 107, Series of 2004 ),
Ordinances concerning GLP, GCP, GMP, etc. Ministerial announcements
Notice
Memorandum Standards for Veterinary Biological Products
Standards for National testing of VMPs, etc. Ministerial ordinance RA for VMP: MAFF
RA for human MP: MHLW<br>
slide4. Act on Securing Quality, Efficacy and Safety of Products including Pharmaceuticals and Medical Devices (Pharmaceuticals Act) 4 Article 1 (Purpose of This Act)
The purpose of this Act is to improve health and hygiene by providing the control required for securing the quality, efficacy and safety of pharmaceuticals, quasi-pharmaceutical products, cosmetics, medical devices, regenerative medicine products (hereinafter referred to as "pharmaceuticals, etc.") and for preventing the occurrence or spread of health and hygiene-related hazards caused by the use of those pharmaceuticals, etc. by taking measures against designated substances, and by taking necessary measures for the promotion of research and development of pharmaceuticals, medical devices and regenerative medicine products which fulfill particularly high medical needs.<br>
slide5. Purpose to regulate matters pertaining to
“pharmaceuticals”,
“quasi-pharmaceutical products” (ex. medical shampoo),
“medical devices” etc to ensure their quality, efficacy and safety at each stage of development, manufacturing, importing, marketing, retailing and usage. Pharmaceuticals Act<br>
slide6. Marketing Approval*1
Act article 14
A person who intends to market pharmaceuticals* must obtain approval from the Minister for each such item.
Marketing license
License for manufacturing*2
etc ＊１ Manufacture, import and market pharmaceuticals. MA has full responsibility for the pharmaceuticals.
＊２ Including packaging and labeling and storage. Types of Approval and License for Marketing VMPs in Japan<br>
slide7. Application for Marketing Approval
Name and Address of Company
License No. & Address of Marketing Approval Holder
Type of License
Name of Drug
Ingredients and Quantities
Manufacturing Method
Administration and dosage
Indications and effects
Condition for storage
Period of validity
Standards and Test Methods
Reference 7 Must be attached Appendixes<br>
slide8. Appendixes 8 App. 1: Origin and background of the discovery
App. 2: Physicochemical properties
App. 3: Production protocol
App. 5: Stability
App. 6: Toxicity (acute toxicity)
App. 7: Toxicity (sub acute and chronic toxicity)
App. 8: Toxicity (special toxicity (e.g. mutagenicity, local irritation, etc.) * App. 4 is only for Medical Devices.<br>
slide9. Appendixes 9 App. 9: Target Animal Safety
App.10: Pharmacology related to efficacy
App.11: General pharmacology
App.12: ADME (absorption, distribution, metabolism and excretion)
App.14: Clinical trial
App.15: Residue for food producing animals * App. 13 is only for Medical Devices.<br>
slide10. Appendix 1 Origin and background of the development Origin and background of development
Condition of outbreaks and coping process in Japan
Necessity of the applied product
Condition of use in foreign countries
Adverse effect for human
Public and animal hygiene (antimicrobial resistance; AMR)
etc. 10<br>
slide11. Appendix 2 Physicochemical properties Name of active pharmaceutical ingredient and biological characteristics
Transmissibility, Reversion to virulence, Shedding
Information of MSB/MSV, WSB/WSV and PSB/PSV
Standard, Test methods (active ingredient and final product) , supporting data and test reports of 3 lots
Residue of Adjuvants
etc. 11<br>
slide12. Appendix 3 Production protocol Manufacturing process
From seed to release
Test protocol
Data for culture, inactivation, purification<br>
slide13. Appendix 5 Stability Final product
(trial/manufacturing scale, 3lots)
Long-term
Time-dependent data after dissolution
Guideline: VICH GL3(R) and other GLs(GL4, GL5, GL17, GL45, GL51) 13<br>
slide14. Appendix 9 Target Animal Safety test 14 Objective
- Evaluation of Target Animal Safety
・Overdose Test
・Route of Administration
・Species, Age, Breed
Guideline: VICH GL44<br>
slide15. Good Laboratory Practice (GLP) Non-clinical study (App.6-9 and 15) should be met GLP
Target drug product ：drug product fulfilled under the following all conditions;
new active ingredient
new combination of active ingredients
new administration route
new target animal
Outline of the assessment：
assess every facility
assess test equipment, buildings and manpower
assess compliance with required documents（SOP etc.）,
record（test record, maintenance log etc.） 15<br>
slide16. Appendix 10 Efficacy Minimum effective dose
Minimum effective antibody titer
Basis of administration route and dosage
Period of immunity establishment
Duration of immunity
Influence of maternal antibody 16<br>
slide17. Appendix 14 Clinical trial Objective :
Evaluation of the efficacy and safety of the final product in the field
Samples: Final product
Number of test sites: ≧2 sites
Number of Animals:
≥ 200 chickens
≥ 60 for mammals
Test period:
Adequate period for evaluation of efficacy and safety 17<br>
slide18. Good Clinical Practice (GCP) 18 Clinical study should be met GCP
Target drug product：drug product fulfilled under the following all conditions;
new active ingredient
new combination of active ingredients
new administration route
new target animal
Outline of the assessment：
assess every facility
assess test equipment, buildings and manpower
assess compliance with required documents（SOP etc.）,
record（test record, maintenance log etc.）<br>
slide19. Notice by the Director-General of the LIB (enforced 2000. Mar. 31, No. 12-Chiku-A-729) 19 Data Required for the Application of Approval
of Veterinary Biological Products Appended table 3 (VMPs for food producing animals) and 4(VMPs for companion animals (CA) )
Data Required for the Application of Approval of Veterinary Medicinal Products (VMPs) flexibility<br>
slide20. 20 Table 3&4. Data Required for the Application of Approval of
Veterinary Biological Products ** Class of biological products for application
(1) Products containing a new active ingredient or a new combination prescription drugs
(2) Products in new composition of the approved ingredient
(3) Products in new route of administration
(4) Products providing a new indication
(5) Products in new dosage
(6) ) The inactivated products of which seed and antigenicity for production is different, and the property of the seed is judged to be equivalent to those of the approved one at the National Veterinary Assay Laboratory. Fall out products.
(7) Though a seed for production is different, the property of the seed is judged to be equivalent to those of the approved one at the National Veterinary Assay Laboratory
(8) Products in similar formulation of products already approved
○: Data shall be submitted.
×: Data may be omitted.
△: Data submission shall be determined depending upon the conditions of products.<br>
slide21. Flow of Marketing Approval Procedure Applicant
（holder of marketing authorization） ④ hear opinion Pre-approval consultation ②⑥ Return of flawed document, Pointing out of problem Pharmaceutical Affairs and Food Sanitation Council (PAFSC) MAFF FSSC APSD ①apprication （requested by article14, 19） ⑨ grant of approval ⑤Pointing out of problem Cooperative processing ③⑦ Improvement of documents & problem Draft prepration of minimun requirement, standard, etc. Pointing out of Problem Data of toxicity, target animal safety or residue has to meet the Good Laboratory Practice (GLP), and data of clinical trial has to meet the Good Clinical Practice (GCP). GMP Inspection a. Minimum requirements for veterinary biological products (Notice No. 1567, 2002)
b. Standard of antibiotics for animals (Notice No.1123, 1999)
c. The source materials standards of biological products for animal use (Notice No. 1911, 2003) ⑧approval<br>
slide22. Council and Commission 22 Act Article 14,(11)
In cases where the Minister receives an application for approval prescribed in paragraph (1), and finds that pharmaceuticals, quasi-pharmaceutical products or cosmetics pertaining to the application are obviously different from those of pharmaceuticals, quasi-pharmaceutical products or cosmetics which have been already approved subject to this Article or Article 19-2 in terms of active, components quantity, dosage, administration, efficacy, etc., the Minister must hear the opinions of the Food Safety Standards Council in advance regarding whether the approval prescribed in the same paragraph should be given.<br>
slide23. VMPs for food producing animals Residues of VMPs
Food Safety Standards Council (FSSC)
Consumer Affairs Agency（CAA）
Human health safety
Food Safety Commission(FSC) of Cabinet Office<br>
slide24. Flow chart from application to approval of VMPs for food producing animals Application MAFF FSSC
(Examination for approval) FSC
(evaluation of ADI) CAA
（Decision of MRL） Approval MAFF<br>
slide25. Responsible authorities for Veterinary Medicinal Products MAFF (Ministry of Agriculture, Forestry and Fisheries) FSCAB (Food Safety and Consumer Affaires Bureau) APSD (Animal Products Safety Division) NVAL (National Veterinary Assay Laboratory) －National assay of veterinary biologics
－Review of application for approval
－Spot sampling test of VMPs
－Review of reliability standard compliance
－Inspection (GLP,GCP,GMP)
－Consultation of VMPs development －Supervision of import of VMPs －Establishment and revision of approval system －Overall control of veterinary pharmaceutical affairs<br>
slide26. Thank you for your attention
Merci pour votre attention
Gracias por su atención
شكراً جزيلاً لكم على انتباهكم.
경청해 주셔서 감사합니다
आपके ध्यान देने के लिए धन्यवाद
Ngā mihi ki a koutou
ご清聴ありがとうございました 26<br>
National Veterinary Assay Laboratory, JMAFF<br>
slide2. Law Hierarchy of Pharmaceutical Affairs in Japan Act on Securing Quality, Efficacy and Safety of Products including Pharmaceuticals and Medical Devices (Law No.145, Series of 1960) Enforcement ordinance (No.11, Series of 1961 )
Regulatory rules for Veterinary Products
( Law No. 107, Series of 2004 ),
Ordinances concerning GLP, GCP, GMP, etc. Ministerial announcements
Notice
Memorandum Standards for Veterinary Biological Products
Standards for National testing of VMPs, etc. Ministerial ordinance RA for VMP: MAFF
RA for human MP: MHLW<br>
slide4. Act on Securing Quality, Efficacy and Safety of Products including Pharmaceuticals and Medical Devices (Pharmaceuticals Act) 4 Article 1 (Purpose of This Act)
The purpose of this Act is to improve health and hygiene by providing the control required for securing the quality, efficacy and safety of pharmaceuticals, quasi-pharmaceutical products, cosmetics, medical devices, regenerative medicine products (hereinafter referred to as "pharmaceuticals, etc.") and for preventing the occurrence or spread of health and hygiene-related hazards caused by the use of those pharmaceuticals, etc. by taking measures against designated substances, and by taking necessary measures for the promotion of research and development of pharmaceuticals, medical devices and regenerative medicine products which fulfill particularly high medical needs.<br>
slide5. Purpose to regulate matters pertaining to
“pharmaceuticals”,
“quasi-pharmaceutical products” (ex. medical shampoo),
“medical devices” etc to ensure their quality, efficacy and safety at each stage of development, manufacturing, importing, marketing, retailing and usage. Pharmaceuticals Act<br>
slide6. Marketing Approval*1
Act article 14
A person who intends to market pharmaceuticals* must obtain approval from the Minister for each such item.
Marketing license
License for manufacturing*2
etc ＊１ Manufacture, import and market pharmaceuticals. MA has full responsibility for the pharmaceuticals.
＊２ Including packaging and labeling and storage. Types of Approval and License for Marketing VMPs in Japan<br>
slide7. Application for Marketing Approval
Name and Address of Company
License No. & Address of Marketing Approval Holder
Type of License
Name of Drug
Ingredients and Quantities
Manufacturing Method
Administration and dosage
Indications and effects
Condition for storage
Period of validity
Standards and Test Methods
Reference 7 Must be attached Appendixes<br>
slide8. Appendixes 8 App. 1: Origin and background of the discovery
App. 2: Physicochemical properties
App. 3: Production protocol
App. 5: Stability
App. 6: Toxicity (acute toxicity)
App. 7: Toxicity (sub acute and chronic toxicity)
App. 8: Toxicity (special toxicity (e.g. mutagenicity, local irritation, etc.) * App. 4 is only for Medical Devices.<br>
slide9. Appendixes 9 App. 9: Target Animal Safety
App.10: Pharmacology related to efficacy
App.11: General pharmacology
App.12: ADME (absorption, distribution, metabolism and excretion)
App.14: Clinical trial
App.15: Residue for food producing animals * App. 13 is only for Medical Devices.<br>
slide10. Appendix 1 Origin and background of the development Origin and background of development
Condition of outbreaks and coping process in Japan
Necessity of the applied product
Condition of use in foreign countries
Adverse effect for human
Public and animal hygiene (antimicrobial resistance; AMR)
etc. 10<br>
slide11. Appendix 2 Physicochemical properties Name of active pharmaceutical ingredient and biological characteristics
Transmissibility, Reversion to virulence, Shedding
Information of MSB/MSV, WSB/WSV and PSB/PSV
Standard, Test methods (active ingredient and final product) , supporting data and test reports of 3 lots
Residue of Adjuvants
etc. 11<br>
slide12. Appendix 3 Production protocol Manufacturing process
From seed to release
Test protocol
Data for culture, inactivation, purification<br>
slide13. Appendix 5 Stability Final product
(trial/manufacturing scale, 3lots)
Long-term
Time-dependent data after dissolution
Guideline: VICH GL3(R) and other GLs(GL4, GL5, GL17, GL45, GL51) 13<br>
slide14. Appendix 9 Target Animal Safety test 14 Objective
- Evaluation of Target Animal Safety
・Overdose Test
・Route of Administration
・Species, Age, Breed
Guideline: VICH GL44<br>
slide15. Good Laboratory Practice (GLP) Non-clinical study (App.6-9 and 15) should be met GLP
Target drug product ：drug product fulfilled under the following all conditions;
new active ingredient
new combination of active ingredients
new administration route
new target animal
Outline of the assessment：
assess every facility
assess test equipment, buildings and manpower
assess compliance with required documents（SOP etc.）,
record（test record, maintenance log etc.） 15<br>
slide16. Appendix 10 Efficacy Minimum effective dose
Minimum effective antibody titer
Basis of administration route and dosage
Period of immunity establishment
Duration of immunity
Influence of maternal antibody 16<br>
slide17. Appendix 14 Clinical trial Objective :
Evaluation of the efficacy and safety of the final product in the field
Samples: Final product
Number of test sites: ≧2 sites
Number of Animals:
≥ 200 chickens
≥ 60 for mammals
Test period:
Adequate period for evaluation of efficacy and safety 17<br>
slide18. Good Clinical Practice (GCP) 18 Clinical study should be met GCP
Target drug product：drug product fulfilled under the following all conditions;
new active ingredient
new combination of active ingredients
new administration route
new target animal
Outline of the assessment：
assess every facility
assess test equipment, buildings and manpower
assess compliance with required documents（SOP etc.）,
record（test record, maintenance log etc.）<br>
slide19. Notice by the Director-General of the LIB (enforced 2000. Mar. 31, No. 12-Chiku-A-729) 19 Data Required for the Application of Approval
of Veterinary Biological Products Appended table 3 (VMPs for food producing animals) and 4(VMPs for companion animals (CA) )
Data Required for the Application of Approval of Veterinary Medicinal Products (VMPs) flexibility<br>
slide20. 20 Table 3&4. Data Required for the Application of Approval of
Veterinary Biological Products ** Class of biological products for application
(1) Products containing a new active ingredient or a new combination prescription drugs
(2) Products in new composition of the approved ingredient
(3) Products in new route of administration
(4) Products providing a new indication
(5) Products in new dosage
(6) ) The inactivated products of which seed and antigenicity for production is different, and the property of the seed is judged to be equivalent to those of the approved one at the National Veterinary Assay Laboratory. Fall out products.
(7) Though a seed for production is different, the property of the seed is judged to be equivalent to those of the approved one at the National Veterinary Assay Laboratory
(8) Products in similar formulation of products already approved
○: Data shall be submitted.
×: Data may be omitted.
△: Data submission shall be determined depending upon the conditions of products.<br>
slide21. Flow of Marketing Approval Procedure Applicant
（holder of marketing authorization） ④ hear opinion Pre-approval consultation ②⑥ Return of flawed document, Pointing out of problem Pharmaceutical Affairs and Food Sanitation Council (PAFSC) MAFF FSSC APSD ①apprication （requested by article14, 19） ⑨ grant of approval ⑤Pointing out of problem Cooperative processing ③⑦ Improvement of documents & problem Draft prepration of minimun requirement, standard, etc. Pointing out of Problem Data of toxicity, target animal safety or residue has to meet the Good Laboratory Practice (GLP), and data of clinical trial has to meet the Good Clinical Practice (GCP). GMP Inspection a. Minimum requirements for veterinary biological products (Notice No. 1567, 2002)
b. Standard of antibiotics for animals (Notice No.1123, 1999)
c. The source materials standards of biological products for animal use (Notice No. 1911, 2003) ⑧approval<br>
slide22. Council and Commission 22 Act Article 14,(11)
In cases where the Minister receives an application for approval prescribed in paragraph (1), and finds that pharmaceuticals, quasi-pharmaceutical products or cosmetics pertaining to the application are obviously different from those of pharmaceuticals, quasi-pharmaceutical products or cosmetics which have been already approved subject to this Article or Article 19-2 in terms of active, components quantity, dosage, administration, efficacy, etc., the Minister must hear the opinions of the Food Safety Standards Council in advance regarding whether the approval prescribed in the same paragraph should be given.<br>
slide23. VMPs for food producing animals Residues of VMPs
Food Safety Standards Council (FSSC)
Consumer Affairs Agency（CAA）
Human health safety
Food Safety Commission(FSC) of Cabinet Office<br>
slide24. Flow chart from application to approval of VMPs for food producing animals Application MAFF FSSC
(Examination for approval) FSC
(evaluation of ADI) CAA
（Decision of MRL） Approval MAFF<br>
slide25. Responsible authorities for Veterinary Medicinal Products MAFF (Ministry of Agriculture, Forestry and Fisheries) FSCAB (Food Safety and Consumer Affaires Bureau) APSD (Animal Products Safety Division) NVAL (National Veterinary Assay Laboratory) －National assay of veterinary biologics
－Review of application for approval
－Spot sampling test of VMPs
－Review of reliability standard compliance
－Inspection (GLP,GCP,GMP)
－Consultation of VMPs development －Supervision of import of VMPs －Establishment and revision of approval system －Overall control of veterinary pharmaceutical affairs<br>
slide26. Thank you for your attention
Merci pour votre attention
Gracias por su atención
شكراً جزيلاً لكم على انتباهكم.
경청해 주셔서 감사합니다
आपके ध्यान देने के लिए धन्यवाद
Ngā mihi ki a koutou
ご清聴ありがとうございました 26<br>