Nam Soo, Kim. Biopharmaceutical Policy Division

Transcription

1 Drug Approval and Review System in Korea Jun. 30, 2017 Nam Soo, Kim Biopharmaceutical Policy Division

2 [ Table of Contents] Introduction of MFDS Overview of Drug Approval System Recent Changes for Safety and Regulatory Reforms 2

3 Introduction of MFDS

4 Ministry of Food and Drug Safety Function (Government Organization Act (Article 25)) In order to administer duties concerning the safety of foods and drugs, Ministry of Food and Drug Safety shall be established under the Prime Minister. Staff (Total 1,797 government officers, ) Headquarter : 589 officers NIFDS : 418 officers Regional FDA : 790 officers Budget (year 2017) About 40 billion USD 4

5 History of MFDS Restructured to Ministry of Food and Drug Safety (1,449 1,760 officers) - Relocation to Osong Health Technology Administration Complex, Osong, Chungbuk - Reorganized in office, 5 bureaus and 48 divisions (1,413 officers) - Restructured to 6 bureaus and 4 departments (1,200 regular employees) - Korea Food and Drug Administration(KFDA) 2 divisions, 6 departments and 5 chief officers, 8 departments, 23 sections (776 officers) - Food and Drug Safety Headquarters (in April) 5

6 MFDS Headquarters MFDS Headquarters General Affairs Division Minister Vice Minister Spokesperson Audit and Inspection Office Criminal Investigation Office Director General for Planning and Coordination Planning and Finance Office Organization and Management Innovation Office Regulatory Reform and Legal Affairs Office International Cooperation Office ICT Management and Statistics Office Customer Support Office Emergency Planning and Safety Office Customer Risk Prevention Bureau Customer Risk Prevention Policy Division Communication and Cooperation Division Risk Information Division Integrated Food Information Service Division Laboratory Audit and Policy Division Food Safety Policy Bureau Food Standard Planning Office Food Safety Policy Division Food Safety Management Division Food Safety Labelling and certification Division Health Functional Food Policy Division Alcoholic Beverages Safety Management and Planning Division Food Standard Division Residues and Contaminants Standard Division Food Additives Standard Division Imported Food Safety Policy Bureau Imported Food Policy Division On-site Inspection Division Imported Food Inspection Management Division Imported Food Distribution Safety Division Food and Consumer Safety Bureau Dietary and Nutritional Safety Policy Division Agro-Livestock and Fishery Products Policy Division Agro-Fishery Products Safety Division Foodborne Diseases Prevention and Surveillance Division Pharmaceutical Safety Bureau Pharmaceutical Policy Division Pharmaceutical Management Division Narcotics Policy Division Narcotics Management Division Pharmaceutical Quality Division Clinical Trials Management Division Pharmaceutical Approval and Patent Management Division Pharmaceutical Safety Evaluation Division Biopharmaceuticals and Herbal Medicine Bureau Biopharmaceutical Policy Division Biopharmaceutical Quality Management Division Herbal Medicine Policy Division Cosmetics Policy Division Quasi-Drug Policy Division Medical Device Safety Bureau Medical Device Policy Division Medical Device Management Division Medical Device Safety Evaluation Division 6

7 NIFDS(Affiliated agency) NIFDS (Affiliated Agency) 7

8 Regional Office of Food and Drug Safety Gyeongin -FDS Seoul -FDS Daejeon -FDS Daegu -FDS Gwangju -FDS Busan -FDS 8

9 Korean Laws and Regulations on Drug Approval

10 Regulatory Hierarchy of Drug Approval Pharmaceutical Affairs Act (Law) Rules of the Safety of Pharmaceuticals (Ordinance of the Prime Minister) Notice on the Approval of Pharmaceuticals (including Biologics) (MFDS Notices) - Detailed interpretation of the law - Legally binding Guidelines for Industry and Reviewers - Provide MFDS s policy directions on current issues - Can be revised anytime 10

11 Overview of Pharmaceutical Safety Management System GLP GCP GMP GSP Safety Management Re-evaluation Re-examination Nonclinical Ⅲ Clinical Approval/ Review Manufacture (Import) Distribution Usage after approval Animal Patients (Confirm Safety and Efficacy) Set Manufacture/ Quality Standards Safety & Efficacy Quality Manufacture Import Hospital Pharmacy Wholesaler Consumer Doctor Pharmacist Issue, Safety Info. Research Development Post- approval Change Discontiue Manufacture/Import Recall / Discard Provide Information Clinical Trials, Approvals Quality Inspection Manufacture(Import) Distribution (Safety Letters) Post-marketing Management 11

12 Drug Classification Origin of Ingredients Chemical, Biological and Herbal drugs Accessibility Prescription and OTC drugs Data Requirements New Drugs (requiring evaluation of safety and efficacy data) Generic Drugs (requiring bioequivalence data), Biosimilars Drugs listed in Korea Pharmacopoeia and Medicines Compendium 12

13 Definitions New drug Drug product containing new chemical entities (NCEs) never previously approved by MFDS in Korea, either alone or in combination. 13

14 Definitions Drugs requiring safety and efficacy evaluation Drugs not containing a new chemical entity and previously approved are subject to safety and efficacy evaluation when any change occurs in: Salt or Isomer Administration route Dosage form or strength Formulation Combination Indication 14

15 Definitions Generic Drug A drug product that is comparable to a reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use 15

16 Definitions Biological Products Biological products, also known as biologics, biological medicinal products and biologicals, are defined as medicines obtained from human or other living organisms which cannot be fully characterized by physiocochemical means alone, and which therefore require the use of some form of bioassay. In general, manufacturing procedures of biological products may include one or more of the following elements: growth of strains of microorganism and eukaryotic cell, extraction of substances from biological tissues, recombinant DNA (rdna) techniques, hybridoma techniques, propagation of microorganisms in embryos or animals. Vaccines Plasma-derived products Therapeutic proteins Cell therapy products Gene therapy products 16

17 Drug Approval Process Application Applicant Pre-reviewreview MFDS(NIFDS) Regional FDS (only generic) Review / Inspection NIFDS (Drug / Biological Evaluation Department ) Regional FDS Approval MFDS(NIFDS) Regional FDS (only generic) Research and development of drug Submission of dossier for drug approval Composition of preliminary report - Examination of submitted application Report Review Efficacy, Safety Quality Evaluation DMF GMP Assessment GMP inspection - Foreign Manufacturing sites (MFDS) - Domestic Manufacturing sites (Regional FDS) Issuing certificate of approval Disclosure of Review Result 17

18 Online System for Pharmaceutical Application ( ezdrug.mfds.go.kr) 18

19 Annual Drug Approval & Notification 3,500 Approval (2010~2016) 3,000 2,500 2,000 1,500 1, , , , , Total Approval Notification 19

20 Annual New Drug Approval New Drug No of items (No of Active ingredients) New Drugs Developed in Korea Chemical 49 (26) 31 (22) 17 (14) 23 (15) 49 (27) 34 (19) Manufacture Import (12) Biologics Herbal Manufacture Import Manufacture Import < New Drugs Developed in Korea > 17 : Hepatitis B(1), 16 : Lung cancer(1), 15 : Diabetes(1), Antibiotics(2), Osteoarthritis(1), Antimicrobial(1), 14 : Pancreatic cancer(1), 13 : Diabetes(1), 12 : Diabetes(1), Leukemia(1), 11 : Malaria(1), Impotence(1), 10 : Hypertension(1) 20

21 Biosimilars Developed in Korea No Company Drug name 1 Celltrion Remsima 100mg 2 Celltrion Herzuma 150, 440mg 3 Samsung Bioepis Brensis 50mg Active ingredient Infliximab Trastuzumab Etarnercept Indication Rheumatoid Arthritis Breast Cancer Rheumatoid Arthritis, Psoriasis 4 Celltrion Truxima Rituximab Rheumatoid Arthritis, Lymphoma 5 Samsung Bioepis Renflexis 100mg Infliximab Rheumatoid Arthritis Approval date Jul 20, 2012 Jan 15, 2014 Sep 7, 2015 Jul 16, 2015 Dec 4,

22 Stem Cell Therapy Products Developed in Korea No Company Drug name 1 Pharmicell Hearticell gram ami Proper name BM MSCs Indication Acute myocartial infarction 2 Medipost Cartistem hucb MSCs Cartilage injury 3 Anterogen Cupistem ASCs Anal pistula in Crohn s disease 4 Corestem Neuronata R BM MSCs Slowing the progression of ALS Approval date Jul 1, 2011 Jan 18, 2012 Jan 18, 2012 Jul 30,

23 WHO PQ products No Company Drug name Proper name Date of prequalification 1 LG Life Science 2 Janssen Vaccine 3 Janssen Vaccine 4 Green Cross 5 Green Cross 6 Green Cross Euvax B (1,2,6,10dose) Hepavax Gene(1,10dose) Hepavax Gene TF(1dose) GC Flu(1dose) GC Flu multidose(10dose) Green Flu S(1dose) Hepatitis B Vaccine(recombinant) Dec 22, 1996 Mar 23, 2004 Jul 31, 2012 Influenza vaccine(seasonal) Apr 12, 2011 Nov 7, 2012 Influenza vaccine(h1n1) May 11,

24 WHO PQ products No Company Drug name Proper name Date of prequalification 7 Janssen Vaccine 8 Janssen Vaccine 9 LG Life Science 10 EuBio logics 11 LG Life Science 12 Janssen Vaccine 13 Green Cross Quinvaxem (1dose) Quinvaxem in CPAD(1dose) Euforvac-Hib (1,2dose) DTwP-HepB-Hib Sep 26, 2006 Dec 24, 2014 Aug 23, 2012 Euvichol(1dose) Oral cholera vaccine Dec 23, 2015 Eupenta DTwP-HepB-Hib Feb 10, 2016 Quinvaxem MDV (5,10dose) GC Flu quardribalant (1dose) DTwP-HepB-Hib Feb 29, 2016 Influenza vaccine(seasonal) Dec 21,

25 Drug Approval & Review Process

26 New Drug Review and Approval Applicant Application Approval MFDS/NIFDS Scientific Review Conformity Audits (GLP/GCP/GMP etc.) Consultation (if necessary) Advice Central Pharmaceutical Affairs Advisory Committee 26

27 Approval Period and Fee for NDA New Drugs Take 120 days (working day) Fee : $6,026 * Generic : 90days / $1,958 MFDS may request supplementary data twice in the review process. Sponsor s response time - At the first request : 60 calendar days - At the second request : 10 working days Sponsor can extend their response time. Pharmaceutical Affairs Consultation 27

28 Data Requirements of NDA CMC GMP Non Clinical Pharmacology ADME Toxicology Clinical Phase I Phase II Phase III Bridging DMF CPP, etc Safety and Efficacy Evaluation 28

29 Dossier for Safety & Efficacy Evaluation Origin or backgrounds leading up to discovery and development Structure physical, chemical and biological nature A. Drug Substance B. Drug Product Clinical data A. Clinical data package B. Bridging Data Comparison with domestic copies & special features of the drug concerned Stability Stability test data A. Drug Substance B. Drug Product Long-term, accelerated, stressed Toxicity A. Single dose toxicity B. Repeated dose toxicity C. Genetic toxicity D. Carcinogenicity E. Reproductive and developmental toxicity F. Others antigenicity, immunotoxicity, local toxicity dependency, etc. Pharmacologic effects A. Efficacy studies data B. Safety or general pharmacology studies data C. ADME D. Other pharmacologic effects Uses in other countries 29

30 Common Technical Document (CTD) Module 1 Regional Administrative Information Module 2.1 Table of Contents 2.2 CTD Introduction - Adopted for New Drugs, Biological Products since March 1, 2009 Course of development, comparison with similar drugs, CPP, etc. Standard and test procedure (including stability data) SE Data (excluding stability data) 2.3 Quality Overall Summary 2.4 Nonclinical Overview 2.6 Nonclinical Written & Tabulated Summaries 2.5 Clinical Overview 2.7 Clinical Summary Module 3 Quality Module 4 Nonclinical Study Reports Module 5 Clinical Study Reports 30

31 GMP Inspection Evaluation process to ensure that drug products are manufactured in compliance with Good Manufacturing Practice(GMP) regulation GMP document review Plant inspection facilities, operations and SOPs 31

32 Recent Changes for Safety and Regulatory Reforms

33 Recent Changes Introduction of Priority Approval( 16.7) Cell therapy products may be used for severe or life threatening diseases * Safety control measures postmarketed : Confirmatory clinical trial, RMP etc Bio IT Platform( 14-) Overseas regulatory information, biologics approval regulations and guidelines, market information, consulting services < Bio IT Platform Homepage ( > * Information of 12 Countrys : USA, EU, Japan, China, Brazil, Turkey, Thailand, India, Mexico, Saudi Arabia, Australia, Russia 33

34 Recent Changes Introduction of Drug Injury Relief System( 15-) 15(Death Compensation), 16(Disability Compensation), 17(Fee for consultation) Introduction of Risk Management Plan( 15.7) New drug, Orphan drug, Stem cell therapy product etc Joining PIC/s( 14.5), ICH( 16.11) Quality improvement, Global Advancement, Special Education Harmonization of Regulation 34

35 Recent Changes Introduction of Generic drug CTD( 16.7) New drug( 09.3), Biological Products( 09.3) Renewal of Drug Approval( 18) Effective period : 5 years Safety management data, Quality management data, Label etc Review Result Disclosure( 04-) Disclosure of Review Results to improve consistency, transparency, and predictability( 35

36 Recent Changes Implement National Lot Release System( 16.4) Differentiated control systems by making comprehensive risk evaluations Improve Biopharmaceutical Manufacturing and Quality Control Introduction of GMP for Blood products( 16.12) Conduct GMP evaluations on orphan drugs, export products( 16.7) 36

37 Spring Summer Fall Winter