Enhancing Review Efficiency (Pharmaceuticals)

Transcription

1 Enhancing Review Efficiency (Pharmaceuticals) Naoto Kato Office of Review Management Review Planning Div. ( PMDA ) September 10th, 2015 The 2nd Brazil-Japan Seminar on Regulations on Pharmaceuticals and Medical Devices 1

2 3 rd 5 year mid term plan of PMDA (FY ) Major challenges Shortening the time from early development to approval Zero review time lag Support for elimination of development time lag Specific measures Accelerated review process (Improvement of approval predictability) Improvement of prior assessment (substantial acceleration of approval review process) Enhanced overseas inspection system Drastic improvement of consultation service Active involvement from the early development phase Improvement of pharmaceutical affairs consultation service on R&D strategy Improvement of clinical trial consultation service High quality review/consultation services Enhancement of regulatory science research and human resource development Development of advanced review/consultation framework using innovative assessment techniques Cross products analysis of accumulated large data sets by PMDA using innovative techniques Utilization of Science Board (cooperation with the academia) Enhancing safety measures Utilization of medical information database Readiness for introduction of risk management plan Globalization Development of Japan s original innovative drugs and medical devices Goal Marketing of cellular and tissue based products Activation of the industry Extending health and life span of Japanese people Contribution to global medicine Appropriately accommodate the most advanced technologies including personalized medicine and regenerative medicine Prerequisites: US/EU equivalent system and human resources with excellent skills Responding to social needs such as Japan Reconstruction Strategy and Health/Medical Care Strategy 2

3 Improvement of Infrastructure(Staff Size) 1,065 Others

4 PMDA s business structure Advanced Review with Electronic Data Promotion Group, Office of Review Administration, Office of Review Management, Kansai Branch(Division of Pharmaceutical Affairs Consultation) Office of Safety Ⅰ, Ⅱ Office of Medical Infomatics and Epidemiology Office of Manufacturing/Quality and Compliance Kansai Branch (Division of Manufacturing/Quality and Compliance) (As of April 1, 2015) Safety 165 staffs Relief 36 staffs Office of New DrugⅠ - Ⅴ Office of Cellular and Tissue-based Products, Office of Vaccines and Blood Products Office of OTC/Quasi-Drugs, Office of Generic Drugs Office of Medical DevicesⅠ - Ⅲ, Office of In Vitro Diagnostics Review Office of Non-clinical and Clinical Compliance 532 staffs Office of International Programs Office of Standards and Guidelines Development Office of Relief Funds 4

5 Review Categories of New Drugs Office Review Category Products Office of New Drug Ⅰ Office of New Drug Ⅱ Office of New Drug Ⅲ Office of New Drug Ⅳ Team1 Team6 2 Team2 Team5 Radiopharmaceuticals In vivo diagnostics Team3 1 Team3 2 Team4 Anti AIDS drugs Team6 1 Office of New Drug Ⅴ Oncology drugs Antineoplastic drugs Office of Cellular and Tissue based Products Office of Vaccines and Blood Products Bio CMC Cellular and tissue based products, Gene therapy products Vaccines Blood products Gastrointestinal drugs, Dermatologic drugs Hormone drugs, Drugs for metabolic disorders Cardiovascular drugs, Antiparkinsonian drugs, Antithrombotics, Anti Alzheimer s drugs Reproductive system drugs, Drugs for urogenital system, combination drugs Radiopharmaceuticals Contrast media Central/peripheral Nervous system drugs(excluding anesthetic drugs) Anesthetic drugs, Sensory organ drugs(excluding drugs for inflammatory diseases),narcotics Antibacterial drugs, vermifuge, Antifungal drugs, Antiviral drugs(excluding AIDS drugs) Anti HIV agents Respiratory tract drugs, Anti allergy drugs(excluding dermatologic drugs), Sensory organ drugs for inflammatory diseases Quality of biologics, Biosimilars Cellular and tissue based products Quality and safety of gene therapy products Vaccines, Antitoxic serum Globullin, Blood coagulation factor products 5

6 Team Reviewing at the PMDA Reviewers are required to have a high level of expertise Office Director Review Director Team Leader CMC Toxicology ADME Biostatistics Pharmacology Clinical Risk Manager 6

7 The Standard Review Timeline for New Drug Applications To achieve the target of 12 months (standard review products) for the total review time from receipt of an application to approval after FY2014, the priority review timeline indicating the timeframes(the total of the times allowed for the regulatory authorities and the applicant) for each review stage, based on past performance in regulatory review, is shown below. This timeline is applicable when there are no particular concerns in the course of review. 25 th percentile median 75 th percentile months months months months months Applicant PMDA MHLW Submission of application for marketing approval Initial meeting Inquiries on important issues GLP/GCP & data integrity assessment GMP inspections Expert discussion Complete preparation of review report Reviews by Drug Committees Marketing approval Note: Inquiries on important issues means inquiries made by PMDA after the initial meeting. 7

8 The Priority Review Timeline for New Drug Applications To achieve the target of 9 months (priority review products) for the total review time from receipt of an application to approval after FY2014, the standard review timeline indicating the timeframes(the total of the times allowed for the regulatory authorities and the applicant) for each review stage, based on past performance in regulatory review, is shown below. This timeline is applicable when there are no particular concerns in the course of review. 25 th percentile median 75 th percentile months months months months months Applicant PMDA MHLW Submission of application for marketing approval Initial meeting Inquiries on important issues GLP/GCP & data integrity assessment GMP inspections Expert discussion Complete preparation of review report Reviews by Drug Committees Marketing approval Note: Inquiries on important issues means inquiries made by PMDA after the initial meeting. 8

9 Number of Approvals and Review Time (Month) 25 New Drugs (Number of approved applications) ~FY2013: 50th percentile FY2014~: 60th percentile FY2008 FY2009 FY2010 FY2011 FY2012 FY2013 FY2014 Number of approved applications Priority Review Products Standard Review Products 0 9

10 審査等業務 New target review times for new drugs In order to further shorten review times, PMDA plans to sequentially increase the target values by 2018 as follows, which were also stated in the Third Mid-term Plan implemented from Review time for new drug (priority review products) Fiscal year Percentile Review time FY % 9 months FY % 9 months FY % 9 months FY % 9 months FY % 9 months 2.Review time for new drug (standard review products) Fiscal year Percentile Review time FY % 12 months FY % 12 months FY % 12 months FY % 12 months FY % 12 months 8.8 months(result) 11.9 months(result) 10

11 PMDA s performance highly evaluated globally Comparison of review time in 6 regulatory agencies from 2004 to 2013 PMDA and Health Canada may have had the most notable improvements over the past decade. Regulatory Affairs Professionals Society 14 January 2015 Reference: The impact of the changing regulatory environment on the approval of new medicines across six major authorities CIRS (Centre for Innovation in Regulatory Science) R&D

12 Implementation of prior assessment consultations Development Approval application Review Creation Seeds of new drug/ medical devices (Standards and Stability of Drug and Drug Substance ) Quality Results Prior Assessment (Quality) Non-clinical (Toxicity, Pharmacology, ADME) Results Drug Stability Assess study results in order coming out, instead of waiting for all results Carcinogenicity Study Prior Assessment (Non-clinical) de facto review before application due to prior assessment consultations phase I study phase II study phase III study Results Application preparation Prior Assessment (Clinical) 12

13 Fiscal year Implementation status of prior assessment consultation Total of the ingredient Number of prior assessment consultation Number of approved ingredient First half 3 9 Second half 7 24 First half 5 17 Second half 2 2 First half 5 14 Second half 6 18 First half 7 25 Second half

14 Before Non Clinical Pharmaceuticals and Medical Devices candidates Clinical trial consultations Timing of clinical trial consultation Non Clinical Clinical Review Post Market PhaseⅠ (Synthesis) (Preparation) (Pharmacology) (Toxicology) etc IND PhaseⅡ PhaseⅢ NDA PhaseⅣ Prior assessment consultations Non-Clinical Assessment Quality Assessment P-I data Assessment P-II data Assessment P-II/III data Assessment Qualification priority review R&D strategic consultations R&D strategy (Drugs/ Medical devices/ Cellular and tissue-based products) Quality and safety of cellular and tissue-based products Regulatory affairs development plans Medically Necessary Unapproved Drugs, etc. 14

15 Pharmaceutical Affairs Consultation on R&D Strategy Valley of Death -Shortage of funds, Knowledge on Regulation and developmental strategy Basic Research Pharmaceuticals and Medical Devices candidates Quality Study Strategic Consultation Non-Clinical Study Clinical Trial (Up to POC studies) Practical Use Innovative Products * Further studies are handled by the Regular Consultation Consultation on quality and battery of pre clinical, including examining tumorigenicity, biological ingredient safety Consultation on endpoints or sample size of early clinical trial Flow of Strategy Consultation Introductory Consultation (775) Pre Consultation (937) Face to Face Consultation (236) (7/1/ /31/2014) 15

16 Number of R&D Strategic Consultation Pre consultation (Face to face) Consultation FY2011 (from july) FY2012 FY2013 FY FY2011 (from july) FY2012 FY2013 FY

17 General Timeframe of SAKIGAKE 17

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19 Thank you for your attention! 19