Regulations of Biologics in Taiwan

Transcription

1 Regulations of Biologics in Taiwan Churn-Shiouh Gau, Ph.D. Executive Director, Taiwan 2013/2/13 1

2 Outlines Regulation of Drugs in Taiwan - Organizations Regulations for Marketing Approval for Drugs including Biologics Regulatory Consultation Services 2013/2/13 2

3 Key Facts 65+ population: 11% Parliamentary democracy GDP per capita (2010) (Nominal): US$18,300 (PPP, IMF): US$ 34, /2/13

4 Some Health Data Life expectancy (2010) Men 76.2 years, Women 82.7 years Top causes of death (2010): Malignant neoplasms % Heart disease % Cerebrovascular disease - 7.0% Pneumonia - 6.2% Diabetes mellitus - 5.7% 42013/2/13

5 TFDA Organizational Chart 2013/2/13 5 5

6 Intensive Regulatory Management throughout the Lifecycle of Drugs Discovery Preclinical Studies Clinical Trials NDA/BL A/ANDA Post- Market GLP IRB/GCP SUSAR Reporting ADR, Product Quality Defects Reporting Systems GLP : Good Laboratory Practice GCP : Good Clinical Practice ADR : Adverse Drug Reaction Drug Injury Relief program cgmp 2013/2/13 6

7 Post-marketing Safety and Quality Surveillance PMS for product quality and safety Surveillance Quality surveillance Safety surveillance Passive Active Active Product Quality Defects Reporting System National Quality Surveillance Program Global Safety Information Monitoring Using NHI Database to Study Safety Issues Reassessment / Inspection Label change Withdrawal/Recall Passive National ADR Reporting system PSUR by Drug Companies Drug-induced liver injury Network (Taiwan DILIN) 2013/2/13 7 7

8 Framework of Drug Safety/Quality Surveillance TFDA Industry (Periodic Safety Update Reports) Taiwan Drug Relief Foundation National ADR Reporting Center (1998) Medical Product Quality Defects Reporting Center (2004) Hospitals, pharmacies, industries, and consumers Local health authorities 2010/09/ /2/13 8 8

9 Framework of Marketing Approval Evaluation Sponsor IND Protocol Review & Consultation TFDA NDA/ANDA/DMF Review & Consultation Arrows in red are for IND and NDA application. Arrows in blue are consultation. 2010/09/ /2/13 9 9

10 NDA, IND Capacity Building of CDE Evaluation of TCM (for Western Indication) SAEs in clinical trials PMA for New Device Health technology assessment (HTA) CDE was established by DOH at Consultation Establishment of CDE Bridging Study Evaluation IDE for New Device ANDA for Generics DMF 2013/2/13 10

11 Major Tasks Dossier Evaluation for Drugs IND, NDA, ANDA, DMF, BSE, BA/BE Regulatory Science Consultation Services Dossier Evaluation for Biologics Health Technology Assessment Dossier Evaluation for Medical Devices PMA, IDE 2013/2/13 11

12 Organization Chart effected 09/01/2012 Board of Directors Auditing Executive Director Office of Executive Director Deputy Executive Director Center of Consultation Division of Health Technology Assessment Division of Medical Devices Division of New Drugs Division of Pharmaceutical Science Division of Regulatory Affairs and Compliance Administration Department of General Affairs Project Management International Cooperation & Public Relations 2013/2/13 12

13 Review Process for NDA Sponsor Application Global New NCE/ Biological product Botanical product Biosimilar etc. Advisory Committee Special Concern consult AC experts Archives CDE Review Team Technical and administrative documents Assessment Report TFDA Decision TFDA PMF/PIC/S GMP 2013/2/13 Sponsors 13

14 NDA Applications in application approval /2/13 imported domestic NCE (Including biological products) New indication, new combination, new route of administration New dosage form, new usage dose, new strength 14

15 Some Issues for NDA Application For NCE and new biologics, it is required to do Bridging Study Evaluation (BSE) for NDA evaluation. Sponsor is encouraged to do BSE before NDA submission. It is required to submit dossiers in ICH Common Technical Document (CTD) format for new drug (NCE + biologics) license applications. (Nov. 1, 2012) 2013/2/13 15

16 IND Regulation on Pharmaceutical Manufacture Site Facility and operation follows the principle of cgmp regulation Provide description of site and facility in the package or verification / certification documents from other regulatory agency NDA GMP/PICS inspection 2013/2/13 16

17 For Biologics Product Specific Regulations: Regulations of Review and Approval of Vaccine (2002) Regulations of Review and Approval of Genetically Engineered Medicinal Product (2002) Regulations of Review and Approval of Blood Products (2001) Regulations of Lot Testing and Release of Biological Product (revised in 2012) 2013/2/13 17

18 For Biologics Product Specific Regulations Guideline of Stability Testing of Biotechnological/ Biological Product (2003) Guidance on Review and Approval of Pandemic Influenza Vaccine (2010) Guidance for Review and Approval of Biosimilar Products (Draft, initiated on 2008, revised on 2012) Points to Consider for Review of Common Technical Document (CTD) of Biosimilar Products for Marketing Approval (2010 ) Guideline for IND Application of Cellular and Gene Therapy (draft 2011) 2013/2/13 18

19 Though with limited guidance, review of biologics also take references from international regulations issued by ICH, WHO, US FDA, and EU EMA. 2013/2/13 19

20 ICH Guidance - quality Q5A: Viral safety evaluation of biotechnology products derived from cell lines of human or animal origin Q5B: Analysis of the expression construct in cells used for production of rdna derived protein products Q5C: Stability testing of biotechnological/biological products Q5D: Derivation and characterization of cell substrates used for production of biotechnological/biological products Q5E: Comparability of biotechnological/biological products subject to changes in their manufacturing process Q6B: Test procedures and acceptance criteria for biotechnological/biological products 2013/2/13 20

21 References- EU Guideline on the requirements to the chemical and pharmaceutical quality documentation concerning investigational medicine products in clinical trials, EMEA, 2005 Chemically defined active substances/radiolabeled substances, synthetic peptides, herbal substance Guideline on virus safety evaluation of biotechnological investigational medicinal products, EMEA, 2008 rdna derived biologics, mab 2013/2/13 21

22 References- USA Guidance for industry: Content and Format of INDs for phase 1 studies of Drugs, including well-characterized, therapeutic, biotechnologyderived products, FDA, 1995 Guidance for industry: cgmp for phase 1 investigational drugs, FDA, 2008 Guidance for industry: Characterization and qualification of cell substrates and other biological starting materials used in the production of viral vaccines for the prevention and treatment of infectious disease, FDA, /2/13 22

23 Clinical trials of biologics in Taiwan Imported products mab, vaccine, blood products Domestic products mab Therapeutic protein product: e.g., PEG modified protein Biosimilar product Vaccines: inactivated bacteria/viruses, polysaccharide conjugate, rdna protein, new adjuvant Cell therapy product 2013/2/13 23

24 Regulation for Biosimilar Products Guidance for Review and Approval of Biosimilar Products Draft, initiated , amend It is mainly based on EMA guidelines with consideration of local regulatory environment General Guideline + Product Specific (Somatropin, Insulin, G-CSF, EPO) 2013/2/13 24

25 Points to Consider for Review of Common Technical Document of Biosimilar Products for Marketing Approval announced TFDA s current thinking The 3-year grace period is incentive for manufacturer if sponsor could submit the BLA before Dec 31, 2013: data such as process validation could be submitted after approval; the clinical trial can be a placebo-controlled trial if it is clinically acceptable. Interactive discussion with regulatory agency is required. 2013/2/13 25

26 Current Status for Biosimilar One case (ominitrope ) was licensed 6-7 cases are in clinical trial stage. Many potential candidates are under development. 2013/2/13 26

27 Examples of Biosmilars under Development by Domestic Biotech Companies in Taiwan Company A B C D E F Active Ingredient EPO Peg-filgrastim Peg-IFN Epoetin alfa Trastuzumab Rituximab Adalimumab Bevacizumab rhg-csf Peg-filgrastim Anti-CD20 G-CSF Trastuzumab 2013/2/13 27

28 Regulatory Consultation Services In order to Enhance transparency Facilitate application submission for medical product registration Consultation General Consultation Index Case Consultation General Presubmission Cases under review Potential candidates of medical products R&D projects from industries and R&D organizations 28

29 How to Apply: 1. Complete the Consultation Service Application Form online. 2. Download the Consultation Service Application Form. Send to CDE via fax or after filling in the relevant fields. 3. Call the Consultation Service Center. 29

30 Prospects Enhance the quality, efficiency, and transparency of product evaluation. Implement good review practice for reviewer training to make a good decision. Strengthen regulatory consultation for index cases to facilitate the R&D capacities of local industries. Establish the international cooperation with other regulatory agencies as well as with China. Quality Efficiency International Cooperation Transparency 2013/2/13 30

31 Thank You for Your Attention 2013/2/13 31