1. Establishment of Medical Device GMP Requirements Hsiau-Wen Huang, Ph. D. Senior Researcher Bureau of Pharmaceutical Affairs Department of Health

2. Background Information Taiwan Population 23 million 23 millionArea 36,006 m 2 36,006 m 2 Per Capita GNP US$12,916 US$12,916 Medical Centers 18 18 MD Manufacturers 410 410

3. Regulation under authorization Pharmaceutical Affairs Law Pharmaceutical Affairs Law Promulgation :1970

4. Medical Device Regulation Promulgation of Law of Pharmaceutical Affairs: 1970 1 st license issued to medical device made in Taiwan: 1973 Definition of medical devices – include the instruments, equipment, apparatus, and their accessories and spare parts which are used for diagnosing, curing, alleviating and directly preventing the human diseases, or changing the structure and function of human body.

5. Historical Perspective before 1999 Product Medical Device Premarket Approval Required Exempted from Approval Non Medical Device Local MD manufacturers need to comply with “pharmaceutical factories establishment standards”

6. 1970 -- Premarket approval & Pharmaceutical factories establishment standards (refer toJapan system) 1982 -- Drug GMP (refer to Japan system) 1993 -- Local Clinical Trial 1996 -- GCP (toward to US FDA regulation) 1999 -- cGMP (toward to US FDA regulation) 2002 -- Overseas on-site Inspection Pharmaceuticals

7. Evolving of Medical Device GMP 1989 Contracted study project of GMP planning 1990~ FDA regulation suggested 1997 DOH started to attend GHTF 1998 Determined to harmonize with ISO 13485 1999 Implementation refer to Japan system

8. Medical Device GMP Committee  1996 DOH proposed to organize a committee/ working group and cooperate with Ministry of Economic Affairs (MOEA)  1997 DOH decided to outsource third parties for GMP auditing  1998 Referred the experience of ISO 9000 and prepare for the WTO/global harmonization  1998 Consulted with industry representatives  1998 Finalized the GMP regulation and implementation procedure  1999 Public Announcement

9. MD GMP Implementation  Effective on February 10, 1999  Adoption of ISO13485  DOH Designated Auditing Organization  Domestic manufacturers: Site inspection  Importing manufacturers: QSD review  Five year transition period

10. MD GMP Facilitation  Industry encouraged by government support  MOEA/DOH funding for the industry associations to promote GMP and set up website for information sharing  Consultant provides on-site assistance  Close communication between DOH/DAO and industry

11. Designated Auditing Organization DOH Request for Qualified DAO  Non-Profit Organization established by government  Shall establish a quality system according to applicable requirements of ISO/IEC Guide 62  Staff with medical device and quality system auditing expertise  Accredited by DOH Medical Device GMP Committee  Prevention of conflict of interest  Confidentiality

12. Designated Auditing Organization Designation Procedure  Non-Profit Organization submit proposal to DOH according to the request  DOH evaluate the proposal  DOH and external experts on site visit of the applicant  DOH report to the Medical Device GMP Committee  Evaluated and accepted by the GMP Committee  DOH announce the designation of auditing organization  DAO report to DOH annually  Routine Inspection by DOH

13. DAO Annual Report  Statistic of GMP/QSD applications (total case number and approval rate, including import and local manufacturers)  Summary of major/minor nonconformities  Records of auditor trainings  Records of industry training programs  Any special topics about auditing procedure and consistency

14. Since 1999 CMS/ITRI Center for Measurement Standards/Industrial Technology Research Institute ETC Electronics Testing Center MIRDC Metal Industries Research & Development Center Since 2004 PIDC Plastic Industry Development Center DOH Designated Auditing Organizations DOH Designated Auditing Organizations GMP audit and QSD review GMP audit and QSD review for Medical Device including IVD

15. Registration Flow Chart DOH Class I/II/III Product Review Advisory Committee (New Device) Lincense Approval Premarket Application GMP/QSD Approval DAO Audit GMP/QSD Application DOH

16. GMP/QSD Application to DOH DAO Recommendation to DOH DOH Issue Approval DAO Review and Audit Not accepted Accepted

17. FDA QSIT ISO GHTF Observation of FDA/EU NB inspections Periodical meeting with DOH/DAO GMP Trainings DOH and DAO

18. GMP Trainings Manufacturer and Local Agency DOH/DAO FDA QSIT ISO

19. Approval Status of Medical Device GMP/QSD Total 1539 approvals in 2004

20. Factors for the Regulation Change Global Harmonization Task Force Quality System Standards Conformance International Cooperation (MRA/EOL) Social Impact (ex. SARS/BSE) Modern Technology (ex. Combination Product)

22. Clinical Trial for Medical Device (?)

23. Harmonization with GHTF Harmonization with GHTF Experience sharing Experience sharing Recognition and Cooperation Recognition and Cooperation Future Works