Changes to International Regulatory Requirements

1. Changes to International Regulatory Requirements Gail Christie December 2, 2009

2. Agenda • Brazil • Mexico • Canada • India • China • Japan • European Union • Saudi Arabia • Turkey

3. Brazil • ANVISA (National Health Surveillance Agency) • Regulates medical device by Law No. 6360, Decree 74.094/97. Brazil is included in Mercosur Harmonization Group (Argentina, Paraguay, Uruguay) • 6 – 24 months review time • Rule RDC 25 – issued and signed into regulation May 22, 2009 • GMP certificate due with all registrations post March 2010 • Applies to all Class III, IV, specific Class II devices, and in-vitro diagnostics

4. Brazil (cont) • ANVISA will require inspection and a GMP Certificate for each manufacturing plant importing devices into Brazil. • Certificates will be valid for two (2) years, audits will occur every two (2) years • Yearly renewal certification fee of approximately US $18,500.00 plus audit expense, when applicable • Open GMP certificate issue, • Legal Manufacture • Manufacturing Site • Both

5. Brazil (cont) • According to industry working groups, ANVISA recently stated that they may accept a Notified Body audit and evidence of a ANVISA audit request due to capacity. • Currently, the auditing task force consists of Brazil state agencies and reviewer regulatory specialists. Industry is concerned that the task force will result in an increase in product review times. • ANVISA committed to answering industry concerns regarding RDC 25 by 12/2009. • RDC 25 audit does not negate the requirement for an IEC audit • http://anvisa.gov.br/eng/index.htm

6. Mexico • COFEPRIS (Comision Federal para a Proteccion contra Riesgos Sanitarios), a div of Mexican Ministry of Health Department (Established 2001) • General Health Law • Issued Regulation of Health Supplies • Grants COFEPRIS power to act independent of the Ministry of Health • Acts as the implementing regulation • Based on a three (3) Class system • Classification guidance document issued

7. Mexico (cont) • New amendment to the regulation posted January 2, 2008 • All current registrations older than 5 years to be renewed by February 24, 2010 • 5 year expiration date • COFEPRIS backlog • New amendment posted June 19, 2009 to amend approval times • National Development Plan 2007 – 2012 • Class 1, no response from COFEPRIS within 30 days, approved • Class 2, no response from COFEPRIS within 30 days, rejected • Class 3, no response from COFEPRIS within 60 days, rejected • Labeling standard change (NOM-137-SSA1-2008) effective February 2009 • Third party manufacture information must be on the label • http://portal.salud.gob.mx/index_eng.html

8. Mexico (cont) • Recent update from Advamed (11/30/09): • Commissioner Toscano publically recognized that getting the medical devices into the Renewal Process was a mistake… • and that the Law would have to be reformed again.. • ..but he is not pushing back on the 24 of February 2010requirement. • http://portal.salud.gob.mx/index_eng.html

9. Canada • Implementation of the Summary Technical Document (STED) - Medical Devices Bureau will update the existing guidance document. • Increased use of outside scientific expertise to reduce current backlog and speed up review times for applications. • Increased emphasis on the use and recognition of standards in pre-market reviews. • E-review Capability – plan to establish an electronic review environment to provide support to the electronic submission and increase efficiency of the review for device applications. • Cost Recovery - Current fees are out-of-date based on Health Canada’s costs of doing business. Updated fees could be in place in 2010/2011. • http://www.hc-sc.gc.ca/dhp-mps/md-im/index-eng.php

10. India • Government assigned Central Drugs Standard Control Organization (CDSCO) and Department of Science and Technology (DST) to develop medical device regulations • Government plans to amend current Drug regulations, rather than create a separate law for the device regulation • Recent information indicates that the CDSCO branch will be responsible for medical device dossier review • M-III Final draft amendment submitted for public review on Feb 23, 2009 • Two (2) year implementation time frame after approval

11. India (cont) • Government created the Expert Committee at the Drugs Controller General of India (DCGI) to review and comment on the M(III) draft • Participants, not inclusive list • Confederation of Indian Industries (CII) • Federation of Indian Chamber of Commerce and Industry (FICCI) • Association of Indian Medical Device Industry (AIMED) • Indian Council of Medical Research (ICMR) • Bureau of Indian Standards • Medical Fraternity

12. India (cont) • Expert Committee Responsibilities • Define modalities of Notified Bodies • List Class C & D devices • Define the required changes to the Drug rules • Develop a plan for Medical Device Regulations Act (MDRA) incorporation into M(III) • Create guideline for 2 year implementation • GHTF alignment • Device class regulated by listing • Current situation at Drugs Controller Government (India) DCG(I) • Chaotic • Misplaced dossiers • Registrations expiring • No response from regulators due to conflicting responsibilities http://cdsco.nic.in/

13. China • State Council Order 276 and SFDA Order 16, draft updates to regulation • AdvaMed and Joint Commission on Commerce and Trade (JCCT) met with SFDA on Sept 10, 2009 • Highlights from meeting: • China agreed to adopt GS1 standard for UDI. • Appeared to consider accepting the GHTF registrations, rather than country of origin registrations. To be determined in the next draft. • Manufacturing site inspections by China officials in the future • Delegation was not successful in gaining agreement to limit China clinical study requirements • Next draft to be submitted to industry before end of year • http://eng.sfda.gov.cn/eng/

14. China (cont) • US Department of Commerce released a news update on October 29, 2009 describing further agreements • China agreed, • product recalls will not be duplicative and will be managed by one government organization • to adopt a risk based approach to clinical study requirements • to accept a prior approval document issued by a foreign country regardless of the country of origin • to consider an exemption of requiring samples to be tested in Chinese test labs prior to approval if manufacturer meets international standards and provides sound scientific evidence • to strive to implement regulations in line with GHTF guidelines

15. China (cont) • Notification on Matters Concerning Registration of Drugs and Medical Device Combination Products, SFDA Issued November 16, 2009 • Drug and medical device combination products in which the drug plays the leading role shall apply for drug registration; drug and medical device combination products in which medical device plays the leading role shall apply for medical device registration. • Article six states that combination products not approved in the country of export and/or products whose drug has not been approved in the country of legal manufacture will not be accepted.   • Not compatible with recent discussions regarding country of origin • Overlooks the situation in which a drug may only be used in combination with a medical device and would not have a separate drug approval

16. Japan • PMDA (Pharmaceuticals and Medical Device Agency) • MHLW (Ministry of Health, Labor, and Welfare) • Action Program Established April 2009 to monitor reform • Update from Action Program Working Groups • Partial change definition in line with FDA 510(k) process • Stability Test Data • MHLW issued a guidance document on accelerated aged data • Clinical Data notification issued 2008 • Clinical evaluation guidance drafted • PMDA is likely to issue a guidance document on this subject sometime next year • Submission bundling subgroup review • orthopedics; pacemakers; dialyzers; oxygenators; and medical equipment/machinery under consideration

17. Japan (cont) • Future • 3 track submission system by 2011 • Yearly 3rd party reviewer to summarize action plan progress against goals • Increase to 104 reviewers by 2013, decrease review times to • 12 months for new device application • 7 months for improved device application http://www/pmda.go.jp/english/index/html

18. European UnionMedical Device Directive 93/42/EE Amendment 2007/47/EC • Amendment to 93/42/EC and AIMDD 90/385/EEC (Active Implantable) • Published Oct 11, 2007 • European Commission issued an interpretative document June 9, 2009 • ENTR/F3/PBE/D(2009)119003 • March 21, 2010 enforcement, not inclusive • Definition of central circulatory system has been expanded for Class III • Includes the vessels aortic arch and descending aorta to the aortic bifurcation. • Record retention; lifetime of the product, not less than five years. Implantable devices at least 15 years after the last product has been manufactured

19. European UnionMedical Device Directive 93/42/EE Amendment 2007/47/EC(cont) • March 21, 2010 enforcement, not inclusive (cont) • Clinical Evaluations required for all devices, regardless of classification • Clarification on single use • Phthalates labelling for all products • Product for use on children or pregnant women require justification in the Technical File and Instructions for Use • Stand alone software as an active medical device • Outsourced design and manufacturing must be more closely monitored • Instructions for Use must be revision controlled • Definitions of continuous use expanded

20. European Union (cont) • Medical Device Directive Recast • On hold, projected to resume 2010 • Machinery Directive 2006/42/EC applicable to Medical Device as of December 29, 2009 • Where a medical device is also a machinery, it shall meet the essential health and safety requirements of the Machinery Directive to the extent to which they are more specific than the essential requirements of the MDD

21. Turkey • Country of Origin Discrimination at Customs due to 2009/16 regulation • Effective January 1, 2009, one day after publication • If country of Origin is not an EU state, 3 day to 3 week hold delay • DOC, EC certificate, Application, Turkish IFU required at Customs • Physical product checks, when requested • Missed tender deadlines • Turkish Labeling Requirements • Checked at customs, hospitals and reimbursement authorities • All words must be translated to Turkish, including symbol statements • Introducing a product to market starts at customs, therefore label must be applied prior to customs entry • Additional label required for importer’s contact information • TITUBB (Turkish National Drug and Medical Data Base) • EAN 13 required on label

22. Saudi Arabia • Saudi Food and Drug Authority (SFDA) • Posted Regulations and Implementing Rules • Medical Device Interim Regulations Decree 1-8-1429, December 27, 2008 (published April 17, 2009) • Implementing Rules for • Establishing Licensing • Establishment Registration • Medical Device Listing • Designation and Oversight of Conformity Assessment Bodies • CAB shall not be the manufacturer's assigned Notified Body or authorized representative • GHTF alignment • http://www.sfda.gov.sa

23. The views expressed are those of the author. They do not necessarily reflect the position of Covidien.

24. Supplemental Information:Global Glossary

25. Global Glossary • Brazil • ABIMO – Domestic Medical Device Association • ANVISA – National Health Surveillance Agency. GOB - Government of Brazil • Mexico • AMID – Association for Medical Industries for Innovative Medical Devices • China • AmCham – The American Chamber of Commerce in China – Industry association • AQSIQ – General Administration of Quality Supervision, Inspection and Quarantine – One of the two main Chinese government agencies that tests medical devices prior to regulatory approval and conducts audits of manufacturing facilities. • CAMDI – China Association for Medical Device Industry – China’s largest domestic medical device industry association, which has a formal relationship with several government agencies, including SFDA and the NDRC. • JCCT - Joint Commission on Commerce and Trade • MHRSS - MHRSS:  Ministry of Human Resources and Social Security • MOFCOM – Ministry of Commerce – Chinese government ministry.. • MOH – Ministry of Health – Chinese government ministry. • NDRC – National Development and Reform Commission – Chinese government agency PRC – People’s Republic of China – The formal legal name of the country of China. • SFDA – State Food and Drug Administration – Chinese government agency

26. Global Glossary • Europe Union • COCIR – Association ofthe European Radiological, Electro medical and Healthcare IT Industry.  • EDMA – European Diagnostic Manufacturers Association • EUCOMED – European medical device association • MDD – Medical Device Directive (93/42/EEC) • France • APIDIM– Association of US-Based device manufacturers in France. • APPAMED– Syndicat de l’Industrie des Dispositifs de Soins Médicaux, Association of Medical Disposables and Therapies • CEPP – Commission d’Évaluation des Produits et Prestations Committee for Assessment of Devices and Health Technologies, within the HAS. • CEPS ­-- Comité Économique des Produits de Santé, Economic Committee for Health Products, within the French Ministry of Health. • GHS – Groupes Homegenes de Sejour, French DRG-style system of payment groups, under the «T2A » payment system.

27. Global Glossary • France (cont) • HAS – French High Authority on Health, responsible for health technology assessment. • SNITEM– Syndicat National de l'Industrie des TechnologiesMédicales, French Medical Devices and Equipment Association • DRG - Diagnosis Related Groups • Germany • Aktion Meditech – joint public relations campaign by BVMed, AdvaMed and interested member companies • BVMed – German medical technology association • GOG – Government of Germany • IQWiG - Institute for Quality and Efficiency in Healthcare (IQWiG) – • JFC - Joint Federal Committee (Bundesausschuss Krankenhaus also called G-BA) - The G-BA performs the political and economical appraisals. • SHI – Statutory Health Insurance • India • DCG(I) – Drug Controller Government (India) – regulatory agency • GOI- Government of India

28. Global Glossary • Italy • Assobiomedica – Italian association for medical devices • CUD – technical body of the MOH with the function to analyze the minimum and maximum unit prices for medical devices. • DEHP – Bis (2-Ethylhexyl) Phthalate • GOI – Government of Italy • MOEF – Ministry of Economy and Finance • MOH – Ministry of Health • NHS – National Health System • REACH - is a new European Community Regulation on chemicals and their safe use (EC 1907/2006). It deals with the Registration, Evaluation, Authorisation and Restriction of Chemical substances. • SVHC – Substance of Very High Concern