Changes to International Regulatory Requirements Gail Christie December

Changes to International Regulatory Requirements Gail Christie December 2, 2009

Agenda Brazil Mexico Canada India China Japan European Union Saudi Arabia Turkey 2 | Covidien | December 3, 2009 | Confidential

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 3 | Covidien | December 3, 2009 | Confidential

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 4 | Covidien | December 3, 2009 | Confidential

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 5 | Covidien | December 3, 2009 | Confidential

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 6 | Covidien | December 3, 2009 | Confidential

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 SSA 1 2008) effective February 2009 – Third party manufacture information must be on the label http: //portal. salud. gob. mx/index_eng. html 7 | Covidien | December 3, 2009 | Confidential

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 2010 requirement. http: //portal. salud. gob. mx/index_eng. html 8 | Covidien | December 3, 2009 | Confidential

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 9 | Covidien | December 3, 2009 | Confidential

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 10 | Covidien | December 3, 2009 | Confidential

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 11 | Covidien | December 3, 2009 | Confidential

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/ 12 | Covidien | December 3, 2009 | Confidential

China • • State Council Order 276 and SFDA Order 16, draft updates to regulation Adva. Med and Joint Commission on Commerce and Trade (JCCT) met with SFDA on Sept 10, 2009 Highlights from meeting: – China agreed to adopt GS 1 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/ 13 | Covidien | December 3, 2009 | Confidential

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 14 | Covidien | December 3, 2009 | Confidential

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 15 | Covidien | December 3, 2009 | Confidential

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 16 | Covidien | December 3, 2009 | Confidential

Japan (cont) • Future – 3 track submission system by 2011 – Yearly 3 rd 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 17 | Covidien | December 3, 2009 | Confidential

European Union Medical 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/F 3/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 18 | Covidien | December 3, 2009 | Confidential

European Union Medical 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 19 | Covidien | December 3, 2009 | Confidential

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 20 | Covidien | December 3, 2009 | Confidential

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 21 | Covidien | December 3, 2009 | Confidential

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 22 | Covidien | December 3, 2009 | Confidential

The views expressed are those of the author. They do not necessarily reflect the position of Covidien. 23 | Covidien | December 3, 2009 | Confidential

Supplemental Information: Global Glossary 24 | Covidien | December 3, 2009 | Confidential

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 Am. Cham – 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: 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 25 | Covidien | December 3, 2009 | Confidential

Global Glossary Europe Union COCIR – Association of the 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 «T 2 A » payment system. 26 | Covidien | December 3, 2009 | Confidential

Global Glossary France (cont) HAS – French High Authority on Health, responsible for health technology assessment. SNITEM – Syndicat National de l'Industrie des Technologies Médicales, French Medical Devices and Equipment Association DRG Diagnosis Related Groups Germany Aktion Meditech – joint public relations campaign by BVMed, Adva. Med and interested member companies BVMed – German medical technology association GOG – Government of Germany IQWi. G - Institute for Quality and Efficiency in Healthcare (IQWi. G) – 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 27 | Covidien | December 3, 2009 | Confidential

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 28 | Covidien | December 3, 2009 | Confidential