Entering the North American Market

1. Entering the North American Market The Regulatory Landscape: Device Regulation in Canada Nancy Ruth Director, Medical Devices AdvaMed September 21, 2008

2. Authority from Food and Drug Act Health Canada - regulator Mandate: protect Health of citizens Safe, effective therapeutics - medical devices Pre-market and post-market activities US - CFR Food Drug and Cosmetic Act FDA Protection – safe/effective Pre-market and post-market activities Canadian Medical Devices Regulations (CMDR)

3. Pre-market Activities • Clinical studies: Investigational Testing Authorization (ITA) US: IDE • Medical Device Licences US: 510(k), PMA • Quality system ISO 13485 certified – 3rd party recognized registrars US: QS Reg not certified; FDA inspection • Medical Device Establishment Licence: US: Establishment registration/device listing

4. Post-Market Activities • Medical Device Establishment Licence – annual update/renewal US: FDA Establishment registration/device listing annual update/renewal • Inspection Program for Medical Devices • Health Canada inspectors • Regulatory compliance – not quality systems • Importers, distributors, manufacturers US: FDA inspection cycle • Investigations – noncompliance, safety US: FDA investigations • Post-market data collection, trend analysis • Mandatory problem reports, recalls, global information sharing US: Medical Device Reports, recalls, global information

5. Canadian Medical Devices Regulations: Risk based classification system • Class 1 (least risk) • Class 2 • Class 3 • Class 4 (most risk)

6. Canadian Medical Devices Regulations: Licences • Class 1 • No product licence needed for manufacturer • No ISO 13485 certificate • Medical Device Establishment Licence (MDEL) – product class, medical specialty • Manufacturer can be exempt if import/distribute through MDEL holder • Retailer, healthcare institution, healthcare professional exempt • $2010** annually, attestations ** fee increases expected in 2009

7. Canadian Medical Devices Regulations: Licences • Class 2, 3, 4 • Medical device licence – held by manufacturer* • Apply to Health Canada • Class 2 – minimal safety/effectiveness; fee $200 • Class 3, 4 – premarket review document for safety/effectiveness; fees vary per submitted information -approx $2000 - $10,000 ** • Amendment for significant changes • No substantial equivalence process – stand alone submissions • Private label licence provision • Exact product, intended use as original licence: attestation • Authorization by original licence holder – cross-reference • No ISO 13485 for private labeler ** fee increases expected in 2009

8. Canadian Medical Devices Regulations:Target timelines- medical device licence review • Class 2 – 15 days + administrative • Class 3 – 15 day screen, 60 day review + administrative • Class 4 – 15 day screen, 75 day review + administrative • Questions: screening, review (additional information); new cycles • Reality: some delays – notably IVDD backlog

9. Canadian Medical Devices Regulations: Quality system • Class 2, 3, 4 licence applications • Quality system certificate submitted • CMDCAS (Canadian Medical Device Conformity Assessment System) • Recognized registrar – third party • Audit, issue certificate • 3 year cycle – certification, 2 x annual surveillance, recertification • Manufacturer contracts registrar, pays fees • Global picture

10. Canadian Medical Devices Regulations: Investigational Testing Authorization • Clinical study- submission to Health Canada – safety, likelihood of achieving study purpose • Class 2 fewer requirements • Protocol, description, instructions for use, informed consent; ethics approval/investigator agreement not submitted • Class 3, 4 - higher risk, more information submitted • Pre-clinical, bench testing, risk analysis • Manufacturing information • ISO 13485 not required but quality/safety assurance needed • Ethics board approval/investigator agreement submitted • 30 day review target – authorization letter needed • No fee

11. Canadian Medical Device Regulations: Differences - US to Canada • ISO 13485 – certified quality system – CMDCAS recognized registrar • No substantial equivalence process – more than 510(k) dossier for Class III, IV • Review fees less costly than PMA • Increasing safety documentation scrutiny • FDA guidances may be used by Health Canada • Classification correlation • device/drug/NHP (natural health product) designation correlation – Canada vs US vs ROW • Manufacturer* definition • Labeling, trade mark issues

12. Canadian Medical Devices Regulations:manufacturer definition • “manufacturer” means a person who sells a medical device under their own name, or under a trade-mark, design, trade name or other name or mark owned or controlled by the person, and who is responsible for designing, manufacturing, assembling, processing, labelling, packaging, refurbishing or modifying the device, or for assigning to it a purpose, whether those tasks are performed by that person or on their behalf. (fabricant) • Label, licence, QS certificate ® • Trade-mark ™

13. US to Canada • Already cleared/approved in US? • QS Regulations compliance • Based on ISO 13485:1996 – nothing contradictory • CMDCAS gap – add quality manual, CMDR compliance references • Procedures- recall, mandatory problem reporting, classification, labeling • Recognized registrar – SCC, Health Canada • Audit – certificate • CMDR compliant labeling • Licence application – Class 2,3,4 • Class 1 manufacturer – MDEL (can be exempt – import/distribute MDEL holder) • Importer – MDEL

14. EU to Canada • US companies already selling to EU – product already CE marked for EU? • Canada and EU are similar – QS, classification • ISO 13485:2003 standard • Additional specific requirements: • CMDCAS – adds CMDR (Canadian Medical Devices Regulations) references, recall, mandatory problem reporting, classification, labeling, etc • Registrar recognized by SCC +Health Canada • Certificate – SCC logo, CMDCAS statement • CMDR compliant labeling

15. Canadian Medical Devices Regulations: Importation to Canada • Medical Device Establishment Licence – entity who imports for “sale” • Money or not – samples • Exceptions: importer of devices for Investigational Testing Authorization, Special Access/Custom Made, retailer, healthcare professional/institution • Attestations • Documented procedures • Complaints, distribution records, mandatory problem reports, recall • Shipping/handling, corrective action, installation, servicing – as applicable • Record keeping, classification, compliant labels • Domestic distributors • No ISO 13485 certificate for MDEL

16. Comparison: US, Canada, EU

19. Nancy Ruthnruth@canreginc.com 905-689-39801-866-722-6734