New European Medical Device Regulations – major changes that will affect all devices Rene van de Zande EMERGO | President & CEO +1 512 327 9997 rvz@emergogroup.com March 31, 2016

New European Medical Device Legislation – Two Drafts: MDR (12040/15) and IVDR (12042/15) Trigger: PIP scandal in 2010 Post-market safety issues Weak oversight of Notified Bodies Lack of market surveillance by Competent Authorities Lack of transparency and traceability Access to external expertise Management of the EU regulatory system

Important proposed changes General management of medical devices in Europe (Medical Device Coordination Group) Pre-market Approval? New or changed definitions – up-classification, non-medical devices Traceability and registration of devices Central database for devices Introduction of UDI Introduction of economic operators Introduction of a Qualified Person More defined role of Notified Bodies (unannounced visits) Extra requirements for clinical evaluations / clinical investigations Post-market surveillance and vigilance procedure much more detailed

Traceability of medical devices Traceability, registration and publication of information concerning medical devices placed on the European market Central database for devices – EUDAMED A summary of safety and clinical performance statement made publicly available for Class III and implantable devices (art. 26) A periodic safety report must be updated annually for every device or group of devices during the life time of the device (art. 60) Accessible by Competent Authorities, Notified Bodies…and by manufacturers, health care professionals, end users and the general public (?) “Appropriate” level of traceability - responsibilities for each in the supply chain

Unique Device Identification - UDI EU COMM Recommendation 2013/172/EU Device identifier placed on the label by manufacturer Stored electronically by economic operators and health institutions EU COM and member states shall operate the system Considerable International activity (IMDRF) United States currently ahead of EU

Qualified Person Qualifications: expert knowledge in the field of in vitro diagnostic or medical devices Three years of professional experience in regulatory affairs or in QMS relating to medical devices or IVD’s Responsible for ensuring: that the conformity of the devices is appropriately assessed Technical documentation and the declaration of conformity are drawn up and kept up-to-date Vigilance requirements have been fulfilled Authorized representatives also required to have person responsible for regulatory compliance

European Authorized Representative Article 9.(4a) provides that where the manufacturer is not based in an EU Member State, the authorized representative “shall be legally liable for defective devices…” Possibly in conflict with other European legislation including the Product Liability Directive Arguments could be made that this could lower patient protection

Already here… Unannounced audits More attention by Notified Bodies into PMS Faster communication between competent authorities in case of vigilance cases or suspected non-compliances More pressure on Notified Bodies to take an active role in preventing non-compliant devices to be placed on the market

Increased scrutiny of and by Notified Bodies EU COMM Implementing Regulation (920/2013) designation supervision Notified Bodies Expect that over half of the current 70 NBs will not be re- notified or may not be notified for the same scope Selection of NBs: Expertise and Competence, Size, Signed Code of Conduct, Which Member State notified the entity, Availability

Unannounced Notified Body audits EU COMM Recommendation for notified bodies’ unannounced visits (2013/473/EU) Be ready for unannounced inspections…

Unannounced NB audits Minimum every 3 years (more frequently for high-risk) Verify that manufacturing in line with documentation Audit at least two critical process: Design control, purchasing, incoming materials, assembling, sterilization, packaging product QC Design Examination/Type Examination sample several products at end of line or warehouse Test in-house or in external labs Sampling and test criteria determined in advance If impossible to take samples from market, where needed supported by competent authority Compare with existing technical documentation, test protocols and results

How to handle unannounced audits SOP for unannounced notified body audit Train staff about unannounced notified body audits Familiar with notified body contract and agreement about critical subcontractors and crucial suppliers Keep notified body informed on production schedule Review contracts with critical subcontractors and crucial suppliers Unannounced audit of critical subcontractors and crucial suppliers

IVDR Risk-based classification system for IVDs based on GHTF recommendations Greater requirements on IVDs that are now self-certified Transition period of 5 years is currently considered, so manufacturers should have time to adjust to changes

New classification for IVDs

Majority of IVDs will require NB intervention Future IVD Regulation IVDD 98/79/EC Require notified body Do not require notified body 80-90% Require notified body Do not require notified body

MDR and IVDR - timelines October 2012 Commission proposal April 2014 Parliament proposal June 2014 Commission position June 2015 Council general approach September 2015 Council draft Next step: negotiation between Council and Parliament (and Commission) “trilogues” Currently, still in First Reading Dutch Minister of Health (January –June 2016), wants to have final version for second reading by June 2016

Main impact of this future legislation Innovative, high risk devices delayed market entry Cost increase industry (MDCG review, unannounced visits, traceability system review, UDI, implant card) Highly qualified staff required for manufacturer, notified body (and AR) NB assessment team: At least one expert in technology Documentation, review technical file, Summary of Safety and Clinical Performance, Essential Requirements text change for General Prescription for Safety and Efficiency

Finding and Evaluating Medical Device Distributors in Europe Don’t forget… Europe has a harmonized approval process but it is not a unified market for business Vastly different cultures, 24 primary languages 28 member states - 19 use the Euro Norway, Iceland, Liechtenstein, and Switzerland members of the EEA 500+ million people! Regulations should not stop you to market your devices in Europe! Europe is a very attractive market, but also very challenging. U.S. products are well respected and innovative products are in high demand. The exchange rate is also in favor of U.S. manufacturers. With almost 500 million people, it is 50% larger than the United States and there are almost twice as many people over age 65 in Europe as in the U.S. Map: Dark blue - 15 original EU countries Yellow - central European countries that joined in 2004, with Poland, Hungary, and Czech Republic as the largest markets Light blue – Romania and Bulgaria joined in 2007; Turkey has applied Note: all of Europe is less than half the size of the USA

Questions? Daryl Wisdahl Rene van de Zande VANCOUVER AREA 15957 84th Ave Suite 205 Surrey, BC, V4N 0W7 Canada +1 604 909 1265 TORONTO AREA 10 Four Seasons Place, Suite 1000 Toronto, ON, M9B 6H7 Canada +1 888 254 3160 Daryl Wisdahl Managing Director, Canada dw@emergogroup.com Rene van de Zande President and CEO rvz@emergogroup.com Global Medical Device Consulting