Mike Winegar, Vice President of Regulatory Affairs for Medpace Medical Device presented at the Medtech Investing conference in May 2012. His session was titled: Obtaining Regulatory Approvals for Medical Devices in a Global Market. Here is a brief outline of his talk. For the emerging or start-up medical device company, corporate objectives and budgets often revolve around clinical trials. Very often, the success or failure of the company mirrors the success or failure of those early clinical trials. In this session, Mike Winegar will be discussing: • How the strategic design, geography, and execution of early-stage clinical trials can have a tremendous impact - positive or negative - on future product and company success • Designing a trial to meet financing, regulatory, and/or marketing objectives • The advantages and pitfalls of various global medical device clinical trial scenarios

1. FOCUSED. TRUSTED. GLOBAL.
Obtaining Clinical/Regulatory Approvals
for Medical Devices in a Global Market
Michael Winegar
Vice President of Regulatory Affairs
Medpace Medical Device

2. medical device EXPERTS
Global Footprint
 North America  Europe
• HQ Cincinnati, US• Munich, Germany
• Minneapolis, US • Rotterdam, Netherlands
 South America • Leuven, Belgium
• São Paulo, Brazil • London, UK
• Mexico City, Mexico • Stirling, UK
• Basel, Switzerland
 Asia/Pacific
• Prague, Czech Republic
• Mumbai , India
• Warsaw, Poland
• Beijing, China
• Milan, Italy
• Hong Kong
• St. Petersburg, Russia Legend
• Melbourne, Australia
• Lyon, France
 Rest of World Countries where Medpace has operations
• Tel Aviv, Israel
• Johannesburg, S. Africa Medpace key offices
© 2012 Medpace - Confidential and Proprietary

3. medical device EXPERTS
Clinical/Regulatory Phases
o First-In-Man
 Small number of subjects (5-10)
 Finalize design, use
o Safety
 Larger number of subjects (30-100)
 Prove safety, provide indications of efficacy
o Pivotal
 Statistically relevant number of subjects (200-
500+)
 Normally randomized
 Prove efficacy and confirm safety
© 2012 Medpace - Confidential and Proprietary

4. medical device EXPERTS
Considerations
Fast
Pick 2…
Good Cheap
© 2012 Medpace - Confidential and Proprietary

5. medical device EXPERTS
Country Selection
© 2012 Medpace - Confidential and Proprietary

6. medical device EXPERTS
Country Selection
# of Trials by Country
70000
60000
50000
40000
30000
20000
10000 # of Trials
0
Australia
Argentina
India
Mexico
China
Italy
Brazil
Canada
France
Germany
US
UK
Source: ClinicalTrials.gov
© 2012 Medpace - Confidential and Proprietary

7. medical device EXPERTS
Country Selection
© 2012 Medpace - Confidential and Proprietary

8. medical device EXPERTS
Country Selection
Cost of Clinical Trials Relative to the
Country United States
United States 1.00
Australia 0.67
Argentina 0.65
Germany 0.50
Brazil 0.50
China 0.50
Russia 0.41
Poland 0.39
India 0.36
Source: The National Center for Biotechnology Information
© 2012 Medpace - Confidential and Proprietary

9. medical device EXPERTS
United States
o Pros
 Quality of research/researchers
 Accessibility
 Data credibility
o Cons
 Costs
 FDA
• Pre-IDE/IDE Process
• Current conservatism related to IDEs
 Visibility
© 2012 Medpace - Confidential and Proprietary

10. medical device EXPERTS
United States
According to the FDA Office of
Device Evaluation (ODE), in fiscal
76% Fiscal 2000
year 2000, 76% of IDEs submitted
would either get a full or
conditional approval on the
56% Fiscal 2009 original submission. In 2009, that
number dropped to 56%. And
although official numbers aren’t
out yet, various industry insiders
state that current IDEs that get
approved either conditionally or
full approval on the first round are
down in the upper 20’s to low
30’s.
© 2012 Medpace - Confidential and Proprietary

11. medical device EXPERTS
United States
Source: FDA
*Times may not add due to rounding
**2009, 2010 some cohorts still open as of July 5, 2011; data
may change
© 2012 Medpace - Confidential and Proprietary

12. medical device EXPERTS
United States
Source: FDA
© 2012 Medpace - Confidential and Proprietary

13. medical device EXPERTS
United States
Source: FDA
© 2012 Medpace - Confidential and Proprietary

14. medical device EXPERTS
Europe
o Pros
 Quality of research/researchers
 Data credibility
 Ease of startup
o Cons
 Costs
 Varying regulation
• ISO 14155
• MEDDEVs
• Country Regulations
 Varying standards of care
© 2012 Medpace - Confidential and Proprietary

15. medical device EXPERTS
Australia
o Pros
 Quality of research/researchers
 Low regulatory barrier
• CTN System
• Tier I country
 Data credibility
o Cons
 Distance
 Sometimes limited patient population
 Varying standard of care
© 2012 Medpace - Confidential and Proprietary

16. medical device EXPERTS
India
# of Trials
2000
1500
1000
# of Trials
500
0
2007 2009 2013
Source: RNCOS India
© 2012 Medpace - Confidential and Proprietary

17. medical device EXPERTS
India
o Pros
 Costs
 Large population
 Motivated researchers
o Cons
 Data use/credibility
 Regulatory barriers, including US export
• Relatively new regulations
• 801(e) export process for Class III devices
 Varying standards of care
© 2012 Medpace - Confidential and Proprietary

18. medical device EXPERTS
China
Cost in China ($) Cost in United States ($)
750–1000
One-day stay in hospital 40–100
150–300
Magnetic resonance 1500–3500
imaging
Yearly salary for senior
40,000 225,000
oncologist
Typical cost to develop
120 million 1 billion
new drug
Source: MDDI
© 2012 Medpace - Confidential and Proprietary

19. medical device EXPERTS
China
o Pros
 Costs
 Large population
 Motivated researchers
o Cons
 Data use/credibility
 Regulatory barriers, including US export
• In-country testing
• Minimum of 2 sites
• 801(e) export issues for Class III devices
 Varying standards of care
© 2012 Medpace - Confidential and Proprietary

20. medical device EXPERTS
Latin America
Adrian Ebner, M.D.
12 trials in Paraguay
per ClinicalTrials.gov
© 2012 Medpace - Confidential and Proprietary

21. medical device EXPERTS
Latin America
o Pros
 Costs
 Large populations
 Motivated researchers
o Cons
 Data use/credibility
 Regulatory barriers, including US export
• Many countries have no specific device
clinical regulations
• 801(e) export issues for Class III devices
 Varying standards of care
© 2012 Medpace - Confidential and Proprietary

22. medical device EXPERTS
FIM Trial
o Design
 Small, nonrandomized
 Safety focus
o Study Sites
 1-2
 EU, Australia site
o Goals
 Proof of concept
 Final iterations to device design and use
© 2012 Medpace - Confidential and Proprietary

23. medical device EXPERTS
Safety Trial
o Design
 50-100 subjects, non-randomized
o Study Sites
 Primarily EU
o Goals
 CE Mark
 FDA feasibility
• Begin pre-IDE/IDE process
 Initial publications
 Regulatory submissions to additional markets
© 2012 Medpace - Confidential and Proprietary

24. medical device EXPERTS
Pivotal Trial
o Design
 Randomized
 Statistically powered primary endpoints
o Study Sites
 Primarily US
 Additional sites from Safety study
o Outcomes
 FDA approval
 Marketing and reimbursement data
 Regulatory submissions to additional markets
© 2012 Medpace - Confidential and Proprietary

25. medical device EXPERTS
Summary
o Protocol Design
 Stepwise progression
 Data collection based on study size/goals
 Assume device/protocol changes will be made over time
o Country/Site Selection
 Consider real costs
 Country ease of access
 Data use and credibility
o Regulatory Considerations
 Understand site/country timelines and requirements
 Engage FDA early
 Don’t ignore export/import requirements
© 2012 Medpace - Confidential and Proprietary

26. FOCUSED. TRUSTED. GLOBAL.
Thank You!
Mike Winegar
Vice President, Regulatory Affairs
Medpace Medical Device
3787 95th Ave. NE Suite 100
Blaine, MN 55014
Tel: +1.612.234.8491 ○ Cell: +1.763.639.0700 ○ Fax: +1.612.392.0468
E-mail: m.winegar@medpace.com
website: www.medpace.com/device