2. The European Union
o 1 continent
o 27 Countries
o 23 Languages
o 4,325,675 km²
o 497,198,740
inhabitants
C
ontinent
3. European Union:
o EU Marketing Access/Authorization
o One Approval – Access to 27 Member States
o What do you need ?
4. European Union:
o CE Mark – Safety + Performance
o ISO 13485 – Quality Standard
o Technical File / Contents
o Notified Body
o Authorized Representative
7. European Union:
o Device Classification – based on indication
o Exit Strategies and Milestones
o CE Mark, Patient Numbers, FU timelines
8. European Union:
o Notified Body Selection / Registered with EU
Commission
o Pre-meeting Notified Bodies
o Determine Fast Track NB reviews
o Determine milestones (CE Mark / Patient FU)
o Literature Review-Equivalence
9. European Union:
o Prototype
o Determine Strategy
o What is available? More important: What is not
available (yet)
o Take into consideration:
Languages
Cultural differences
o Fastest Route to Marketing Authorization
o LIMIT Sites / Indications
Case Study:
10. EU/US Marketing Authorization:
o Define „Two Continent‟ Marketing Strategy
o Testing done in accordance with ISO Standards
o Clinical Protocol to cover “Two Continents” in
line with Notified Body and FDA
o Site Selection/Qualification for FDA-
experienced Sites
12. EU/US Marketing Authorization:
o Coordinating the Strategies: Why?
Save $$
More efficient use of resources
Faster realization of revenue
Avoid redundancy
13. United States:
o Quality System and Manufacturing Information –
Controls and procedures
To ensure consistency in product
To ensure ongoing review of product/system
To ensure management commitment
To ensure investigation of defects and corrective
action
o 21 CFR 820 and ISO 13485
14. United States:
o Manufacturing and QS
Complexity of Manufacturing
• Process requiring validation
Outside testing requirement
Number of design iterations
o Manufacturing documents and validation
reports can be used for US and EU
o ISO 13485 and the QSR are similar, not identical
15. “EU/US Marketing Authorization:
Coordinating a Two Continent-Strategy”
o Human Clinical Data
o First-in-human Clinical Experience
Longest duration follow-up data
o Pivotal Study Results
Demonstrate Safety and Effectiveness or SE
Sufficient sample size for statistical support
16. “EU/US Marketing Authorization:
Coordinating a Two Continent-Strategy”
o Clinical Study Focus: Safety and Efficacy
o Class II Devices and Non-invasive Class III
Single phase is usually adequate
o Class III Devices
Two phase approach often required
• Pilot phase – 20-50 subjects with 6 month
• Pivotal phase – 100-1000 subjects with significant long term
follow-up (multi-year) in a controlled, comparative design
17. “EU/US Marketing Authorization:
Coordinating a Two Continent-Strategy”
o Study Duration = TIME
Study duration is critical path item
• Delays market release and revenue
• Quarterly monitoring
• Data management
Investigators over-estimate their subject volume
18. “EU/US Marketing Authorization:
Coordinating a Two Continent-Strategy”
o Investigator / Sites Payments
In the US, sites and IRBs are commanding more in
payments
Competition for Investigators in studies
Institutions are often a party to the contracts and
charge overhead
o EU experience can often suffice for US feasibility
requirements