The document discusses coordinating marketing authorization strategies for the European Union and United States. Some key points include: - Obtaining CE Mark approval in the EU allows access to its 27 member states, while US approval through the FDA is also needed. - Clinical studies can be designed to obtain data that satisfies requirements for both regions to gain approval more efficiently. - Manufacturing documentation like quality system processes and validation reports can be leveraged for both regions' standards. - Human clinical trial designs need sufficient safety and efficacy data, and duration is an important consideration for approval timelines.

1. EXPERTS“EU/US Marketing Authorization:
Coordinating a Two Continent-
Strategy”

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

5. European Union:
o Timelines to Market Authorization
o Actual Placing on the Market

6. European Union:
o Contents CE Mark Technical File
o EU Clinical Data for CE Mark and FDA
Submissions

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

11. EU/US Marketing Authorization:
o Animal Testing – safety considerations
 Device placement
 Acute tissue effects
 Chronic Tissue effects
 Gross pathology and histological response

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

19. “EU/US Marketing Authorization:
Coordinating a Two Continent-Strategy”
o First, understand totality of the requirements
 In Europe
 In the US

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