Evolving Medical Device Regulation: US and EU Markets

1. Evolving Medical
Device Regulation:
US and EU Markets
Orna Oz, PhD
BioMedical Strategy (2004) Ltd
Clinical & Regulatory Affairs Group
September 2011

2. Medical Product
Technological
Solution
Market
Medical Need Analysis
Regulatory
R l t
Patentability Scientific
Evidence &
Reimbursement
Funding
September 2011

3. Main Target Markets
g
EU USA
September 2011

4. Medical Device
Definition
D fi i i
• an instrument apparatus … implant in
instrument, apparatus, implant,
vitro reagent, or other similar or related
article,
article including a component part or
part,
accessory
• Used for the diagnosis treatment or prevention of
diagnosis,
disease or condition
and that
• Affects the structure or function of the body
• Does not achieve its function through chemical
action
• Is not metabolized to achieve effect
September 2011

5. Medical Device
Examples
E l
September 2011

6. US Market
Food D
F d & Drug Ad i i t ti
Administration
FDA/CDRH
Ensuring that medical
g
devices are “reasonably”
safe and effective
September 2011

7. Food & Drug Administration
September 2011

8. Product Life Cycle
Premarket Phase
Regulatory Strategy
Pre IDE
Quality Assurance
September 2011

9. Regulatory Strategy
• Intended use & Indications for use (Claim)
• Regulatory Classification
• Proposed pre-clinical Testing
• Clinical Strategy (pre and post market)
•Re-assess intended use and/or indications for use
•Re-assess technological (engineering) approach and R&D plan
•Re-assess business plan – designated product, timelines and
budget
Alternative approaches
September 2011

10. Regulatory Strategy
g y gy
Proof of Concept
US EU
Regulatory Pathway Finalize discussion with Notified
gy
and Clinical Strategy body for Strategy
Pre-
IDE
Verification &
Quality System
Q
Validation Plan
Poolability
Clinical Study
(OUS)
IDE Clinical Study
(US and OUS)
IDE
CE Mark
510(k) Clearance/PMA
Approval
September 2011

11. Regulatory Implications of Claim
SPECIFICITY LEVEL
1. Identification of function Tool Claim
2. Identification of tissue type
an organ system or
(higher clinical
Identification of a specific evidence))
organ
3. Identification of a particular
disease or target population
4. Identification of an effect on
clinical outcome
Clinical Claim
September 2011

12. Regulatory Implications of Claim
SPECIFICITY LEVEL
Tool vs. Clinical – Cardiac Pacing Devices
Tool:
The Frontier Biventricular Cardiac Pacing System is
indicated for maintaining synchrony of the left and
right ventricles in patients who…….
Clinical:
Cli i l
The InSync model 8040 pulse generator is indicated for
the reduction of the symptoms of moderate to severe
heart failure (NYHA Functional III or IV) in those
patients who…….
September 2011

13. Claim / Intended Use
GENERAL VS. SPECIFIC INTENDED USE
The claim(s) for a device can be general or specific.
When deciding the claims for the device it is
important t consider not only th marketing goals
i t t to id t l the k ti l
but also the regulatory process.
Examples of General vs. Specific Use:
Skin resurfacing vs. Wrinkle removal
vs
Evaluation of soft tissue vs. Aid in differentiation of
benign from malignant breast lesions
g g
Cut/coagulate soft tissue vs. Photorefractive
keratectomy (PRK) for myopia
September 2011

14. Claim / Intended Use
GENERAL VS. SPECIFIC INTENDED USE
September 2011

15. Classification
Determination of Ri k
D t i ti f Risk
User/Pt g
Mitigation
Environment RISK Generic
type
Circumstances Claim
September 2011

16. Classification
Medical devices are divided into three regulatory classes based on the risk
and level of control necessary to assure their safety and
effectiveness.
ff ti
Risk Level
•Exempt – Class I & II (SE) Low
De Novo (NSE)
•510(k) – Class I, II (SE)
•PMA – Class III HDE High
September 2011

17. Regulatory Routes
510(k) vs. PMA
510(k) devices must only demonstrate that
there are as safe and as effective as similar
h f d ff i i il
device/s (predicates) already marketed SE
determination Challenging the IP
portfolio
PMA devices must demonstrate, on their
own merit, safety and effectiveness
through valid scientific evidence
Regulation poses less risks to IP
portfolio
tf li
September 2011

18. Clinical Arena
SR vs. NSR Devices
For the purpose of clinical investigation
Significant Risk ( ) – presents a p
g (SR) p potential for serious
risk to the health safety, or welfare of a subject…
Is for a use of substantial importance in diagnosing, curing,
mitigating, or treating disease……
Non SR (NSR) – do not pose a significant risk to the
human subjects.
• SR devices undergo FDA approval (IDE) prior to
initiating clinical investigations in the US
• Relevant to 510(k) and PMA classified devices
September 2011

19. CDRH’s Risk Based Paradigm
g
Class I
Class II
Class III
September 2011

20. 510(k)
SE Determination
A device is substantially equivalent if, in comparison
to a legally marketed device it:
has the same intended use; AND
has the same technological characteristics as the legally
marketed device,
OR
has different technological characteristics, and
submitted information does not raise new questions of
safety and effectiveness, and it demonstrates that the
device is as safe and as effective as the legally marketed
device.
d i
September 2011

21. 510(k)
SE D t
Determination
i ti
Ref: 2010 RAPS Annual Conference, Christy Foreman, Acting Director, Office of Device Evaluation, FDA
September 2011

22. 510(k)
SE D t
Determination
i ti
Ref: 2010 RAPS Annual Conference, Christy Foreman, Acting Director, Office of Device Evaluation, FDA
September 2011

23. 510(k)
SE D
Determination
i i
Ref: 2010 RAPS Annual Conference, Christy Foreman, Acting Director, Office of Device Evaluation, FDA
September 2011

24. 510(k)
SE D t
Determination
i ti
Ref: 2010 RAPS Annual Conference, Christy Foreman, Acting Director, Office of Device Evaluation, FDA
September 2011

25. Evaluation of the 510(k) Program
( ) g
• 2009: The FDA turned to the IOM to review the 510(k)
process and recommend on action it
d d ti items
• 2011: The IOM most critical comments:
• Th current 510(k) process i fl
The (k) is flawed b
d based on i legislative
d its l i l i
foundation.
• Rather than continuing to modify the 35-year-old 510(k) process,
the IOM concludes that the FDA’s finite resources would be better
FDA s
invested in developing an integrated premarket and postmarket
regulatory framework that provides a reasonable assurance of
safety and effectiveness throughout the device life cycle.
•Jeffrey Sh
J ff Shuren, M D di
M.D., director of the CDRH “
f h CDRH: “…..FDA b li
FDA believes that
h
the 510(k) process should not be eliminated but we are open to
additional proposals and approaches for continued improvement
of our device review programs…….. Any major modifications made
to the agency’s premarket review programs should be based on
sound science and through thoughtful and transparent
discussion….”
September 2011

26. Device Approval in Europe
CE M ki
Marking
September 2011

27. Relevant Authorities
• Member State of the European Union is any one of the 27
sovereign states that have acceded to the European Union
(EU)
• Competent Authority has the authority to act on behalf of
the government of the Member State to ensure that the
requirements of the Medical Device Directives are transposed
into National Law and are applied
• The Notified Body (NB) is a private, commercial testing
laboratory or certification organization approved by the
y g pp y
Competent Authority in the Member State in which they
have their head-office to carry out some or all of the
Conformity Assessment procedures in the medical device
directives.
September 2011

28. EC Directives
• Medical Devices are regulated by the EC
Directives:
– the Active Implantable Medical Device (AIMD) Directive -
90/385/EEC
– the Medical Device Directive (MDD) 93/42/EEC
– the In Vitro Diagnostic Device Directive (IVD) - 98/79/EC.
h I Vi Di i D i Di i / /EC
– AIMD and MDD are now governed b the Amended Directive
2007/47/EC
• Medical devices may be classified (risk based) as
Class I, Class IIa, IIb and III
• MEDDEV guidance documents
September 2011

29. Assessment Route
• Within the scope of which Directive?
• Classification (The classification rules are based
on different criteria such as the duration of contact
with the patient, the degree of invasiveness and the
part of the body affected by the use of the device).
• Conformity Assessment Route (design and
manufacturing inspections, manufacturing ONLY,
etc.)
t )
• Technical File (Contains all the relevant
information to demonstrate that the product meets
the Essential Requirements of the Directive)
September 2011

30. Meeting the Regulatory
Authorities
September 2011

31. Pre Ruling
FDA
• Pre IDE
– Regulatory strategy: regulatory classification,
test plan (
p (bench test methodologies animal
g
studies), clinical strategy
– Prior to expanding clinical trials from feasibility
to pivotal phase
Notified Body (NB)
– Introductory meeting followed by discussions,
and pre agreement on proposed regulatory plan
agreement,
(mainly testing, animal data, clinical
evaluation)
September 2011

32. Clinical Evidence
September 2011

33. The Key to Market Penetration
y
A breakthrough technology is great but does not
ensure
ens re market s ccess
success
Regulatory approvals are meaningful milestones
•In creating value for strategic agreements
and funding
•In entrance to the market
Clinical evidence (data) is the leading force
to successful market penetration and
positioning
September 2011

34. Clinical Strategy
Need for premarket clinical data?
US (FDA):
• Yes - for a PMA route
• No and Yes – for a 510(k) route
EU:
• Yes – Clinical evaluation (MEDDEV 2.7.1)
(1) Clinical data (study/ies, experience) OR
(2) Controlled systematic literature review of data reported
on equivalent devices OR
i l d i
(3) a combination of (1) and (2)
September 2011

35. Clinical Strategy
MEDDEV 2 7 1
2.7.1
Stage 1* Stage 2
Identify clinical data from Appraisal of individual data sets
• Suitability
• Literature searching &/or
• Clinical experience &/or • Contribution of performance
• Clinical investigation and safety
Generate new or additional
clinical data
N
O
Is clinical evidence
Stage 3
sufficient to be
able to declare Analysis of relevant data
conformity with • Strength of overall evidence
relevant ERs ? • Conclusions about performance
and safety
Y
E
S
Produce clinical evaluation
report
September 2011

36. Clinical Strategy
gy
Post-market
Post market
.
.
.
Study # 3
Study #2
FIM
Investigational/pre-market
September 2011

37. Hierarchy of Medical
Scientific Evidence
S i tifi E id
Randomized
Controlled
Trial
T i l
Observational Trial
Case-control
Case control
Cohort
Descriptive study
p y
Physiologic study Case
series Expert opinion
Ref: 2010 ICI Meeting, Andrew Farb MD Interventional Cardiology Devices Branch, Office of Device Evaluation
Meeting Farb, MD, Branch
September 2011

38. September 2011

39. Some Common Pitfalls
• Bad study design
• Inappropriate selection of sites and/or investigators
• Incomplete and/or inappropriate study management
tools (procedures, logs CRFs…)
• Using under-qualified clinical research personnel
( p
(sponsor and/or site)
)
• Poor compliance with GCP– not only necessary for
regulatory reasons b also to reduce the company’s
l but l d h ’
risk from potential adverse publicity and lawsuits
September 2011

40. Site Selection
IP
Laws of
Country
Costs
Scientific
Publications
Location /
Market
Availability
Personnel &
Facilities Regulatory
Expected subjects eligibility
subjects-
September 2011

41. Investigator Selection
Opinion Leader Availability
September 2011

42. In Summary
C
Clinical & Regulatory Affairs is
ca g ato y a s s
about claiming and branding
It is the umbrella that covers the Company
act v t es o early development through
activities from ea y deve op e t t oug
market approval and up to post-marketing
ac v es expediting market pe e a o
activities in e pe g a e penetration
Strategic planning is the key role for
g p g y
a least burdensome and valuable
marketing route
September 2011

43. Thank You!!!
Moshe Aviv Tower, 34th, Floor
7 Jabotinsky Street, Ramat Gan
E-mail: biomedical@ebms.co.il
Tel: 03-6123281
September 2011