Stefan Menzl, Director of International Regulatory Affairs at Abbott Medical Optics, discusses post-market clinical surveillance and follow-up. He outlines the requirements for post-market surveillance under the current Medical Device Directive and proposed new Medical Device Regulation. Key elements of a post-market surveillance plan include vigilance reporting, literature review, registries, and clinical studies. Challenges to meeting requirements include non-harmonized regulations worldwide and ensuring safety data is consistently updated from various sources.

1. Post Market
Clinical Surveillance
View from Industry
2nd Qserve Conference
18-19 November, 2013
Stefan Menzl, PhD
Director, International Regulatory Affairs,
Abbott Medical Optics

2. Content of the Presentation 1/2
• What is Post Market …
– Surveillance?
– Clinical Follow-Up / Surveillance?
• Requirements for Post Market (Clinical) Surveillance
– Current Medical Device Directive
– New Medical Device Regulation
– MEDDEV 2.12-2
– QM-System (ISO13485)
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3. Content of the Presentation 2/2
• Elements of Post Market (Clinical) Surveillance
– PM(C)F Plan
– Vigilance (incl. Trending)
– Literature Review
– Registries
– Studies
• Challenges for Industry to meet Requirements
– Non harmonized requirements worldwide
– The ‚human factor‘
– Language
–…
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4. Post Market (Clinical) Surveillance / Follow-Up
 Post-market follow-up, ... is a continuous
process …and
shall be part of the manufacturer's postmarket surveillance plan
 To this end, the manufacturer shall proactively
collect and evaluate clinical data from the use in
or on humans of a device which is authorized to
bear the CE marking, within its intended purpose
... with the aim of confirming the safety and
performance throughout the expected
lifetime of the device, the continued
acceptability of identified risks and to detect
emerging risks on the basis of factual evidence
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PMCF
definition
Emphasis
on the
proactive
nature of
the program
PMCF plan
mandatory
unless duly
justified

5. MDD
Requirements for Post Market (Clinical) Follow Up
MDD, new Annex X, 1.1c
Requirement to actively update clinical assessment with data from
‘Post Market Surveillance’
ACTION
Required update of risk assessment
and
clinical assessment in defined frequency
Consider PMS data
(incl. Events and Literature)
Requirement to have PMS-Plan for every
Product-family
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6. MDD
Post Market (Clinical) Surveillance / Follow-Up
MDD (93/42/EEC) requires PMS and PMCF
Additional requirement to comply with ‚state of the art‘
Literature-screening as part of PMS, clinical assessment and PMCF
Clinical assessment required for all classes of devices (2007/47/EEC)
ER (6a)
• Safety & Effectiveness
• Beneficial risk/benefit ratio
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7. New Medical Device Regulation
Proposal Post Market Clinical Follow-Up
″ ... PMCF shall be performed pursuant to a
documented method laid down in a PMCF plan ...
″ specify general methods and procedures, such as
gathering of clinical experience gained, feedback from
users, screening of scientific literature and of other
sources of clinical data ...
″ The notified body shall periodically, at least once
every 12 months, carry out appropriate audits and
assessments to make sure that the manufacturer
applies the approved quality management system
and the post-market surveillance plan.”
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8. MEDDEV 2.12-2
Post Market (Clinical) Surveillance / Follow-Up
MEDDEV 2.12-2
Definitions
PMCF study: a study carried out following the CE marking of a
device and intended to answer specific questions relating to
clinical safety or performance (residual risk) of a device when
used in accordance with its approved labeling
PMCF plan: the documented, proactive, organized methods
used to collect clinical data from actual use in humans on a
specific CE marked device (or device group) with the aim of
confirming long term clinical performance and safety, the
acceptability of identified risks, and to detect emerging risks on
the basis of factual evidence
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9. QMS ISO13485
Post Market (Clinical) Surveillance / Follow-Up
Requirements of Quality-management System (Annex II.3)
• Known risks (e.g. from literature or event reporting)
need to be addressed in Risk-Management-Process and
have to be considered in clinical assesssment
• Remaining risks need to be addressed in labeling
• Medical benefit needs to outweigh remaining risk
(risk-benefit ratio)
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10. Elements of Post Market (Clinical) Surveillance / Follow-Up
Post Market Surveillance Plan
Featured prominently
in the proposal of MD
regulations released
on Sept 26
Importance of
Post Market Clinical Follow Up
Importance to apply the
concept throughout the life-cycle
of the device
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11. Elements of Post Market (Clinical) Surveillance / Follow-Up
Post Market Surveillance Plan
• PMCF should be conducted for any device that has used clinical
data from equivalence devices alone as the basis for the clinical
evaluation.
• The plan should ensure that residual risks identified for the
equivalent devices are addressed
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12. Elements of Post Market (Clinical) Surveillance / Follow-Up
Post Market Surveillance Plan
 The data shall be reviewed at regular intervals
 The plan shall define:
– Frequency of review to ensure continuous monitoring of benefit/risk
ratio (including patient quality of life and public health impact)
– By whom
– Trending methodology: identification of trend and need for
preventive/corrective action
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13. Elements of Post Market (Clinical) Surveillance / Follow-Up
Post Market Surveillance Plan- Content
The plan shall define the source of data and the means to
collect those data and shall be proportional to the risk of
device/device family
The plan may include:
– Complaints Handling
– Return Product Analysis
– Vigilance Reports
– Literature Review
– Registry Review
– PMCF
– Regulatory Feedback
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14. Elements of Post Market (Clinical) Surveillance / Follow-Up
PMCF – Vigilance (New Medical Device Regulation)
″ ... European system for the notification and
evaluation of incidents and field safety corrective
actions ...
 Advantage
Existing company system
Low additional cost
 Challenges
Reactive
Issues late in the game
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15. Elements of Post Market (Clinical) Surveillance / Follow-Up
PMCF – Literature Review (New Medical Device Regulation)
″ The process of reading, analyzing, evaluating, and
summarizing scholarly materials about a specific topic.”
 Options
Review relevant sources at regular intervals, e.g. PubMed
Conferences
Journal alerting Services
 Advantage
Relatively cheap
Access to data world wide
 Challenges
Reactive
Data typically limited and heterogeneous
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16. Elements of Post Market (Clinical) Surveillance / Follow-Up
PMCF – Registries (New Medical Device Regulation)
 Options – several
Paper/ EDC forms
Single/ multi center
...
 Advantages
Value for money
Low site threshold
...
 Challenges
No efficacy/ added value data
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17. Elements of Post Market (Clinical) Surveillance / Follow-Up
PMCF – Studies (New Medical Device Regulation)
 Options
Small scale single arm
RCT
 Advantages
Efficacy and/ or added value
RCT is gold standard
 Challenges
Not daily practice
Huge investment
Blinding
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18. Elements of Post Market (Clinical) Surveillance / Follow-Up
PMCF – Studies
When to do a PMCF study
• Presence of residual risk that may impact the benefit/risk ratio
• To examine long term performance and/or safety
• To examine the performance and/or safety of the device in a more
representative population of users and patients
• PMCF study is expected, a justification needs to be given when not
performed, e.g. medium/long term safety is already known from
previous use, other appropriate PMS activities provide sufficient data
to address the risks
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19. Elements of Post Market (Clinical) Surveillance / Follow-Up
PMCF – Studies
Elements of a PMCF study
• PMCF plan:
– Research questions, objectives and related endpoints
– Scientifically sound design with appropriate rationale and statistical
analysis plan
• Implementation of the study according to plan
• Analysis of the data
• Appropriate conclusions
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20. Elements of Post Market (Clinical) Surveillance / Follow-Up
PMCF – Studies
Outcome
• Conclusions to be part of the clinical evidence report
• Depending on the conclusions, an update of the Essential
Requirements checklist and risk assessment may be appropriate
• Changes could result in corrective/preventive actions like
– Labeling changes
– Changes to manufacturing process
– Design changes
– Public health notifications
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21. Post Market Clincal Follow Up
Role of the Notified Body
• The Notified Body will review the PMCF procedures and plans as
part of design review (class III) or tech file review and
– Verify compliance of the plans to Annex X, meddev guidance and
standards
– Evaluate the need for a PMCF plan
– Assess the appropriateness of the PMCF plan
– Assess the justification given for not conducting a specific PMCF
plan
– Verify that data from PMCF plans is used to update the clinical
evaluation
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22. Practically meeting post-market requirements
The Challenge of non-harmonized Requirements
The challenge to meet international Vigilance requirements
• Country specific requirements
• Other challenges
Possible solutions to meet the challenge
• Harmonization
• Company internal processes and systems
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23. Practically meeting post-market requirements
Challenges besides Regulations – the “human factor”
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24. Practically meeting post-market requirements
Other Challenges (than diverse regulation)
• The available information is different from country to country and from
customer to customer
• The language barrier
• Cultural approach to the reporting of complaints
• Availability of technical expertise in every country
• Different classification of products (drug / device) depending on country
regulation
• Responsibility for reporting are different from country to country
(subsidiary or distributor)
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25. Ensuring safety data is consistently up-to-date
Elements in addition to complaint handling and vigilance
• Literature reviews
• Post market clinical follow up, Post market clinical studies
• Customer surveys
• Feedback from technical service
•…
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26. Ensuring safety data is consistently up-to-date
Literature reviews
• Proactive measure for PMS
• Which journals
• Abstracts
• Presentations at conventions
• ‚yellow press‘ (e.g. BSE crisis)
• Define the process !!!
• Responsibility & Frequency
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27. Ensuring safety data is consistently up-to-date
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28. New Medical Device Regulation
PMCF - Conclusion
 PMS under new Medical Device Regulation
More stringent and controlled
 Various Options
Literature Review
Registries
Randomised Controlled Studies
…..
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29. New Medical Device Regulation
Post Market Surveillance – Potential Consequences
 PMS plan itself
 Product Improvements
 Extend, maintain or reduce PMCF/registry
 Product Labeling / IFUs
 Extend, maintain or reduce Product Training / User Training
 Update of Risk Management
 FSCAs
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30. AMO Products covered by the PMS/PMCF program
Vision. For Life.
AMO’s strategy is to deliver advanced life-improving vision technologies for people of all ages

31. Three Integrated Businesses Provide
Vision. For Life.
Eye Care Professionals
Corneal
Refractive
Cataract
Proprietary formulations designed
to protect and lubricate ocular
surfaces
Advanced laser technologies
designed to deliver freedom from
eyeglasses
Leading products for intraocular
procedures that optimize visual
function

32. Abbott Medical Optics
3,700+ employees worldwide
• Direct sales in 29 countries & presence in more than 60 countries
Russia
Sweden
Canada
Ireland
Netherlands
Spain
United States
Japan
China
Mexico
India
Puerto Rico
Africa
Singapore
South
America
3 Mfg/R&D sites
3 Mfg sites
1 Global R&D site
4 Regional hubs
Australia

33. Cataract -- IOL Platforms
• Tecnis® IOL
– Monofocal, aspheric IOL designed to correct spherical
aberration to zero
• Tecnis® Toric IOL
– Toric IOL designed to correct preexisting corneal astigmatism
• Tecnis® Multifocal IOL
– Diffractive, aspheric IOL that provides near, intermediate and
distance vision with exceptionally high spectacle
independence
– Enjoys premium pricing and patient-shared billing in the U.S.;
co-pay in several markets outside U.S.
• Synchrony® Accommodating IOL
– Addresses presbyopia in cataract patients
– Dual optic accommodating IOL designed to allow patients to
see near, intermediate and distance vision
– Approved in Europe; pending FDA approval in U.S.

34. Cataract -- Phaco and Visco Platforms
• Healon® Viscoelastics
– Family of viscoleastics that provides a range
of viscosity to satisfy different surgical needs
• WhiteStar Signature™
Phacoemulsification System
• Ultrasonic device that emulsifies and extracts
a cataractous lens using less heat and
turbulence and FusionTM Fluidics to optimize
outcomes
• Ellips™ handpiece provides longitudinal
combined with transversal motion

35. Refractive Technology Suite
• iFSTM Laser
– Femtosecond laser that focuses pulses of light
below the surface of the cornea to create the flap
before a LASIK procedure is performed
• WaveScan WaveFront System
– Diagnostic device that captures unique
imperfections in each patient’s eyes and creates a
personalized treatment plan
– iDesignTM system is next generation technology
• Star S4 IR Laser System
– Computer-driven excimer laser that corrects
refractive errors by reshaping the cornea
– Performs Advanced CustomVue procedure,
which corrects unique imperfections in each
patient’s eyes and is capable of treating the
industry’s broadest range of refractive conditions

36. Corneal Products
• RevitaLens Ocutec Multipurpose Disinfecting
Solution
– Next-generation multipurpose disinfecting
solution for silicone hydrogel and conventional
soft contact lenses
• Complete Multipurpose Solution
– Convenient, single-bottle solution formulated to
effectively clean and disinfect contact lenses
• Oxysept Ultracare System
– Hydrogen peroxide system that provides
powerful disinfection efficacy for contact lenses
• Blink Tears
– Family of lubricating eye drops designed to
provide relief to dry eye patients

37. Post Market Clinical Follow-UP
“Everything should
be made as simple
as possible, but not
simpler”
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38. Stefan Menzl 2013
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