Post Market Clinical Surveillance, Experience of the Industry by S. Menzl - Abbott Medical Optics (Qserve Conference 2013)

Stefan Menzl, PhD

Director, International Regulatory Affairs,

Abbott Medical Optics

Post Market

Clinical Surveillance

View from Industry

2nd Qserve Conference

18-19 November, 2013

Stefan Menzl 2013 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)

Content of the Presentation 1/2

Stefan Menzl 2013 3

• 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

– …

Content of the Presentation 2/2

Stefan Menzl 2013 4

Post Market (Clinical) Surveillance / Follow-Up

PMCF definition

Emphasis on the proactive nature of the program

Post-market follow-up, ... is a continuous process …and shall be part of the manufacturer's post-

market 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

PMCF plan mandatory unless duly justified

Stefan Menzl 2013 5

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

ACTION

MDD, new Annex X, 1.1c

Requirement to actively update clinical assessment with data from

‘Post Market Surveillance’

MDD Requirements for Post Market (Clinical) Follow Up

Stefan Menzl 2013 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

Stefan Menzl 2013 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.”

Stefan Menzl 2013 8

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

MEDDEV 2.12-2 Post Market (Clinical) Surveillance / Follow-Up

Stefan Menzl 2013 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)

Stefan Menzl 2013 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


• 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




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


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


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


Elements of Post Market (Clinical) Surveillance / Follow-Up PMCF – Literature Review (New Medical Device Regulation)

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

″ The process of reading, analyzing, evaluating, and summarizing scholarly materials about a specific topic.”


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


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


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


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



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



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

Post Market Clincal Follow Up


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


Practically meeting post-market requirements

Challenges besides Regulations – the “human factor”


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)


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

• …



Literature reviews

• Proactive measure for PMS

• Which journals

• Abstracts

• Presentations at conventions

• ‚yellow press‘ (e.g. BSE crisis)

• Define the process !!!

• Responsibility & Frequency




New Medical Device Regulation PMCF - Conclusion

PMS under new Medical Device Regulation

More stringent and controlled

Various Options

Literature Review Registries Randomised Controlled Studies …..


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

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

Three Integrated Businesses Provide Vision. For Life.

Corneal Proprietary formulations designed

to protect and lubricate ocular

surfaces

Refractive Advanced laser technologies

designed to deliver freedom from

eyeglasses

Cataract Leading products for intraocular

procedures that optimize visual

function

Eye Care Professionals

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Abbott Medical Optics 3,700+ employees worldwide

3 Mfg/R&D sites

3 Mfg sites

4 Regional hubs

• Direct sales in 29 countries & presence in more than 60 countries

Puerto Rico Mexico

United States

Canada

Russia

China

Australia

Singapore

India

Spain

Africa

South

America

Ireland

Japan

Sweden

Netherlands

1 Global R&D site

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.

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

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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

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


Post Market Clinical Follow-UP

“Everything should be made as simple as possible, but not simpler”


Post Market Clinical Surveillance, Experience of the Industry by S. Menzl - Abbott Medical Optics (Qserve Conference 2013)

Business

surveillance

practically

medical device

ensuring safety

market surveillance

identified

factual evidence

market requirements