Update on the New NEW EUROPE CE Marking Rules in Europe · PDF fileCE Marking Rules in Europe May 3, 2016 TÜV SÜD Product Service NEW EUROPE. Agenda ... 5 ISO 13485:2016. Guidance

Update on the New

CE Marking Rules in Europe

May 3, 2016

TÜV SÜD Product Service

NEW EUROPE

Agenda

1 Overview

2 Medical Device Regulation (MDR)

3In Vitro Diagnostic Medical Device

Regulation (IVDR)

03/05/2016TÜV SÜD Product Service

4 Update

5 ISO 13485:2016

What is happening in Europe?

TÜV SÜD Product Service Slide 3

New Medical Device

Regulation

New In-vitro DiagnosticRegulation

New MEDDEV GuidanceDocument

New ISO 13485

Standard

DISCLAIMER


DISCLAIMERThe negotiations on the MDR and IVDR are not finished, yet. EVERYTHING may change. As the communication by all three

parties at this time is very limited, or even non-existent, the information available at this time is limited too.

Commission

Council Parliament

Agenda

1 Overview



Regulation (IVDR)


4 Status Update

5 ISO 13485:2016

The EU’s New Medical Device Regulation (MDR)


2008 EU Commission launches consultation

on medical device framework

2012

2014 Q2

2015 Q3

2015 Q4

2016 (est.)

EU Parliament adopts position on

Medical Device Regulation

EU Council adopts position on

proposed Regulation

Trilogue between Commission,

Parliament and Council commences

Expected publication of final Medical

Device Regulation

Expected end of three-year transition

period2019 (est.)

EU Commission publishes proposal

for new Medical Device Regulation

Where are we headed?


More streamlined regulation but more rigorous and consistent oversight of all medical devices.

A reasonable increase in the number and type of products requiring pre-market review and approval by Notified Bodies.

A significant investment of money, time and resources to conduct required investigations and studies and to maintain required post-market documentation, i.e. annual safety and performance report.

Qualified persons - Qualifications of responsible persons will be subject to Notified Body review to assure requisite knowledge and skill.

Eudamed (the European Databank on Medical Devices) will be significantly expanded to provide efficient access to accurate device information.



Device manufacturers will also be subject to product sample

checks and product testing to reduce risks from unsafe devices.

Common Specifications are to be taken into account by

manufacturers and shall exist beside to Harmonized Standards

to define State of the Art.

Existing documentation must be carefully reviewed and updated or amended as necessary to meet

content requirements.

Scrutiny - Involvement of Competent Authorities, more devices requiring certification, combined with fewer qualified

Notified Bodies, will likely result in elongation of certification process.

Manufacturers with currently approved devices will have three years to demonstrate compliance with the MDR’s new requirements.


New Medical Device Regulation Proposal

Consultations of Pharmaceuticals

• EMA for biotech, recombinant, etc.

• Member States for any others

• 210 days after receipt of valid documentation to provide a scientific opinion

• No way to overrule negative opinion

• 60 days for any change relating to the pharmaceutical part

Consultations of Human tissue/cells

• Consultation with human tissues and cells competent authority

• 120 days after receipt of valid documentation to provide a scientific opinion

• No way to overrule negative opinion

• 60 days for any change relating to the pharmaceutical part

Animal tissue/cells, TSE susceptible (EC 722/2012)

• Consultation as per current TSE Regulation (EDQM 4 weeks, no EDQM 12 weeks)

Consultations of absorbable as per intended purpose

• EMA or Member States drug authority

• 150 days to provide a scientific opinion

General Obligations of the Manufacturer


• establish, execute, maintain and document a system for risk management as described in Section 1a in Annex I.

• conduct a clinical evaluation in accordance with the requirements set out in Article 49 and Annex XIII, including post-market clinical follow-up.

• draw up and keep up to date the technical documentation … include the elements set out in Annex II and IIa, etc.

Manufacturers shall



• A manufacturer … outside the Union shall … ensure that theauthorized representative has the necessary documentationpermanently available.

• Article 9 (3): EU Representative keeps a copy of

• Technical documentation

• EU Declaration of Conformity

• Relevant certificates including any amendments and supplements

EU Representative



Single Authorized Representative

Designation is valid for all

devices in the same generic

device group

Authorized Representative legally responsible for

defective devices

Permanently available regulatory

compliance person

Importer Distributor

COMPLIANCE

Scrutiny Procedure

Suggestion of the EU Council of the European Union is currently under discussion


Manufacturer

SubmissionNB

Notification to the authorities

Art 42(2a)

Competent authority or Commission

may apply appropriate measures

Expert Panel*1. Summary of safety and

performance

2. NB Assessment Report

3. Instructions for Use

4. Expert Panel Decision

5. Justification of NB in

case of divergent views

*For Class III Devices and Implantable Class IIb Devices

EUDAMED

Automatically

Monitoring and assessment of NB

Review NB Assessment

Changes to designations and notifications

Challenge to the competence of NB

Evaluation regarding devices suspected topresenting an unacceptable risk or non-compliance

60

Days

Fees to be paid by the manufacturer. Reduced Fees for SMEs.

Scrutiny Procedure


In the case of implantable devices and devices falling within class III, clinicalinvestigations shall be performed except if the device has been designed bymodifications of a device already marketed by the same manufacturer if themodifications have been scientifically demonstrated by the manufacturer and acceptedby the Notified Body as being equivalent.

In this case the Notified Body shall check that the PMCF plan is appropriate and includes post market studies to demonstrate the safety and performance of the device.

*Clear contract between different device manufacturer

PMCF Requirements


A PMCF Study

To be performed according to a PMCF Plan with the aim of:

• confirming the safety and performance of the device throughout its expected lifetime

• identifying previously unknown side-effects and monitoring the identified side effects/contra-indications

• identifying and analyzing emergent risks on the basis of factual evidence

• assuring the continued acceptability of the benefit/risk ratio

identifying possible systematic misuse or off-label use of the device

Summary update


For devices classified as class III and implantable devices, the summary of safety and clinical

performance referred to in Article 26(1) shall be updated at least annually with these data.

Agenda

1 Overview



Regulation (IVDR)


4 Update

5 ISO 13485:2016

The EU’s New In Vitro Diagnostic Medical Device Regulation

(IVDR)

TÜV SÜD Slide 183-May-16

2010

2012

2014 Q2

2015 Q3

2015 Q4

2016 (est.)

2021 (est.)

EU Commission launches consultation

on revision of IVD Directive

EU Commission publishes proposal for

In Vitro Diagnostic Device Regulation

EU Parliament adopts position on In

Vitro Diagnostic Device Regulation

EU Council adopts position on

proposed Regulation

Trilogue between Commission,

Parliament and Council commences

Expected publication of final In Vitro

Diagnostic Device Regulation

Expected end of five-year transition

period



The increased product scope will mean that significantly more device manufacturers will be subject to EU requirements for IVDs.

Except for Class A (low risk) devices, most IVDs (> than 70%) will require some form of pre-market review and approval by Notified Bodies.

A significant investment of time, money and resources to conduct required clinical performance studies and to maintain required post-market documentation.

Qualifications of responsible persons will be subject to Notified Body review to assure requisite knowledge and skill.

Eudamed (the European Databank on Medical Devices) will be significantly expanded to provide efficient access to accurate device information.



Device manufacturers will also be subject to

product sample checks and product testing to

reduce risks from unsafe devices

Involvement of Competent Authorities and Reference Labs, more devices requiring certification, combined

with fewer qualified Notified Bodies, will likely

result in elongation of certification process.

Manufacturers with currently approved

devices are likely to have up to five years to

demonstrate compliance with the IVDR’s new

requirements.

Approval requirements will be uniformly

enforced throughout the EU, providing a level

playing field for all device manufacturers.

Agenda

1 Overview



Regulation (IVDR)


4 Update

5 ISO 13485:2016

Guidance Document as an Immediate Act of the Member States


Revision 4

MEDDEV 2.7.1 rev. 4 – Not Published


Main Updates

Life Cycle Methodology

Documentation requirements including plans/protocols for appraisal, methods, clinical

investigation, PMCF studies, registries and for related

reports

Examples

Detailed information for sources of literature

(MEDLINE, EMBASE, CENTRAL, ICTRP and

clinical Trials.gov)

Literature research: on device in question/equivalent device

and on State of the art)

Detailed principals of clinical evaluation

Reference to relevant Directives in more details and

better structure

GAP analysis on compliance of clinical data generated

outside of EU

Points for sufficient clinical evidence (intended purpose,

clinical performance and benefits, risk

mitigation/avoidance, usability, target population)

Requirements for updating CER

Need and concept of PMCF studies

Risk/benefit profileQualification requirements of evaluator or evaluator team

Scope of clinical evaluation before and after CE marketing

State of the art /Current knowledge concept

Scientific validity Relevance of data Weightening criteria for dataAnalysis to demonstrate the

compliance to Essential Requirements

Release criteria for a CER Structure and content of CER Equivalence (clinical, technical, biological)

Considerations for a clinical investigation and state of the art, compare to alternative

methods

Role of NB

Equivalence Approach per MEDDEV 2.7.1 rev. 4 – Not Published


For assuming equivalence:

• only be based on a single device

• all three characteristics (clinical, technical, biological)

• no clinically significant difference in the performance and safety of the device

• the differences between the device under evaluation and the device presumedto be equivalent need to be identified, fully disclosed, and evaluated

• manufactured via a special treatment (e.g. a surface modification, a processthat modifies material characteristics)

• if measurements are possible, clinically relevant specifications and propertiesshould be measured both in the device under evaluation and the devicepresumed to be equivalent

Clinical, technical and biological characteristics shall be taken into consideration for the demonstration of equivalence

Equivalence Approach per MEDDEV 2.7.1 rev. 4 – Not Published


The notified body should challenge the ability of the manufacturer to

access information that are relevant to the demonstration of equivalence. Demonstration of equivalence might be difficult or impossible in case of

limited access to the technical documentation of the devices.

Current Clinical Investigation Requirements


Risk associated with theinvestigational device shall be

estimated in accordance with EN ISO 14971 prior to conducting a clinical

investigation.

The design of a clinical investigationshall be based on the evaluation ofpre-clinical data and the results of a

clinical evaluation.

The clinical investigation shall bedesigned to evaluate whether the

investigational device is suitable forthe purpose (s) and the population (s)

for which it is intended.

General Rule for Clinical Investigation



Examples of studies that lack scientific validity for demonstration of adequate

Clinical Performance and/or Clinical Safety

Lack of information on elementary aspects

Numbers too small for statistical significance

Improper statistical methods

Lack of adequate controls

Improper collection of mortality and Serious Adverse Events data

Misinterpretation by the authors

Illegal activities

Slowing Access to Innovative Devices


Will innovation be first approved in

Europe? Unmet Medical Needs



Devices for Unmet Medical Needs

Medical conditions that are life threatening, or cause permanent impairment of a body function,

and for which current medical alternatives are insufficient or carry significant Risks.

Exact indication

Explanations why current medical alternatives are

considered to be insufficient or to carry

significant Risks

Explanations of the benefits delivered by

the device

Clear IFU presenting theclinical evidence level

PMCF Plan to further evaluate the Clinical

Performance and Clinical Safety of the

device

Including all patients in PMCF Studies



• when the manufacturer receives new information from post-market surveillance that has the potential to change the current evaluation;

• if no such information is received, at least

• annually if the device carries significant risks and/or is not yet well established;

• every 2 to 5 years if the device is not expected to carry significant risks and is well established;

• Justification

Typically the clinical evaluation is updated:



• the device technology and its application;

• research methodology (including clinical investigation design and biostatistics);

• diagnosis and management of the conditions intended to be managed or diagnosed by the device, knowledge of alternative treatments, treatment standards and technology (e.g. specialist clinical expertise in the relevant medical specialty);

• information management (e.g. scientific background or librarianship qualification; experience with relevant databases such as Embase and Medline)

• regulatory requirements; and

• medical writing (e.g. post-graduate experience in a relevant science or in medicine; training and experience in medical writing, systematic review and clinical data appraisal);

The evaluators should possess knowledge of the following

• A higher degree & 5 years of documented professional experience

• 10 years of documented professional experience (if higher degree is not a prerequisite)

Least experienced in relevant field

Who should perform a clinical evaluation?

Note: There may be circumstances where the level of evaluator expertise may be less or different; this should be documented and duly justified.



Demonstration of conformity based on clinical data is not deemed appropriate

Where demonstration of conformity with Essential Requirements based on clinical data is not deemed

appropriate, adequate justification for any such exclusion has to be given:

The justification must be based on the output of the risk management process.

The device/body interaction, the clinical performances intended and the claims of the manufacturer have to be

specifically considered.

Adequacy of demonstration of conformity with the Essential Requirements based on performance evaluation, bench

testing and pre-clinical evaluation in the absence of clinical data has to be duly substantiated.

A clinical evaluation is still required and the above information and evidenced justification should be

presented in the clinical evaluation report.



The CEAR at a minimum should address the notified body’s assessment of manufacturer’s application relating to the following:

• Device description and product specification

• Intended purpose of the device

• Classification proposed for the device

• Pre-clinical evaluation data presented by the manufacturer

• Risk analysis and risk management and alignment with the CER

• Clinical evaluation process

• Clinical evaluation report authors

• Clinical equivalence assessment – if data from equivalent is used

• Clinical investigation assessments and reports

• Justification if no clinical investigation performance

• Instructions for use, labelling and training

• Justification if no post-market clinical follow up is planned

• Post-market surveillance

• Post-market clinical follow up

• Planned frequency/criteria for updates to the clinical evaluation

• Summary of review

• Conclusion on clinical benefit/risk profile

• Conformance of the device to the relevant Essential Requirements

Agenda

1 Overview



Regulation (IVDR)


4 Status Update

5 ISO 13485:2016

NEW ISO 13485 - History


Work to revise ISO 13485 began in April 2012

Activity related to the current revision of ISO 13485 has accelerated in 2015 with the publication of:

• a second version of the Draft International Standard (DIS)/ISO 13485 in February 2015

• the release of a Final Draft International Standard (FDIS)/ISO 13485 in early October 2015 for balloting by ISO member countries.

• the FDIS 13485 passed within ISO and CEN beginning of 2016. The accepted editorial comments have been incorporated into the editorial proof and submitted to the Central Secretariat for publication.

• the final version of the revised standard was published by the beginning of March 2016

NEW ISO 13485 - Structure


ISO

General

EN for

Medical Devices

ISO for

Medical Devices

ISO 9001:1994 EN 46001:1996

ISO 9001:2000 ISO 13485:2003

ISO 9001:2008

ISO 13485:1996

NEW

ISO 9001 2016

NEW

ISO 13485

Based on HLS

Not based on HLS

NEW ISO 13485


“High Level Structure” (HLS) is considered to be

NOT suitable for the base of regulatory requirements.

Many of TC210 delegates share the feeling that ISO 13485

cannot be based on HLS also in the future.

There are important structural differences between the revised

ISO 13485 and the recently published ISO 9001:2015.

NEW ISO 13485 – Key Changes


All processes that are part of a manufacturer’s

quality management system will now need to

be developed using a risk-based approach.

Processes that are outsourced must also

apply a risk-based thinking approach.

Any software used as part of the quality

system be validated and documented.

Maintenance of a comprehensive technical

file for each manufactured device

that includes a description of the device along with

all relevant specifications and records.



Manufacturers must define the specific skills and experience required for

personnel involved in the maintenance of the quality

management system.

Organizations are required to maintain systems for ensuring that personnel

maintain the requisite knowledge through ongoing training, as well as a

mechanism for assessing the effectiveness of such training.

A new clause regarding contamination control issues for sterile medical

devices is added. This clause includes requirements related to the validation of

processes intended to ensure the integrity and effectiveness of sterile device manufacturing requirements.



New sub-clauses have been added in design and development for

• transfer of design and development outputs to manufacturing

• maintaining a design and development file

• Particular requirements for validation of processes for sterilization and sterile barrier systems



New sub-clauses have been created in monitoring and measurement for

complaint handling and reporting to regulatory authorities.

Strength requirements regarding to corrective and preventative actions.

Strength requirements regarding the investigation and control of nonconforming products related to

Actions in response to nonconforming product detected before delivery

Actions in response to nonconforming product detected after delivery

Rework

Device manufacturers will be expected to formalize their processes for obtaining feedback from both production and post-production activities, and to develop sound methods for incorporating that feedback into

its risk management program.

Stay informed about the expected changes and prepare for

transition


Prepare for the transition

We are closely following the regulation

developments, and will provide updates to

medical devices manufacturers to help

them stay informed about the transition.

For the latest information, visit the following

webpages:

Medical Device Regulation:

www.tuv-sud.com/mdr

In Vitro Diagnostic Device

Regulation:

www.tuv-sud.com/ivdr

Contact us today for one-stop

quality, safety and sustainability

solutions.

• www.tuv-sud.com/medicaldevice

• [email protected]



http://www.tuv-sud.com/mdr

http://www.tuv-sud.com/ivdr

mailto:[email protected]



Save the Date! 2016 MHS Roadshow

Influence of the New Regulations on the CE Marking Approval in Europe

TÜV SÜD Slide 43

City Date

Boston, MA August 2, 2016

Tampa, FL August 3, 2016

Minneapolis, MN August 5, 2016

Toronto, CAN August 8, 2016

Irvine, CA August 10, 2016

San Diego, CA August 11, 2016

These live, 1/2 day events includes technical information,

Q&A and networking with TÜV SÜD experts.

Attendees will learn about the following:

• New medical device regulations and increased requirements

• New essential requirements checklist

• Update of the classification rules

• Up-classification of In-Vitro Diagnostic Devices

• New clinical evaluation requirements

• Increased expectations on the post-market surveillance activities

• Scrutiny process

• Transparency - New EUDAMED offering access to patients,

manufacturers, notified bodies and authorities

• And more...

Early bird registration - $149 (by May 15th)

Full price registration - $249

Visit www.tuv-sud-america.com/MHSRoadshows

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Documents

Update on the New NEW EUROPE CE Marking Rules in Europe · PDF fileCE Marking Rules in Europe May 3, 2016 TÜV SÜD Product Service NEW EUROPE. Agenda ... 5 ISO 13485:2016. Guidance