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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
TÜV SÜD Product Service Slide 4
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
2 Medical Device Regulation (MDR)
3In Vitro Diagnostic Medical Device
Regulation (IVDR)
03/05/2016TÜV SÜD Product Service
4 Status Update
5 ISO 13485:2016
The EU’s New Medical Device Regulation (MDR)
TÜV SÜD Product Service Slide 6
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?
TÜV SÜD Product Service Slide 7
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.
Where are we headed?
TÜV SÜD Product Service Slide 8
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.
TÜV SÜD Product Service Slide 9
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
TÜV SÜD Product Service Slide 10
• 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
General Obligations of the Manufacturer
TÜV SÜD Product Service Slide 11
• 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
General Obligations of the Manufacturer
TÜV SÜD Product Service Slide 12
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
TÜV SÜD Product Service Slide 13
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
TÜV SÜD Product Service Slide 14
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
TÜV SÜD Product Service Slide 15
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
TÜV SÜD Product Service Slide 16
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
2 Medical Device Regulation (MDR)
3In Vitro Diagnostic Medical Device
Regulation (IVDR)
03/05/2016TÜV SÜD Product Service
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
Where are we headed?
TÜV SÜD Product Service Slide 19
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.
Where are we headed?
TÜV SÜD Product Service Slide 20
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
2 Medical Device Regulation (MDR)
3In Vitro Diagnostic Medical Device
Regulation (IVDR)
03/05/2016TÜV SÜD Product Service
4 Update
5 ISO 13485:2016
Guidance Document as an Immediate Act of the Member States
TÜV SÜD Product Service Slide 22
Revision 4
MEDDEV 2.7.1 rev. 4 – Not Published
TÜV SÜD Product Service Slide 23
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
TÜV SÜD Product Service Slide 24
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
TÜV SÜD Product Service Slide 25
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
TÜV SÜD Product Service Slide 26
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
MEDDEV 2.7.1 rev. 4 – Not Published
TÜV SÜD Product Service Slide 27
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
TÜV SÜD Product Service Slide 28
Will innovation be first approved in
Europe? Unmet Medical Needs
MEDDEV 2.7.1 rev. 4 – Not Published
TÜV SÜD Product Service Slide 29
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
MEDDEV 2.7.1 rev. 4 – Not Published
TÜV SÜD Product Service Slide 30
• 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:
MEDDEV 2.7.1 rev. 4 – Not Published
TÜV SÜD Product Service Slide 31
• 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.
MEDDEV 2.7.1 rev. 4 – Not Published
TÜV SÜD Product Service Slide 32
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.
MEDDEV 2.7.1 rev. 4 – Not Published
TÜV SÜD Product Service Slide 33
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
2 Medical Device Regulation (MDR)
3In Vitro Diagnostic Medical Device
Regulation (IVDR)
03/05/2016TÜV SÜD Product Service
4 Status Update
5 ISO 13485:2016
NEW ISO 13485 - History
TÜV SÜD Product Service Slide 35
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
TÜV SÜD Product Service Slide 36
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
TÜV SÜD Product Service Slide 37
“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
TÜV SÜD Product Service Slide 38
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.
NEW ISO 13485 – Key Changes
TÜV SÜD Product Service Slide 39
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 ISO 13485 – Key Changes
TÜV SÜD Product Service Slide 40
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 ISO 13485 – Key Changes
TÜV SÜD Product Service Slide 41
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
TÜV SÜD Product Service Slide 42
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
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
for more information and to register!