New European Medical Device Regulations: Keeping Your Orthopaedic and Spine Products on the Market - OMTEC 2017

Workshop | New European Medical Device Regulations: Keeping Your Orthopaedic and Spine Products on the Market Matthias Fink, M.D. Clinical Centre of Excellence TÜV SÜV Product Service

OMTEC 2017 Chicago June 13-15

TÜV SÜD, Clinical Centre of Excellence OMTEC 2017 Slide 2

New European Medical Device Regulations

2008 Commission: consultation on medical device framework

2012

2014 Q2

2015 Q3

2015 Q4

2017

Parliament: position on MDR

Council position on proposed Regulation

Trilogue: Commission, Parliament, Council

May 5th: MDR is published

End of three-year transition period 2020

Commission: proposal for new MDR


Disclaimer

This presentation is based on information available as of today and prepared to my best knowledge. This presentation presents my personal understanding

of the medical device requirements in Europe. The presentation includes figures that were copied from public websites. A

citation to the original source is included in the Footnote of this presentation.



Life Cycle Methodology

Documentation requirements including

plans/protocols for appraisal, methods, clinical investigation,

PMCF studies, registries

Clinical Evaluation Plan

Detailed information for sources of literature (MEDLINE, EMBASE, CENTRAL, ICTRP and

clinical Trials.gov)

Literature research: device in

question/equivalent device and

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

Sufficient clinical evidence (intended use, clinical performance and

benefits, risk management, usability,

target population)

Requirements for updating CER

Need and concept of PMCF studies Risk/benefit profile Qualification of

clinical evaluator Scope of clinical

evaluation before and after CE marketing

State of the art /Current knowledge concept Scientific validity Relevance of data

Weightening criteria for clinical data

Analysis 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


MDR wording regarding clinical data

MDR • (63) To ensure a high level of safety and performance, demonstration

of compliance with the general safety and performance requirements laid down in this Regulation should be based on clinical data that, for class III devices and implantable devices should, as a general rule, be sourced from clinical investigations that have been carried out under the responsibility of a sponsor.



• 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 61 and Annex XIV, including post-market clinical follow-up.

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

Manufacturers shall



Stages of the Clinical Evaluation

Equivalent Approach

Clinical Expertise (Evaluator Expectations)

Update of the Clinical Evaluation

Devices for unmet medical needs



An ongoing process, conducted throughout the life cycle of a medical device.

It is performed during the conformity assessment process leading to the marketing of a medical device

First performed during the development of a medical device

Is mandatory for initial CE-marking and must be actively updated thereafter

Ensures that the evaluation of safety and performance of the device is based on sufficient clinical evidence throughout the lifetime

When is a clinical evaluation undertaken?



What should the clinical evaluator address?

the intended purpose including all medical

indications

the clinical performance and

benefits

measures for risk avoidance and risk

mitigation

the usability of the device for the

intended users

the suitability of the supplied information

materials

instructions for target population groups



How is a clinical evaluation performed?

Stage 0 Scoping, Plan

Section 7 App. A3

Stage 1 Identification of pertinent data

Section 8 App. A4-A5

Stage 2 Appraisal of pertinent

data Section 9 App. A6

Stage 3 Analysis of clinical

data Section 10 App. A7-A8

Stage 4 Clinical Evaluation

Report incl. PMS/PMCF

Section 11 App. A9-A10



Stage 0 – Scope Definition and Clinical Evaluation Plan

Before a clinical evaluation is undertaken the manufacturer should define its scope, based on the Essential Requirements that need to be addressed from a clinical perspective and the

nature and history of the device.




The scope serves as a basis for further steps, including the identification of pertinent data

Device description Clinical Evaluation Plan



Product and related accessories

List of affected products (sizes)

Which requirements are to be fulfilled (e.g. MDD, AIMDD, [MDR])

Which guidance documents are followed (MEDDEV, Common Specifications)

List of applicable clinically relevant standards (e.g. ISO 14155)

Reason of submission (Type: DD, Extension, Change Notification, Follow up Condition)

Specific attention (new/innovative technology, unmet medical need, vulnerable population)

Source of clinical data

List of additional applicable documents (incl. revision and release date)




Stage 1 – Identification of pertinent data

Data generated and held by the manufacturer

Data retrieved from literature

Abstracts lack relevant information for a full appraisal but

can give an initial overview

Full-text copies for the appraisal

The literature search protocol(s)

The literature search report(s)

Full-text copies of all relevant documents


Clinical Evidence

• clinical evidence means the clinical data and clinical evaluation results, pertaining to a device of sufficient amount and quality to allow a qualified assessment of whether the device achieves the intended clinical benefit(s) and safety, when used as intended by the manufacturer

MDR Definition

• Sufficient clinical evidence - an amount and quality of clinical evidence to guarantee the scientific validity of the conclusions.

MEDDEV rev.4


Clinical Data Sources


Chapter 9.1 Data generated and held by the manufacturer

All data generated and held by the manufacturer need to be identified.

Complete data needs to be entirely disclosed and made available to the evaluators; this includes data from Europe and other countries; it includes clinical studies as well as Use data (such as vigilance reporting, complaints, PMS reports, PMCF and Device Registry data, other data held by the manufacturer).

The data should be entirely disclosed, adequately summarised and referenced in the Clinical Evaluation Report to the extent that it can be critically reviewed by others



Clinical Studies Market Experience / Real World Evidence


Clinical Studies (any kind, systematic search strategy)

Systematic Reviews Cochran HTA Meta-analysis Guidelines, Consensus Papers

Implant Registries National Regional Institutional Manufacturers




Medline/PubMed – starting point, possible incomplete coverage of European Journals

Additional Databases – EMBASE / Excerpta Medica, Cochrane CENTRAL trials registry, etc.

Internet searches (e.g. Google Scholar)

Information coverage and search features I scientific database can change over time

Criteria need to be defined and re-evaluated


Clincial Data Sources - Goals


Checks and Balances needed for a more robust system

New data sources required

Independent data collection

Independent interpretation of clinical data by expert groups (Cochrane, Meta-analysis, Health Technology Assessment )

Real World Evidence / Registries / Big Data


Clinical Data Sources - Registries

In fact any data collection without defined termination

Examples: Quality Registries (e.g. arthroplasty, spine, cardiology)

National Regional Institutional (e.g. Mayo Clinic Orthopedic Registry) By Manufacturers

Reimbursement and discharge data „Sick funds“ Internal quality monitoring at public health institutions HTA

Data generated by active medical devices (e.g. pacemakers) Telemedicine (therapeutic, diagnostic)

Apps Cohort studies ???



Use of Clinical Data Under the MEDDEV 2.7/1, Rev.4

Fundamental Changes in the processes of clinical data acquisition

Conventional follow up studies still appropriate? Often underpowered Subject to confounders Expensive

Clinical Studies:

Targeted study plan according to relevant hypotheses Performance Claims Concentration to expert centers conducting studies (bias, reproducibility)

Real word evidence:

Verification of claims Safety endpoints (dependent on users, indications...) Market monitoring (off label use, vigilance…)



Stage 2 – Appraisal of pertinent data

Determine the value of each

data

Quality of the data

Relevance of the data

Appraisal Plan (9.2)




Appraisal Plan

The plan typically includes: • criteria for determining the methodological quality and the

scientific validity of each data set. • criteria for determining the relevance to the clinical evaluation

(relevance to the device and to the different aspects of its intended purpose).

• criteria for weighing the contribution of each data set against the overall clinical evaluation.




Conduct of Appraisal

• Study design of pre-market and post-market clinical investigations

• Additional aspects for appraisal of the quality of clinical investigations generated and held by the manufacturer

• Information derived from vigilance data, device registry data, case series, patient dossiers, and other use data

• Quality Assurance • Report Quality

Examples of aspects that can

be taken into consideration for

evaluating the methodological quality and the

scientific validity of the evidence

are:




Determination of Relevance

Pivotal data must have the data quality necessary for demonstration of adequate clinical performance and clinical safety of the device under evaluation

Data must be generated either with the device under evaluation or with an equivalent device used in its intended purpose

Data coming from an equivalent device can only be used after demonstration of equivalence



Determination of Relevance

To what extent are the data representative of the device under evaluation?

What aspects are covered?

Are the data relevant for the intended purpose or the claims for the device?

If the data are relevant to specific aspects of the intended purpose or claims, are they relevant to a specific…

Model, size, or setting of the device?

User group?

Medical indication?

Age group?

Gender?

Type and severity of the medical condition?




Weight the contribution of data

The evaluators should identify appropriate criteria to be applied for a specific evaluation

The pre-defined criteria should be followed strictly by the evaluators

Clinical data should receive the highest weighting, when generated through a well designed and monitored randomized controlled clinical investigation

When rejecting evidence, the evaluators should document the reasons


Use of Clinical Data under the MEDDEV 2.7/1, Rev.4

– Scientific standards are the same for all types of clinical data Transparency Reproducibility Transferability to target population

– The processes to perform that have to be done according to the needs of the data sources

– Requires higher expertise in these fields Meta-analyses Registries, Real World Routine Data Wider range of reasons for data collection and evaluation by stakeholders/data owners

– Prospective data evaluation plan (Clinical Investigation Plan) – Data interpretation Rational for weighting the data Defined process how to deal with inconsistencies and contradictory results

(more complex than in past)




Stage 3 – Analysis of the clinical data

The goal of the analysis stage is to determine if the appraised data sets available for a medical device collectively demonstrate compliance with each of the Essential Requirements pertaining to the clinical performance and clinical safety of the device, when the device is used according to its intended purpose.

Appraisal criteria should be reflected in the analysis




Comprehensive Analysis

Determine compliance

with each ER

Relevance of Pre-Clinical

Data Usability Test

Relevance of Bench Tests and Animal

Studies

Benefits of the device

Confirmation of all Claims

Adequacy of promotional

materials including IFU

Range of devices

Consistency of

documents Etc.



Examples of studies that lack scientific validity for demonstration of adequate Clinical Performance and/or Clinical Safety (A6)

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



Data needed to address the identified gaps should be determined so that conclusions can be drawn with confidence in relation to conformity with the essential requirements, including:

• evaluation of the safety, performance and the benefit/risk profile • compatibility with a high level of protection of health and safety

(that can be determined by considering current knowledge/ the state of the art, with reference to standards and available alternatives, risk minimization, patient needs and preferences)

• the acceptability of any undesirable side-effects • the risk of use error and the adequacy of the IFU to

the intended users • consistency between available information



MDR - Article (61) 6.a

• which have been lawfully placed on the market or put into service in accordance with Directive 90/385/EEC or Directive 93/42/EEC and for which the clinical evaluation

• is based on sufficient clinical data • is in compliance with the relevant

product-specific common specification for the clinical evaluation of that kind of device, where such a common specification is available

The requirement to perform clinical investigations pursuant to previously presented requirements shall not apply to implantable devices and devices falling into class III:


MDR - Article (61) 6.b

The requirement to perform clinical investigations pursuant to previously presented requirements shall not apply to implantable devices and devices falling into class III: • that are sutures, staples, dental fillings, dental braces, tooth crowns,

screws, wedges, plates, wires, pins, clips or connectors for which the clinical evaluation is based on sufficient clinical data and is in compliance with the relevant product-specific common specification, where such a common specification is available.



The post-market surveillance system shall be suited to actively and systematically gathering, recording and analyzing relevant data on the quality, performance and safety of a device throughout its entire lifetime, and to drawing the necessary conclusions and to determining, implementing and monitoring any preventive and corrective actions.

The manufacturers should:

establish a comprehensive post-market surveillance

(PMS) system

set up under the quality management

system

and based on a PMS plan.




PMCF (Yes/No)

Residual Risks

Unanswered Questions

Uncertainties

Rare Complications

Medium- and Long-Term

Performance

Medium- and Long-Term

Safety

Wide-spread use


The Notified Body shall always decide, based on the results of its assessment of the clinical evaluation and risk management, whether the post-market surveillance plan, including the PMCF plan, is adequate.




Is a PMCF Always a Clinical Study?

A PMCF can follow several methodologies, such as:

• the extended follow-up of patients enrolled in premarket investigations; • a new clinical investigation; • a review of data derived from a device registry; or • a review of relevant retrospective data from patients previously exposed to

the device.


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What is a proactive PMS?

Examples of PROACTIVE PMS Methods Planned Customer Surveys

Prospective and retrospective Post-market clinical studies or trials

Company-supported Investigator-Sponsored Studies (ISS)

Extended clinical investigations

Company registry based on the output of the risk management file and the CER

Planned Analysis of Regional or National Device Registries - Hospital Databases, Registries


What is a reactive PMS?

Examples of REACTIVE PMS Methods Customer Complaints

Unsolicited User Feedback

Maintenance/Service Reports

Routine and not planned In-house Testing Investigation Initiated Studies (IIS)

Social Media Analysis

Literature Review

Published Data from Regional or National Device Registries Expert Opinion



All promotional material (incl. website content) will be assessed by the

Notified Body

All claims have to be substantiated by data from the device itself or a device for which equivalence was demonstrated

How the information materials supplied by the manufacturer (including label, IFU, available promotional materials) are reviewed by the clinical evaluator or clinical evaluation team

Process will be audited during a Clinical Audit

Promotional Material



Stage 4 – The clinical evaluation report

A clinical evaluation report shall be compiled to document the clinical evaluation and its output.

The clinical evaluation report should contain sufficient information to be read and understood by an independent party.

The contents of the clinical evaluation report shall be cross-referenced to the relevant documents that support them.

The report should include references to literature-based data and the titles and investigational codes of any clinical investigation reports, with cross-references to the location in the manufacturer’s technical documentation.



Stage 4 – The clinical evaluation report Summary

Scope of the clinical evaluation

Clinical background, current knowledge, state of the art

Device under evaluation • Type of evaluation • Demonstration of equivalence (if applicable) • Clinical data generated and held by the manufacturer • Clinical data from literature • Analysis of the clinical data

• Requirements on clinical safety • Requirements on clinical performance • Requirement on acceptable benefit-risk profile • Requirement on acceptability of risks and side effects

Conclusions

Date of the next clinical evaluation

Dates and signatures

Qualification of the responsible evaluators

References TÜV SÜD, Clinical Centre of Excellence OMTEC 2017 Slide 44


Stage 4 – The clinical evaluation report

The amount of information may differ according to the history of the device or technology.

The report of a new device or a new technology would need to include an overview of the developmental process and the points in the development cycle at which

all clinical data have been generated.


MDR XIV §3 - Demonstration of Equivalence

3. A clinical evaluation may be based on clinical data relating to a device for which equivalence to the device in question can be demonstrated. The following technical, biological and clinical characteristics shall be taken into consideration for the demonstration of equivalence:



— Technical: the device is of similar design; is used under similar conditions of use; has similar specifications and properties including physicochemical properties such as intensity of energy, tensile strength, viscosity, surface characteristics, wavelength and software algorithms; uses similar deployment methods, where relevant; has similar principles of operation and critical performance requirements; — Biological: the device uses the same materials or substances in contact with the same human tissues or body fluids for a similar kind and duration of contact and similar release characteristics of substances, including degradation products and leachables; — Clinical: the device is used for the same clinical condition or purpose, including similar severity and stage of disease, at the same site in the body, in a similar population, including as regards age, anatomy and physiology; has the same kind of user; has similar relevant critical performance in view of the expected clinical effect for a specific intended purpose.



The characteristics listed in the first paragraph shall be similar to the extent that there would be no clinically significant difference in the safety and clinical performance of the device. Considerations of equivalence shall be based on proper scientific justification.

It shall be clearly demonstrated that manufacturers have sufficient levels of access to the data relating to devices with which they are claiming equivalence in order to justify their claims of equivalence.


Is this a New Definition of Equivalence?

MEDDEV 2.7/1, Rev. 3 Appendix F, p.42


Clinical Equivalence

Used for the same clinical condition (including when applicable similar severity and stage of disease, same medical indication)

The manufacturer shall define the same clinical condition! - similar severity of disease - similar stage of disease - same medical indication



used for the same intended purpose

used at the same site in the body



Used in a similar population (this may relate to age, gender*, anatomy, physiology, possibly other aspects*)

Not included in the MDR XIV §3



not foreseen to deliver significantly different performances (in the relevant critical performances such as the expected clinical effect, the specific intended purpose, the duration of use, etc.).

MDR XIV §3: The characteristics listed in the first paragraph shall be similar to the extent that there would be no clinically significant difference in the safety and clinical performance of the device.


Technical Equivalence

comparative drawings or pictures should be included in order to compare shapes and sizes of elements that are in contact with the body

be of similar design



used under the same conditions of use

≠



Have similar specifications and properties (e.g. physicochemical properties such as type and intensity of energy, tensile strength, viscosity, surface characteristics, wavelength, surface texture, porosity, particle size, nanotechnology, specific mass, atomic inclusions such as nitrocarburising, oxidability)

Full access to the Technical Documentation of the proposed equivalent device is expected!



Demonstration of equivalence

Same Material

Same is not Identical

Polymer A1 is the same as Polymer A2

It is not necessary that A1 and A2 are from the identical supplier and are manufactured under identical process parameters with the identical machinery



The ability of the manufacturer to access information that are relevant to the demonstration of equivalence.

Scenario A

• The manufacturer A has full access to the technical documentation of manufacturer B

Scenario B • The manufacturer

A has access to devices from manufacturer B and can test them in comparison to his device under the same test methods against the specifications of his device

Scenario C

• The manufacturer A develops devices that are following specifications set in the standard or in guidance documents


Biological Equivalence

Use the same materials or substances in contact with the same human tissues or body fluids



Equivalence can only be based on a single device*

*Evaluators may wish to refer to several devices that are equivalent. In such a situation, equivalence of every single device to the device under evaluation should be fully investigated, demonstrated, and described in the clinical evaluation report.



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

presumed to be equivalent need to be identified, fully disclosed, and evaluated

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

• if measurements are possible, clinically relevant specifications and properties should be measured both in the device under evaluation and the presumed equivalent device

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



Examples when equivalence is not demonstrated: Composed of different materials in contact with tissue (e.g. biologic

vs. synthetic)

Dissimilar material form (e.g. granules vs. blocks)

Dissimilar principles of operation (e.g. antimicrobial activity by coating or ancillary medicinal substance)

Different fixation technique (e.g. cemented vs. non-cemented endoprosthesis)

Different clinical uses (e.g. diagnostic vs. therapeutic catheter)



Examples when equivalence is not demonstrated:

Off label clinical data from the equivalent device will not be accepted

Partial equivalence by comparison to different devices

Potential clinical impact of differences not discussed (e.g. pore sizes of a bone void filler)

Gaps in demonstration of equivalence – insufficient data


Demonstration of Equivalence

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. (A12)



A manufacturer of a device demonstrated to be equivalent to an already marketed device not manufactured by him, may also rely on the previous wording in order not to perform a clinical investigation provided that the following conditions are fulfilled in addition to what is required in that paragraph: • the two manufacturers have a contract in place that explicitly allows the manufacturer

of the second device full access to the technical documentation on an ongoing basis

• the original clinical evaluation has been performed in compliance with the requirements of this Regulation

MDR Art. 61


A=100%

B= A – x%

C= B – x%



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• 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)

Minimum experience in the relevant medical field

Who should perform a clinical evaluation? (chapter 6.4)

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



From whom will we expect the CV?

The Clinical Evaluator

• In case this person fulfills the total experience expectations • In case the manufacturer was subject to a clinical audit

The Clinical Evaluation Team • In case the manufacturer was not subject to a clinical audit • In case the manufacturer is not willing to have a clinical audit

What will be audited?

The process showing the involvement of all pre-defined resources/teams in the preparation of a clinical evaluation report for a

specific device over its expected lifetime



Who should perform a clinical evaluation?

Category A Physician

• Implantable devices and Class III devices

• Class IIb active devices intended to administer and/or remove a medicinal product

Category B Experienced Person

• Non-implantable and Non-Class III devices

• The remaining Class IIb devices


MEDDEV 2.7/1 Rev. 4

Declarations of Interests (A11)

• employment by the manufacturer • participation as an investigator in clinical studies of the device, or in pre-clinical

testing of the device • ownership/shareholding possibly affected by the outcome of the evaluation • grants sponsored by the manufacturer • benefits such as travelling or hospitality (if beyond what is reasonably necessary

for the work as an employee or external evaluator) • interests in connection with the manufacturing of the device or its constituents • interests in connection with intellectual property, such as patents, copyrights and

royalties (whether pending, issued or licensed) possibly affected by the outcome of the evaluation

• other interests or sources of revenues possibly affected by the result of the evaluation

Typical contents


Updating Clinical Evaluation Report MEDDEV 2.7/1 Rev. 4

• 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:



Which device shall be updated

annually?

Not well-established devices

Implantable devices and Class III devices

Class IIb active devices intended to administer

and/or remove a medicinal product

When is a device well-established?

Implantable devices are well-established as soon

as they have clinical data over their

expected lifetime

Non-implantable devices are well-established as

soon as they are for more than 1 year

on the market



if new claims the manufacturer intends to use are substantiated

if existing claims are still justified

When updating the clinical evaluation, the evaluators should verify: if the benefit/risk profile, undesirable

side-effects (whether previously known or newly emerged) and risk mitigation measures are still compatible with a high level of protection of health and safety and acceptable according to

current knowledge/ the state of the art

correctly addressed in the information materials supplied by the manufacturer

of the device correctly addressed by the

manufacturer's current PMS plan



Devices for Unmet Medical Needs (A8)

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

IFU presenting the clinical evidence

level

PMCF Plan to prove

safety and performance

Including all patients in

PMCF Studies


MEDDEV 2.7/1 Rev. 4


http://creativethinking.net/what-i-learned-from-charles-darwin-about-creative-thinking/

MEDDEV 2.7/1 Rev. 4

Prepare for the transition For the latest information, visit the following

webpages: Medical Device Regulation:

www.tuv-sud-america.com/mdr

In Vitro Diagnostic Device Regulation: www.tuv-sud-america.com/ivdr

Contact Matthias Fink, M.D.

[email protected]


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


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

mailto:[email protected]

Impact of the NEW Medical Device

Regulation

2017-05-18

One-stop testing, inspection, certification and training solutions

TÜV SÜD Product Service

1866 On 6 January, 22 industrialists united to establish the Steam Boiler Inspection Association Baden in Mannheim.

1881 The first binding standards related to boiler safety were agreed upon, paving the way for uniform technical inspections.

1906 Our first vehicle periodic technical inspection was carried out.

1951 TÜV organisations were tasked with performing regular inspections of all motorised vehicles.

1989 TÜV Product Service GmbH was launched, pioneering the concept of worldwide approvals.

1996 The TÜVs from Germany’s southern states united to form TÜV SÜD.

2001 The TÜV SÜD octagon certification mark became the official company logo.

Today TÜV SÜD continues to pursue a strategy of internationalisation and growth.

Our heritage: More than 150 years of business success

TÜV SÜD Slide 78

TÜV SÜD TÜV SÜD Slide 79

TÜV SÜD at a glance

Note: Figures have been rounded off.

1-STOP SOLUTIONS PROVIDER

1,000 LOCATIONS

WORLDWIDE

€2.3 BILLION

IN ANNUAL REVENUE

24,000 EMPLOYEES

43% OF REVENUE

OUTSIDE GERMANY

574,000 CERTIFICATES

100% INDEPENDENT &

IMPARTIAL

150+ YEARS OF

QUALITY, SAFETY & SUSTAINABILITY

Market approval and certification

TÜV SÜD Slide 80

Brazil INMETRO Certification of electrical

Medical Devices, including Factory Inspections

Canada CMDCAS (ISO 13485) CAN/CSA C22.2 No. 60601-1 as NRTL

USA NRTL Certification FDA 510(k) Third Party Review FDA Third Party Inspections

Europe Conformity assessment procedures

according to AIMDD, MDD, IVDD (notified body number 0123)

Australia Conformity Assessment Body (CAB)

under the current EU-AUS MRA

Malaysia Conformity Assessment Body (CAB) under the MDA Technical File Review for product registration

Russia Registration Certificate by Roszdravnadzor

and declaration of conformity

China CFDA Registration Agent service Test Agent service Clinical Trial Agent Service

Singapore CAB for medical devices in Singapore GDPMDS certification Product Safety Testing

South Korea Technical Document Review of class II medical

devices CB test reports

Japan Medical Device Safety Testing according to JIS Certification of certain class II and class III

medical devices and IVDs Audits according to J-QMS requirements

Taiwan Audits according to TGMP

requirements under the Taiwanese/European Technical Cooperation Program

Hong Kong Conformity assessment according to MDACS

MDSAP (Medical Device Single Audit Program) Single regulatory audit that satisfies the needs of the following regulatory jurisdictions: Australia, Brazil, Canada, Japan, USA

Specialists in worldwide regulations, we ensure that your products are tested in compliance with the latest requirements.

Independence and impartiality

TÜV SÜD Slide 81

TÜV SÜD e.V.

INDUSTRY MOBILITY CERTIFICATION

TÜV SÜD Foundation

74.9% 25.1%

Subsidiaries in CENTRAL & EASTERN

EUROPE

Subsidiaries in

GERMANY Subsidiaries in

MIDDLE-EAST & AFRICA

Subsidiaries in the ASIA-PACIFIC REGION

Subsidiaries in WESTERN EUROPE

Subsidiaries in the AMERICAS

Gesellschafterausschuss GbR (Shareholder committee)

TÜV SÜD AG

Medical Device

Regulation

In Vitro Diagnostic Regulation

New MEDDEV Guidance Document

ISO 13485:2016

MDSAP – CMDCAS Deadline

What is happening in Europe?

TÜV SÜD Slide 82

Disclaimer

TÜV SÜD Slide 83

This presentation is based on information available as of today and prepared to my best knowledge. This presentation presents my personal understanding

of the medical device requirements in Europe. The presentation includes figures that were copied from public websites. A citation

to the original source is included in the footnote of this presentation.

What are the challenges of today and tomorrow?

TÜV SÜD Slide 84

Summary: • MDR is much bigger and includes

more details than the current MDD/AIMDD

• 65 Pages MEDDEV 2.7/1 rev. 4 vs. 46 Pages MEDDEV 2.7/1 rev. 3

EU’s Medical Device Regulation (MDR)

TÜV SÜD Slide 85

2008 Commission: consultation on medical device framework

2012

2014 Q2

2015 Q3

2015 Q4

2017 (est.)

Parliament: position on MDR

Council position on proposed Regulation

Trilogue: Commission, Parliament, Council

Expected: MDR published 5 May 2017

Expected: end of three-year transition 2020 (est.)

Commission: proposal for new MDR

Timelines

TÜV SÜD Slide 86

It is still unclear if the 25th or the 26th of May is correct. Different interested parties interpret the regulation differently.

https://www.google.de/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwij99CYsejTAhUE0xoKHSLpBYwQjRwIBw&url=https://southernsophistication.net/a-long-way-to-go-lyrics/&psig=AFQjCNEJhjYEnSmKDv9YSZOe2DdbADwBbg&ust=1494610763501588

How long is the grace period?

TÜV SÜD Slide 87

Certificates issued by notified bodies in accordance with Directives 90/385/EEC and 93/42/EEC shall remain valid until the end of the

period indicated on the certificate, which shall not exceed five years from its issuance. They shall, however, become void at the latest four years after the date of application of the Regulation.

Important Changes and Improvements*

TÜV SÜD Slide 88

Stricter pre-market control of high-risk devices with the involvement of a pool of experts at EU level

Reinforcement of the criteria for designation and processes for oversight of notified bodies

Inclusion of certain aesthetic products which present the same characteristics and risk profile as analogous medical devices

EU database on medical devices and a device

EU-wide requirement for an 'implant card' to be provided to patients’ traceability system

Reinforcement of the rules on clinical data, including an EU-wide coordinated procedure for the authorisation

Reinforced requirement for manufacturers to collect data about the real-life use of their devices

* Source: http://ec.europa.eu/growth/tools-databases/newsroom

Structure of the MDR - New Chapters

TÜV SÜD Slide 89

• Scope and definitions Chapter I • Making available and putting into service of devices, obligations of economic operators,

reprocessing, CE marking, free movement Chapter II • Identification and traceability of devices, registration of devices and of economic operators,

summary of safety and clinical performance, European databank on medical devices Chapter III • Notified bodies Chapter IV • Classification and conformity assessment Chapter V • Clinical evaluation and clinical investigations Chapter VI • Post-market surveillance, vigilance and market surveillance Chapter VII • Cooperation between Member States, Medical Device Coordination

Group, Expert laboratories, Expert panels and device Chapter VIII • Confidentiality, data protection, funding, penalties Chapter IX • Final provisions Chapter X

Article 2 – Definitions “Economic Operators“

TÜV SÜD Slide 90

Manufacturer inside EU

Manufacturer outside EU

Authorised Representative Distributor Importer

Economic Operators

means the manufacturer,

the authorized representative,

the importer,

the distributor and the

person referred to in

− Article 22(1), i.e. person who put together systems or procedure packs and

− Article 22(3), i.e. person who sterilizes systems or procedure packs


TÜV SÜD Slide 91

Manufacturer means the natural or legal person who manufactures or fully refurbishes a device or has a device designed, manufactured or fully refurbished, and markets that device under his name or trademark

Fully refurbishing for the purposes of the definition of manufacturer, means the complete rebuilding of a device already placed on the market or put into service, or the making of a new device from used devices, to bring it in conformity with this Regulation, combined with the assignment of a new lifetime to the refurbished device


TÜV SÜD Slide 92

Authorized representative means any natural or legal person established within the Union who has received and accepted a written mandate from a manufacturer, located outside the European Union, to act on his behalf in relation to specified tasks with regard to the latter's obligations under this Regulation

Distributor means any natural or legal person in the supply chain, other than the manufacturer or the importer, who makes a device available on the market, up until the point of putting into service

Importer means any natural or legal person established within the Union who places a device from a third country on the Union market

Authorized representative

TÜV SÜD Slide 93

Single Authorized Representative

is Legally responsible for defective devices

shall have permanent Regulatory Affairs person

shall have access to the Technical Documentation

Introduction and classification process

TÜV SÜD Slide 94

MDR Rules Annex IX of

the MDD

MEDDEV Guidelines e.g.

2.4/1, 2.1/6 Borderline

Manual

MDD amendments e.g.

COMMISSION DIRECTIVE 2003/12/EC

TÜV SÜD Slide 95

Changes between MDD/AIMDD and MDR

Classification Rules • There were 18 rules within the current MDD (Annex IX) • Active implantable medical devices were covered in a seperate Directive • Within the new MDR, there will be 22 Rules (Annex VIII) • Some definitions were changed

http://www.google.de/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwie_6OsgsTTAhUo7YMKHbm1AcoQjRwIBw&url=http://thesalespitch.com/stepping-back-reassess/&psig=AFQjCNELiIcVIhUZfZwQTMfD1s1V1F1BjQ&ust=1493361230706306

TÜV SÜD Slide 96

New MDR Proposal

New Process in case of dispute between NB and Manufacturer

Addition of the active implantable medical devices to the

classification rules

Addition of tissue engineered products

Rule 6-8 Up-classification of devices in direct contact with the

heart or the central circulatory system

Up-classification of orthopedic devices and devices in contact

with the spinal column

Rule 19 - Addition of Nanomaterials

Rule 18 - Update of the wording regarding human origin material

Rule 1 – 22 (8 Special Rules)

TÜV SÜD Slide 97

New MDR Proposal – Classification Dispute Art. 51

Manufacturer (registered place of business) and notified body in the same Member State

Manufacturer

Classification

NB

Accepted Dispute Accepted Dispute

Competent authority of the Member State

of the manufacturer (address of business)

Notification to MDCG

Manufacturer (registered place of business) and notified body in different Member States

Competent authority of the

Member State of the manufacturer

(address of business)

Consultation with competent

authority of the Member State

which designated the notified body

Active Devices Annex VIII

TÜV SÜD Slide 98

Rule 9 Active therapeutic devices intended to

adminster or exchange energy

control/monitor or influence directly

the performance of class IIb

Administer / exchange energy

in potentially hazardous way

ionizing radiation for therapeutic purposes

including control or monitor

such devices, or directly influence their performance

controlling, monitoring, or directly influencing the performance of active implantable

devices

IIa

IIb IIb IIb III

http://www.google.de/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjl45vO4vjTAhWCyhoKHQEIB2AQjRwIBw&url=http://www.vitatron.com/ous/pacemakers3.html&psig=AFQjCNEYro5-0WkCxfguZxrbFj6UFsKxSA&ust=1495173805551433

Active Devices Annex VII, Chapter III, Rule 9-12

TÜV SÜD Slide 99

Rule 10 Active devices for

diagnosis and monitoring

monitoring vital physiological parameters or

diagnose clinical situations immediate danger of the patient

Devices intended to illuminate the patient's body

(in the visible spectrum)

IIa

I IIb

Active Devices Annex VIII

TÜV SÜD Slide 100

Rule 11 Software

monitor physiological processes information for decisions with diagnosis or therapeutic purposes

death or irreversible deterioration of state of

health

deterioration of state of health or a surgical

intervention

nature of variations could result in immediate danger to the patient

I

IIa IIa

IIb III IIb

Special rules Annex VIII

TÜV SÜD Slide 101

Rule 19 Devices incorporating or consisting

of nanomaterials

High/medium potential for internal

exposure

Low potential for internal exposure

Negligible potential for internal exposure

III IIb IIa


TÜV SÜD Slide 102

Rule 20 invasive devices with respect to body orifices, other than surgically invasive devices, which are intended

to administer medicinal products by inhalation

mode of action has an essential impact on the efficacy and safety of the administered medicinal product or to treat life-threatening conditions

IIa

IIb


TÜV SÜD Slide 103

Rule 21 composed of substances intended to be introduced via body orifice, or applied on skin and that are absorbed

or locally dispersed

device, or its products of metabolism, systemically absorbed for

intended purpose

in the stomach or lower gastrointestinal tract and the device or its

products of metabolism are systemically

absorbed

applied on skin or in nasal or oral cavity as far as

pharynx and achieving the intended purpose on

these cavities

All other cases

III IIb III IIa

General Obligations of the Manufacturer

TÜV SÜD Slide 104

• 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 61 and Annex XIV, including post-market clinical follow-up.

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

Manufacturers shall

General Overview – Technical Documentation

TÜV SÜD Slide 105

MDR Article 10 – Number 4 General obligations of manufacturers Manufacturers of devices other than custom-made devices shall draw up and keep up to date technical documentation for those devices. The technical documentation shall be such as to allow the conformity of the device with the requirements of this Regulation to be assessed. The technical documentation shall include the elements set out in Annexes II and III. The Commission is empowered to adopt delegated acts in accordance with Article 115 amending, in the light of technical progress, the Annexes II and III.


TÜV SÜD Slide 106

The technical documentation shall be presented in a:

clear organised readily searchable

unambiguous manner

https://www.google.de/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwilloSmksTTAhXl4IMKHVydAYYQjRwIBw&url=https://alankent.me/2013/11/15/technical-documentation-writing/&psig=AFQjCNF26lio4g4BF4TCip-4HmdKJiQlUw&ust=1493365535972586


TÜV SÜD Slide 107

Process Data Validation Data

Pre-clinical Data Information on Design Stages

Major elements

https://www.google.de/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjl1OKGk8TTAhUm94MKHarJBcUQjRwIBw&url=https://enauczanie.pg.edu.pl/moodle/course/index.php?categoryid=8&browse=courses&perpage=20&page=1&psig=AFQjCNHC6cL9xI_UXe1Hxy4ZyIw8uLpe-A&ust=1493365714911003

General Overview - Chapters of Annex II

TÜV SÜD Slide 108

Device description and specification, including variants and accessories • Device description and specification • Reference to previous and similar generation of the device

Information to be supplied by the manufacturer

Design and manufacturing

General safety and performance requirements

Benefit-risk analysis and risk management

Product verification and validation • Pre-clinical and clinical data • Additional information required in specific cases


TÜV SÜD Slide 109







Device description and specification including variants and accessories

TÜV SÜD Slide 110

Similar devices shall be consistent throughout the technical documentation

Clinical data Equivalence claims Pre-clinical data Risk management

An overview of identified similar devices available on the Union or international markets, where such devices exist.

An overview of the previous generation or generations of the device produced by the manufacturer

Device description and specification Product, trade name, general description

Intended purpose and intended users, intended patient population, patient

selection criteria

Indications, contra-indications, warnings, risk

class … Principle of operation Novel features Accessories Variants and/or

configurations Raw materials Technical specifications


TÜV SÜD Slide 111








TÜV SÜD Slide 112

A complete set of:

the label or labels on the device and on its packaging, such as single unit packaging, sales packaging, transport packaging in case of specific management conditions

in the languages accepted in the Member States where the device is envisaged to be sold


TÜV SÜD Slide 113








TÜV SÜD Slide 114

Annex II – Article 3 Design and manufacturing information • Design stages applied to device • Manufacturing processes information

– Process validation – Adjuvants – Continuous monitoring – Final product testing

• The data shall be fully included in the technical documentation

• Identification of all sites, suppliers, sub-contractors

Identified similar devices • For high risk devices, the data needs to be

submitted to the notified body for review • Class IIa / IIb during TD assessment


TÜV SÜD Slide 115







Annex I: General Safety and Performance Requirements

TÜV SÜD Slide 116

Safety and effectiveness

Risk management

Risk/benefit ratio

Post market data

General Safety and Performance Requirements

TÜV SÜD Slide 117

Chapter I • General Requirements • Clause 1 – 9

Chapter II • Requirements regarding

design and manufacture • Clause 10 – 22

Chapter II • Requirements regarding

the information supplied with the device

• Clause 23

Clause 10: Chemical, physical and biological / substances

• compatibility between different parts (more than one implantable) • the impact of processes on material properties; • mechanical properties / surface properties;

Chemical, physical, biological

• carcinogenic, mutagenic or toxic to reproduction CMR • endocrine disrupting properties • phthalates • Nanomaterials

Substances (limits of concentrations) /materials

• Instruction for Use • Labels • Patient Information • Information on Substances and Materials when exceeding a specific limit

• e.g. 0,1 % weight by weight (w/w))

Labeling

TÜV SÜD Slide 118

Clause 10: Chemical, physical and biological / substances

TÜV SÜD Slide 119

Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by substances or particles, including wear debris, degradation products and processing residues, that may be released from the device.

Justification regarding the presence of CMR and/or endocrine-disrupting

The benefit-risk assessment shall take into account the intended purpose and context of the use of the device, as well as any available alternative substances and alternative materials, designs or medical treatments.

Applicable Regulations • Regulation (EC) No 1272/2008 • Regulation (EC) No 1907/2006 • Regulation (EU) No 528/2012

Clause 11 – 13 material

Infection and microbial contamination

• More details and structure

• Disinfection • Cleaning • Re-Sterilization • Microbial leakage,

exposure • Microbial contamination

of specimens or fluids

Devices incorporating a substance considered to be a medicinal product

• And devices that are composed of substances or combination of substances that are absorbed by or locally dispersed in the human body

• Consultation • Proof

• Quality • Usefulness • Safety

• Directive 2001/83/EC

Devices incorporating materials of biological

origin

• HO / non-viable • AO / non-viable • other

TÜV SÜD Slide 120

Clause 14 Environment

• the risks associated with the use of the device when it comes into contact with materials, liquids and substances, including gases, to which it is exposed during normal conditions of use

Contact

• the risks associated with the possible negative interaction between software and the IT environment within which it operates and interacts

IT

• the safe disposal of related waste substances by the user, patient or other person • Identify and test procedures and measures as a result of which their devices can

be safely disposed after use • Such procedures shall be described in the instructions for use

Safe disposal

TÜV SÜD Slide 121

Clause 17 Programmable systems / software

• risk management • information security • verification and validation

Development lifecycle

• Specific platform features: screen size, contrast ratio • external use factors: varying environment, level of light or noise

Mobile devices/apps

• minimum requirements on hardware • networks characteristics • security measures: protection against unauthorized access

IT security

TÜV SÜD Slide 122

Clause 18 Active devices

TÜV SÜD Slide 123

Clause 23

• Website to be updated

Information supplied by manufacturer

• Indication that the device contains or incorporates, • a medicinal substance, including a human blood or plasma derivative, or • Tissues/cells (or derivatives) of HO • Tissues/cells (or derivatives) of AO (commission regulation (EU) No 722/2012)

• Unique Device Identification (UDI) carrier according to Article 24 and Annex V Part C. • Qualitative composition of the device and quantitative information on the main constituent(s)

For devices composed of substances or combinations that are introduced into the body via body orifice or applied on skin, that are absorbed by or locally dispersed in the human body for achieving the principal intended action

Label

• specification of clinical benefits to be expected • links to the summary of safety and clinical performance

IFU

TÜV SÜD Slide 124

Safety and Performance Requirements

TÜV SÜD Slide 125

Same approach • Risk Control • State of the art • Safety principles • Usability

Larger scope/ more detailed • Non-medical • Technical aspects

(material, IT…)

General Overview – Annex III

TÜV SÜD Slide 126

Annex III – Post-Market Surveillance Introduction The technical documentation on post-market surveillance to be drawn up by the manufacturer in accordance with Articles 83 to 86 shall be presented in a clear, organised, readily searchable and unambiguous manner and shall include in particular the elements described in this Annex.

Changes compared to MDD & AIMDD Completely new Annex with new content and requirement to keep Post-Market Surveillance data as part of the Technical Documentation.

Major Elements

• Post Market Surveillance Plan – Post Market Clinical Follow Up plan / justification

why not applicable • Periodic Safety Update Report (PSUR)

Current Comformity Assessment Procedures under MDD

TÜV SÜD Slide 127

Annex II

Annex II.3 Full QMS System

Annex II.4 Design

Examination (Design Dossier)

Annex VII

Class I Without Notified

Body

Annex III

PART A:

Type Examination

PART B:

Annex IV Product

verification

Annex III

PART A:

Type Examination

PART B:

Annex V or VI

Comformity Assessment Procedures under MDR

TÜV SÜD Slide 128

Annex IX

Chapter I: A QUALITY

MANAGEMENT SYSTEM

Chapter II: ASSESSMENT OF

TECHNICAL DOCUMENTATION

Annex X

TYPE EXAMINATION

Annex XI

PART A:

PRODUCTION QUALITY

ASSURANCE

PART B:

PRODUCT VERIFICATION

Annex XIII

PROCEDURE FOR CUSTOM-

MADE DEVICES

TÜV SÜD Folie 129

By procedure: old versus new

• Will be deleted • Manufacturers certified for such conformity

procedure must choose another procedure Old Annex VI

• This is the old EC Product Verification • Sampling will not be possible anymore,

only testing of all produced devices

Old Annex IV > Annex XI, Part B

• This is the old production quality system assurance

Old Annex V > Annex XI, Part A

Article 52: Conformity Assessment Procedures

Article 52: Conformity Assessment Procedures

TÜV SÜD Folie 130

• Annex IX • Quality Management System Old Annex II.3 >

• Annex IX • Chapter II: Technical Documentation Old Annex II.4 >

Class I

TÜV SÜD Slide 131

New CAP based on risk class

Step 1 • Conduct Product Assessment according to Annex I • Conduct verification of compliance with requirements of MDR

Step 2 • Create Technical Documentation according to Annex II • Include evidence of compliance with Annex I

Step 3 • Create Declaration of Conformity according to Annex IV • Translate Declaration of Conformity in neccessary languages

Step 4 • Sign Declaration of conformity after necessary

steps of verification have been done

Class I *

TÜV SÜD Slide 132

Sterile

• Annex IX (w/o chapter II), or

• Part A of Annex XI (production audit)

• Limited to the aspects concerned with establishing, securing and maintaining sterile conditions

With Measuring Function



• Limited to the aspects concerned with the conformity of the devices with the metrological requirements

Reusable Surgical Instruments



• Limited to the aspects related to the reuse of the device; in particular cleaning, disinfection, sterilization, maintenance and functional testing, and the related instructions for use

Class IIa (other than custom-made or investigational)

TÜV SÜD Slide 133

• Chapter I (QMS) and III of Annex IX, coupled with Technical documentation assessment.

Option 1

• Technical documentation per Annex II and III coupled with a conformity assessment as specified in Section 10 or Section 18 of Annex XI. (Product conformity verification)

Option 2

• Assessment of the technical documentation of at least one representative device for each category of devices by the Notified Body

Technical Documentation

Class IIb (other than custom-made or investigational)

TÜV SÜD Slide 134

• Chapter I (QMS) and III of Annex IX, coupled with Technical documentation assessment.

Option 1

• Assessment of the technical documentation of at least one representative device for each category of devices by the Notified Body


• Conformity assessment based on type examination per Annex X coupled with product conformity verification per Annex XI

Option 2

Implantable Class IIb

TÜV SÜD Slide 135

Option 1

• Annex IX • Chapter I and

Chapter II

Option 2

• Annex X coupled with Part A or Part B of Annex XI


• Assessment of each file according to Annex II

Except for sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips and connectors.

This list may be extended by delegated acts

Class III (other than custom-made or investigational)

TÜV SÜD Slide 136

• Conformity assessment as specified in Annex IX (QMS coupled with Technical Documentation assessment)

Option 1

• Conformity assessment based on type examination per Annex X coupled with product conformity verification per Annex XI

Option 2

Eudamed: Purpose

TÜV SÜD Slide 137

Registration Notification

Collaboration Dissemination

Eudamed: Modules

TÜV SÜD Slide 138

Eudamed

Traceability (UDI)

Devices

Actors

Studies / CI

NBs

Certificates

Vigilance

Market surveillance

Information flow and interfaces

TÜV SÜD Slide 139

Contract Review Audit


Testing

Certification

Certificate

MDCG

Eudamed

National Authority Manufacturer

↓

Notified Body

Expert Panel

What is needed in the transition period?

To June 2016 MEDDEV 2.7/1 rev. 3 and

Directives

Transition MEDDEV 2.7/1 rev. 4, Directives and MDR

Future Amendements to the MEDDEV

2.7/1 rev. 4 and MDR

http://ec.europa.eu/growth/sectors/medical-devices/guidance/index_en.htm

TÜV SÜD Slide 140




QMS Procedures State of the Art Expectations

TÜV SÜD Slide 141

The notified body shall, as part of the review of the manufacturer’s quality system, assess the establishment, maintenance and application of the manufacturer’s documented procedures for the evaluation of clinical data. • the proper assignment of responsibilities to suitably

qualified persons involved in the clinical evaluation • the integration of clinical evaluation into the quality system as a

continuous process, to be specifically inter-related to, and informed by, preclinical evaluation and risk management

• standard operating procedures to assure proper planning, conduct, evaluation, control and documentation planning of the clinical evaluation, identification of clinical data, literature searching, collection of clinical experience, clinical investigation, appraisal of clinical data, analysis of clinical data (previous section), concluding, reporting and update of clinical evaluation, procedures, reporting and updating based on data from the PMS system and from PMCF (MEDDEV 2.12/2 rev.2)

• document control as part of overall documentation of procedures, reporting, qualifications and technical documentation

• identification and evaluation of undesirable side-effects and of clinical performance(s)

Stay informed about the expected changes and prepare for transition

TÜV SÜD Slide 142

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-america.com/mdr

In Vitro Diagnostic Device Regulation: www.tuv-sud-america.com/ivdr



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

Presentations & Public Speaking

New European Medical Device Regulations: Keeping Your Orthopaedic and Spine Products on the Market - OMTEC 2017