This document summarizes key aspects of clinical evaluation requirements for medical devices in Europe. It discusses the stages of clinical evaluation, including scope definition, identification of pertinent clinical data, appraisal of data, and analysis of clinical data. It notes that clinical evaluation is mandatory for initial CE marking and must be updated. It outlines criteria for determining the quality, relevance and contribution of clinical data sources. Equivalence must be demonstrated when using data from equivalent devices. Clinical investigations are generally required for class III and implantable devices to demonstrate safety and performance.

1. By Katarzyna Zofia Chrusciel
1
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.

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MDR wording regarding clinical data

3. Why?
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(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.

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 establish, execute, maintain and document a system for risk
management (RMS)as described in Section 1a in Annex I.
 conduct a clinical evaluation (CER) in accordance with the
requirements set out in Article 61 and Annex XIV, including post-
market clinical follow-up (PMCF).
 draw up and keep up to date the technical documentation
(TD)… include the elements set out in Annex II, etc.
Manufacturers shall

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Stages of the Clinical Evaluation
Equivalent Approach
Clinical Expertise (Evaluator Expectations)
Update of the Clinical Evaluation
Devices for unmet medical needs
Key concepts

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First performed during the development of a
medical device
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
When is a clinical evaluation undertaken?

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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?

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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

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Stages of a
clinical
evaluation and
references to
sections and
appendices of
MEDDEV 2.7.1
REV.04.
By Katarzyna Zofia Chrusciel

11. 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.
10/04/2018 By Katarzyna Zofia Chrusciel

12. Stage 0 – Scope Definition and Clinical Evaluation Plan
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13. Stage 0 – Scope Definition and Clinical Evaluation Plan
The scope serves as a basis for further steps, including the
identification of pertinent data
Device description  Clinical Evaluation Plan
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14. Stage 0 – Scope Definition and 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)
10/04/2018 By Katarzyna Zofia Chrusciel

15. Stage 0 – Scope Definition and Clinical Evaluation Plan
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)
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16. Stage 1 – Identification of pertinent data
Data generated and held by the manufacturer
Data retrieved from literature
AND/OR
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17. 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
Chapter 9.1 Data generated and held by the manufacturer
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18. Clinical Data Sources
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Clinical StudiesClinical Studies
Clinical Studies (any kind,
systematic search strategy)
Systematic Reviews:
Cochran
HTA
Meta-analysis
Guidelines, Consensus
Papers
Market Experience /Market Experience /
Real World Evidence
Implant
Registries:
National
Regional
Institutional
Manufacturers

19. Clinical Data Sources (some…)
10/04/2018 By Katarzyna Zofia Chrusciel
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 / scientific database
can change over time /Criteria need to be defined and re-
evaluated

20. Clincial Data Sources - Goals
10/04/2018 By Katarzyna Zofia Chrusciel
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

21. Clinical Data Sources - Registries
10/04/2018 By Katarzyna Zofia Chrusciel
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
In fact any data collection without defined termination:

22. Stage 1 – Identification of pertinent data
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
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23. 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:
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24. Clinical Evidence
Sufficient clinical evidence - an amount and quality of
clinical evidence to guarantee the scientific validity of the
conclusions.
MEDDEV rev.4 :
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25. Stage 2 – Appraisal of pertinent data Appraisal Plan (9.2)
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Determine
the value
of each
data
Quality of the
data
http://www.consort-
statement.org/
Weight the
contribution
Relevance of
the data

26. Conduct of Appraisal
10/04/2018 By Katarzyna Zofia Chrusciel
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.

27. Appraisal Plan
10/04/2018 By Katarzyna Zofia Chrusciel
Examples of aspects that can be taken into consideration for
evaluating the methodological quality and the scientific validity
of the evidence are reported in Appendix C: Some Examples to
Assist with the Formulation of Criteria SG5/N2R8:2007

28. Reporting guidelines for main study types
10/04/2018 By Katarzyna Zofia Chrusciel
Randomised trials CONSORT Extensions Other
Observational studies STROBE Extensions Other
Systematic reviews PRISMA Extensions Other
Case reports CARE Extensions Other
Qualitative research SRQR COREQ Other
Diagnostic / prognostic studies STARD TRIPOD Other
Quality improvement studies SQUIRE Other
Economic evaluations CHEERS Other
Animal pre-clinical studies ARRIVE Other
Study protocols SPIRIT PRISMA-P Other
Clinical practice guidelines AGREE RIGHT Other

29. Determination of Relevance
10/04/2018 By Katarzyna Zofia Chrusciel
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

30. Determination of Relevance
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See the MEDDEV 2.7/1 revision 4 p.25

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34. Stage 3 – Analysis of the clinical data
10/04/2018 By Katarzyna Zofia Chrusciel
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

35. Comprehensive Analysis
10/04/2018 By Katarzyna Zofia Chrusciel
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.

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Mapping Guide to map the MDR Safety and Performance
Requirements (SPRs) to the Essential Requirements for
Medical Device Directive (MDD)

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MDR
SPRs
Description of the three categories
MDD
ERs
1
Performance and safety
SPR 1 generally corresponds to MDD ER 1. In fact, much of the
text is the same. This requirement states that the devices shall
be ‘designed and manufactured in such a way’ that safety of
patients and users shall not be compromised. As with ER 1 in
the directives, this is under the normal conditions of use.
The concept of ‘performance’ is brought in from MDD ER 3 to
this requirement. The design and construction should conform to
safety principles, taking into account the ‘generally
acknowledged state of the art’ as required in to MDD ER 2.
The risks related to ergonomic features and consideration of the
use environment, present in MDD ER 1, have been moved to
SPR 5.
1, 2, 3

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MDR
SPRs
Description of the three categories
MDD
ERs
5
Risks related to use
SPR 5 addresses reduction of risks relating to use error.
This requirement generally corresponds to the latter part of ER
1 in the MDD. As already required by the MDD, the risk of use
error shall be reduced as far as possible including ergonomic
considerations and the knowledge, experience and types of
users (e.g. clinicians, patients or caregivers). This is commonly
known as usability or human factors. These requirements are
now explicitly included in the MDR.
1

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MDR
SPRs
Description of the three categories
MDD
ERs
8
Risk-benefit ratio
The MDR includes an updated definition of the ‘risk-benefit
ratio’ to be assessed by the manufacturer in SPR 8. This risk-
benefit evaluation per MDD ER 6 corresponds to new SPR 8. It
now includes ‘all known and foreseeable risks,’ and that the
risks ‘shall be minimized.’ The risks are explicitly weighed
against the ‘evaluated benefits to the patient and/or user
arising from the achieved performance,’ rather than the
‘performances intended.’ Lastly, the risk-benefit evaluation is
clarified to be ‘during normal conditions of use.’ This might
be interpreted as per the intended use and reasonably expected
conditions of use. The intent of the risk-benefit evaluation
remains the same, and the requirement itself is not new
compared to the two Directives.
6, (1)

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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

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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)
Stage 3 – Analysis of the clinical data

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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
Stage 3 – Analysis of the clinical data

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MDR - Article (61) 6.a
The requirement to perform clinical investigations pursuant
to previously presented requirements shall not apply to
implantable devices and devices falling into class III:
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

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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.

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Post-Approval Requirements op Medical Device Manufacturer
The manufacturers should:
establish a comprehensive post-market
surveillance (PMS) system
set up under the quality management
system
and based on a PMS plan.

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Post-Approval Requirements op Medical Device Manufacturer
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.

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Post-Approval Requirements op Medical Device Manufacturer
PMCF
(Yes/No)
Residual
Risks
Unanswer
ed
Questions
Uncertai
nties
Rare
Complica
tions
Medium-
and Long-
Term
Performa
nce
Medium-
and Long-
Term
Safety
Wide-
spread
use

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Post-Approval Requirements op Medical Device Manufacturer
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.

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Is a PMCF Always a Clinical Study?
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.
A PMCF can follow several methodologies, such as:

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Is a PMCF study required for CE Marking?
For CE Marking applications of medical devices, all medical devices
are required to have evidence of a post-market clinical follow-
up (PMCF) study protocol or a justification for why a post-
market clinical follow-up (PMCF) study is not required.
justification ≠ post-market surveillance (PMS) procedure
justification ≠ post-market surveillance (PMS) plan for product
family
justification ≠ because the device is similar to several other
devices on the market (Substantial Equivalence)

51. 10/04/2018 By Katarzyna Zofia Chrusciel
Why Substantial Equivalence Isn’t Enough
Because although products can be approved for CE Marking based
upon substantial equivalence, the manufacturer must continue to
monitor the performance of the device after the product is
launched to make sure of two critical things:
Is the equivalent device actually as safe and efficacious?
Are there new risks that are identified when the device is
used for a long duration (e.g., implanted), by a broader user
population or to treat a broader patient population / broader
indication for use?

52. 10/04/2018 By Katarzyna Zofia Chrusciel
PMCF Justification example
The Post-market clinical follow-up studies (PMCF) are not required
because the medium/long-term safety and clinical performance are
already known from previous use of the device and because other
appropriate post-market surveillance activities have provide sufficient
data to address the risks.

53. 10/04/2018 By Katarzyna Zofia Chrusciel
A PMCF study MIGHT be needed…example
If you have a high-risk device that is
implantable, has an innovative design
and you are using new treatment for the
patient contacting materials you obviously
need a post-market clinical follow-up
study. If you make a generic version of
sterile bandage with a Cartoon for
decoration, you obviously don’t need
PMCF study.

54. 10/04/2018 By Katarzyna Zofia Chrusciel
A PMCF study MIGHT be needed
Most products fall into the “might be needed” category rather than
a “yes” or “no.”
You need the systematic methods of evaluation.

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Step-by-Step Procedure: How to?
Step 1 – Read MEDDEV 2.12/2.
Step 2 – Make a table with each of the 17 “might be needed”
categories from the guidance document in the far left column.
Step 3 – In the second column, indicate whether the risk category
from the table applies to your device–”yes” or “n/a.”

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Step-by-Step Procedure: How to?
Step 4 – As with all good checklists, you need to explain your
rationale for non-applicability wherever the category doesn’t apply.
Enter your explanation in the third column next to the “N/A”

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Step-by-Step Procedure: How to?
Step 5 – If you typed “yes” in the second column, then you need to
provide a cross-reference to the information in your technical
documentation (TD) that explains how you address this risk.

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Step-by-Step Procedure: How to?
Step 5 – continued…
There are three places you can look:
1) your design requirements
2) as a risk control in your risk analysis that you performed
during the design process prior to “design freeze”,
3) in your clinical evaluation report (CER).
Ideally, you can easily cross-reference to a section of you controlled
document that is in outline format.

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Step-by-Step Procedure: How to?
Step 6 – After you add a cross-reference to the risk control(s) in
your table, now you need to indicate whether the risk controls are
adequate or not.
“Yes” is probably the answer only if you can cross-reference to a
state-of-the-art guidance document or harmonized standard
that has been implemented as a pre-market risk control to
evaluate the specific risk.

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Step-by-Step Procedure: How to?
Step 6 – continued…
For longevity of implants, usability by all intended users and
patient satisfaction the tests are seldom adequate; while usability
and patient selection often are only evaluated by clinical studies. If
the tests and pre-market clinical studies are not adequate, then
“No” is your your answer and you need to conduct a post-
market clinical follow-up (PMCF) study in order to address
that specific residual risk.

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Step-by-Step Procedure: How to?
Step 7 – If you indicate that your pre-market risk controls are
adequate, then in your post-market surveillance plan you can
indicate “no post-market clinical follow-up (PMCF) study
required.” However, if you were unable to verify that your pre-
market risk controls are adequate to address one of the 17 risk
categories identified in MEDDEV 2.12/2, then you need to conduct a
post-market clinical follow-up (PMCF) study.

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What is a proactive PMS?
Planned Customer Surveys
Prospective and retrospective PMCF or trial
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
Examples of PROACTIVE PMS Methods:

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What is a reactive PMS?
Customer Complaints
Unsolicited User Feedback
Maintenance/Service Reports
Routine and not planned In-house Testing
Investigati Initiated Studies (IIS)
Social Media Analysis
Literature Review
Published Data from Regional or National Device Registries
Expert Opinion
Examples of REACTIVE PMS Methods

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Promotional Material
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
All promotional material (incl. website content) will be
assessed by the Notified Body

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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.

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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

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The clinical evaluation report example
1. SUMMARY
2. SCOPE OF THE CLINICAL EVALUATION
3. CLINICAL BACKGROUND, CURRENT KNOWLEDGE, STATE OF THE ART
3.1 Search protocol
3.1.1 Search methods for identification of studies
3.1.2 Electronic searches
3.1.3 Searching other resources
3.2 Literature search report
3.2.1 Device name/model
3.2.2 Scope of the literature search
3.2.3 Methods
3.2.4 Literature sources used to identify data
3.2.5 Database search details
3.2.5 Selection criteria used to choose articles
3.2.5 Outputs
3.2.5 Data selection process
3.3 A review of the current knowledge/ the state
3.3.1 Other references

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The clinical evaluation report example
4. DEVICE UNDER EVALUATION
4.1. Type of evaluation
4.2. Demonstration of equivalence (only when equivalence is claimed)
4.3 Clinical data generated and held by the manufacturer
4.5.1 Pre market Tests
4.5.2 Trend reports
4.5.3 PMS reports
4.5.4 Customer Complaints
4.5.5 Corrective and Preventive Action
4.4 Clinical data from literature
4.5 Summary and appraisal
(Summary of findings, Characteristics of ongoing studies, Excluded studies)

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The clinical evaluation report example
4.6. Analysis of the clinical data
4.6.1. Requirement on safety (MDD ER1)
4.6.2. Requirement on acceptable benefit/risk profile (MDD ER1)
4.6.3. Requirement on performance (MDD ER3)
4.6.4. Requirement on acceptability of side-effects (MDD ER6)
5. CONCLUSIONS
6. DATE OF THE NEXT CLINICAL EVALUATION
7. DATES AND SIGNATURES
8. QUALIFICATION OF THE RESPONSIBLE EVALUATORS
9. DECLARATION OF INTERESTS FOR CLINICAL EVALUATION REPORT
10. DEFINITIONS
11. SOURCES
12. ATTACHMENTS

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The clinical evaluation report - ATTACHMENTS
Attached 1 Full-text of relevant documents
Attached 2 Post-market data
Attached 3 Equivalent and simile devices
Attached 4 CVs

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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.

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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:

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MDR XIV §3 - 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;

74. 10/04/2018 By Katarzyna Zofia Chrusciel
MDR XIV §3 - Demonstration of Equivalence
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;

75. 10/04/2018 By Katarzyna Zofia Chrusciel
MDR XIV §3 - Demonstration of Equivalence
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.

76. 10/04/2018 By Katarzyna Zofia Chrusciel
MDR XIV §3 - Demonstration of Equivalence
The characteristics listed in before 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.

77. 10/04/2018 By Katarzyna Zofia Chrusciel
Is this a New Definition of Equivalence?
MEDDEV 2.7/1, Rev. 3 Appendix F, p.42

78. 10/04/2018 By Katarzyna Zofia Chrusciel
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

79. 10/04/2018 By Katarzyna Zofia Chrusciel
Clinical Equivalence
https://aospine.aofoundation.org/Structure/Pages/default.aspx

80. 10/04/2018 By Katarzyna Zofia Chrusciel
Clinical Equivalence
used for the same intended purpose
used at the same site in the body

81. 10/04/2018 By Katarzyna Zofia Chrusciel
Clinical Equivalence
•Used in a similar population (this may relate to age, gender*,
anatomy, physiology, possibly other aspects*)
*Not included in the MDR XIV §3
Syrup for dry and productive cough
Tussolven (PA) vs DicoTUSS baby med (P)

82. 10/04/2018 By Katarzyna Zofia Chrusciel
Clinical Equivalence
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.).

83. 10/04/2018 By Katarzyna Zofia Chrusciel
Technical Equivalence
be of similar design
comparative drawings or pictures should be included in order to compare
shapes and sizes of elements that are in contact with the body

84. 10/04/2018 By Katarzyna Zofia Chrusciel
used under the same conditions of use
≠
Technical Equivalence

85. 10/04/2018 By Katarzyna Zofia Chrusciel
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!
Technical Equivalence

86. 10/04/2018 By Katarzyna Zofia Chrusciel
Demonstration of equivalence exaples
Technical Equivalence
It is not necessary that A1 and A2 are from the identical
supplier and are manufactured under identical process
parameters with the identical machinery
Same Material
Same ≠ Identical
Polymer A1 = Polymer A2

87. 10/04/2018 By Katarzyna Zofia Chrusciel
Technical Equivalence
Demonstration of equivalence
=
The ability of the manufacturer to access information that
are relevant to the demonstration of equivalence.

88. 10/04/2018 By Katarzyna Zofia Chrusciel
Technical Equivalence
Scenario A Scenario B Scenario C
The manufacturer A
has full access to the
technical
documentation of
manufacturer B
(eg.OEM with OBL,
VM)
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
The manufacturer A
develops devices that
are following
specifications set in
the standard or in
guidance
documents

89. 10/04/2018 By Katarzyna Zofia Chrusciel
Biological Equivalence
Use the same materials or substances in contact with the same
human tissues or body fluids

90. 10/04/2018 By Katarzyna Zofia Chrusciel
New European Medical Device Regulations
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.
A = B AND A = C
A ≠ B +C

91. 10/04/2018 By Katarzyna Zofia Chrusciel
New European Medical Device Regulations
Clinical, technical and biological characteristics shall be taken
into consideration for the demonstration of equivalence

92. 10/04/2018 By Katarzyna Zofia Chrusciel
New European Medical Device Regulations
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

93. 10/04/2018 By Katarzyna Zofia Chrusciel
New European Medical Device Regulations
Equivalence:
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

94. 10/04/2018
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)
By Katarzyna Zofia Chrusciel

95. 10/04/2018
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
By Katarzyna Zofia Chrusciel

96. 10/04/2018
Examples when equivalence is not demonstrated
By Katarzyna Zofia Chrusciel

97. 10/04/2018
Examples when equivalence is not demonstrated
By Katarzyna Zofia Chrusciel
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)

98. 10/04/2018
MDR Art. 61
By Katarzyna Zofia Chrusciel
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

99. 10/04/2018
Who should perform a clinical evaluation? (chapter 6.4)
By Katarzyna Zofia Chrusciel
The evaluators should possess knowledge of the following
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);

100. 10/04/2018
Who should perform a clinical evaluation? (chapter 6.4)
By Katarzyna Zofia Chrusciel
The evaluators should possess knowledge of the following
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);

101. 10/04/2018
Who should perform a clinical evaluation? (chapter 6.4)
By Katarzyna Zofia Chrusciel
Minimum experience in the relevant medical field
A higher degree & 5 years of documented professional experience
10 years of documented professional experience (if higher degree is
not a prerequisite)
There may be circumstances where the level of evaluator expertise
may be less or different; this should be documented and duly
justified.

102. 10/04/2018
Who should perform a clinical evaluation? (chapter 6.4)
By Katarzyna Zofia Chrusciel
From whom will we expect the CV?
The Clinical Evaluator
The Clinical Evaluation Team
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
What will be audited?

103. New European Medical Device Regulations
Categor 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
Who should perform a clinical evaluation?

104. MEDDEV 2.7/1 Rev. 4
Declarations of Interests (A11)
Typical contents
 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
10/04/2018 By Katarzyna Zofia Chrusciel

105. MEDDEV 2.7/1 Rev. 4
 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
10/04/2018 By Katarzyna Zofia Chrusciel

106. Updating CER MEDDEV 2.7/1 Rev. 4
10/04/2018 By Katarzyna Zofia Chrusciel
Which device shall beWhich device shall be
updated annually?
Not well establish
devices
Implantable devices and
Class III devices
Class IIb active devices
intended to administer
and/or remove a medicinal
product
When is a deviceWhen 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

107. Updating CER MEDDEV 2.7/1 Rev. 4
10/04/2018 By Katarzyna Zofia Chrusciel
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

108. Updating CER MEDDEV 2.7/1 Rev. 4
10/04/2018 By Katarzyna Zofia Chrusciel
When updating the clinical evaluation, the evaluators should
verify:
if existing claims are still justified
if new claims the manufacturer intends to use are substantiated

109. New European Medical Device Regulations
10/04/2018 By Katarzyna Zofia Chrusciel
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.

110. New European Medical Device Regulations
10/04/2018 By Katarzyna Zofia Chrusciel
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

111. SUMMING UP
10/04/2018 By Katarzyna Zofia Chrusciel
The Safety and Performance requirements identified in Annex I do
not include a specific requirement for Clinical Evidence.
Requirements related to clinical data and clinical evaluations are now
defined in Article 2, Article 61 and Annex XIV. Many of the
requirements of the Regulation are covered by MedDev 2.7.1 Rev 4.

112. Class III and IIb implants: clinical investigations are required unless
exclusions described in Article 61(4) – (6) apply, and justification in
accordance with Article 61(7) is provided
Class III implants and IIb devices intended to remove or administer
a medicinal substance: will be subject to an additional EU scrutiny
process, including assessment of the clinical evaluation, information
for use, and PMCF plan (Article 55)
10/04/2018 By Katarzyna Zofia Chrusciel
SUMMING UP - Some key issues to consider are

113. Class III and Class IIb active devices intended to remove or
administer a medicinal substance: Manufacturers may request a
consultation from an expert panel prior to its clinical evaluation and /
or investigation (Article 61(2))
10/04/2018 By Katarzyna Zofia Chrusciel
SUMMING UP - Some key issues to consider are

114. A clinical evaluation and development plan (Annex XIV Part A(1a))
Summary of Safety and Clinical Performance (Article 32), with
frequency of update described in Article 61
For Class III and Class IIb active devices intended to remove or
administer a medicinal substance: evidence related to any expert
consultations requested under Article 61(2)
10/04/2018 By Katarzyna Zofia Chrusciel
SUMMING UP - You will also need to provide

115. The Regulation applies to clinical investigations conducted in
the EU concerning devices/products which fall within the
scope.
Clinical investigations are required to be carried out as per Chapter
VI and NB reviews of clinical investigation data will check for
conformity to Annex XV.
10/04/2018 By Katarzyna Zofia Chrusciel
SUMMING UP - You will also need to provide

116. As per Article 120 on-going Clinical Investigations conducted in
accordance with 93/42/EEC and 90/385/EEC may continue, however
reporting of serious adverse event will need to be in
accordance with the Medical Devices Regulation.
10/04/2018 By Katarzyna Zofia Chrusciel
SUMMING UP - You will also need to provide

117. 10/04/2018 By Katarzyna Zofia Chrusciel
SUMMING UP - You will also need to provide
You should review the MDR requirements to identify provisions you
will need to make to ensure the clinical investigations requirements
will be met for your products. Document gaps between EN ISO
14155 and the MDR.
Please note: Reporting of Serious Adverse events must now
follow the MDR, and as such you should have provisions in place.

118. 10/04/2018 By Katarzyna Zofia Chrusciel
Fine
THANK YOU