The following listed GSPRs shall require clinical data.
1.
Normal
conditions of the intended use of the device
2.
Evaluation
of the undesirable side-effects
3.
Acceptability
of the benefit-risk- ratio (Sections 1 and 8 of Annex I)
Medical device characteristics
and its intended purpose shall determine the level of clinical evidence
required to demonstrate the conformity with the relevant GSPRs. Level of
clinical evidence need to specify and justified by the manufacturer.
Clinical evaluation is
one of the general obligations of manufacturers (Article 10). Clinical
evaluation is conducted per Article 61 and Part A of Annex XIV.
Clinical evaluation
definition is given below.
|
MDR |
Meddev 2.7.1 Rev 4 |
Meddev 2.7.1 Rev 3 |
|
clinical evaluation’ means a systematic and
planned process to continuously generate, collect, analyse and assess
the clinical data pertaining to a device in order to verify the
safety and performance, including clinical benefits, of the device when
used as intended by the manufacturer; |
A methodologically sound ongoing procedure to collect,
appraise and analyse clinical data pertaining to a medical device and to
evaluate whether there is sufficient clinical evidence to confirm compliance
with relevant essential requirements for safety and performance when
using the device according to the manufacturer’s Instructions for Use. |
Clinical evaluation is the assessment and analysis
of clinical data pertaining to a medical device in order to verify the
clinical safety and performance of the device. |
Clinical evaluation
shall follow a defined and methodologically sound procedure based on the
following:
·
a
critical evaluation of the relevant scientific literature
·
a
critical evaluation of the results of all available clinical investigations*
·
a
consideration of currently available alternative treatment options for that
purpose, if any.
Based on MDR, the
below listed options are available to perform CER.
1. MDR Article 61, Section 10. Appropriate to justify no clinical data
required
2. Literature
a. Subject Devices: Critical evaluation
of relevant scientific literature or
b. Equivalent devices:
Critical evaluation of relevant scientific literature or
c. both
3. Clinical investigations / other clinical experience (e.g. PMS/PMCF)
a. Subject Devices: Critical evaluation of
the results of all available clinical investigations / other clinical
experience (e.g. PMS/PMCF) or
b. Equivalent devices: Critical evaluation of
the results of all available clinical investigations / other clinical
experience (e.g. PMS/PMCF) or
c. both
4. Critical evaluation of combined clinical data
Clinical
evaluation of Implantable and Class III devices must use
clinical investigations data. There are some exemptions are given in article 61
section 5 to 7.
Section
4:
1.Same
manufacturer à Modified their existing marketed device
2.Equivalence
demonstration (Section 3 of Annex XIV): Modified device vs marketed device
3.CER
of the marketed device is sufficient to demonstrate conformity of the modified
device relevant GSPRs.
4.Modified
device PMCF plan shall includes post market studies to demonstrate the safety
and performance
Section
5:
1.Manufacturer
à Modified existing marketed device (Different manufacturer)
2.
Contract between two manufacturers to get full technical documentation access
3.
Existing marketed device Clinical evaluation shall follow MDR requirements and
this needs to be submitted to notified body
4.Modified
device PMCF plan shall include post market studies to demonstrate the safety
and performance
Section
6:
1.Class
III and implantable devices are placed on market as per Directive 90/385/EEC or
93/42/EEC
and have sufficient clinical data and is in compliance with Common
Specifications (CS) (if available); or
2.
Device is a Well-Established Technology (WET) and clinical evaluation is based
on sufficient clinical data and is in compliance with the relevant product-specific
CS (if available)
“sufficient
clinical evidence” is understood as “the present result of the qualified
assessment which has reached the conclusion that the device is safe and
achieves the intended benefits”. It is important to note that clinical
evaluation is a process where this qualified assessment has to be done on a
continuous basis.
Manufacturer
technical documentation shall have an adequate justification to demonstrate
conformity with GSPRs based on the non-clinical testing methods alone.
The
following points need to be considered while providing the justification
·
based on the results
of the manufacturer's risk management and
·
on consideration of
the specifics of the interaction between the device and the human body,
·
the clinical
performance intended and the claims of the manufacturer.
Plan
shall include the below points,
|
CEP Contents |
|
Identification of the
applicable GSPRs |
|
Intended purpose,
Intended target groups with clear indications and contra-indications |
|
Intended clinical
benefits to patients with relevant and specified clinical outcome parameters |
|
Specification of methods
to be used for examination of qualitative and quantitative aspects of
clinical safety with clear reference to the determination of residual risks
and side-effects |
|
Indicative list and
specification of parameters to be used to determine, based on the state of
the art in medicine, the acceptability of the benefit-risk ratio for the
various indications and for the intended purpose or purposes of the device |
|
An indication how
benefit-risk issues relating to specific components such as use of
pharmaceutical, non- viable animal or human tissues, are to be addressed |
|
Clinical development plan |
|
MDD
DEV 2.7.1 rev4 clinical evaluation |
MDR
clinical evaluation |
|
Stage 0: Define the scope, plan the clinical evaluation (also referred
to as scoping and the clinical evaluation plan). |
1.To plan,
continuously conduct and document a clinical evaluation, a manufacturer
shall: (a)establish and
update a clinical evaluation plan, (including clinical
development plan) |
|
Stage 1: Identify pertinent data. |
(b)Identify
available clinical data relevant to the device and its intended purpose and
any gaps in clinical evidence through a systematic scientific literature
search; |
|
Stage 2: Appraise each individual data set,
in terms of its scientific validity, relevance and weighting. |
(c)Appraise all
the clinical data sets by evaluating their suitability for establishing the
safety and performance of the device; |
|
(d)
Generate, through properly designed clinical investigations in accordance
with the clinical development plan, any new or additional clinical data
necessary to address outstanding issues; |
|
|
Stage 3: Analyze the data, whereby conclusions are reached about. Stage 4: Finalise the clinical evaluation report |
(e) Analyze all
relevant clinical data to reach conclusions about the safety and clinical
performance including its clinical benefits. |
|
Characteristics |
MDD DEV 2.7.1 rev4
clinical evaluation |
MDR ANNEX XIV Section 3 |
|
Clinical |
- same clinical condition
(including when applicable similar severity and stage of disease, same
medical indication), and - used for the same
intended purpose, and - used at the same site in
the body, and - used in a similar
population (this may relate to age, gender, anatomy, physiology, possibly other aspects),
and - 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.). |
-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. |
|
Technical |
- be of similar design, and - used under the same
conditions of use, and - 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), and - use similar deployment
methods (if relevant), and - have similar principles
of operation and critical performance requirements. |
-the device is of similar
design; -used under similar
conditions of use; -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; -similar principles of
operation and critical performance requirements; |
|
Biological |
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; |
Use the same materials or
substances in contact with the same human tissues or body fluids. Exceptions can be foreseen for devices
in contact with intact skin and minor components of devices; in these cases
risk analysis results may allow the use of similar materials taking into
account the role and nature of the similar material. Different aspects of equivalence
and compliance to different Essential Requirements can be affected by
materials. Evaluators should consider
biological safety (e.g. in compliance to ISO 10993) as well as other aspects
necessary for a comprehensive demonstration of |
Notified
body will share the CER of class III and class IIb devices to expert panel to
scrutinise their clinical evaluation assessment report.
Below listed cases where this procedure is not applicable.
·
Renewal of a
certificate issued under MDR
·
Same manufacturer à Modified their existing marketed
device for the same intended purpose. Manufacturer demonstrated that the
modifications do not adversely affect the benefit-risk ratio of the device. Per
MDCG 2019-3 “device already marketed” cannot be intended to refer
to a device already marketed uniquely under the new Regulation (MDR)
·
clinical evaluation is
based on sufficient clinical data and is in compliance with the relevant
product-specific CS.
MDR
provides the timelines for class III & implantable devices. CER shall have
a justification for frequency of update
CER
shall be updated throughout the life cycle of the device using clinical
data obtained from the post market clinical follow-up (PMCF)
|
Class |
Timelines |
|
Class III/Implantable
devices (Class II b/II a) |
Annually
(Article 61(11)) |
|
Class II b Non Implants |
Annually (based on
PSUR timelines) |
|
Class II a Non Implants |
Every 2 years (based
on PSUR timelines) |
|
Class I |
When required based
on PMS timelines) |
References:
1. MDCG 2020-5 Clinical Evaluation - Equivalence A guide for manufacturers
and notified bodies
2. MDCG 2020-6 Regulation (EU) 2017/745: Clinical evidence needed for
medical devices previously CE marked under Directives 93/42/EEC or 90/385/EEC
.A guide for manufacturers and notified bodies
3. MDCG 2019-3 Interpretation of Article 54(2)b
4. Boobalan C., & Mathiyazhagan.M (2017). Medical Devices-Clinical
Evaluation Reports
(MDR-CER) [White paper]. HCL technologies. https://www.hcltech.com/white-papers/engineering-and-rd-services/medical-devices-clinical-evaluation-reports
5. Boobalan C., & Mathiyalazhan.M (2019). TECHNICAL DOCUMENTATION
REMEDIATION European Medical Device Regulations 2017/745. HCL technologies. https://www.hcltech.com/white-papers/engineering-and-rd-services/technical-documentation-remediation-european-medical-device
6. REGULATION (EU) 2017/745 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL
of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation
(EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council
Directives 90/385/EEC and 93/42/EEC
7. MEDDEV 2.7.1 Rev 4. CLINICAL EVALUATION:A GUIDE FOR MANUFACTURERS AND
NOTIFIED BODIES
UNDER DIRECTIVES 93/42/EEC and 90/385/EEC
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