WELCOME TO THE COURSE

 The course is spread over 3 days with adequate breaks in between

 There will be an open-book online test at the end of the course
 You will be provided with an soft copy of participant’s material before the
test begins
 Some of the material in this presentation are taken from publicly
available sources.
 The EU MDR is a very complex document. This training aims to simplify it
as far as possible but doesn’t claim to cover each and every aspect of the
evolving regulation
2
Agenda day 1
▸ 1. Framework
▸ 2. Economic Operators
▸ 3. Actors in the regulatory structure
▸ 4. Classification
▸ 5. Eudamed
▸ 6. Declaration of Conformity
▸ 7. Risk Management
▸ 8. General Safety & Performance Requirements

3
Agenda day 2
▸ 1. General Safety & Performance Requirements
▸ 2. UDI
▸ 3. Implant Card
▸ 4. Clinical Evaluation

4
Agenda day 3
▸ 1. Clinical Investigations
▸ 2. PMS
▸ 3. Reporting
▸ 4. Technical Documentation
▸ 5. Routes for assessment
▸ 6. QMS
▸ 7. Transitional Provisions
▸ 8. Test

5
MDR
FRAMEWORK
Purpose of the MDR

 For free movement of goods and services in the EU

 High level of protection of health for patients and users

2
Triggers
 Variation in interpretation among member states
 Loose oversight of NBs leading to fraudulent practices

3
The final trigger was a series of scandals, most notable
among them being the PIP scandal
Achieving the purpose
 Stricter approval of high-risk devices
 Reinforcement of the criteria for designation & processes for
oversight of NBs
 Inclusion of certain aesthetic devices
 Improved transparency
 Introduction of implant card
 Reinforcement of rules of clinical evidence
 Strengthening of PMS
 Improved co-ordination mechanisms between EU countries

5
Comparison with the MDD
MDD MDR
60 pages

12 Annexes

23 Articles

6
Medical device definition
‘Medical device’
 any instrument, apparatus, appliance, software, implant, reagent, material or other
article
 intended for human beings
 for diagnosis, prevention, monitoring, prediction, prognosis, treatment or
alleviation of disease,
 for diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury
or disability,
 for investigation, replacement or modification of the anatomy or of a physiological
or pathological process or state,
 for providing information by means of in vitro examination of specimens derived
from the human body, including organ, blood and tissue donations,
7
Medical device definition (contd)
 Which does not achieve its principal intended action by pharmacological,
immunological or metabolic means, in or on the human body, but which may
be assisted in its function by such means
 The following products shall also be deemed to be medical devices: —
 devices for the control or support of conception;
 products specifically intended for the cleaning, disinfection or
sterilisation of devices
 list provided in Annex XVI (devices without a medical purpose)

8
List of devices without medical purpose
 Contact lenses or other items intended to be introduced into or
onto the eye.
 Products intended to be totally or partially introduced into the
human body through surgically invasive means for the purpose of
modifying the anatomy or fixation of body parts with the
exception of tattooing products and piercings.
 Substances, combinations of substances, or items intended to be
used for facial or other dermal or mucous membrane filling by
subcutaneous, submucous or intradermal injection or other
introduction, excluding those for tattooing.

9
List of devices without medical purpose
(contd)
 Equipment intended to be used to reduce, remove or destroy adipose
tissue, such as equipment for liposuction, lipolysis or lipoplasty.
 High intensity electromagnetic radiation (e.g. infra-red, visible light and
ultra-violet) emitting equipment intended for use on the human body,
including coherent and non-coherent sources, monochromatic and
broad spectrum, such as lasers and intense pulsed light equipment, for
skin resurfacing, tattoo or hair removal or other skin treatment.
 Equipment intended for brain stimulation that apply electrical currents
or magnetic or electromagnetic fields that penetrate the cranium to
modify neuronal activity in the brain.

10
Legal Framework
 MDR is a regulation unlike MDD which is a directive
 The MDR is issued by the Commission. After the date of coming into
force, it becomes a law simultaneously in all the member states
without modification
 MDD was issued by the Commission but needed to implemented by
each member state after making necessary changes and ratified by
their parliament
 In case of the MDD if someone wants to sue a manufacturer or a NB
for instance, they have to do as per the local law of the member state
 In case of the MDR this has to be done through the European court.

11
Scope of the MDR
 Medical devices for general use including custom made
 Medical devices for clinical investigations
 Devices listed in Annex XVI A device without a medical purpose

 In-vitro diagnostic devices

 Active Implantable devices
A device offered by means of
 Distance Sales information society services, as
defined in point (b) of Article 1(1) of
Directive (EU) 2015/1535

12
CE mark (Art 20) & special purpose device (Art
21)
 Needed for placing on the market/putting into service– the CE mark
and the declaration of conformity
 But no CE mark required for:
 Devices for clinical investigation
 Custom made devices
 ‘Only for presentation/demonstration’and ‘not available on the EU
market’
 Health institutions are allowed to manufacture, modify and use
certain devices without a CE mark
13
Timelines for MDR
Timelines for MDR
Timelines for MDR
Timelines for MDR
DUTIES OF
ECONOMIC
OPERATORS
Agenda
 Who are the economic operators
 What are their roles and responsibilities

2
Economic Operators

MANUFACTURER
(ARTICLE 10)

AUTHORISED REPRTICLE
(A 11 AND 12)

IMPORTER (ARTICLE 13)

DISTRIBUTOR (ARTICLE 14)

PERSON WHO PUTS TOGETHER OR STERILIZES

SYSTEM OR PROCEDURE PACK
ARTICLE
( 22)
 Responsibilities
1
of the
manufacturer
Compliance to the MDR

When placing their devices on the market or putting them into

service, manufacturers shall ensure that they have been designed
and manufactured in accordance with the requirements of the MDR

5
Risk Management

Manufacturers shall establish, document, implement and maintain a

system for risk management

6
Clinical Evaluation

Manufacturers shall conduct a clinical evaluation including a PMCF

7
Technical Documentation
Manufacturers shall draw up and keep up to date technical
documentation for its devices. The technical
documentation shall be such as to allow the conformity of
the device to be assessed.

8
Declaration of Conformity

Manufacturers shall draw up an EU declaration of

conformity in accordance with Article 19, and affix
the CE marking of conformity in accordance with
Article 20.

9
Unique Device Identification

Manufacturers shall comply with the obligations relating to the

UDI system referred to in Article 27 and with the registration
obligations referred to in Articles 29 and 31.

Article 27: UDI

Article 29: Registration of devices
Article 31: Registration of economic operators

10
Maintaining Records

 Manufacturers shall keep the technical documentation, the

declaration of conformity and certificate for a period of at
least 10 years after the last device covered has been placed
on the market. In the case of implantable devices, the period
shall be at least 15 years.
 Provide that technical documentation to the Competent
Authority

11
Quality Management System
Manufacturers shall establish, document, implement, maintain,
keep up to date and continually improve a quality management
system that shall ensure compliance with this Regulation in the
most effective manner and in a manner that is proportionate to the
risk class and the type of device.

12
Post Market Surveillance

Manufacturers of devices shall implement and keep up to date the post

-
market surveillance system

13
Information to user

Manufacturers shall ensure that the device is accompanied by the

information as required by the GSPR in an official Union
language(s) determined by the Member State in which the device
is made available to the user or patient. The particulars on the
label shall be indelible, easily legible and clearly comprehensible
to the intended user or patient.

14
Recall Procedures

 Devices if found non-conforming must be corrected,

withdrawn or recall
 Inform the distributors, authorised representative and
importers
 Where the device presents a serious risk, manufacturers
shall immediately inform the competent authorities of the
Member States in which they made the device available and,
the notified body

15
Incident Reporting

Manufacturers shall have a system for recording and reporting of

incidents and field safety corrective actions as described in
Articles 87 and 88

Article 87: Reporting of serious incidents & FSCA

Article 88: Trend Reporting

16
Co-operation with Competent Authorities

 Provide CA of technical documentation if requested.

 Provide samples of the device free of charge or, where that is
impracticable, grant access to the device.
 Cooperate with a competent authority on any corrective action taken
to eliminate or mitigate the risks posed by devices which they have
placed on the market or put into service.

17
Information on outsourcing

Where manufacturers have their devices designed or manufactured

by another legal or natural person the information on the identity of
that person shall be provided to the Competent Authority
electronically

18
Liability Insurance

Manufacturers shall, in a manner that is proportionate to the risk class,

type of device and the size of the enterprise, have measures in place
to provide sufficient financial coverage in respect of their potential
liability under Directive 85/ 374/ EEC

Directive 85/ 374/ EEC: Product Liability Directive

19
Person responsible for regulatory compliance

▸ Degree or equivalent 4 years professional

recognized in EU in law, experience in regulatory affairs
medicine, pharmacy, or QMS of medical devices
engineering or another
OR
relevant scientific
discipline
▸ 1 year experience in
regulatory affairs or QMS of
medical devices

20
Responsibilities of the RA person (Art 15)

 Product release verification

 Technical documentation and Declaration of Conformity
 PMS
 Reporting obligations

21
Responsibilities of importers
 Verify that device is CE marked and a declaration of conformity is drawn up
 Device is labelled and IFU is there in accordance with the MDR
 Manufacturer is identified and EC Representative is designated
 Provide additional labelling mentioning its own name and place of business
 Verify that device is registered in EUDAMED
 Register itself in EUDAMED
 Maintain a register of complaints, non-conforming products, recalls and withdrawals
 Forward complaints to manufacturer
 Maintain declaration of conformity and certificate
 Device stored & transported as required by the manufacturer
 Co-operate with competent authority
22
Responsibilities of distributors
 Verify that device is CE marked and a declaration of conformity is drawn up
 The device is accompanied by an Information for Use
 UDI has been assigned
 Take appropriate action in case of a non-conforming device
 Device stored & transported as required by the manufacturer
 Forward all complaints to the manufacturer
 Co-operate with competent authorities
 Maintain traceability of devices

23
Responsibilities of EC Rep

 Verify that declaration of conformity and technical documentation are drawn up

 Verify that appropriate conformity procedures were followed
 Keep copy of technical documentation, declaration of conformity and CE certificate
 Register itself in EUDAMED
 Verify that manufacturer and devices are registered in EUDAMED
 Appoint a person responsible for regulatory compliance
 Co-operate with the Competent Authorities
 Forward any requests from Competent Authorities to manufacturer
 Inform manufacturer of any complaints
 Shall be legally liable for defective devices
24
Change in EC Rep

If an EC Rep is changed, a three

-party agreement must be drawn out
between manufacturer, the old EC Rep and the new EC Rep. This
agreement must cover the following:
 Date of termination of old contract and commencement of new
contract
 Date until which the old EC Rep name shall appear on label and
other materials
 Transfer of documents
 Obligation of old EC Rep for forwarding of complaints

25
Situations in which importers, distributors &
other persons become manufacturers (Art 16)
 Makes available on the market a device under its name, registered
trade name or registered trademark
 Changes the intended purpose of a device already placed on the
market or put into service
 Modifies a device already placed on the market or put into service
in such a way that compliance with the applicable requirements
may be affected

26
Re-processors of single-use devices
 A re-processor of a single-use device is considered as a manufacturer
 The re-processor must ensure that the device meets the original
general safety and performance requirements
 The re-processor must put his name and address on the label and IFU

27
Summary
 Economic operators include manufacturers, importers,
distributors and persons who sterilize or make procedure
packs
 Manufacturers & EC Rep have to appoint a person responsible
for regulatory compliance
 Manufacturers and EC Rep are now liable financially for
defective products
 Responsibilities of economic operators are now well defined

29
MODULE: ECONOMIC OPERATORS
GROUP EXERCISE

Review a distributor agreement and EC Rep

agreement. Identify if they need to be revised based
on the MDR? If yes, then what points must you add?
ACTORS & THEIR
ROLES
Actors within the Regulation

Commissi Competen Notified Medicine Expert Expert

MDCG EMA
on t Authority Body Authority Panels Labs

2
Medical Device Coordination Group
 Set up as per Article 103
 Consists of persons designated by the Member States based on their
role and expertise in the field of medical devices, for a 3 year term
 Provide advice to the Commission and to assist the Commission and
the Member States in ensuring a harmonised implementation of the
MDR.
 Full list of roles provided in Article 105

3
Notified Bodies
 Notified Bodies are approved by an authority appointed by the
Member State where the Notified Body exists
 Once a NB is designated, its name and scope is uploaded in the
NANDO database
 The NB’s activities are subject to review by the approving authority
 If a NB loses designation, then certificates remain valid till 9 months
with the condition that there is no safety issue and the another NB
assumes responsibility within 12 months
 NBs shall establish lists of their standard fees for their activities
and shall make those lists publicly available

4
European Medicine Agency & Medicine
Authorities
 Provide consultation to NB
 NB takes EMA’s opinion for devices with ancillary medicinal
products, products with human blood or tissue derivatives and
products that are wholly or partially absorbed
 Opinion for devices with ancillary medicinal products can also be
sought from a medicine authority appointed by the Competent
Authority

5
Expert Panels
Consultation to manufacturers on clinical
evaluation strategy for Class III & certain
Class IIb devices

Scrutinise clinical evaluation assessment

report of NB for Class III implantable &
certain Class IIb devices

Provide scientific advice to Commission &

MDCG

6
CLASSIFICATION
RULES
Agenda

 How many classes?

 Logic of classification
 Defining the classes
 Differences

2
I

IIa

IIb

III

3
Is Im Ir

4
Comparison between MDD & MDR

Group Rules
MDD MDR
Non-Invasive 1-4 1-4
Devices
Invasive Devices 5-8 5-8
Active Devices 9-12 9-13
Special Rules 13-18 14-22

5
Reusable Surgical Instrument
An instrument intended for surgical use in cutting, drilling, sawing,
scratching, scraping, clamping, retracting, clipping or similar
procedures, without a connection to an active device and which is
intended by the manufacturer to be reused after appropriate
procedures such as cleaning, disinfection and sterilisation have
been carried out.

6
Dispute Resolution
 Any dispute between manufacturer and NB regarding a classification of
a device has to be referred to the Competent Authority
 The Competent Authority shall notify the MDCG and the Commission of
its decision

7
 Location

Specific
Duration
materials

Class

8
 Transient < 1
hour

Duration
Short Term = 1
hour to 30 days
Long Term > 30
days

9
Continuous Use

Entire duration of use Accumulated use of a

when the device is device when a device is
temporarily removed for replaced by another device
purpose like cleaning & of the same type
disinfection

10
 Through
Surgically
natural body
invasive
orifice

Invasive

11
Non-Invasive Devices
RULE CHANGE CLASS

1 No change I

2 Storing of “cells” added I, IIa

2 Blood Bags (were in rule 18 in MDD) IIb

3 Added “modifying the biological or chemical composition IIa, IIb

of human tissues or cells, blood, other body liquids or
other liquids intended for implantation or administration”
3 Added “non-invasive devices consisting of a substance or III
a mixture of substances intended to be used in vitro in
direct contact with human cells, tissues or organs taken
from the human body or used in vitro with human embryos
before their implantation or administration”
12
Injured Skin or Mucous Membrane
An area of skin or a mucous membrane presenting a
pathological change or change following disease or a wound

13
Non-Invasive Devices
RULE CHANGE CLASS

4 Injured “mucous membrane” added to injured skin I, IIa, IIb

Applies also to invasive devices that come in contact with

injured mucous membrane

14
Surgically Invasive

Device enters the body Device which penetrates

surface including through other than through body
mucous membrane of body orifice
orifices in the context of a
surgical operation

15
Invasive Devices
RULE CHANGE CLASS

5 No change I, IIa, IIb

6 Specifies “direct contact with the heart or central III

circulatory system”
7 Specifies “direct contact with the heart or central III
circulatory system”

7 Added new item “are intended to administer medicines” IIb

16
Implantable Devices
Any device, including those that are partially or wholly absorbed, which
is intended:
 to be totally introduced into the human body
 to replace an epithelial surface or the surface of the eye, by clinical
intervention and which is intended to remain in place after the
procedure
 Any device intended to be partially introduced into the human body
by clinical intervention and intended to remain in place after the
procedure for at least 30 days shall also be deemed to be an
implantable device;
17
Implantable Devices
RULE CHANGE CLASS

8 Added “intended to administer medicinal products” III

Added “active implantable devices & their accessories” III

Added “breast implants and surgical meshes” III

Added “total or partial joint implants” III

Added “spinal disc replacement implants or are implantable III

devices that come in contact with the spinal column”

18
Active Device
Any device, the operation of which depends on a source of energy
other than that generated by the human body for that purpose, or
by gravity, and which acts by changing the density of or converting
that energy.

19
Active Devices
RULE CHANGE CLASS

9 Added “intended to emit ionizing radiation for therapeutic IIb

purposes, including devices which control or monitor such
devices, or which directly influence their performance”
Added “intended for controlling, monitoring or directly III
influencing the performance of active implantable
devices”
10 Illuminate the patient’s body in visible spectrum I

Intended for diagnosis in clinical situations where the IIb

patient is in immediate danger

20
Software
RULE CHANGE CLASS

11 Software intended to provide information which is used to take IIa

decisions with diagnosis or therapeutic purposes is classified
as classIIa, except if such decisions have an impact that may
cause:

death or an irreversible deterioration of a person's state of III

health

serious deterioration of a person's state of health or a surgical IIb

intervention

21
Software
RULE CHANGE CLASS

11 Software intended to monitor physiological processes is IIa

classified as classIIa, except if it is intended for:

monitoring of vital physiological parameters, where the nature IIb

of variations of those parameters is such that it could result in
immediate danger to the patient
All other software I

22
Active Devices
RULE CHANGE CLASS

12 Corresponds to rule 11 of MDD without changes. IIa

All active devices intended to administer and/or remove
medicinal products, body liquids or other substances to or
from the body are classified as classIIa
unless this is done in a manner that is potentially hazardous, IIb
taking account of the nature of the substances involved, of the
part of the body concerned and of the mode of application
13 Corresponds to rule 12 of MDD without changes I
All other active devices

23
Special Rules
RULE CHANGE CLASS

14 Corresponds to rule 13 of MDD III

Added “medicinal product derived from human blood or human
plasma”
Removed “which is liable to act on the human body”
15 Corresponds to rule 14 of MDD without changes IIb, III

16 Corresponds to rule 15 of MDD. IIa

Added “devices used for sterilizing medical devices”

Disinfecting solutions or washer- disinfectors for disinfecting IIb

invasive devices, as the end point of processing

24
Special Rules
RULE CHANGE CLASS

17 Corresponds to rule 16 of MDD without change IIa

18 Corresponds to rule 17 of MDD. III

Added “cells” and “human origins”

25
Special Rules
RULE CHANGE CLASS

19 This is a new rule. This rule is for devices with nano materials. IIa, IIb, III
The class depends on the risk of potential internal exposure.

20 invasive devices with respect to body orifices, other than IIa

surgically invasive devices, which are intended to administer
medicinal products by inhalation

This type of device was in class I under MDD

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

26
Special Rules
RULE CHANGE CLASS

21 Devices that are composed of substances or of combinations IIa, IIb, III

of substances that are intended to be introduced into the
human body via a body orifice or applied to the skin and that
are absorbed by or locally dispersed in the human body
22 Active therapeutic devices with an integrated or incorporated III
diagnostic function which significantly determines the patient
management by the device, such as closed loop systems or
automated external defibrillators

27
Guidelines to help

28
Conclusions
 Clarifications & more precise explanations
 Up-classifications
 Additional or new wording in some rules
 New rules
 Dispute mechanism

29
EUDAMED
Agenda

 Why Eudamed
 Modules
 Getting access
 Entering data
 Timelines

2
EUDAMED under MDD
 Concept of EUDAMED is not new. A EUDAMED under MDD already
exists
 Current EUDAMED data is entered by Competent Authorities
 Nobody has access to the current EUDAMED except Competent
Authorities

3
Types of access

 Data entry, data validation– SRN and authorization required

 Data viewing – SRN and authorization required
 Public access https:/ /ec.europa.eu/ tools/eudamed

4
Vigilance & PMS
Clinical Investigation
Market Surveillance
UDI
Registration of devices
Registration of economic operators
NBs and Certificates

5
Unambiguous Data Identification

 Economic Operators identified by Single Registration Number (SRN)

 Devices identified by their UDI
 Studies identified by Single Identification Number (SIN)
 Vigilance cases and FSCAs identified by case numbers

6
Electronic System for Vigilance & PMS
Serious incidents & FSCA

Periodic Summary Reports

Trend Reports

PSUR

FSN

Information exchanged between CAs and

Commission

7
Who can access the database?
 Competent Authorities & Commission
 NBs for the certificates issued by them
 Appropriate levels of access to healthcare providers & public
 Competent Authorities of third countries or international
organisations based on agreements

8
Electronic System for Clinical
Investigations
Provide SIN for investigations

Submission of applications & notifications

Exchange of information

Sponsor’s reports

Serious adverse events & deficiencies

9
Who can access the database?
 Competent Authorities & Commission
 Except the part on information exchange, rest will be available to
the public with safeguards on data protection

10
Electronic System for Market Surveillance
Results of surveillance activities

Inspection Reports

Information on devices presenting

unacceptable risks

Information on non-compliant products

Information about preventive health

protection measures

Summaries of reviews and assessments of

surveillance activities
11
Electronic System for UDI & registration
of devices
 Accessible by general public
 Will contain Basic UDI-DIs & UDI-DIs issued to manufacturers
 Will contain all information as per Annex VI part B
 This database will be used for registration of devices

12
Electronic System for registration of
economic operators
 Will be used for generating Single Registration Numbers for
manufacturers
 Will be used to register manufacturers, importers, distributors
and authorized representatives

13
Electronic System for NBs and certificates

 List of subsidiaries of NBs

 List of experts for assessments of NB applications
 Information on certificates issued by NBs
 Reports of summary of safety and clinical performance
 Reports of monitoring of NBs and subcontractors by Competent
Authorities
 Information on withdrawal of certificates and refusal of
applications for certificates

14
Timelines for EUDAMED
 Will go live on 26 March 2020
 Will apply from 26 May 2020
 Will be fully functional from 21 Nov 2021

15
Changes in EUDAMED

 Within one week of any change occurring in relation to the

information in the database of registration of the economic
operator,
 Not later than one year after submission of the information in and
every second year thereafter, the economic operator shall
confirm the accuracy of the data. In the event of a failure to do so
within six months of those deadlines, any Member State may take
appropriate corrective measures within its territory until that
economic operator complies with that obligation.

16
Summary

 The European Database on Medical Devices (EUDAMED) is

a key aspect to fulfil the requirements of the MDR
 The EUDAMED is an integration of several databases
handling different information pertaining to the MDR

17
Declaration of
Conformity
“ The Declaration of Conformity
is a document by which the
manufacturer states that the
device in scope fulfils the
requirements of the MDR & all
other applicable Union
regulations

2
Who makes the declaration

 The manufacturer draws the declaration of conformity

 Manufacturer cannot delegate the responsibility to someone
else
 The person responsible for regulatory compliance is responsible
to draw and update the declaration

3
Content of the Declaration

 Name of the manufacturer

 Single Registration Number
 Name and address of Authorised Representative
 Statement that the declaration is on the sole responsibility of the
manufacturer
 Basic UDI-DI
 Product name, trade name, product code, intended purpose
 Risk Class

4
Content of the Declaration

 A statement that the device that is covered by the present declaration is in

conformity with this Regulation and, if applicable, with any other relevant
Union legislation
 Reference to any Common Specification used
 Name and number of Notified Body
 Conformity Assessment Procedure
 Certificate number
 Place and date of issue, name and function of the person who signed it as
well as an indication for, and on behalf of whom, that person signed,
signature
5
Record keeping

 The declaration shall be kept by the manufacturer or the

Authorised Representative for 10 years and in case of
implantable devices for 15 years
 Importers shall also keep copy of the declaration for the
same time period as mentioned above

6
GROUP EXERCISE

Please review your declaration of

conformity. Identify where changes are
required as per the MDR
RISK
MANAGEMENT
MDR is aligned to EN ISO14971:2012 and
ISO13485:2016

2
“ Risk is defined as a
combination of the
probability of occurrence
of harm and the severity of
that harm

3
“
Benefit risk determination is
defined as the analysis of all
assessments of benefit and risk of
possible relevance for the
use of the device for the intended
purpose, when used in accordance
with the intended purpose given by
the manufacturer

4
 Risk
1
Management as
per the GSPR
GSPR 1
Devices shall be designed and manufactured such that any risks
constitute acceptable risks when weighed against the benefits.
The benefit risk determination shall take into account generally
acceptable state-of-art.

6
GSPR 2

Reduce risk as far as possible without adversely affecting

benefit risk ratio

New clarification

7
GSPR 3

Estimate risks Consider Amend control

Make a risk Identify known during intended information from measures if
Eliminate or
management and foreseeable use and production and necessary
control risks
plan hazards foreseeable post-production
misuse phase

3.4 4.3 5 6 9 6

8
GSPR 4
Risks shall be managed Risks shall be reduced in Inform users of any
such that both the the following order of residual risks
residual risks of each priority
hazard and overall  Eliminate through
residual risks are judged design & manufacture
acceptable
 Take adequate
protection measures
 Provide IFU

9
GSPR 5
While managing risks related to use error:

Reduce as far as possible Give consideration to the

risks related to the technical knowledge,
ergonomic features of the experience, education,
device and the training and use
environment where it is environment, and the
used medical and physical
conditions of intended
users

10
GSPR 8
All known and foreseeable risks, and any
undesirable side-effects, shall be minimised and
be acceptable when weighed against the
evaluated benefits to the user when used under
normal conditions.

11
GSPR 9
For devices without a medical purpose, when used
under the conditions and for the intended
purpose, must not present any risk or present a
risk that is not more than the maximum acceptable
risk

12
GENERAL
SAFETY &
PERFORMANCE
REQUIREMENTS
 MDR
MDD 13 23 CLAUSES
CLAUSES

2
Groups of requirements
General Requirements
[1 to 9]

Design & Manufacturing

[10 to 22]

Information supplied with

device
[23]
3
Complying to the requirements
• Identify whether the requirement is applicable or not

• Identify appropriate standards to comply to the

requirement

• Refer to records, procedures and other documents to

provide evidence

• If not applicable provide justification

4
SPR 1: Performance & Safety
 Corresponds to MDD ER1
 The devices shall be ‘designed and manufactured in such a way’that safety of
patients and users shall not be compromised during normal condition 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 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.

5
SPR 2: Reduction risks
 Reduce risks as far as possible without affecting the risk benefit ratio
 This is a new requirement in MDR but is more of a clarification of the
requirements of MDD ER2
 This requirement continues to be to reduce risks as far as possible
without regard for economic consideration.

6
SPR 3: Risk Management System
 This is a new requirement without a general equivalent in the MDD
 The basics of the risk management process are more explicitly
defined in SPR 3, in alignment with EN ISO 14971:2012

7
SPR 4: Risk control measures & residual risks
 SPR 4 generally corresponds to ER 2 in the MDD
 The requirement that both the overall residual risks and the residual risk
associated with each hazard is evaluated and judged to be acceptable, with
respect to the benefits is explicitly included
 Warnings, precautions and contraindications be provided to users
 All residual risks including possible adverse events and side effects
identified by the manufacturer in the risk management process should be
disclosed in IFU
 This is in contrast with the MDD which required users to be informed of the
‘residual risks due to any shortcomings of the protection measures adopted’

8
SPR 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
 The risk of use error shall be reduced as far as possible
including ergonomic considerations and the knowledge,
experience and types of users

9
Group Exercise

Identify the differences between MDR and

MDD for the requirement of risk-benefit
ratio (MDD clause 6, MDR clause 8) and
how do they impact your current risk
benefit analysis

10
MDD MDR

Any undesirable side- All known and foreseeable

effect must constitute an risks, and any undesirable
acceptable risk when side-effects, shall be
weighed against the minimised and be
performances intended. acceptable when weighed
against the evaluated
benefits to the patient
and/or user arising from
the achieved performance
of the device during
normal conditions of use.

11
SPR 6: Device Lifetime
 The ‘device lifetime’ requirement generally corresponds to ER 4 in the MDD
 SPR 6 requires that the device characteristics and performance shall not
be adversely impacted to such a degree that health or safety of a patient
or user would be compromised, when under the stresses of ‘normal
conditions of use.’
 The lifetime is defined here as the lifetime ‘as indicated by the
manufacturer’
 Device performance must not be adversely impacted when the device ‘has
been properly maintained in accordance with the manufacturer’s
instructions.’

12
Group Exercise
“The characteristics and performance of a device
shall not be adversely affected to such a degree
that the health or safety of the patient or the user
and, where applicable, of other persons are
compromised during the lifetime of the device, as
indicated by the manufacturer, when the device is
subjected to the stresses which can occur during
normal conditions of use and has been properly
maintained in accordance with the manufacturer's
instructions”.
Identify what documents will you provide as
evidence of complying to this requirement. 13
SPR 7: Packaging, Storage & Transportation

 This requirement is similar to ER 5 in the MDD

 The requirement states that device design, manufacturing and
packaging will protect a device’s characteristics and
performance for intended use during transportation and storage,
taking into account the instructions provided by the
manufacturer
 The requirement specifically gives the example of potential
temperature and humidity fluctuations

14
SPR 8: Risk-Benefit ratio
 This requirement corresponds to MDD ER 6
 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.’
 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.

15
SPR 9: Devices without a medical purpose
 This is a new requirement since devices without a medical purpose are
now in the scope of the MDR
 This clause clarifies on how to apply the ‘risk-benefit’and ‘performance’
requirements

16
SPR 10: Chemical, Physical & Biological
properties
 10.1: General considerations for materials
 10.2: Risks from contaminants & residues
 10.3: Compatibility with materials & substances
 10.4: Substances contained in and released from the device
 10.5: Risks of unintentional ingress
 10.6: Risks related to particle size

17
SPR 10.1: General considerations for materials
 Corresponds to ER 7.1 of MDD but much expanded
 Requires compatibility of materials & substances with biological
tissues, cells & fluids
 Consideration to be given to body’s processes like absorption,
distribution, metabolism and excretion
 Consideration of the impact of manufacturing processes on material
properties
 A lot of focus on the considerations of material properties during
design of the product

18
SPR 10.2: Risks from contaminants & residues
 Corresponds to ER 7.2 and contents remain same
 Devices shall be designed, manufactured and packaged in such a
way as to minimise the risk posed by contaminants and residues to
patients, and to the persons involved in the transport, storage and
use of the devices

19
SPR 10.3: Compatibility with materials &
substances
 Generally corresponds to ER 7.3 of the MDD
 The clause deals with compatibility of the device with materials and
substances with which it is used
 If it is designed to deliver medicines, then it has to be compatible
with the medicine, as long as both the device and the medicine are
used in accordance with its intended use

20
SPR 10.4: Substances contained in and released
from device
 This clause gives a detailed requirement of substances in the device
 The clause is divided into 5 sub-clauses
10.4.1: Design & Manufacture of devices
10.4.2: J ustification regarding the presence of CMR and/ or EDs
10.4.3: Guidance on phthalates
10.4.4: Guidance on other CMRs and EDs
10.4.5: Labelling

21
SPR 10.4.1: Limits on substances
 Requirement for certain substances of concern that invasive devices or
devices administering/ storing substances must contain a concentration
below 0.1 per cent by weight unless justified with reference to SPR 10.4.2.
 This includes carcinogenic, mutagenic, or toxic to reproduction (referred to
as ‘CMR’) substances and substances with endocrine-disrupting properties.
 For identification of such substances the references given are
EU Regulation 1272/ 2008 (Classification, Labelling and Packaging
of Chemicals)
EU Regulation 1907/ 2006 (REACH: Registration, Evaluation,
Authorisation, and Restriction of Chemicals)
EU Regulation 528/ 2012 (Market and Use of Biocidal Products).
22
SPR 10.4.1: Limits on substances (contd)
 Requirement to design & manufacture devices such as risks are minimized
from materials and substances including from
 Wear debris,
 Degradation products
 Process residues
 Variety of ISO10993 standards are there to identify degradation products
 ISO10993-9:2009 – Framework
 ISO10993-13:2010 – Polymeric Devices
 ISO10993-14:2001 – Ceramic Devices
 ISO10993-15: 2000 – Metals & Alloys
23
SPR 10.4.2: Justification
 If a substance is present in concentration of more than 0.1%, then a
justification has to be provided
 J ustification must be based on:
 An analysis and estimation of potential patient or user exposure to the
substance;
 An analysis of possible alternative substances;
 An argumentation why possible substance and/ or material substitutes,
or design changes, are inappropriate in relation to maintaining the
functionality, performance and the benefit-risk ratios of the product;
 Where applicable and available, the latest relevant scientific committee
guidelines
24
SPR 10.4.3: Phthalates
 At present no limit of phthalates set
 A scientific committee shall prepare a guideline before 26 May 2020
 The committee shall also conduct a benefit risk assessment for the
presence of phthalates based on
 The intended purpose and context of the use of the device,
 Available alternative substances and alternative materials
 Designs or Medical treatments

25
SPR 10.4.4: Guidelines on CMR and
endocrine disrupting substances
 There is no guidance at present and will be prepared by a
scientific committee

26
SPR 10.4.5: Labelling requirements
 If a device contains CMR or endocrine disruptors above 0.1% by weight, then
the following must be on the label
 Presence of those substances shall be labeled on the device itself
and/ or on the packaging for each unit or, where appropriate, on the
sales packaging, with the list of such substances.
 Appropriate precautionary measures shall be given in the IFU (If the
intended use of such devices includes treatment of children or
treatment of pregnant or breastfeeding women or treatment of other
patient groups considered particularly vulnerable to such substances
and/ or materials, information on residual risks for those patient groups)

27
Comparison between MDD & MDR
MDD (ER 7.5)
If parts of a device (or a device itself)
▸ intended to administer and/ or
remove medicines, body liquids
or other substances to or from
the body, or
▸ intended for transport and
storage of such body fluids or
substances
Focus on phthalates. Special
attention to CMR substances
MDR (SPR 10.4)
Devices, or those parts thereof or those
materials usedtherein that:
▸ are invasive and come into direct contact
with the human body, or
▸ (re)administer medicines, body liquids or
other substances, including gases, to/ from
the body, or
▸ transport or store such medicines, body
fluids or substances, including gases, to be
(re)administered to the body
Focus on phthalates, more on CMRs and EDs
28
Steps to comply to SPR 10.4

If yes- then either

Calculate if the re-design, find
0.1% w/w threshold alternative
If yes, gather
is exceeded or not suppliers, adjust the
Determine if SPR information on CMR
i.e. device level; manufacturing
10.4 applies and ED substances
worst case at the processes or
from suppliers
part/component/ develop the needed
sub-assembly level justifications and
labeling

29
SPR 10.5: Risk of unintentional ingress
 Corresponds to ER 7.6 of MDD
 The risk of unintentional ingress is to be reduced as far as possible.

30
SPR 10.6: Risks related to particle size
 This is a new requirement
 Risks linked to the size and properties of particles should be reduced
as far as possible, unless these come into contact with intact skin
 Special attention to be given to nanomaterials

‘Nanomaterial’ means a natural, incidental or manufactured

material containing particles, in an unbound state or as an
aggregate or as an agglomerate and where, for 50 % or more
of the particles in the number size distribution, one or more
external dimensions is in the size range 1 nm-100 nm.

31
SPR 11: Infection & Microbial Contamination
 Similar to ER 8 of MDD
 Has the following sub-clauses:
 11.1: Risk of infection
 11.2: Design for reuse
 11.3: Devices with a specific microbial state
 11.4: Devices delivered sterile
 11.5: Validation for sterile devices
 11.6: Environmental controls
 11.7: Packaging for non-sterile devices
 11.8: Labelling for sterile state
32
SPR 11.1: Risk of infection
 SPR 11.1 generally corresponds to MDD ER 8.1, but SPR 11.1 contains
more specific examples
 The design shall reduce the risks from unintended cuts and pricks
(such as needle sticks) as far as possible ‘and appropriate.’
 Requires easy and safe handling and is aligned with MDD ER 8.1
 Reduce as far as possible any microbial leakage from the device
and/ or microbial exposure during use.
 Prevent microbial contamination of the device or its content such as
specimens or fluids.

33
SPR 11.2: Design for reuse
 This is a new requirement
 Requires that devices be designed to facilitate safe cleaning,
disinfection and/ or resterilization
 This requirement may be interpreted as not applicable to those
devices intended by the original manufacturer to be for single
use, but primarily applicable to devices specifically designed for
reuse, given the words ‘where necessary’in the text.

34
SPR 11.3: Devices with a specific microbial
state
 This is a new requirement
 Devices labelled as having a specific microbial state shall be designed,
manufactured and packaged to ensure that they remain in that state
when placed on the market
 Also under the transport and storage conditions specified by the
manufacturer

35
SPR 11.4: Devices delivered sterile
 SPR 11.4 corresponds to MDD ER 8.3, with the language having
been updated
 The ‘non-reusable pack’language has been removed, and the
storage and transport conditions are clarified as those
‘indicated by the manufacturer.’
 The integrity of the sterile packaging must be clearly evident
to the final user.

36
SPR 11.5: Validation for sterile devices
 Sterile devices must be manufactured and sterilized by an
appropriate, validated method
 The MDR has changed ‘devices delivered in a sterile state’to ‘devices
labelled as sterile,’which better reflects the capability of a
manufacturer; handling and storage cannot be controlled to ensure
delivery in a sterile state.
 Additionally, the requirement now includes that devices labelled as
sterile shall be ‘packaged’by appropriate validated methods

37
SPR 11.6: Environmental Controls
 Similar to MDD ER 8.5
 ‘Packaging’has been added along with manufacturing in
appropriately controlled facilities for devices intended to be
sterilised

38
SPR 11.7: Packaging for non-sterile devices

 Similar to MDD ER 8.6

 States that packaging shall maintain the ‘integrity and
cleanliness’rather than keeping the product ‘without
deterioration at the level of cleanliness stipulated.’

39
SPR 11.8: Labelling for sterile state
 Similar to MDD ER 8.7
 The MDR has added the wording that the label distinguishing
between sterile and non-sterile conditions is ‘additional to the
symbol used to indicate that a product is sterile.’

40
SPR 12: Devices incorporating a medicinal
product; substances absorbed or locally
dispersed
 Similar to MDD ER 7.4 with significant change in scope
 Consists of the following sub-clauses:
 12.1: Devices incorporating a medicinal product
 12.2: Devices composed of substances absorbed or locally
dispersed

41
SPR 12.1: Devices incorporating a medicinal
product
 Directive 2001/83/EC (covering medicinal products for
human use) is referenced for the definition of medicinal
products. However, the qualification of ‘liable to act upon
the body with action ancillary to that of the device’is gone

42
SPR 12.2: Devices composed of substances
absorbed or locally dispersed
 This is a new requirement
 This requirement states that such devices should comply with the
relevant requirements in Directive 2001/ 83/ EC for medicinal products
 Such devices require a consultation process with the EMA

43
SPR 13: Devices incorporating materials of
biological origin
 The requirements in SPR 13 generally correspond to MDD ER 7.4
and 8.2
 There are three sub-clauses
 13.1: Tissues, cells or derivatives of human origin
 13.2: Tissues, cells or derivatives of animal origin
 Other non-viable biological substances

44
SPR 13.1: Tissues, cells or derivatives of
human origin
 Although human blood derivatives were previously within scope of
MDD ER 7.4, the MDR now includes requirements for devices
utilizing non-viable tissues or cells of human origin, or their
derivatives
 The SPR refers to Directive 2004/ 23/EC (donation, procurement,
testing, processing, preservation, storage and distribution of
human tissues and cells) and Directive 2002/ 98/ EC (collection,
testing, processing, storage and distribution of human blood and
blood components)

45
SPR 13.2: Tissues, cells or derivatives of animal
origin
 The requirements in SPR 13.2 generally correspond to MDD ER 8.2
 The text in SPR 13.2 has been expanded and made consistent with
the requirements of EN ISO 22442-2 and Regulation 722/ 2012 (both
concerning requirements for utilizing tissues of animal origin in
medical devices).

46
SPR 13.3: Other non-viable biological substances
 This is a new requirement
 This category would include any non-viable biological substances
derived from or produced by a living organism, other than the more
specific human and animal categories previously outlined

47
SPR 14: Construction of devices and interaction
with their environment
 SPR 14 corresponds to ER 9 in the MDD, along with ER 10.2 for ergonomic
principles
 There are seven sub-clauses:
 14.1: Use in combination
 14.2: Risks of interaction with the environment
 14.3: Risks of fire or explosion
 14.4: Design for adjustment, calibration and maintenance
 14.5: Design for compatibility
 14.6: Measurement, monitoring or display scales
 14.7: Design and manufacture for safe disposal
48
SPR 14.1: Use in combination
 SPR 14.1 corresponds to ER 9.1 in the MDD, with new text added in the
last sentence.
 Connections which the user has to handle, such as fluid, gas transfer,
electrical or mechanical coupling, shall be designed and constructed in
such a way as to minimize all possible risks, such as misconnection.

49
SPR 14.2: Risks of interaction with the
environment
 Much of SPR 14.2 (a, b, f and g) is traceable to MDD ER 9.2.
 SPR 14.2 (c) relates to MDD ER 7.3, and SPR 14.2 (e) is again similar to ER 7.6.
SPR 14.2 (d) is new in comparison to the MDD.
 SPR 14.2 (b) adds consideration of ‘radiation associated with diagnostic or
therapeutic procedures,’‘humidity,’and ‘radio signal interferences’to the list
of specific risks to be removed or reduced as far as possible.
 Addresses risks for software at the system and network level. This includes
consideration of the final system configuration during software/ product
validation, consideration of cybersecurity and network potential risks and
information to the user for IT networks that cannot be validated by the
manufacturer.
50
SPR 14.3: Risks of fire or explosion
 Corresponds to ER 9.3 of the MDD
 Devices shall be designed and manufactured in such a way as to
minimise the risks of fire or explosion during normal use and in
single fault condition

SINGLE FAULT CONDITION –a condition in

which a single means for reducing a risk is
defective or a single abnormal condition is
present.

51
SPR 14.4: Design for adjustment, calibration
and maintenance
 This is a new requirement
 Devices must be designed and manufactured for safe and
effective adjustment, calibration and maintenance.

52
SPR 14.5: Design for compatibility
 SPR 14.5 corresponds to MDD ER 9.1
 Devices that are intended to be operated together with other
devices or products shall be designed and manufactured in such a
way that the interoperability and compatibility are reliable and
safe.

53
SPR 14.6: Measurement, monitoring or
display scales
 SPR 14.6 can be correlated to MDD ER 10.2
 It elaborates on taking account of the ‘intended purpose,’
including also the intended users and intended environmental
conditions of use with respect to ergonomics of the
measurement, monitoring or display scales.

54
SPR 14.7: Design and manufacture for safe
disposal
 This is a new requirement
 Requires that devices are specifically designed and manufactured
to facilitate their safe disposal, and the safe disposal of any related
waste substances by the user, patient, or other person
 Manufacturers are required to identify and test procedures and
measures for disposal of their devices and describe these
procedures in the IFU

55
SPR 15: Devices with a diagnostic or measuring
function
 SPR 15 generally corresponds to ER 10.1 and 10.3 in the MDD
 There are 2 sub-clauses
 In comparison to the MDD, ‘diagnostic devices’have been added to
the scope of the requirement
 The consideration of ‘precision’has been added.
 Measurements from measuring devices are required to be
expressed in legal units per Directive 80/ 181/ EEC (Units of
measurement directive).

56
SPR 16: Protection against radiation
 Correspond to parts of ER 11 in the MDD
 SPRs 16.1 (a) and 16.2 (b), ‘General’requirements correspond to MDD ERs
11.1 and 11.4, respectively.
 New requirement that ‘Information regarding the acceptance testing, the
performance testing and the acceptance criteria, the maintenance
procedure shall also be specified in the operating instructions for devices
emitting hazardous or potentially hazardous radiation.
 SPRs 16.2 (a) and 16.2 (b) ‘Intended radiation’requirements correspond to
MDD ERs 11.2.1 and 11.2.2, respectively, with only slight rewording

57
SPR 16: Protection against radiation (contd)
 SPR 16.3 for ‘Unintended radiation’ corresponds to MDD ER 11.3,
 Addition of the following sentence: Where possible and appropriate,
methods shall be selected which reduce the exposure to radiation of
patients, users and other persons who may be affected
 SPR 16.4 ‘Ionizing radiation’can be related to MDD ERs 11.5 and 8, with
some changes
 SPR 16.4 (a), (c) and (d) can be mapped to MDD ERs 11.5.1, 11.5.2 and 11.5.3,
respectively, while SPR 16.4 (b) is a new requirement
 There is a reference to Directive 2013/ 59/ Euratom (safety standards for
protection against ionizing radiation)

58
SPR 17: Electronic programmable systems and
software
 SPR 17 defines requirements for electronic programmable systems
and software considered to be a medical device in itself.
 SPR 17.1 generally corresponds to ER 12.1 (first sentence) in the MDD,
and SPR 17.2 generally corresponds to MDD ER 12.1a
 The wording in the MDR now includes ‘software that are devices in
themselves’more explicitly
 Principles of ‘information security’are new and cyber security is given
emphasis

59
SPR 17: Electronic programmable systems and
software (contd)
 SPR 17.3 defines specific requirements for software to be used with
mobile computing platforms.
 Manufacturers are asked to consider the specific features of mobile
platforms, including screen size and limitations, and light and noise in
the use environment.
 SPR 17.4 is new when compared to the MDD. Manufacturers shall set
out minimum requirements concerning hardware, IT networks
characteristics and IT security measures, including protection
against unauthorised access, necessary to run the software as
intended.
60
SPR 18: Active devices and devices
connected to them
 A majority of this requirement corresponds to subparts of ER 12 in the
MDD.
 SPR 18.1 generally corresponds with MDD ER 12.1 (second sentence) with
the clarification now for ‘non-implantable active devices.’
 SPR 18.2 corresponds in part to ER 12.2, with the addition of a warning or
indication for low power supply.
 SPRs 18.3 and 18.4 are essentially identical to MDD ERs 12.3 and 12.4

61
SPR 18: Active devices and devices
connected to them (contd)
 SPR 18.5 generally corresponds to MDD ER 12.5. The instruction to redu
risks of creating ‘electromagnetic fields’has been clarified to
‘electromagnetic interference’and the interference that could impair
‘other devices’is clarified to ‘this or other devices.’
 SPR 18.6 includes a new requirement to design and manufacture devices
for intrinsic immunity to electromagnetic disturbance
 SPR 18.7 corresponds to MDD ER 12.6 with minor wording changes
 SPR 18.8 is a new requirement. It relates to cybersecurity

62
SPR 19: Particular requirements for active
implantable devices

63
SPR 20: Protection against mechanical and
thermal risks
 Requirements in SPR 20 correspond to ER 12.7 in the MDD
 SPR 20 is nearly identical to MDD ER 12.7 with the exception of
subpart 20.5. This new requirement relates to errors that could be
made in fitting or refitting parts.

64
SPR 21: Protection against the risks posed to the
patient or user by devices supplying energy or
substances
 SPR 21 corresponds to ERs 12.8.1, 12.8.2 and 12.9 in the MDD
 The requirements in SPR 21 are considered to be a very low impact
item for MDD manufacturers
 The changes in comparison to the MDD are limited to minor rewording
of the requirement; the intent is unchanged.

65
SPR 22: Protection against the risks posed by
medical devices intended by the manufacturer
for use by lay persons
 This is a new requirement. ‘Lay person’ was not mentioned earlier in the
MDD
 For devices with lay persons as end users, SPR 22 outlines
requirements and considerations for the device’s instructions,
variation in user technique, risks of error and injury, and verification of
device function by the user.

66
SPR 23: Label & Instructions for Use
 This clause is entirely dedicated to labelling
 The requirements are much expanded in comparison to the MDD
 There are four sub-clauses:
 23.1: General Requirements
 23.2: Label Requirements
 23.3: Sterile Package Requirements
 23.4: Instructions for Use

67
SPR 23.1: General Requirements
 General information needed to identify the device and its
manufacturer, and communicate safety and performance related
information to the users should be made available on
manufacturer’s website (if available). The information has to be
kept up-to-date
 While MDD ER 13.6 (b) requires the intended performance of the
device to be included, it does not require information on clinical
benefits or any clinical summary. The MDR requires performance
related information also to be provided to the user.

68
SPR 23.1: General Requirements (contd)
 SPR 23.1 (a) requires that the label and IFU should be clear in
format, medium, legibility, content, etc., with respect to the
intended users and their expected knowledge and experience.
 SPR 23.1 (b) which identifies that the information on the label shall
be provided on the device itself (if practicable and appropriate) is
not new to the MDD, and aligns with MDD ER 13.1.
 SPR 23.1 (c) requires that labels be human-readable although this
may be supplemented by machine-readable information such as
bar codes or RFID.

69
SPR 23.1: General Requirements (contd)
 SPR 23.1 (d) states that an IFU must accompany the devices (if
required to use safely). This requirement is not new and aligns
with MDD ER 13.1
 SPR 23.1 (e) states that when multiple devices are provided to a
single user or location, a single copy of the IFU may be provided if
agreed with the purchaser, so long as additional copies may be
requested and provided free of charge.
 SPR 23.1 (f) allows IFU to be provided electronically, only in
accordance with existing EU Regulation 207/ 2012

70
SPR 23.1: General Requirements (contd)
 SPR 23.1 (g) generally aligns with MDD ER 13.3 (k); 13.6 (e), (f), (h), (k)
- (o) on the inclusion of residual risks as warnings, precautions,
limitations, or contraindications in the IFU. This also aligns with
MDD ER 2 which requires that users should be informed of the
residual risks
 SPR 23.1 (h) largely aligns with MDD ER 13.2 relative to the use of
internationally recognized symbols and colors from harmonized
standards but also references conformity to Common
Specifications

71
SPR 23.2: Label Requirements

 SPR 23.2 (a): Can be correlated to MDD ER 13.3 (b).

 SPR 23.2 (b): Can be correlated to MDD ERs 13.3 (b) and 13.4
 SPR 23.2 (c): Can be correlated to MDD ER 13.3 (a)
 SPR 23.2 (d): This SPR can be correlated to MDD ER 13.3 (a).

MDD previously allowed for the authorized EU representative to

be on the label, outer package, or the IFU (it was not required to
be in all places). In contrast, the MDR requires the EU
representative to be on both the label, and does not explicitly
require it to be on the IFU.

72
SPR 23.2: Label Requirements (contd.)
 SPR 23.2 (e): An indication if the device contains or incorporates a
medicinal substance including a human blood/ plasma derivative, tissues
or sales of human or animal origin, or derivatives of animal tissue as
defined in EU Regulation 722/ 2012.
 SPR 23.2 (f): Labelling information in accordance with SPR 10.4.5. This
refers back to the CMR and endocrine disruptors as outlined in SPR 10.4.1
If the device contains CMR and ED substances above 0.1% by weight, this
information must be disclosed on the label. Specific
information on treatment of vulnerable groups including children and
pregnant and breastfeeding women must be
included in the IFU.

73
SPR 23.2: Label Requirements (contd.)
 SPR 23.2 (g): Can be correlated to MDD ER 13.3 (d).
 SPR 23.2 (h): UDI is being implemented in the MDR, and the UDI carrier per
Article 27(4) and Annex VII Part C is required to be on the product label and
all higher level packaging except for the shipping container level as per
Article 27(4).
 SPR 23.2 (i): Can be generally correlated to MDD ER 13.3 (e). The SPR
wording for expiration dates here includes the time limit for ‘using’or
‘implanting’the device safely
 SPR 23.2 (j): Can be correlated to MDD ER 13.3 (l). A clarification is added
that the date of manufacture may be included as part of the lot number or
serial number, provided the date is clearly identifiable
74
SPR 23.2: Label Requirements (contd.)
 SPR 23.2 (k): Can be correlated to MDD ER 13.3
i) (
 SPR 23.2 (l): Can be correlated to MDD ER 13.3 (c)
 SPR 23.2 (m): While similar to MDD ER 13.3 (k), this requirement is now
much more detailed. SPR 23.2 (m) requires that the label include any
warnings or precautions that ‘need to be brought to the immediate
attention of the user.’
 SPR 23.2 (n): Can be correlated to MDD ER 13.3 (n)
 SPR 23.2 (o): This is a new requirement. If a device is a reprocessed single
use device, this must be indicated along with the number of reprocessing
cycles performed and any limitation on the number of reprocessing
cycles
75
SPR 23.2: Label Requirements (contd.)
 SPR 23.2 (p): Can be correlated to MDD ER 13.3 (g)
 SPR 23.2 (q): ‘An indication that the device is a medical device’and if for
clinical investigation then an indication that it is only for clinical
investigation
 SPR 23.2 (r): For devices composed of substances absorbed or locally
dispersed, the ‘overall qualitative composition’and ‘quantitative
information on the main constituents responsible for achieving the
principal intended action.’This requirement has no correlation to the
Directives.
 SPR 23.2 (s): Serial number for active implantable devices.. For other
implantable devices, the serial number or lot number must be included.

76
SPR 23.3: Sterile package label requirements
 This is a new requirement. Sterile packaging is separated from
other packaging
 If there is a primary packaging label and a secondary packaging
label, then information of this SPR must appear on the primary label
 Other than the general requirement of SPR 23.2, there is a new
requirement ‘instruction to check the IFU for what to do if the
sterile package is damaged or unintentionally opened before use’

77
SPR 23.4: Instruction for Use
 There are expanded requirements in the MDR compared to MDD
 There are a total of 28 sub-clauses

78
SPR 23.4: Information for Use
 SPR 23.4(a):This requirement references back to most of the
labelling requirements for inclusion in the IFU. This is similar
to the current requirements of MDD ER 13.6 (a)
 There are 3 additional requirements compared to MDD:
 clear identification of not only medicines as in the current
MDD, but of tissues or cells of human or animal origin or
animal tissue derivatives contained in the device.
 information about CMR and Eds
 particulars of substances absorbed or locally dispersed

79
SPR 23.4: Information for Use (contd)
 SPR 23.4(b): This requirement is similar to MDD ER 13.4. The
requirement goes further in requiring a clear specification of
indications, contraindications, the patient target groups and
the intended users.
 SPR 23.4 (c, d): Specification of expected clinical benefits and
links to the publicly available ‘Summary of Safety and Clinical
Performance’as defined in Article 32
 SPR 23.4 (e): Can be correlated to ER 13.6 (b)

80
SPR 23.4: Information for Use (contd)
 SPR 23.4 (f): This loosely corresponds to MDD ER 13.6(c) on
combinations of devices. Information allowing the healthcare
professional to ‘verify if the device is suitable and select
corresponding software and accessories.’
 SPR 23.4 (g): the MDR now explicitly requires that residual
risks be identified in the IFU. Information regarding residual
risks, including contraindications and undesirable side
effects and information to be conveyed to the patient

81
SPR 23.4: Information for Use (contd)
 SPR 23.4 (h): This generally correlates to MDD ER 13.6
 SPR 23.4 (i): Details of preparation or handling including disinfection.
This is a new requirement.
 SPR 23.4 (j): Any special facilities, training, or qualifications for the
user must be included in the IFU. This is a new requirement
 SPR 23.4 (k): This requirement for device installation is similar to
MDD ER 13.6 (d), but adds additional text for information regarding
disinfection and cleaning, identification of consumable components,
maintenance and methods of eliminating risks for persons installing,
calibrating or servicing the devices

82
SPR 23.4: Information for Use (contd)
 SPR 23.4 (l): Can be correlated to MDD ER 13.6 (g)
 SPR 23.4 (m): Can be correlated to MDD ER 13.6 (h)
 SPR 23.4 (n): For reusable devices, the requirement is similar to MDD
ER 13.6 (h) Paragraph 1, but additional text is added. The new text
refers to re-sterilization ‘as appropriate to the Member State,’and
requires that information be provided to identify when the device
should not be reused, such as a defined number of uses or signs of
material degradation.

83
SPR 23.4: Information for Use (contd)
 SPR 23.4 (o): If appropriate, the manufacturer should indicate in the
IFU that a device can only be reused if it is reconditioned under the
responsibility of the manufacturer to comply with the general SPRs.
This is a new requirement.
 SPR 23.4 (p): Correlates to MDD ER 13.6 (h). However, this SPR now
further specifies that the information shall be based on a specific
section of the manufacturer’s risk management documentation, with
the technical factors addressed in detail. This should be clearly
identifiable in risk management documents for every device.

84
SPR 23.4: Information for Use (contd)
 SPR 23.4 (r): This SPR is partially aligned with MDD ER 13.6 (j)
regarding the requirements for devices emitting radiation for
medical purposes. However, in addition to detailed information
about the emitted radiation, information about the ‘means of
protecting the patient, user, or other person from unintended
radiation during use’must be included in the IFU

85
SPR 23.4: Information for Use (contd)
 SPR 23.4 (s): This multi
-part requirement outlines information in the
IFU needed to brief the patient. Some aspects of this are similar to
MDD ER 13.6 (k-m). Some more are added
 SPR 23.4 (t): For devices with substances absorbed by or locally
dispersed in the body, the IFU must contain warnings and
precautions relating to the interaction profile and products of
metabolism with other devices, medicines, or substances,
contraindications, undesirable side effects and risks relating to
overdose

86
SPR 23.4: Information for Use (contd)
 SPR 23.4 (u): This is a new requirement for implantable devices to
include in the IFU information (qualitative and quantitative) on the
materials and substances to which patients can be exposed.
 SPR 23.4 (v): This requirement is much more explicit that the MDD ER
13.6 (n) of safe disposal of the device, accessories and the
consumables used with the device. IFU to include specifically
identified and tested procedures for safe disposal of the device and
related waste substances. Consideration to be given to items
contaminated with potentially infectious substances, including
human or microbial hazards, and physical hazards such as sharps

87
SPR 23.4: Information for Use (contd)
 SPR 23.4 (w): A new requirement for devices ‘for use by lay persons.’
The IFU must include information on circumstances when the user
should consult with a healthcare professional.
 SPR 23.4 (x): This is a specific requirement for the devices without a
medical purpose as defined in Article 1(2). For these devices, the
absence of clinical benefit as well as the risks related to use of the
device must be disclosed in the IFU.
 SPR 23.4 (y): Can be correlated to MDD ER 13.6 (q)

88
SPR 23.4: Information for Use (contd)
 SPR 23.4 (z): A notice to the user and/or patient that serious
incidents should be reported to the manufacturer and competent
authority. This is a new requirement since previously it was not
required to inform users or patients in the IFU that such incidents
should be reported

89
SPR 23.4: Information for Use (contd)
 SPR 23.4 (aa): Information to be supplied to the patient for an
implanted device per Article 18.
 SPR 23.4 (ab): For electronic programmable systems including
software and software as a medical device, the IFU must include
information on minimum requirements for hardware, networks,
security and protections against unauthorized access, necessary to
run the software as intended

90
UNIQUE DEVICE
IDENTIFIER
 UDI consists of a code on the label
of a device.

“ The first part of this code is unique

and linked to all devices of that
specific type;
The second part of the code is
linked to homogenous production of
devices (e.g. batch, serial number,
etc.).

2
Hierarchy of UDI

Basic UDI-DI

UDI-DI UDI-PI

3
Basic UDI-DI

 The primary identifier of a device model. It is the DI assigned at

the level of the device unit of use.
 It is the main key for records in the UDI database
 It is referenced in relevant certificates, EU declarations of
conformity, technical documentation and summary of safety
and clinical performance.
 Devices with same intended purpose, risk class and essential
design and manufacturing characteristics will have a common
Basic UDI-DI

4
Different designs of
surgical blades but same
class, intended use and
design.
So will have a common
Basic UDI-DI

5
UDI-DI
 A unique numeric or alphanumeric code specific to a model of
device
 Also used as the ‘access key’to information stored in a UDI
database
 Allows for the unequivocal identification of the device
 It is assigned by the manufacturer in compliance with the rules of
the issuing entity. GTIN of GS1 is one such example of UDI-DI
 Unique at each level of device packaging

6
Do you need two different UDI-DI for the
primary and secondary packaging?
The answer is NO

Packaging levels means the various levels of

device packaging that contain a defined quantity
of devices, such as a carton or case.

7
8
BASIC UDI-DI

GTIN A
GTIN B
GTIN C

GTIN D
GTIN E

9
UDI-PI

 The UDI- PI is used to identify specific production series of a

device (batch, serial number etc.)
 UDI-PI can consist of information like manufacturing date, expiry
date, lot number, serial number

10
UDI Carrier
The UDI Carrier is the means to convey the UDI

MACHINE READABLE

HUMAN READABLE

11
 HUMAN
HUMAN READABLE READABLE PART
INTERFACE (HRI) OF THE UDI
CARRIER

MACHINE
AUTOMATIC READABLE PART
IDENTIFICATION & DATA OF THE UDI
CAPTURE (AIDC) CARRIER

12
UDI-DI (STATIC) UDI-PI (DYNAMIC)

13
General Rules: Placing the UDI?
 UDI must appear on the device itself or its packaging
 UDI must appear on all higher levels of packaging, except shipper box.
 If there is space constraint, only the AIDC carrier can be there on label
 If there is space constraint on the unit of use packaging, the UDI carrier may
be placed on the next higher packaging level.
 If a device is intended to be used outside healthcare facilities, the HRI shall
however appear on the label even if this results in there being no space for
the AIDC.
 UDI carrier must be placed in a way that the AIDC can be accessed during
normal operation or storage

14
UDI Rules: Class I/IIa devices
 If packed individually: UDI can appear on higher level of packaging
 If the device is used by someone who doesn’t have access to the
higher level of packaging then UDI must be on individual package

15
UDI Rules: Implantable Devices

 UDI must appear on the lowest level of packaging using an AIDC

 UDI-PI of active implantable device must have the serial number
 UDI-PI of other implantable device must have the serial number or lot
number
 Economic operators & health institutions shall store and keep,
preferably by electronic means, the UDI of implantable devices which
they have supplied or with which they have been supplied

16
UDI Rules: Reusable Device

 UDI must appear on the device itself

 If the device is reused after refurbishing, cleaning, sterilization,
decontamination, then the UDI must still be visible
 The above rules don’t apply if it interferes with the device
functioning or is not technically feasible

17
UDI Rules: Procedure Packs
 As a general rule, the UDI must appear on the outside of the
packaging
 If a device inside the procedure pack is well known and cannot be
used on its own, then a UDI is not required on such a device

18
UDI Database

 Database is freely available to the general public

 Database shall contain the Basic UDI-DI and all other UDI-DIs
 The manufacturer shall provide information for the database as
provided in Annex VI part B

19
Changes in UDI-DI
 Change in UDI
-DI is required in case of change in
- Name or trade name
- Device version or model
- Single use labelling
- Sterile packaging or sterilization type
- Need for sterilization before use
- Quantity of devices in a package
- Critical warnings or contraindications
 In case the change doesn’t require a new UDI-DI then the manufacturer has
to update UDI Database within 30 days
20
UDI roll out dates

Class III Class II Class I

26 May 2021 26 May 2023 26 May 2025
IMPLANT CARD
Implant Card
 Mandatory for implantable devices
 Exemptions are sutures, staples, dental fillings, dental
braces, tooth crowns, screws, wedges, plates, wires, pins,
clips and connectors.
 To be provided to the patient

2
Roles

Manufacturer Health Institution

 Provide the Implant  Provide the Implant
Card with each Card to the patient
implantable device
 Updated information
about the device to be
uploaded on website

3
Contents
 Device name, serial number, lot number, the UDI, the device model, as
well as the name, address and the website of the manufacturer
 Warnings, precautions or measures to be taken by the patient or a
healthcare professional with regard to reciprocal interference with
reasonably foreseeable external influences, medical examinations or
environmental conditions
 Expected lifetime of the device and any necessary follow-up;
 The overall qualitative and quantitative information on the materials
and substances to which patients can be exposed
 Any other information to ensure safe use of the device by the patient

4
CLINICAL
EVALUATION
Agenda
 Where is clinical evaluation addressed in MDR
 Definitions
 Methods to conduct clinical evaluation
 Documents required for clinical evaluation

2
MDR Chapters Articles
CHAPTER VI: Clinical Evaluation 61, Clinical evaluation
and Clinical Investigation
62 – 82, Clinical investigations

MDR Annexes
ANNEX XIV: Clinical Evaluation and Post‐market Clinical Follow‐up

ANNEX XV: Clinical Investigations

3
Article 61: Clinical Evaluation
▸ Conformity to the general performance & safety requirements shall
be based on clinical data providing sufficient clinical evidence
▸ The manufacturer shall specify and justify the level of clinical
evidence necessary

4
Modified Definitions
CLINICAL DATA IN MDD & MEDDEV
- Clinical investigation of device concerned
- Clinical investigation of equivalent device
in scientific literature
- Published and/or unpublished reports on
other clinical experience of device
concerned or equivalent device
CLINICAL DATA IN MDR
- Clinical investigation of device
concerned
- Clinical investigation of
equivalent device in scientific
literature
- Peer reviewed scientific
literature reports on other clinical
experience of device in question
or equivalent device
- Clinically relevant information
coming from PMS, in particular,
PMCF
5
Modified Definitions
CLINICAL EVALUATION DEFINITION IN
MEDDEV
Methodologicallysound ongoing
procedure to collect, appraise and analyse
clinical data pertaining to a medical device and to
evaluatewhether there is sufficient clinical evide
nce to confirm compliance with relevant
essential requirements for safety and performanc
e when using the device according to the manufa
cturer’s Instructions for Use.
CLINICAL EVALUATION
DEFINITION IN MDR
Systematic and planned process to
continuously generate, collect,
analyseand 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.
6
Modified Definitions
CLINICAL EVIDENCE DEFINITION IN
MEDDEV
The clinical data and the clinical evaluation
report pertaining to a medical device.
CLINICAL EVIDENCE DEFINITION
IN MDR
Clinical data and clinical evaluation
results pertaining to a device of a
sufficient amount and quality to allow
a qualified assessment of whether
the device is safe and achieves the
intended clinical benefit(s), when
used as intended by the
manufacturer
7
Clinical Evaluation is based on

Critical evaluation of Clinical Investigations Alternative treatments

literature
- Literature pertaining to
equivalent device
- Data demonstrates
compliance to GSPR
- Critical evaluation of results - Consideration of currently
of clinical evaluation carried available alternative
out as per MDR treatment options

8
Clinical Investigations are mandatory for
Class III and Implantable devices
9
Expert Panel Consultation

▸ Class III and class IIb active devices intended to administer

and/ or remove a medicinal product, may consult with an
expert panel regarding clinical development strategy and
proposals for clinical investigation
▸ The views of the expert panel shall be given due consideration
by the manufacturer and documented in its clinical report
▸ But the manufacturer shall not invoke any rights to the views
expressed by the expert panel with regard to any future
conformity assessment procedure.

10
Exemptions
Modifications Equivalence Specific devices
- Device is a modification - Device is equivalent to a - Device is a suture, staple,
of an already marketed marketed device of dental filling, dental
another manufacturer braces, tooth crown,
?
device
- Modified device is - The second manufacturer screw, wedge, plate, wire,
equivalent to the
marketed device
has and contract with
first manufacturer and
?- pin, clip or connector
Clinical evaluation is
- Clinical data of the full access to the based on “sufficient”
marketed device is technical documentation clinical data
“sufficient” of the first manufacturer - Device complies to
The - The original clinical specific Common
equivalence evaluation has been Specification if available
is for conducted as per the
modifications
MDR 11
Other rules of exemptions

Devices certified under MDD Devices without intended Specific devices

- If the existing clinical medical purpose
data is “sufficient” - Clinical evaluation would
- Device complies to include relevant data
specific Common concerning safety,
Specifications if available including data from PMS,
PMCF, and, where
applicable, specific
clinical investigation.
- Devices where clinical
data is not deemed
appropriate
- Clinical evaluation of such
devices are based on pre -
clinical data and risk
management

12
Proving Technical Equivalence
 Be of similar design
 Used under similar conditions of use
 Have similar specifications and properties (e.g. intensity of energy,
tensile strength, viscosity, surface characteristics, wavelength and
software algorithms)
 Uses similar deployment methods
 Has similar principles of operation and critical performance
requirements

13
Proving Biological Equivalence
 Uses the same materials or substances in contact with the same
human tissues or body fluids
 Used for a similar kind and duration of contact and similar release
characteristics of substances, including degradation products and
leachables

14
Proving Clinical Equivalence
 Used for the same clinical condition or intended purpose (including
similar severity and stage of disease, medical indication)
 Used at the same site in the body
 Used in a similar population (including age, gender, anatomy,
physiology)
 Have same kind of user
 Has similar relevant critical performance in view of the expected
clinical effect for a specific intended purpose.

15
Documents for clinical evaluation

Clinical Clinical Summary of

Evaluation Evaluation clinical evaluation
Plan for all Report for all for Class III &
devices devices implantable
devices

Update based Update at least Update every year

on state of art every year for high-
risk devices & 2-5
years for low-risk
devices

16
The Clinical Evaluation Process

17
Clinical Evaluation Plan
 Identification of GSPRs that require support from relevant clinical data
 Intended purpose of device
 Intended target groups with indications and contra‐indications
 Intended clinical benefits with relevant and specified clinical outcome
parameters
 Methods to be used for examination of qualitative and quantitative
aspects of clinical safety with reference to determination of residual
risks and side‐effects

18
 Clinical Evaluation Plan
 Indicative list and specification of parameters for determining
acceptability of benefit‐risk ratio for various indications and for
intended purpose of device
 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 indicating progression from exploratory
investigations (e.g., FIMstudies, feasibility and pilot studies), to
confirmatory investigations (e.g., pivotal clinical investigations), and a
PMCF with an indication of milestones and a description of potential
acceptance criteria
19
Summary of clinical evaluation (SSCP)

▸ Required for implantable devices and for class III devices,

other than custom‐made or investigational devices
▸ Must be clear to intended user or if relevant, the patient
▸ NB must validate the summary and upload it to EUDAMED
▸ Manufacturer must mention on label or IFU where summary is
available

20
Elements of the summary
▸ Identification of device, manufacturer, Basic UDI
-DI and SRN
▸ Intended purpose, indications, contraindications, target
population
▸ Description of device and any accessories
▸ Therapeutic alternatives
▸ Reference to harmonized standards and CS
▸ Summary of clinical evaluation and information on PMCF
▸ Suggested profile & training for users
▸ Information on residual risks, side-effects, warnings &
precautions
21
What is sufficient clinical evidence?

“Will you use the device on yourself or your child

based on the data available?”

22
Evidence Based Medicine
Evidence based medicine is the
use of current best evidence in
making decisions about the
care of individual patients.
The practice of evidence-based
medicine means integrating
individual clinical expertise with
the best available external
clinical evidence from
systematic research.
23
Summary
 Clinical evaluation canbe done through review of
literature and/ or clinical investigation with consideration
given to alternate therapies
 Clinical investigation is mandatory for Class III &
implantable devices, with exemptions
 Clinical evaluation documentation consists of a plan, a
report and a summary

24
CLINICAL
INVESTIGATIONS
Agenda
 Where is clinical investigation addressed in the MDR
 When is a clinical investigation needed
 Objectives
 Ethical considerations
 Application
 Clinical Investigation Plan

2
MDR Chapters Articles
CHAPTER VI: Clinical Evaluation 61, Clinical evaluation
and Clinical Investigation
62 – 82, Clinical investigations

MDR Annexes
ANNEX XIV: Clinical Evaluation and Post‐market Clinical Follow‐up

ANNEX XV: Clinical Investigations

3
Articles 62-82
 Article 62: General Requirements
 Articles 63-69: GCP/ Ethical Considerations
 Articles 70-71: Application for approval
 Article 72: Conduction of the investigation
 Article 73: Electronic System
 Articles 74-79: Modifications, exchange of information
 Article 80: adverse event reporting
 Article 81: formats developed by Commission
 Article 82: other clinical investigations not conducted as per MDR

4
When is a clinical investigation required

Identify
essential Data required
requirements
Testing
required Clinical data
required and
existence of
data

5
Situations in which an investigation may be
required
 Class III or implantable device
 Completely new type of device
 Modification of a device
 Untested materials
 New purpose or function
 In-vitro or animal testing not adequate

6
Objectives of a clinical investigation
Performance
establish and verify that,
under normal conditions of
use, a device is designed,
manufactured and packaged
in such a way that it achieves
the performance intended as
specified by its
manufacturer
Risk-Benefit
establish and verify the
clinical benefits of a device
as specified by its
manufacturer
Side-Effects
establish and verify the
clinical safety of the device
and to determine any
undesirable side-effects,
under normal conditions of
use of the device, and assess
whether they constitute
acceptable risks when
weighed against the benefits
to be achieved by the device
7
8
ISO14155

The MDR is now more aligned to

ISO14155

9
 MDR ISO14155:2011
Definitions Article 2 Clause 3
Responsibility of sponsor Article 62(2) Clause 8
Ethical Considerations Article 62(3) Clause 4
Ethics Committee Article 62(3) Clause 4.5
Vulnerable populations Article 62(4) Clause 4.6
Informed Consent Article 62(5) Clause 4.7
Investigator Article 62(6) Clause 9
Insurance Article 69 Clause 4
Regulatory Authority Article 70 Clause 6.1

10
 MDR ISO14155:2011
Assessment by member states Article 71

Conduct of investigation Article 73

Devices with a CE mark Article 74 Clause 1

Modification to CIP Article 75 Clause 8.2

Communication between member states Article 76

Suspension or termination Article 77 Clause 7

Multi-site in different member states Article 78

SAE/ deficiency reporting Article 80 Clause 6.4

11
Key conditions before conducting clinical
investigation

 Approved by the member state

 Ethics committee approval
 A sponsor or it’s representative is established in the EU
 Vulnerable population protected
 Benefits are expected to be more than risks
 Informed consent
 Privacy and data protection

12
Key conditions before conducting clinical
investigation

 Involve as little pain, distress or discomfort

 Patient care by qualified medical professional
 Undue influence not exerted
 Device meets the GSPR

13
Applying for a clinical investigation

 Applications for clinical investigations must be forwarded

electronically
 Applications shall be forwarded to the member state where
the investigation will be carried out
 Documentation required is provided in Chapter II of Annex XV
 A single identification number shall be generated
 Investigation can proceed, subject to conditions and approval
by the member state

14
Clinical Investigation Plan
 All clinical investigations must be done in accordance with a
Clinical Investigational Plan (CIP)
 Summary of the CIP to be provided to the Member State during
application for a clinical investigation
 The contents of a CIP are given in Annex XV chapter II

15
Group Exercise
Review an existing Clinical Investigation Plan and evaluate
whether it includes all requirements of the MDR (Annex XV,
chapter II, clause 3)

16
Summary
 A clinical investigation may be required when the device is high
-risk or
there are unknown risks
 Clinical investigations are governed by Good Clinical Practices as
prescribed in ISO14155
 A clinical investigation (in EU) can proceed only after an approval is
taken from a Member State
 Clinical investigations require a Clinical Investigation Plan
 Information sharing on clinical investigations are done through the
electronic system

17
POST MARKET
SURVEILLANCE
Agenda
 What is PMS
 Sources of PMS
 Objectives of a PMS system
 PMS plan
 PMS report and PSUR
 What is PMCF
 When is a PMCF required
 PMCF plan
 Methods & objectives of a PMCF
2
1 Defining PMS
 All activities carried out by manufacturers in
cooperation with other economic operators to

“
institute and keep up to date a systematic
procedure to proactively collect and review
experience gained from devices they place on
the market, make available on the market or
put into service for the purpose of identifying
any need to immediately apply any necessary
corrective or preventive actions

4
3
Let’s clear the
definitions
 Making available on the
Placing on the market
market
First making available of a
Supply of a device for
device on the Union market
distribution, consumption or
use on the Union market in
the course of a commercial
activity, whether in return for
payment or free of charge;
Putting into service
The stage at which a device
has been made available to
the final user as being ready
for use on the Union market
for the first time for its
intended purpose
6
 PUTTING INTO
SERVICE
MAKING
PLACING
AVAILABLE

Hospital
Distributor

Manufacturer Hospital
or Importer

Distributor Patient

7
2 PMS in the MDR
Article 83: PMS System of Annex III: Technical
Manufacturer Documentation for PMS
Article 84: PMS Plan
Article 85: PMS Report
Article 86: Periodic Safety
Update Report

9
PMS PROCESS

Collect data Write Provide Inform CA of

Make a
as per the PSUR/PMS report to any CAPA
PMS Plan
plan report NB/CA taken

10
4
Why need a
PMS?
Update Benefit-Risk Update clinical evaluation Improve usability,
Determination performance & safety

Update Design & Update summary of safety & Use for PMS of other devices
Manufacturing Information clinical performance

Update IFU & labelling Take corrective and Detect & Report Trends of
preventive actions non-serious incidents & side
effects

12
5
Sources of
information
 Databases
of adverse
events Feedbacks
Literature
&
Reviews
Complaints

Data on
Incident
similar
Reports
devices

Sources for Production

PMCF
PMS Data

Sales Data

14
6 PMS Plan
 Method to collect and assess data
 Define performance indicators for the device
 Define safety indicators and threshold values
 Methods to investigate customer complaints
 Methods to analyze market-related experience
 Methods to determine statistical trends of incidents
 Methods to communicate to Competent Authorities, Notified Bodies,
Economic Operators and Users
 Reference to procedures for PMS and PSUR
 Reference to procedures for CAPA
 Reference to PMCF Plan. If no PMCF is planned, then justification
 Methods for traceability of devices
16
Group Exercise
Please review the PMS procedure given to you. If you want to
make a PMS plan, is the information in the procedure sufficient or
you have to add some information?

17
8 Key Concepts
 PERFORMANCE INDICATORS

YOUR COMPETITOR COMPETITOR

COMPANY A B

TIME TO
WOUND 10 20 7
CLOSURE

REDUCTION IN
PAIN SCORE 30 15 10

VISION
IMPROVEMENT 5 24 16

19
SAFETY INDICATORS

THRESHOLD

INFECTION RATE 5

DEHISENCE RATE 4

PAIN SCORE 5

20
 DATA TRENDS
6

0
Q1 Q2 Q3 Q4
Infection Rate Dehisence Rate Pain Score

21
 CHARACTERISTICS OF USERS

AGE

SPECIFIC DISEASE CONDITIONS

FREQUENCY OF USAGE

22
7
Types of PMS reports

Class I devices Class II and III devices

PMS Report PSU Report

24
PERIODIC SAFETY UPDATE REPORT (PSUR)

• All elements of • Volume of

SUMMARY OF PMS
RESULTS

DATA OF SALES
PMS plan sales
• Summary of • Characteristics
PMCF of users
• Frequency of
use

25
 Reporting of PSUR

Class III & Implantable Other classes

Manufacturer NB CA Manufacturer NB

26
PMS REPORT VS PSUR REPORT
PMS REPORT PSUR REPORT
 Required for Class I devices  Required for ClassIIa, IIb and III
 Summary of PMS results devices

 Update whenever necessary  Summary of PMS and PMCF

results, risk benefit
 Make available to Competent determination, volume of sales,
Authority on request characteristics of usage
population, frequency of usage
 Update every year for Class III &
IIb devices. Biannually for Class
IIa devices
 Class III & implantable device:
ManufacturerNBCA
(electronic system)
 Other classes:ManufacturerNB 27
Group Exercise

Please read the CER given to you. Identify the

performance indicators, safety indicators,
threshold values which you will follow up through a
PMS system.

28
 Post Market Clinical Follow-up

“
A continuous process that updates the clinical
evaluation with the aim of confirming the
safety and performance throughout the
expected lifetime of the device, of ensuring
the continued acceptability of identified risks
and of detecting emerging risks on the basis
of factual evidence.

29
PMCF – when is it needed
 Innovation, novel technology or novel indications
 Significant changes after certification
 High product related risk – anatomical locations, materials, target
population, disease severity
 Unanswered questions of long-term safety and performance;
 Due to results from any previous clinical investigation or PMS
activities
 Identification of previously unstudied subpopulations which may
show different benefit/ risk-ratio e.g. hip implants in different ethnic
populations;

30
PMCF – when is it needed (contd)
 Risks identified from the literature or other data sources for
similar marketed devices
 Verification of safety and performance of device when
exposed to a larger and more varied population of clinical
users;
 Where CE marking was based on equivalence.

31
Objectives of a PMCF
 Confirming the safety and performance of the device throughout its
expected lifetime,
 Identifying previously unknown side-effects and monitoring the
identified side-effects and contraindications,
 Identifying and analysing emergent risks on the basis of factual
evidence,
 Ensuring the continued acceptability of the benefit-risk ratio
 Identifying possible systematic misuse or off-label use of the
device, with a view to verifying that the intended purpose is correct.

32
Methods to conduct PMCF
 Extended follow-up of patients enrolled in premarket
investigations
 A new clinical investigation;
 Review of data derived from a device registry; or
 Review of relevant retrospective data from patients previously
exposed to the device.

33
PMCF Plan
 General methods- feedback from users, screening of scientific literature
 Specific methods - evaluation of suitable registers, PMCF studies
 A rationale for the appropriateness of the methods
 Reference to the clinical report referred and the risk management referred
 Objectives of the PMCF;
 Evaluation of clinical data relating to equivalent or similar devices;
 Reference to any relevant CS, harmonised standards and relevant guidance
 A time schedule for PMCF activities

34
Group Exercise
Please read the PMS report provided to you. If you now want
to make a PSUR, please identify what information is missing
from the current PMS report.

35
Summary
 PMS is a continuous process to evaluate the
performance, safety and risk benefit ratio of the device
 There are various sources of PMS, one of which is a PMCF
 A PMS plan must be prepared to set up a PMS system
 PMCF is required in case of certain types of devices
 A PSUR must be prepared including the information
collected through PMS

36
 Definitions
Field Safety Corrective
Action
corrective action taken by a
manufacturer for technical
or medical reasons to
prevent or reduce the risk of
a serious incident in relation
to a device made available on
the market
Incident
‘Any malfunction or
deterioration in the
characteristics or
performance of a device
made available on the
market, including use-error
due to ergonomic features,
as well as any inadequacy in
the information supplied by
the manufacturer and any
undesirable side-effect
Serious Incident
‘Any incident that directly or
indirectly led, might have led
or might lead to any of the
following: (a) the death of a
patient, user or other person,
(b) the temporary or
permanent serious
deterioration of a patient's,
user's or other person's state
of health, (c) a serious public
health threat;
2
 Definitions

Serious Public Health Threat Field Safety Notice

An event which could result ‘A communication sent by a
in imminent risk of death, manufacturer to users or
serious deterioration in a customers in relation to a
person's state of health, or field safety corrective
serious illness, that may action;
require prompt remedial
action, and that may cause
significant morbidity or
mortality in humans, or that
is unusual or unexpected for
the given place and time;

3
Reporting Requirements

Serious Incidents
except side effects

FSCA

Any corrective or
preventive action in
course of PMS

4
Serious Incident
Reporting
Involving devices placed on the EU
market except side-effects.
Side-effects must be clearly
documented in the IFU and
quantified in the technical file .

5
Field Safety Corrective Action Reporting

EU Outside EU
Any FSCA in respect of Any FSCA undertaken in a third
devices made available on country in relation to a device
the Union market which is also legally made
available on the Union market,
if the reason for the field
safety corrective action is not
limited to the device made
available in the third country.

6
Reporting Timelines

Depends on:

 Severity of the incident – death, serious public health threat?

 Causal factor – is the device responsible for the incident?

7
Reporting Timelines

Serious Incident Death or unanticipated Serious Public Health Threat

Not later than 15 days serious deterioration of Not later than 2 days
health
Not later than 10 days

8
 If not a If it is a
serious genuine
Report to Give final
Incident incident or is serious Provide a
competent report to
report a side-effect incident then FSN to
authority competent
received then provide do users
electronically authority
explanatory investigation
statement & take FSCA

9
Periodic Summary Reporting

Similar serious Root cause is Periodic Summary

identified
incidents with or Reports
the same
FSCA has been taken
device
or

Well-documented &
common incident

10
Trend Reports
Any increasing trend of
non-serious incidents
and side-effects during a
specific period must be
reported

11
Electronic System

Information
Periodic
Vigilance Trend between
Summary PSUR FSN
Reports Reports Member
Reports
States

12
Group Exercise
Please review your Vigilance Procedure and evaluate whether it
discusses:
1. Types of incidents to report
2. Timelines
3. Reporting method
4. Trend reports
5. Periodic summary reports

13
 PMS
DEVICE DOCUMENTATION
DOCUMENTATION

2
Device Documentation
Device Description

Design & Manufacturing Information

IFU & Labels

GSPR

Risk Management

Product Testing

Clinical Evaluation

3
Key changes
 Design and development information
 Manufacturing process validation
 Identification of all sites including subcontractors’sites
involved in design and manufacturing
 Documentation for medicine, substances absorbed and
substances derived from animal or human tissue

4
PMS Documentation

PMS Plan

PSUR

5
Conformity
Assessment
Routes
There are several
approaches to do a
conformity assessment

2
Conformity Assessment Procedures
 Addressed in Articles 52-55 and Annexes IX-XIII
 The choice of a route depends on class and type of device
 A manufacturer can apply to only one NB for a device
 A manufacturer shall declare whether they have withdrawn their application
to a previous NB prior to a decision by that NB
 A manufacturer shall declare if its application for the device was refused by
another NB previously
 A NB shall inform electronically other NBs of the manufacturer of its
decision to withdraw an application prior to a decision has been taken by the
NB

3
 Comparison of Conformity Assessment
Procedures
MDR Description MDD

Annex IX Conformity Assessment based on QMS and Annex II

assessment of technical documentation
Annex X Conformity Assessment based on Type Examination Annex III

Annex XI Conformity Assessment based on Product

Conformity Verification
Part A Production Quality Assurance Annex V

Part B Product Verification Annex IV

Annex XIII Procedure for custom-made devices Annex VIII

4
Routes for Class I devices

5
Class I devices – NB involvement

Is Im Ir

Aspects Aspects Aspects

related to related to related to
establishing, metrological reuse such as
securing and conditions sterilization,
maintaining cleaning,
sterile disinfection,
conditions maintenance

6
Routes for Class IIa devices

7
Difference between Annex XI Parts A and B

Production QA Product Verification

 NB verifies the quality  NB tests each product or
system of the batch
manufacturer  Certificate is issued only
 Manufacturer must have for a product or batch
a technical file  Manufacturer must have a
PMS system and technical
file

8
Routes for Class IIb Rule 12 devices

9
Routes for Class IIb implantable WET & non-implantable non-WET
non-rule 12

10
Routes for Class IIb non-WET implantable devices

11
Type Examination

The NB examines the technical

documentation of the type of
medical device and verifies that
the device is made as per this
documentation. This examination
is done for a representative
sample.

12
Routes for Class III non-implantable devices

13
Routes for Class III implantable devices

14
Routes for Class III implantable custom-made
devices

15
Route for other custom-made devices

16
Routes for Procedure Packs

Devices inside the pack ▸ Devices inside the pack are

are CE marked. The pack not all CE marked and not
may or may not be sterilized as recommended
sterilised by the manufacturer

NB will do assessment as
NB will do assessment per
per Annex IX or part A of
Art 52 considering this as
Annex XI only for
a complete device
sterilization aspects
17
Clinical Evaluation Consultation Procedure
 A clinical evaluation consultation procedure is required for Class III
implantable and Class IIb active devices classified as per rule 12
 The consultation will be taken by the NB with a expert panel set up
for the purpose by the Commission
 The expert panel shall inform within 21 days whether it intends to
provide an opinion
 If an opinion is not received within 60 days of submission, then the
NB may proceed with the certification procedure

18
Consultation Procedure for devices with
ancillary medicine
 For devices with ancillary medicine, the NB shall consult the EMA
or one of the Competent Authorities designated under 2001/ 83/ EC
 If the medicine is derived from human blood or plasma, then the
NB will exclusively consult the EMA
 The medicinal products authority shall give its opinion with 210
days
 The NB shall consider the opinion of the medicinal products
authority before giving a decision on the certification

19
Consultation Procedure for tissues & cells of
human origin
 Specific consultation procedure for devices using derivatives from
tissues & cells of human origin, that have an ancillary action
 NB shall seek a scientific opinion from one of the competent
authorities designated by the Member States in accordance with
Directive 2004/ 23/ EC
 Opinion will be sought on the aspects relating to the donation,
procurement and testing of tissues or cells of human origin or their
derivatives
 The Authority shall provide its opinion within 120 days

20
Consultation Procedure for devices with
substances that are dispersed or absorbed
 Specific consultation procedure for devices having substances which
are absorbed or locally dispersed
 NB shall seek a scientific opinion from one of the competent
authorities designated by the Member States in accordance with
Directive 2001/ 83/ EC or from the EMA
 The Authority shall provide its opinion within 150 days

21
Summary

 Several approaches to get a conformity assessment done

based on device class and type
 Approaches are similar to MDD
 Special consultation procedures for specific types of
devices

22
QMS
Maintaining a QMS
 One of the obligations of a manufacturer is to maintain a QMS
 QMS requirements are explicitly given in:
 Article 10 section 9
 Annex IX chapter 1 and 2
 Annex XI part A

 The MDR doesn’t say which standard to be followed for the QMS,
but ISO13485:2016 is most likely to the preferred choice

2
Elements of the QMS
Strategy for
regulatory UDI PMS
compliance

Management
Communica
Responsibiliti Production
es tion

Implementa Clinical
Vigilance
tion of GSPR evaluation

Monitoring,
Resource Risk
management management Measureme
nt, CAPA

3
4
5
6
7
8
9
10
 TRANSITIONAL
TRANSITIONAL
PROVISIONS
PROVISIONS
Agenda

 Where are the transitional provisions

 Who can use them
 What are the steps

2
Transitional provisions in the MDR

3
 PMS

QMS Vigilance

Registrati
Market
on of
Surveillance
devices
Registration of
economic
operators

4
 Registration of economic operator as per Annex VI part A
 Maintain a PMS system as per Article 83-86
 Maintain a vigilance system as per Article 87-89.
 Co-operate with Competent Authorities on market surveillance
activities as per Article 93
 Implement parts of QMS for implementing the requirements of
registration, PMS, vigilance and market surveillance