MDA/GD/0002

July 2013
First Edition

MEDICAL DEVICE
GUIDANCE DOCUMENT

ESSENTIAL PRINCIPLES OF SAFETY AND

PERFORMANCE OF IVD MEDICAL DEVICES

Medical Device Authority

MINISTRY OF HEALTH MALAYSIA
MDA/GD/0002

Contents Page

Preface...................................................................................................................... iii
Introduction .............................................................................................................. iv
1 Purpose .......................................................................................................... 1
2 Scope ............................................................................................................. 1
3 Terms and definitions ................................................................................... 1
4 Safety and performance of medical devices – general principles ............. 2
5 Essential principles of safety and performance of IVD medical
devices ........................................................................................................... 3
5.1 General principles ......................................................................................... 3
5.2 Chemical, physical and biological properties ............................................. 4
5.3 Infection and microbial contamination ........................................................ 4
5.4 IVD medical devices incorporating materials of biological origin ............. 5
5.5 Manufacturing and environmental properties ............................................. 6
5.6 Performance characteristics ........................................................................ 7
5.7 Protection against radiation ......................................................................... 7
5.8 IVD medical devices that incorporate software and standalone IVD
medical device software ............................................................................... 8
5.9 IVD Medical devices connected to, or equipped with, an energy
source ............................................................................................................ 8
5.10 Protection against mechanical and thermal risks ....................................... 8
5.11 Protection against the risks posed by IVD medical devices intended
by the manufacturer for self-testing ............................................................ 9
5.12 Label and instructions for use ..................................................................... 9
5.13 Performance evaluation including analytical performance and, where
appropriate, clinical performance ................................................................ 9

ii
MDA/GD/0002

Preface

This Guidance Document was prepared by the Medical Device Authority (MDA)
to help the industry and healthcare professionals in their quest to comply with the
Medical Device Act (Act 737) and the regulations under it.

This Guidance Document shall be read in conjunction with the current laws and
regulations used in Malaysia, which include but not limited to the following-

a) Medical Device Act 2012 (Act 737); and

b) Medical Device Regulations 2012.

In this Guidance Document, the following verbal forms are used:

- “shall” indicates a requirement;

- “should” indicates a recommendation;

- “may” indicates a permission; and

- “can” indicates a possibility or a capability.

Irrespective of the requirements of this Guidance Document, MDA has the right
to request for information or material, or define conditions not specifically
described in this document that is deemed necessary for the purpose of
regulatory control.

MDA has put much effort to ensure the accuracy and completeness of this
guidance document. In the event of any contradiction between the contents of
this document and any written law, the latter should take precedence.

MDA reserves the right to amend any part of the guidance document from time
to time.

CONTACT INFORMATION
For further information, please contact:

MEDICAL DEVICE AUTHORITY

Ministry of Health Malaysia
Level 6, Prima 9, Prima Avenue II,
Block 3547, Persiaran APEC,
63000 Cyberjaya, Selangor,
MALAYSIA
Fax: (03) 8230 0200
Email: [email protected]
Website: http://www.mdb.gov.my

iii
MDA/GD/0002

Introduction

Regulatory controls are intended to safeguard the health and safety of patients,
users and others by ensuring that manufacturers of medical devices follow
specified procedures during design, manufacture and marketing.

It is the responsibility of the manufacturer to demonstrate that its product is safe

and perform as its intended use based on essential safety and performance
criteria for an IVD medical device.

iv
ESSENTIAL PRINCIPLES OF SAFETY AND PERFORMANCE OF
IVD MEDICAL DEVICES

1 Purpose
The purpose of this document is to describe generic safety and performance
criteria of an IVD medical device collectively referred to as ‘essential principles’
that may be used to assess the safety of a particular IVD medical device. A
manufacturer is able to demonstrate its medical device is safe by reviewing these
essential principles, selecting those that are relevant to a particular device, and
ensuring through its design and manufacturing controls that the device meets
them.

2 Scope
This document applies to products that fall within the definition of an IVD medical
device, as defined in MDA/GD/0006: Definition of Medical Device.

3 Terms and definitions

For the purposes of this document, the following terms and definitions apply.

3.1 Analytical performance

The demonstration of the analytical performance characteristics supporting the

intended use of the IVD medical device.

3.2 Clinical performance of an IVD medical device

The demonstration of the clinical performance characteristics supporting the

intended use of the IVD medical device.

3.3 Harm

The demonstration of the clinical performance characteristics supporting the

intended use of the IVD medical device.

3.4 Hazard

Potential source of harm.

3.5 Intended use / purpose

The objective intent of the manufacturer regarding the use of a product, process
or service as reflected in the specifications, instructions and information provided

1
MDA/GD/0002

by the manufacturer.

3.6 IVD medical device for self-testing

Any IVD medical device intended by the manufacturer for use by lay persons.

3.7 Lay person

Individual that does not have formal training in a relevant field or discipline.

3.8 IVD medical device

Refer to MDA/GD/0006: Definition of Medical Device.

3.9 Performance evaluation for an IVD medical device

Investigation process of an IVD medical device for the purpose of establishing or

verifying its performance.

3.10 Authority

Medical Device Authority, Ministry of Health.

3.11 Risk

Combination of the probability of occurrence of harm and severity of that harm.

3.12 Specimen

The discrete portion of a body fluid or tissue or other sample associated with the
body taken for examination, study, or analysis of one or more quantity or
characteristic to determine the character of the whole.

4 Safety and performance of medical devices – general principles

A manufacturer of a medical device is expected to design and manufacture a

product that is safe and performs as intended. This guidance document
describes fundamental design and manufacturing requirements, referred to as
‘Essential Principles of Safety and Performance’, to ensure this outcome. This
document is structured to provide general essential principles that apply to all
IVD medical devices.

The medical device manufacturer’s design and manufacturing activities are

under the control of its quality management system. Conformity of the device to
all the applicable Essential Principles will be demonstrated and assessed
according to procedures designated by the Regulatory Authority and described
in other guidance document.

2
MDA/GD/0002

5 Essential principles of safety and performance of IVD medical

devices

5.1 General principles

5.1.1 Medical devices shall be designed and manufactured in such a way that,
when used under the conditions and for the purposes intended and, where
applicable, by virtue of the technical knowledge, experience, education or
training of intended users, they will not compromise the clinical condition or the
safety of patients, or the safety and health of users or, where applicable, other
persons, provided that any risks which may be associated with their use
constitute acceptable risks when weighed against the benefits to the patient and
are compatible with a high level of protection of health and safety.

5.1.2 The solutions adopted by the manufacturer for the design and
manufacture of the devices shall conform to safety principles, taking account of
the generally acknowledged state of the art. When risk reduction is required, the
manufacturer shall control the risk(s) so that the residual risk(s) associated with
each hazard is judged acceptable. The manufacturer shall apply the following
principles in the priority order listed:

a) identify known or foreseeable hazards and estimate the associated risks

arising from the intended use and foreseeable misuse;

b) eliminate risks as far as reasonably practicable through inherently safe

design and manufacture;

c) reduce as far as is reasonably practicable the remaining risks by taking

adequate protection measures, including alarms;

d) inform users of any residual risks.

5.1.3 Devices shall achieve the performance intended by the manufacturer and
be designed, manufactured and packaged in such a way that they are suitable
for one or more of the functions within the scope of the definition of a medical
device applicable in each jurisdiction.

5.1.4 The characteristics and performances referred to in Clauses 5.1.1, 5.1.2

and 5.1.3 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.

5.1.5 The devices shall be designed, manufactured and packed in such a way
that their characteristics and performances during their intended use will not be
adversely affected under transport and storage conditions (for example,
fluctuations of temperature and humidity) taking account of the instructions and
information provided by the manufacturer.

3
MDA/GD/0002

5.1.6 The benefits must be determined to outweigh any undesirable side

effects for the performances intended.

5.2 Chemical, physical and biological properties

5.2.1 The IVD medical devices shall be designed and manufactured in such a
way as to ensure the characteristics and performance referred to in Section 5.1.
Particular attention shall be paid to the possibility of impairment of analytical
performance due to incompatibility between the materials used and the
specimens and/or analyte (measurand) to be detected (such as biological
tissues, cells, body fluids and micro-organisms) intended to be used with the
device, taking account of its intended purpose.

5.2.2 The IVD medical devices shall be designed, manufactured and packaged
in such a way as to minimize the risk posed by contaminants and residues to the
persons involved in the transport, storage and use of the devices and to patients,
taking account of the intended purpose of the product.

5.2.3 The IVD medical devices shall be designed and manufactured in such a
way as to reduce as far as reasonably practicable and appropriate the risks
posed by substances that may leach or leak from the IVD medical device.
Special attention shall be given to substances which are carcinogenic, mutagenic
or toxic to reproduction.

5.2.4 IVD medical devices shall be designed and manufactured in such a way
as to reduce as far as reasonably practicable and appropriate risks posed by the
unintentional ingress or egress of substances into or from the IVD medical device
taking into account the device and the nature of the environment in which it is
intended to be used.

5.3 Infection and microbial contamination

5.3.1 The IVD medical devices and manufacturing processes shall be

designed in such a way as to eliminate or to reduce as far as reasonably
practicable and appropriate the risk of infection to user, professional or lay
person, or, where applicable, other person . The design shall:

a) allow easy and safe handling;

and, where necessary;

b) reduce as far as reasonably practicable and appropriate any microbial

leakage from the IVD medical device and/or microbial exposure during use;
and

c) prevent microbial contamination of the IVD medical device or specimen

where applicable, by the user, professional or lay person, or other person.

4
MDA/GD/0002

5.3.2 IVD medical devices labelled either as sterile or as having a special

microbiological state shall be designed, manufactured and packaged to ensure
they remain so when placed on the market and remain so under the transport
and storage conditions specified by the manufacturer, until the protective
packaging is damaged or opened.

5.3.3 IVD medical devices labelled either as sterile or as having a special

microbiological state shall have been processed, manufactured and, if
applicable, sterilized by appropriate, validated methods.

5.3.4 IVD medical devices intended to be sterilized shall be manufactured in

appropriately controlled (e.g. environmental) conditions.

5.3.5 Packaging systems for non-sterile IVD medical devices shall maintain the
integrity and cleanliness of the product.

5.4 IVD medical devices incorporating materials of biological origin

5.4.1 Where IVD medical devices include tissues, cells and substances
originating from animals, processing, preservation, testing and handling of
tissues, cells and substances of animal origin shall be carried out so as to provide
optimal safety for user, professional or lay person, or other person.

In particular safety with regard to viruses and other transmissible agents shall be
addressed by implementation of validated methods of elimination or inactivation
in the course of the manufacturing process. This may not apply to certain IVD
medical devices if the activity of the virus and other transmissible agent are
integral to the intended purpose of the IVD medical device or when such
elimination or inactivation process would compromise the performance of the IVD
medical device.

The manufacturer shall retain information on the geographical origin of the

animals.

5.4.2 Where IVD medical devices include human tissues, cells and
substances, the selection of sources, donors and/or substances of human origin,
the processing, preservation, testing and handling of tissues, cells and
substances of such origin shall be carried out so as to provide optimal safety for
user, professional or lay person, or other person.

In particular safety with regard to viruses and other transmissible agents shall be
addressed by implementation of validated methods of elimination or inactivation
in the course of the manufacturing process. This may not apply to certain IVD
medical devices if the activity of the virus and other transmissible agent are
integral to the intended purpose of the IVD medical device or when such
elimination or inactivation process would compromise the performance of the IVD
medical device.

5.4.3 Where IVD medical devices include cells and substances of microbial
origin, processing, preservation, testing and handling of cells and substances

5
MDA/GD/0002

shall be carried out so as to provide optimal safety for user, professional or lay
person, or other person.

In particular, safety with regard to viruses and other transmissible agents shall
be addressed by implementation of validated methods of elimination or
inactivation in the course of the manufacturing process. This may not apply to
certain IVD medical devices if the activity of the virus and other transmissible
agent are integral to the intended purpose of the IVD medical device or when
such elimination or inactivation process would compromise the performance of
the IVD medical device.

5.5 Manufacturing and environmental properties

5.5.1 If the IVD medical device is intended for use in combination with other
devices or equipment, the whole combination, including the connection system
shall not impair the specified performance of the devices. Any restrictions on use
applying to such combinations shall be indicated on the label and/or in the
instructions for use.

5.5.2 IVD medical devices shall be designed and manufactured in such a way
as to remove or reduce as far as reasonably practicable and appropriate-

a) the risk of injury to user, professional or lay person, or other person in

connection with their physical and ergonomic features;

b) the risk of use error due to the ergonomic features, human factors and the
environment in which the IVD medical device is intended to be used;

c) risks connected with reasonably foreseeable external influences or

environmental conditions, such as magnetic fields, external electrical and
electromagnetic effects, electrostatic discharge, pressure, humidity,
temperature or variations thereof;

d) the risks associated with the use of the IVD medical device when it comes
into contact with materials, liquids, and gases to which it is exposed during
normal conditions of use;

e) the risk associated with the possible negative interaction between software
and the environment within which it operates and interacts;

f) the risks of accidental penetration of substances into the IVD medical device;

g) the risk of incorrect identification of specimens; and

h) the risks of reasonably foreseeable interference with other devices such as

carry over between IVD medical devices.

5.5.3 IVD medical devices shall be designed and manufactured in such a way
as to minimize the risks of fire or explosion during normal use and in single fault

6
MDA/GD/0002

condition. Particular attention shall be paid to IVD medical devices whose

intended use includes exposure to or use in association with flammable
substances or substances which could cause combustion.

5.5.4 IVD medical devices must be designed and manufactured in such a way
as to facilitate the safe disposal of any waste substances.

5.6 Performance characteristics

5.6.1 IVD medical devices shall be designed and manufactured in such a way
that the performance characteristics support the intended use, based on
appropriate scientific and technical methods. In particular, where appropriate,
the design shall address sensitivity, specificity, accuracy which is trueness and
precision (repeatability and reproducibility), control of known relevant
interference and limits of detection.

These performance characteristics need to be maintained during the lifetime of

the IVD medical device as indicated by the manufacturer.

5.6.2 Where the performance of devices depends on the use of calibrators

and/or control materials, the traceability of values assigned to such calibrators
and/or control materials shall be assured through available reference
measurement procedures and/or available reference materials of a higher order.

5.6.3 Wherever possible values expressed numerically shall be in commonly

accepted, standardised units, and understood by the users of the device.

5.7 Protection against radiation

5.7.1 IVD medical devices shall be designed, manufactured and packaged in

such a way that exposure of user, professional or lay person, or other person to
the emitted radiation (intended, unintended, stray or scattered) is reduced as far
as practicable and appropriate.

5.7.2 When IVD medical devices are intended to emit potentially hazardous,
visible and / or invisible radiation, they shall as far as practicable and appropriate
be-

a) designed and manufactured in such a way as to ensure that the

characteristics and the quantity of radiation emitted can be controlled and /
or adjusted; and

b) fitted with visual displays and / or audible warnings of such emissions.

7
MDA/GD/0002

5.8 IVD medical devices that incorporate software and standalone IVD
medical device software

5.8.1 For IVD medical devices which incorporate software or for standalone
software that are IVD medical devices in themselves, the software must be
validated according to the state of the art taking into account the principles of
development lifecycle, risk management, verification and validation.

5.9 IVD Medical devices connected to, or equipped with, an energy source

5.9.1 IVD medical devices where the safety of the patient depends on an
internal power supply in the IVD medical device, shall be equipped with a means
of determining the state of the power supply.

5.9.2 IVD medical devices shall be designed and manufactured in such a way
as to reduce as far as practicable and appropriate the risks of creating
electromagnetic interference which could impair the operation of this or other
devices or equipment in the usual environment.

5.9.3 IVD medical devices shall be designed and manufactured in such a way
as to provide an adequate level of intrinsic immunity to electromagnetic
disturbance to enable them to operate as intended.

5.9.4 IVD medical devices shall be designed and manufactured in such a way
as to avoid, as far as reasonably practicable, the risk of accidental electric shocks
to the user, professional or lay person, or other person both during normal use
of the device and in the event of a single fault condition in the device, provided
the IVD medical device is installed and maintained as indicated by the
manufacturer.

5.10 Protection against mechanical and thermal risks

5.10.1 IVD medical devices shall be designed and manufactured in such a way
as to protect the user, professional or lay person, or other person against
mechanical risks connected with, for example, resistance to movement,
instability and moving parts.

Where there are risks due to the presence of moving parts, risks due to break-
up or detachment, or leakage of substances, then appropriate protection means
must be incorporated.

5.10.2 IVD medical devices shall be designed and manufactured in such a way
as to reduce to the lowest practicable level the risks arising from vibration
generated by the devices, taking account of technical progress and of the means
available for limiting vibrations, particularly at source, unless the vibrations are
part of the specified performance.

8
MDA/GD/0002

5.10.3 IVD medical devices shall be designed and manufactured in such a way
as to reduce to the lowest practicable level the risks arising from the noise
emitted, taking account of technical progress and of the means available to
reduce noise, particularly at source.

5.10.4 Terminals and connectors to the electricity, gas or hydraulic and

pneumatic energy supplies which the user, professional or lay person, or other
person has to handle shall be designed and constructed in such a way as to
minimize all possible risks.

5.10.5 Accessible parts of the IVD medical devices (excluding the parts or areas
intended to supply heat or reach given temperatures) and their surroundings
shall not attain potentially dangerous temperatures under normal use.

5.11 Protection against the risks posed by IVD medical devices intended
by the manufacturer for self-testing

5.11.1 IVD medical devices intended for self-testing shall be designed and
manufactured in such a way that they perform appropriately for their intended
purpose taking into account the skills and the means available to lay persons and
the influence resulting from variation that can reasonably be anticipated in the
lay person’s technique and environment. The information and instructions
provided by the manufacturer shall be easy for the lay person to understand and
apply.

5.11.2 IVD medical devices intended for self-testing shall be designed and
manufactured in such a way as to reduce as far as practicable the risk of error
by the lay person in the handling of the device and, if applicable, the specimen,
and also in the interpretation of results.

5.11.3 IVD medical devices intended for self-testing shall, where reasonably
possible, include a procedure by which the lay person can verify that, at the time
of use, the product will perform as intended by the manufacturer.

5.12 Label and instructions for use

5.12.1 Users shall be provided with the information needed to identify the
manufacturer, to use the device safely and to ensure the intended performance,
taking account of their training and knowledge. This information shall be easily
understood.

5.13 Performance evaluation including analytical performance and, where

appropriate, clinical performance

5.13.1 For an IVD medical device a performance evaluation shall be conducted

in accordance with MDA guidance. The performance evaluation shall review
analytical performance data and, where appropriate, clinical performance data in

9
MDA/GD/0002

the form of any-

- literature;

- performance study reports; and

- experience gained by routine diagnostic testing.

to establish that the IVD medical device achieves its intended performance
during normal conditions of use and that the known, and foreseeable risks, and
any undesirable effects, are minimised and acceptable when weighed against
the benefits of the intended performance.

The depth and extent of a performance evaluation shall be appropriate to the

nature, intended use and risks of the IVD medical device, and in accordance with
MDA guidance.

Note: Further information is provided in MDA/GD/0003: Principles of Conformity

Assessment for IVD Medical Devices.

5.13.2 Clinical performance studies using specimens from human subjects shall
be carried out in accordance with the spirit of the Declaration of Helsinki. This
includes every step in the clinical performance study from first consideration of
the need and justification of the study to publication of the results.

10
 MEDICAL DEVICE AUTHORITY
MINISTRY OF HEALTH, MALAYSIA

Contact Information:
Registration, Licensing and Enforcement Division
IVD Registration Unit
Medical Device Authority
Ministry of Health
Malaysia

Level 6, Prima 9, Prima Avenue II,

Block 3547, Persiaran APEC,
63000 Cyberjaya, Selangor,
MALAYSIA
T: (03) 8230 0300
F: (03) 8230 0200
Website: http://www.mdb.gov.my