MT
IN VITRO DIAGNOSTIC MEDICAL DEVICES REGULATIONS
Table of Provisions (25)
Statutory Text (25 Articles)
SUBSIDIARY LEGISLATION 427.16
IN VITRO DIAGNOSTIC MEDICAL DEVICES
REGULATIONS
1st January, 2003
LEGAL NOTICE 61 of 2002, as amended by Legal Notices 30 of 2004,
21 of 2010, 371 of 2012 and 318 of 2020.
1. The title of these regulations is the In Vitro Diagnostic
Medical Devices Regulations.
1.2. These regulations shall become operative on the 1st
January, 2003.
Based on Annex I of the Directive
ESSENTIAL REQUIREMENTS
A.
GENERAL REQUIREMENTS
1. The devices must be designed and manufactured in such a way that, when
used under the conditions and for the purposes intended, they will not compromise,
direcdy or indirectly, the clinical condition or the safety of the patients, the safety or
health of users or, where applicable, other persons, or the safety of property. Any
risks, which may be associated with their use, must be acceptable when weighed
against the benefits to the patient and be compatible with a high level of protection
of health and safety.
2. The solutions adopted by the manufacturer for the design and construction
of the devices must conform to safety principles, taking account of the generally
acknowledged state of the art. In selecting the most appropriate solutions, the
manufacturer must apply the following principles in the following order
-
eliminate or reduce risks as far as possible (inherently safe design and
construction),
-
where appropriate take adequate protection measures in relation to risks
that cannot be eliminated,
-
inform users of the residual risks due to any shortcomings of the
protection measures adopted.
3. The devices must be designed and manufactured in such a way that they are
suitable for the purposes referred to in regulation 3.1.3, as specified by the
manufacturer, taking account of the generally acknowledged state of the art. They
must achieve the performances, in particular, where appropriate, in terms of
analytical sensitivity, diagnostic sensitivity, analytical specificity, diagnostic
specificity, accuracy, repeatability, reproducibility, including control of known
relevant interference, and limits of detection, stated by the manufacturer. The
traceability of values assigned to calibrators and, or control materials must be
assured through available reference measurement procedures and, or available
reference materials of a higher order
4. The characteristics and performances referred to in points 1 and 3 of this
section must not be adversely affected to such a degree that the health or the 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. When no
lifetime is stated, the same applies for the lifetime reasonably to be expected of a
device of that kind, having regard to the intended purpose and the anticipated use of
the device.
5. The devices must be designed, manufactured and packed in such a way that
their characteristics and performances during their intended use will not be adversely
affected under storage and transport conditions (temperature, humidity, etc.) taking
account of the instructions and information provided by the manufacturer.
B.
DESIGN AND MANUFACTURING REQUIREMENTS
1. Chemical and physical properties
1.1. The devices must be designed and manufactured in such a way as to achieve
the characteristics and performances referred to in section A on the "General
requirements". Particular attention must be paid to the possibility of impairment of
IN VITRO DIAGNOSTIC MEDICAL DEVICES
analytical performance due to incompatibility between the materials used and the
specimens (such as biological tissues, cells, body fluids and micro-organisms)
intended to be used with the device, taking account of its intended purpose.
1.2. The devices must be designed, manufactured and packed in such a way as to
reduce as far as possible the risk posed by product leakage, contaminants and
residues to the persons involved in the transport, storage and use of the medical
devices, taking account of the intended purpose of the products.
2. Infection and microbial contamination
2.1. The devices and their manufacturing processes must be designed in such a
way as to eliminate or reduce as far as possible the risk of infection to the user or
other persons. The design must allow easy handling and, where necessary, reduce as
far as possible contamination of, and leakage from, the device during use and, in the
case of specimen receptacles, the risk of contamination of the specimen. The
manufacturing processes must be appropriate for these purposes.
2.2. Where a device incorporates biological substances, the risks of infection
must be reduced as far as possible by selecting appropriate donors and appropriate
substances and by using appropriate, validated inactivation, conservation, test and
control procedures.
2.3. Devices labelled either as "STERILE" or as having a special microbiological
state must be designed, manufactured and packed in an appropriate pack, according
to procedures suitable for ensuring that they remain in the appropriate
microbiological state indicated on the label when placed on the market, under the
storage and transport conditions specified by the manufacturer, until the protective
packaging is damaged or opened.
2.4. Devices labelled either as "STERILE" or as having a special microbiological
state must have been processed by an appropriate validated method.
2.5. Packaging systems for devices other than those referred to in point 2.3 of
this section must keep the product without deterioration at the level of cleanliness
indicated by the manufacturer and, if the devices are to be sterilised prior to use,
reduce as far as possible the risk of microbial contamination.
Steps must be taken to reduce as far as possible microbial contamination
du rin g sel ectio n an d h andli ng of raw m aterials, m anufactu re, storage and
distribution where the performance of the device can be adversely affected by such
contamination.
2.6. Devices intended to be sterilised must be manufactured in appropriately
controlled (e.g. environmental) conditions.
2.7. Packaging systems for non-sterile devices must keep the product without
deterioration at the level of cleanliness stipulated and, if the devices are to be
sterilised prior to use, minimise the risk of microbial contamination; the packaging
system must be suitable taking account of the method of sterilisation indicated by the
manufacturer.
3. Manufacturing and environmental properties
3.1. If the device is intended for use in combination with other devices or
equipment, the whole combination, including the connection system, must be safe
and must not impair the specified performances of the devices. Any restrictions on
use must be indicated on the label and, or in the instructions for use.
3.2. Devices must be designed and manufactured in such a way as to reduce as
far as possible the risks linked to their use in conjunction with materials, substances
and gases with which they may come into contact during normal conditions of use.
3.3. Devices must be designed and manufactured in such a way as to remove or
reduce as far as possible
-
the risk of injury linked to their physical features (in particular aspects
of volume x pressure, dimension and, where appropriate, ergonomic
features),
-
risks linked to reasonably foreseeable external influences, such as
magnetic fields, external electrical effects, electrostatic discharge,
pressure, humidity, temperature or variations in pressure or acceleration
or accidental penetration of substances into the medical device.
Devices must be designed and manufactured in such a way as to provide an
adequate level of intrinsic immunity of electromagnetic disturbance to enable them
to operate as intended.
3.4. Devices must be designed and manufactured in such a way as to reduce as
far as possible the risks of fire or explosion during normal use and in single fault
condition. Particular attention must be paid to devices whose intended use includes
exposure to or use in association with flammable substances or substances which
could cause combustion.
3.5. Devices must be designed and manufactured in such a way as to facilitate
the management of safe waste disposal.
3.6. The measuring, monitoring or display scale (including colour change and
other visual indicators) must be designed and manufactured in line with ergonomic
principles, taking account of the intended purpose of the device.
4. Devices which are instruments or apparatus with a measuring function
4.1. Devices which are instruments or apparatus having a primary analytical
measuring function must be designed and manufactured in such a way as to provide
adequate stability and accuracy of measurement within appropriate accuracy limits,
taking into account the intended purpose of the medical device and of available and
appropriate reference measurement procedures and materials. The accuracy limits
have to be specified by the manufacturer.
4.2. When values are expressed numerically, they must be given in legal units
conforming to the provisions of Council Directive 80/181/EEC of 20 December 1979
on the approximation of the laws of the Member States relating to units of
measurement.
5. Protection against radiation
5.1. Devices shall be designed, manufactured and packaged in such a way that
exposure of users and other persons to the emitted radiation is minimised.
5.2. When devices are intended to emit potentially hazardous, visible and, or
invisible radiation, they must as far as possible be
-
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,
-
fitted with visual displays and, or audible warnings of such emissions.
5.3. The operating instructions for medical devices emitting radiation must give
detailed information as to the nature of the emitted radiation, means of protecting the
user, and on ways of avoiding misuse and of eliminating the risks inherent in
installation.
6. Requirements for devices connected to or equipped with an energy source
6.1. Devices incorporating electronic programmable systems, including
software, must be designed to ensure the repeatability, reliability and performance of
these systems according to the intended use.
6.2. Devices must be designed and manufactured in such a way as to minimise
the risks of creating electromagnetic perturbation which could impair the operation
of other devices or equipment in the usual environment.
6.3. Devices must be designed and manufactured in such a way as to avoid, as far
as possible, the risk of accidental electric shocks during normal use and in single
fault condition, provided the devices are installed and maintained correctly.
6.4. Protection against mechanical and thermal risks
Devices must be designed and manufactured in such a way as to
protect the user against mechanical risks. Devices must be
sufficiently stable under the foreseen operating conditions. They
must be suitable to withstand stresses inherent in the foreseen
working environment, and to retain this resistance during the
expected life of the devices, subject to any inspection and
maintenance requirements as indicated by the manufacturer.
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.
Any guards or other means included with the device to provide
protection, in particular against moving parts, must be secure and
must not interfere with access for the normal operation of the
medical device, or restrict routine maintenance of the device as
intended by the manufacturer.
Devices must be designed and manufactured in such a way as to
reduce to the lowest possible 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.
Devices must be designed and manufactured in such a way as to
reduce as far as possible the risks arising from the noise emitted,
taking account of technical progress and of the means available to
reduce noise, particularly at source, unless the noise emitted is part
of the specified performance.
Terminals and connectors to electricity, gas or hydraulic and
pneumatic energy supplies which the user has to handle must be
designed and manufactured in such a way as to minimise all possible
risks.
Accessible parts of the devices (excluding the parts of areas
intended to supply heat or reach given temperatures) and their
surroundings must not attain potentially dangerous temperatures
under normal use.
7. Requirements for devices for self-testing
Devices for self-testing must 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 users and the influence resulting from variation that
can reasonably be anticipated in users’ technique and environment. The information
and instructions provided by the manufacturer should be easily understood and
applied by the user.
7.1. Devices for self-testing must be designed and manufactured in such a way as
to
-
ensure that the device is easy to use by the intended lay user at all stages
of the procedure, and
-
reduce as far as practicable the risk of user error in the handling of the
device and in the interpretation of the results.
7.2. Devices for self-testing must, where reasonably possible, include user
control, i.e. a procedure by which the user can verify that, at the time of use, the
product will perform as intended.
8. Information supplied by a manufacturer
8.1. Each device must be accompanied by the information needed to use it safely
and properly, taking account of the training and knowledge of the potential users,
and to identify the manufacturer. This information comprises the data on the label
and in the instructions for use.
As far as practicable and appropriate, the information needed to use the
device safely and properly must be set out on the device itself and, or, where
appropriate, on the sales packaging. If individual full labelling of each unit is not
practicable, the information must be set out on the packaging and, or in the
instructions for use supplied with one or more devices.
Instructions for use must accompany or be included in the packaging of one
or more devices.
In duly justified and exceptional cases no such instructions for use are
needed for a device if it can be used properly and safely without them.
The decision whether to translate the instructions for use and the label into
one or more languages of the European Union shall be left to the Member States,
except that, for devices for self-testing, the instructions for use and the label must
include a translation into the official language(s) of the Member State in which the
device for self testing reaches its final user.
8.2. Where appropriate, the information to be supplied should take the form of
symbols. Any symbol and identification colour used must conform to the harmonised
standards. In areas for which no standards exist, the symbols and colour used must
be described in the documentation supplied with the device.
8.3. In the case of devices containing a preparation which may be considered as
being dangerous, taking account of the nature and quantity of its constituents and the
form under which they are present, relevant danger symbols and labelling
requirements of Directive 671548/EEC * and Directive 88/379/EEC † shall apply.
Where there is insufficient space to put all the information on the device itself or on
its label, the relevant danger symbols shall be put on the label and the other
information required by those Directives shall be given in the instructions for use.
*Council Directive 67/548/EEC of 27 June 1967 on the approximation of laws, regulations and
administrative provisions relating to the classification, packaging and labeling of dangerous substances (OJ
No. L 196, 16.08.67, P. 1 ). Directive as last amended by Commission Directive 97/69/EC (OJ No. L 343,
1. These regulations shall apply to in vitro diagnostic medical
devices and their accessories.
2.1.1.
For the purposes of these regulations, accessories
shall be treated as medical devices in their own
right.
2.1.2.
Both in vitro diagnostic medical devices and
accessories shall hereinafter be termed "devices".
2.2. These regulations shall not apply to devices manufactured
and used only within the same health institution and on the
premises of their manufacture or used on premises in the immediate
vicinity without having been transferred to another legal entity.
2.3. These regulations shall not affect national laws which
provide for the supply of medical devices by a medical
prescription.
L.N. 371 of 2012.
Based on Annex II of the Directive
LIST OF DEVICES REFERRED TO IN REGULATIONS 7.2 AND 7.3
1. List A
Reagents and reagent products, including related calibrators and control
materials, for determining the following blood groups: ABO system,
rhesus (C, c, D, E, e) anti-Kell,
reagents and reagent products, including related calibrators and control
materials, for the detection, confirmation and quantification in human
specimens of markers of HIV infection (HIV 1 and 2), HTLV I and II,
and hepatitis B, C and D,
Variant Creutzfeldt-Jakob disease (vCJD) assays for blood screening,
diagnosis and confirmation.
2. List B
Reagents and reagent products, including related calibrators and control
materials, for determining the following blood groups: anti-Duffy and
anti-Kidd,
reagents and reagent products, including related calibrators and control
materials, for determining irregular anti-erythrocytic antibodies,
reagents and reagent products, including related calibrators and control
materials, for the detection and quantification in human samples of the
following congenital infections: rubella, toxoplasmosis,
reagents and reagent products, including related calibrators and control
materials, for diagnosing the following hereditary disease
phenylketonuria,
reagents and reagent products, including related calibrators and control
materials, for determining the following human infections
cytomegalovirus, chlamydia,
reagents and reagent products, including related calibrators and control
materials, for determining the following HLA tissue groups: DR, A, B,
reagents and reagent products, including related calibrators and control
materials, for determining the following tumoral marker: PSA,
reagents and reagent products, including related calibrators, control
materials and software, designed specifically for evaluating the risk of
trisomy 21,
the following device for self-diagnosis, including its related calibrators
and control materials: device for the measurement of blood sugar.
1. For the purposes of these regulations, the following
definitions shall apply
3.1.1.
"the Directive" means Council Directive 98/79/EC
of the European Parliament and of the Council on
in vitro diagnostic medical devices.
3.1.1.1.
This Directive is a specific directive
within the meaning of Article 2(2) of
Directive 89/336/EEC, which shall cease
to apply to medical devices which have
complied with this Directive.
3.1.2.
"medical device" means any instrument, apparatus,
appliance, material or other article, whether used
alone or in combination, including the software
necessary for its proper application intended by the
manufacturer to be used for human beings for the
purpose of
- diagnosis, prevention, monitoring, treatment
or alleviation of disease,
- diagnosis, monitoring, treatment, alleviation
of or compensation for an injury or handicap,
IN VITRO DIAGNOSTIC MEDICAL DEVICES
- investigation, replacement or modification of
the anatomy or of a physiological process,
- control of conception,
and which does not achieve its principal intended
action in or on the human body by
pharmacological, immunological or metabolic
means, but which may be assisted in its function by
such means;
3.1.3.
"in vitro diagnostic medical device" means a
medical device which -
3.1.3.1.
is a reagent, reagent product, calibrator,
control
material,
kit,
instrument,
apparatus, equipment, or system,
whether used alone or in combination;
and
3.1.3.2.
is intended by the manufacturer to be
used in vitro for the examination of
specimens, including blood and tissue
donations, derived from the human body,
solely or principally for the purpose of
providing information
- concerning a physiological or
pathological state,
- concerning
a
congenital
abnormality,
- to deternune the safety and
compatibility
with
potential
recipients, or
- to monitor therapeutic measures,
and includes a specimen receptacle but
not a product for general laboratory use,
unless that product, in view of its
characteristics, is specifically intended
by its manufacturer to de used for in
vitro diagnostic exaxnination;
3.1.3.3.
Products for general laboratory use are
not in vitro diagnostic medical devices
unless such products, in view of their
characteristics, are specifically intended
by their manufacturer to be used for in
vitro diagnostic examination.
3.1.4.
"accessory" means an article intended specifically
by its manufacturer to be used together with an in
vitro diagnostic medical device to enable that
device to be used in accordance with its intended
purpose, which is not -
3.1.4.1.
itself an in vitro diagnostic medical
device;
3.1.4.2.
an invasive sampling medical device; or
3.1.4.3.
a medical device which is directly
applied to the human body for the
purpose of obtaining a specimen within
the meaning of Directive 93142/EEC;
3.1.5.
"calibration and control material" means any
substance, material or article intended by its
manufacturer either to establish measurement
relationships or to verify the performance
characteristics of a relevant device in conjunction
with the intended use of that device;
3.1.6.
"device for self-testing" means any device intended
by the manufacturer to be able to be used by lay
persons in a home environment;
3.1.7.
"device for performance evaluation" means any
device intended by the manufacturer to be subject
to one or more performance evaluation studies in
laboratories for medical analyses or in other
appropriate environments outside his own
premises;
3.1.8.
"manufacturer" means the natural or legal person
with responsibility for the design, manufacture,
packaging and labelling of a device before it is
placed on the market under his own name,
regardless of whether these operations are carried
out by that person himself or on his behalf by a
third party;
3.1.8.1.
The obligations of the regulations to be
met by manufacturers also apply to the
natural or legal person who assembles,
packages, processes, fully refurbishes
and, or labels one or more ready-made
products and, or assigns to them their
intended purpose as devices with a view
to their being placed on the market under
his own name.
3.1.8.2.
Regulation 3.1.8.1 does not apply to the
person who, while not a manufacturer
within the meaning of regulation 3.1.7,
assembles or adapts devices already on
the market to their intended purpose for
an individual patient;
3.1.9. "Medicines Authority" means the Authority as
established under article 4 of the Medicines Act;
3.1.10. "intended purpose" means the use for which the
device is intended according to the data supplied
by the manufacturer on the labelling, in the
instructions for use and, or in promotional
materials;
3.1.11. "placing on the market" means the first making
available in return for payment or free of charge of
a device other than a device intended for
performance evaluation with a view to distribution
IN VITRO DIAGNOSTIC MEDICAL DEVICES
and, or use on the market, regardless of whether it
is new or fully refurbished;
3.1.12. "putting into service" means the stage at which a
device has been made available to the final user as
being ready for use on the market for the first time
for its intended purpose;
3.1.13. "specimen receptacles" are those devices, whether
vacuum-type or not, specifically intended by their
manufacturers for the primary containment and
preservation of specimens derived from the human
body for the purpose of in vitro diagnostic
examination;
3.1.14. for the purposes of these regulations, the removal,
collection and use of tissues, cells and substances
of human origin shall be governed, in relation to
ethics, by the principles laid down in the
Convention of the Council of Europe for the
protection of human rights and dignity of the
human being with regard to the application of
biology and medicine and by any Member States
regulations for that matter;
3.1.15. in these regulations, unless the context otherwise
requires, a reference -
3.1.15.1. to a numbered regulation is to the
regulation of these regulations bearing
that number;
3.1.15.2. in a regulation to a numbered or lettered
paragraph is to the paragraph of that
regulation bearing that number or letter;
3.1.15.3. in a paragraph to a numbered or lettered
sub-paragraph is to the sub-paragraph in
that paragraph bearing that number or
letter; and
3.1.15.4. to a numbered article or Annex is to the
article or Annex of the Directive bearing
that number.
3.1.16. "harmonised standard" means a technical
specification adopted by the European Committee
for Standardisation (CEN) or the European
Committee for Electrotechnical Standardisation
(CENELEC) or the European Telecommunications
Standards Institute (ETSI), upon a remit from the
European Commission in accordance with
Directive 98/34/EC of the European Parliament and
of the Council laying down a procedure for the
provision of information in the field of technical
standards and regulations as amended by Directive
98/48/EC of the European Parliament and of the
Council;
3.1.16.1. Where, in these regulations, reference is
made to harmonised standards, this is
also meant to refer to the common
technical specifications;
3.1.17. "national standard transposing the harmonised
standard" means a standard issued by one of the
members of CEN/CENELEC/ETSI which is
declared and noted to be technically equivalent to
the harmonised standard originally issued by CEN/
CENELEC/ETSI;
3.1.18. "OJ" means the Official Joumal of the European
Communities;
3.1.19. "Community" means the European Community;
3.1.20. "essential requirements" means the requirements in
Annex I of the Directive which is set out in
Schedule I;
3.1.21. "notified body" means a body responsible for
carrying out functions relating to the conformity
assessment procedures set out in Article 9 of the
Directive and described in regulation 7 of these
regulations which has been notified by the Member
State concerned to the Commission and the other
Member States pursuant to Article 15(1) of the
Directive;
3.1.22. "CE marking" means marking as set out in Annex
10 of the Directive, which is set out in Schedule X;
3.1.23. "local autliorised representative" means any person
(or organisation) established in Malta who has been
appointed by the manufacturer to act on his behalf
in carrying out certain tasks required by these
regulations;
3.1.24. "importer" means any person who places medical
devices from a foreign country on to the Maltese
market so that he supplies such devices on the first
occasion that it is supplied in Malta;
3.1.25. "person who supplies medical devices" means
wholesalers, distributors, retailers, etc.;
3.1.26. "responsible person" in relation to medical devices
means
3.1.26.1. the manufacturer thereof;
3.1.26.2. the manufacturer’s local authorised
representative; or
3.1.26.3. where
the
manufacturer
is
not
established in Malta and he has not
appointed
a
local
authorised
representative, the person who places the
devices on the local market;
3.1.27. "common technical specification" means a
technical specification for a relevant device
referred to in a list in Annex II of the Directive, set
out in Schedule II, which has been adopted in
accordance with the procedure set out in Article
7(2) of the Directive and published in the OJ, as set
out in Schedule XI.
Based on Annex III of the Directive
EC DECLARATION OF CONFORMITY
1. The EC declaration of conformity is the procedure whereby the
manufacturer or his authorised representative who fulfils the obligations imposed by
sections 2 to 5 of this Schedule and additionally, in the case of devices for self-
testing, the obligations imposed by section 6 of this Schedule, ensures and declares
that the products concerned meet the provisions of these regulations which apply to
them. The manufacturer must affix the CE marking in accordance with regulation 12
of these regulations.
2. The manufacturer must prepare the technical documentation described in
section 3 of this Schedule and ensure that the manufacturing process follows the
principles of quality assurance as set out in section 4 of this Schedule.
3. The technical documentation must allow assessment of the conformity of the
product with the requirements of these regulations. It must include in particular
a general description of the product, including any variants planned,
the documentation of the quality system,
design information, including the determination of the characteristics of
the basic materials, characteristics and limitation of the performance of
the devices, methods of manufacture and, in the case of instruments,
design drawings, diagrams of components, sub-assemblies, circuits,
etc.,
in the case of devices containing tissues of human origin or substances
derived from such tissue, information on the origin of such material and
on the conditions in which it was collected,
the descriptions and explanations necessary to understand the
abovementioned characteristics, drawings and diagrams and the
operation of the product,
the results of the risk analysis and, where appropriate, a list of the
standards referred to in Article 5 of the Directive, applied in full or in
part, and descriptions of the solutions adopted to meet the essential
requirements of the Directive if the standards referred to in Article 5 of
the Directive have not been applied in full,
in the case of sterile products or products with a special microbiological
state or state of cleanliness, a description of the procedures used,
the results of the design calculations and of the inspections carried out,
etc.,
if the device is to be combined with other medical device(s) in order to
operate as intended, proof must be provided that it conforms to the
essential requirements when combined with any such device(s) having
the characteristics specified by the manufacturer,
the test reports,
adequate performance evaluation data showing the performances
claimed by the manufacturer and supported by a reference measurement
system (when available), with information on the reference methods,
the reference materials, the known reference values, the accuracy and
measurement units used; such data should originate from studies in a
clinical or other appropriate environment or result from relevant
biographical references,
the labels and instructions for use,
the results of stability studies.
4. The manufacturer shall take necessary measures to ensure that the
manufacturing process follows the principles of quality assurance as appropriate for
the products manufactured.
The system shall address
the organisational structure and responsibilities,
the manufacturing processes and systematic quality control of
production,
the means to monitor the performance of the quality system.
5. The manufacturer shall institute and keep up to date a systematic procedure
to review experience gained from devices in the post-production phase and to
implement appropriate means to apply any necessary corrective actions, taking
account of the nature and risks in relation to the product. He shall notify the
competent authorities of the following incidents immediately on learning of them
(i)
any malfunction, failure or deterioration in the characteristics and, or
performance of a device, as well as any inadequacy in the labelling or
the instructions for use which, directly or indirectly, might lead to, or
might have led to, the death of a patient or user or other persons or to a
serious deterioration in his or their state of health;
(ii)
any technical or medical reason connected with the characteristics or
the performance of a device for the reasons referred to in paragraph (i)
leading to systematic recall of devices of the same type by the
manufacturer.
6. For devices for self-testing the manufacturer shall lodge an application or
examination of the medical design with a notified body.
6.1. The application shall enable the design of the device to be understood and
shall enable conformity with the design-related requirements of the regulations to be
assessed.
It shall include
-
test reports including, where appropriate, results of studies carried out
with lay persons,
-
data showing the handling suitability of the device in view of its
intended purpose for self-testing,
-
the information to be provided with the device on its label and its
instructions for use.
6.2. The notified body shall examine the application and, if the design conforms
to the relevant provisions of these regulations, shall issue the applicant with an EC
design-examination certificate. The notified body may require the application to be
completed by further tests or proof to allow assessment of conformity with the
design-related requirements of the regulations. The certificate shall contain the
conclusions of the examination, the conditions of validity, the data needed for
identification of the approved design and, where appropriate, a description of the
intended purpose of the product.
6.3. The applicant shall inform the notified body which issued the EC design-
examination certificate of any significant change made to the approved design.
Changes to the approved design must receive further approval from the notified body
which issued the EC design-examination certificate wherever the changes could
affect conformity with the essential requirements of the regulations or with the
conditions prescribed for use of the product. This additional approval shall take the
form of a supplement to the EC design-examination certificate.
1. The provisions of these regulations are applicable to all
imported in vitro diagnostic medical devices as well as those
manufactured for the local market.
4.1.1.
No person may manufacture, import, place on the
market or put into service any in vitro diagnostic
medical devices which do not comply with the
provisions of these regulations.
4.2. Subject to regulation 4.3, the provisions of these
regulations shall not apply to in vitro diagnostic medical devices
intended exclusively for export.
4.3. Subject to regulation 11, regulation 4.2 shall not apply if
the CE marking or any inscription liable to be confused therewith is
affixed to the in vitro diagnostic medical devices.
Based on Annex IV of the Directive
EC DECLARATION OF CONFORMITY
(FULL QUALITY ASSURANCE SYSTEM)
1. The manufacturer must ensure application of the quality system approved
for the design, manufacture and final inspection of the devices concerned, as
specified in section 3 of this Schedule, and is subject to audit as laid down in point
3.3 and to the surveillance as specified in section 5 of this Schedule. In addition, the
manufacturer must follow, for devices covered by Annex II, List A, of the Directive,
which is set out in Schedule II, the procedures laid down in sections 4 and 6 of this
Schedule.
2. The declaration of conformity is the procedure whereby the manufacturer
who fulfils the obligations imposed by section 1 ensures and declares that the
devices concerned meet the provisions of these regulations which apply to them.
The manufacturer shall affix the CE marking in accordance with regulation
12 of these regulations, and shall draw up a declaration of conformity covering the
devices concerned.
3. Quality system
3.1. The manufacturer must lodge an application for assessment of his quality
system with a notified body.
The application must include
the name and address of the manufacturer and any additional
manufacturing site covered by the quality system,
adequate information on the device or device category covered by the
procedure,
a written declaration that no such application has been lodged with any
other notified body for the same device-related quality system,
the documentation on the quality system,
an undertaking by the manufacturer to fulfil the obligations imposed by
the quality system approved,
an undertaking by the manufacturer to keep the approved quality system
adequate and efficacious,
an undertaking by the manufacturer to institute and keep up to date a
systematic procedure to review experience gained from devices in the
post-production phase and to implement appropriate means to apply any
necessary corrective action and notification as referred to in Annex III,
section 5 of the Directive, which is set out in Schedule III.
3.2. Application of the quality system must ensure that the devices conform to
the provisions of these regulations which apply to them at every stage, from design
to final inspection. All the elements, requirements and provisions adopted by the
manufacturer for his quality system must be documented in a systematic and orderly
manner in the form of written policies and procedures, such as quality programmes,
quality plans, quality manuals and quality records.
It shall include in particular an adequate description of
(a) the manufacturer’s quality objectives;
(b) the organisation of the business and in particular
-
the organisational structures, the responsibilities of the
managerial staff and their organisational authority where quality
of design and manufacture of the devices is concerned,
-
the methods of monitoring the efficient operation of the quality
system and in particular its ability to achieve the desired quality
of design and of product, including control of devices which fail
to conform;
(c) the procedures for monitoring and verifying the design of the devices
and in particular
-
a general description of the device, including any variants
planned,
-
all documentation referred to in Annex III, section 3, indents 3 to
13 of the Directive, which is set out in Schedule III,
-
in the case of devices for self-testing, the information referred to
in Annex III, section 6.1 of theþirective, which is set out in
Schedule III,
-
the techniques used to control and verify the design and the
processes and systematic measures which will be used when the
devices are being designed;
(d) the inspection and quality assurance techniques at the manufacturing
stage and in particular
-
the processes and procedures which will be used, particularly as
regards sterilisation,
-
the procedures in relation to purchasing,
-
the product identification procedures drawn up and kept up to
date from drawings, specifications or other relevant documents at
every stage of manufacture;
(e) the appropriate tests and trials which will be carried out before, during
and after manufacture, the frequency with which they will take place,
and the test equipment used; it must be possible to trace back the
calibration.
The manufacturer shall carry out the required controls and tests according to
the latest state of the art. The controls and tests shall cover the manufacturing
process including the characterisation of the raw material and the individual devices
or each batch of devices manufactured.
In testing the devices covered by Annex II, List A of the Directive, which is
set out in Schedule II, the manufacturer shall take into account the most recent
available information, in particular as regards the biological complexity and
variability of the specimens to be tested with the in vitro device concerned.
3.3. The notified body must audit the quality system to determine whether it
meets the requirements referred to in point 3.2 of this Schedule. It must presume that
quality systems which implement the relevant harmonised standards conform to the
requirements.
The assessment team must have experience of assessments of the technology
concerned. The assessment procedure must include an inspection on the
manufacturer’s premises and, in duly substantiated cases, on the premises of the
manufacturer ’s suppliers and, or subcontractors to inspect the manufacturing
processes.
The decision shall be notified to the manufacturer. It must contain the
conclusions of the inspection and a reasoned assessment.
3.4. The manufacturer must inform the notified body which approved the quality
system of any plan for substantial changes to the quality system or the product-range
covered.
The notified body must assess the changes proposed and verify whether after
these changes the quality system still meets the requirements referred to in point 3.2
of this Schedule. It must notify the manufacturer of its decision. This decision must
contain the conclusions of the inspection and a reasoned assessment.
4. Examination of the design of the product
4.1. For devices covered by Annex II, List A of the Directive, which is set out in
Schedule II, in addition to the obligations imposed by section 3 of this Schedule, the
manufacturer must lodge with the notified body an application for examination of
the design dossier relating to the device which he plans to manufacture and which
falls into the category referred to in point 3.1 of this Schedule.
4.2. The application must describe the design, manufacture and performances of
the device in question. It must include the documents needed to assess whether the
device conforms to the requirements of these regulations, as referred to in point
IN VITRO DIAGNOSTIC MEDICAL DEVICES
3.2(c) of this Schedule.
4.3. The notified body must examine the application and, if the device conforms
to the relevant provisions of the regulations, issue the application with an EC design-
examination certificate. The notified body may require the application to be
completed by further tests or proof to allow assessment of conformity with the
requirements of the regulations. The certificate must contain the conclusions of the
examination, the conditions of validity, the data needed for the identification of the
approved design and, where appropriate, a description of the intended purpose of the
device.
4.4. Changes to the approved design must receive further approval from the
notified body which issued the EC design-examination certificate wherever the
changes could affect conformity with the essential requirements of the regulations or
with the conditions prescribed for use of the device. The applicant shall inform the
notified body which issued the EC design-examination certificate of any such
changes made to the approved design. The additional approval must take the form of
a supplement to the EC design-examination certificate.
4.5. The manufacturer shall inform the notified body without delay if it has
obtained information about changes to the pathogen and markers of infections to be
tested, in particular as a consequence of biological complexity and variability. In this
connection, the manufacturer shall inform the notified body whether any such
change is likely to affect the performance of the in vitro diagnostic device
concerned.
5. Surveillance
5.1. The aim of surveillance is to ensure that the manufacturer duly fulfils the
obligations imposed by the approved quality system.
5.2. The manufacturer must authorise the notified body to carry out all the
necessary inspections and supply it with all relevant information, in particular
-
the documentation on the quality system,
-
the data stipulated in the part of the quality system relating to design,
such as the results of analyses, calculation, tests, etc.,
-
the data stipulated in the part of the quality system relating to
manufacture, such as inspection reports and test data, calibration data,
qualification reports of the personnel concerned, etc.
5.3. The notified body must periodically carry out appropriate inspections and
assessments to make sure that the manufacturer applies the approved quality system
and must supply the manufacturer with an assessment report.
5.4. In addition, the notified body may pay unannounced visits to the
manufacturer. At the time of such visits, the notified body may, where necessary,
carry out or ask for tests in order to check that the quality system is working
properly. It must provide the manufacturer with an inspection report and, if a test has
been carried out, with a test report.
6. Verification of manufactured products covered by Schedule II, List A
6.1. In the case of devices covered by Annex II, List A of the Directive, which is
set out in Schedule II, the manufacturer shall forward to the notified body without
delay after the conclusion of the controls and tests the relevant reports on the tests
carried out on the manufactured devices or each batch of devices.
Furthermore, the manufacturer shall make the samples of manufactured
devices or batches of devices available to the notified body in accordance with pre-
agreed conditions and modalities.
6.2. The manufacturer may place the devices on the market, unless the notified
body communicates to the manufacturer within the agreed time-frame, but not later
than thirty days after reception of the samples, any other decision, including in
particular any condition of validity of delivered certificates.
1. All necessary steps shall be taken to ensure that devices are
placed on the market and, or put into service only if they comply
with the requirements laid down in these regulations when duly
supplied and properly installed, maintained and used in accordance
with their intended purpose.
5.1.1.
This regulation applies also to devices made
available for performance evaluation.
5.2. Devices must meet the essential requirements set out in
Annex I of the Directive, which is set out in Schedule I, which
apply to them, taking account of the intended purpose of the
devices concerned.
5.3. A device shall be treated as complying with an essential
requirement if as respects that requirement, it complies with the
relevant national standard, unless there are reasonable indications
that the device does not comply with that requirement.
5.4. Without prejudice to regulation 5.3, a device specified in
List A or B of Annex II of the Directive, set out in Schedule II,
shall be treated as complying with the relevant essential
requirements if the device is designed and manufactured in
conformity with the common technical specifications drawn up for
the device, unless there are reasonable indications that the device
does not comply with those requirements.
5.4.1.
A device to which regulation 5.4 relates shall be
treated as having been manufactured in accordance
with the common technical specifications drawn up
for the device if, for justifiable reasons, it is not so
manufactured but is manufactured in accordance
with technical specifications that are at least
equivalent
to
such
common
technical
specifications, unless there are reasonable
indications that the device does not comply with
those requirements.
5.4.1.1.
The technical specifications set out in
Schedule XI are adopted as common
technical specifications for devices in
list A of Schedule II.
5.5. No person shall place on the market any device to which
these regulations apply unless the requirements of regulation 5.2
have been complied with in relation to it.
Based on Annex V of the Directive
EC TYPE-EXAMINATION
1. EC type-examination is the part of the procedure whereby a notified body
ascertains and certifies that a representative sample of the production envisaged
fulfils the relevant provisions of these regulations.
2. The application for EC type-examination shall be lodged by the
manufacturer or by his authorised representative with a notified body.
The application shall include
the name and the address of the manufacturer and the name and address
of the authorised representative if the application is lodged by the
representative,
the documentation described in section 3 of this Schedule needed to
assess the conformity of the representative sample of the production in
question, hereinafter referred to as the "type", with the requirements of
these regulations. The applicant shall make a "type" available to the
notified body. The notified body may request other samples as
necessary,
a written declaration that no application has been lodged with any other
notified body for the same type.
3. The documentation must allow an understanding of the design, the
manufacture and the performances of the device. The documentation shall contain
the following items in particular
a general description of the type, including any variants planned,
all documentation referred to in Annex III, section 3, indents 3 to 13 of
the Directive, which is set out in Schedule III,
in the case of devices for self-testing, the information referred to in
Annex III, section 6.1 of the Directive, which is set out it Schedule III.
4. The notified body shall
4.1. examine and assess the documentation and verify that the type has been
manufactured in conformity with that documentation; it shall also
record the items designed in conformity with the applicable provisions
of the standards referred to in Article 5 of the Directive, as well as the
items not designed on the basis of the relevant provisions of the
abovementioned standards;
4.2. perform or have performed appropriate examinations and the tests
necessary to verify whether the solutions adopted by the manufacturer
meet the essential requirements of these regulations if the standards
IN VITRO DIAGNOSTIC MEDICAL DEVICES
referred to in Article 5 of the Directive have not been applied; if the
device is to be combined with other device(s) in order to operate as
intended, proof must be provided that it conforms to the essential
requirements when combined with any such device(s) having the
characteristics specified by the manufactucer;
4.3. carry out or ask for the appropriate examinations and the tests necessary
to verify whether, if the manufacturer has chosen to apply the relevant
standards, these have actually been applied;
4.4. agree with the applicant on the place where the necessary examinations
and tests will be carried out.
5. If the type conforms to the provisions of these regulations, the notified body
shall issue the applicant with an EC type-examination certificate. The certificate
shall contain the name and address of the manufacturer, the conclusions of the
examination, the conditions of validity and the data needed for identification of the
type approved. The relevant parts of the documentation shall be annexed to the
certificate and a copy shall be kept by the notified body.
6. The manufacturer shall inform the notified body without delay if it has
obtained information about changes to the pathogen and markers of infections to be
tested, in particular as a consequence of biological complexity and variability. In this
connection, the manufacturer shall inform the notified body whether any such
change is likely to affect the performance of the in vitro device concerned.
6.1. Changes to the approved device must receive further approval from the
notified body which issued the EC type-examination certificate wherever the
changes may affect conformity with the essential requirements of the regulations or
with the conditions prescribed for use of the device. The applicant shall inform the
notified body which issued the EC type-examination certificate of any such change
made to the approved device. This new approval shall take the form of a supplement
to the initial EC type-exanunation certificate.
7. Administrative provisions
7.1. Other notified bodies may obtain a copy of the EC type-examination
certificates and, or the supplements thereto. The annexes to the certificates must be
available to the other notified bodies on reasoned application, after the manufacturer
has been informed.
1. The placing on the market or putting into service under the
conditions specified by the manufacturer of devices referred to in
regulation 3, which comply with these regulations and bear the CE
marking provided for in regulation 11, indicating that they have
undergone conformity assessment in accordance with regulation 7
shall not be prohibited, restricted or impeded.
6.2. No obstacle shall be created to devices intended for
performance evaluation being made available for that purpose to
the laboratories or other institutions listed in the statement referred
to in Annex VIII of the Directive, which is set out in Schedule VIII,
if they meet the conditions laid down in regulation 7.4 and Annex
VIII of the Directive, which is set out in Schedule VIII.
6.3. At trade fairs, exhibitions, demonstrations, scientific or
technical gatherings, etc., no obstacle shall be created to the
showing of devices which do not conform to these regulations,
provided that such devices are not used on specimens taken from
the participants and that a visible sign clearly indicates that such
devices cannot be marketed or put into service until they have been
made to comply.
6.4. The information to be supplied pursuant to Annex I, part B,
section 8 of the Directive, which is set out in Schedule I, is required
to be in either the Maltese or English language, when the device
reaches the final user.
6.4.1.
Provided that safe and correct use of the device is
ensured, the information referred to in regulation
6.4 may be authorised to be in one or more other
official Community language(s).
6.4.1.1.
In the application of this provision,
account shall be taken of the principle of
proportionality and, in particular
- whether the information can be
supplied by harmonised symbols or
recognised codes or other measures;
- the type of user anticipated for the
device.
Based on Annex VI of the Directive
EC VERIFICATION
1. EC verification is the procedure whereby the manufacturer or his authorized
representative ensures and declares that the products which have been subject to the
procedure set out in section 4 of this Schedule conform to the type described in the
EC type-examination certificate and meet the requirements of these regulations
which apply to them.
2.1. The manufacturer must take all the measures necessary to ensure that the
manufacturing process produces products which conform to the type described in the
EC type-examination certificate and the requirements of the regulations which apply
to them. Before the start of manufacture, the manufacturer must prepare documents
defining the manufacturing process, in particular as regards sterilisation and the
suitability of starting materials, where necessary, and define the necessary testing
procedures according to the state of the art. All the routine, pre-established
provisions must be implemented to ensure homogeneous production and conformity
of the products with the type described in the EC type-examination certificate and
with the requirements of these regulations which apply to them.
2.2. To the extent that for certain aspects the final testing according to point 6.3
of this Schedule is not appropriate, adequate process testing, monitoring and control
methods shall be established by the manufacturer with the approval of the notified
body. The provisions of Annex IV, section 5 of the Directive, which is set out in
Schedule IV, shall apply accordingly in relation to the abovementioned approved
procedures.
3. The manufacturer must undertake to institute and keep up to date a
systematic procedure to review experience gained from devices in the post-
production phase and to implement appropriate means to apply any necessary
corrective and notification action as referred to in Annex III, section 5 of the
Directive, which is set out in Schedule III.
4. The notified body must carry out the appropriate examinations and tests
taking account of point 2.2 of this Schedule in order to verify the conformity of the
product with the requirements of the regulations either by examining and testing
every product as specified in section 5 of this Schedule or by examining and testing
products on a statistical basis as specified in section 6 of this Schedule, as the
manufacturer decides. When carrying out statistical verification according to section
6, the notified body has to decide when statistical procedures for lot-by-lot
inspection or isolated lot inspection have to be applied. Such decision must be taken
in consultation with the manufacturer.
In as far as the conduct of examinations and tests on a statistical basis is not
appropriate, examinations and tests may be carried out on a random basis provided
that such procedure in conjunction with the measures taken in accordance with point
2.2 of this Schedule ensures an equivalent level of conformity.
5. Verification by examination and testing of every product
5.1. Every product is examined individually and the appropriate tests defined in
the relevant standard(s) referred to in Article 5 of the Directive or equivalent tests
must be carried out in order to verify the conformity of the products with the EC type
described in the type-examination certificate and with the requirements of the
regulations which apply to them.
5.2. The notified body must affix, or have affixed, its identification number to
each approved product and must draw up a written certificate of conformity relating
to the tests carried out.
6. Statistical verification
6.1. The manufacturer must present the manufactured products in the form of
homogeneous batches.
6.2. One or more random samples, as necessary, are taken from each batch. The
products which make up the sample are examined and the appropriate tests defined
in the relevant standard(s) referred to in Article 5 of the Directive or equivalent tests
must be carried out to verify, where appropriate, the conformity of the products with
the type described in the EC type-examination certificate and with the requirements
of the regulations which apply to them in order to determine whether to accept or
reject the batch.
IN VITRO DIAGNOSTIC MEDICAL DEVICES
6.3. Statistical control of products will be based on attributes and, or variables,
entailing sampling schemes with operational characteristics which ensure a high
level of safety and performance according to the state of the art. The sampling
scheme will be established by the harmonised standards referred to in Artic1e 5 of
the Directive taking account of the specific nature of the product categories in
question.
6.4. If the batch is accepted, the notified body affixes, or has affixed its
identification number to each product and draws up a written certificate of
conformity relating to the tests carried out. All products in the batch may be put on
the market except any in the sample which failed to conform.
If the batch is rejected the competent notified body must take appropriate
measures to prevent the batch from being placed on the market. In the event of
frequent rejection of batches, the notified body may suspend the statistical
verification.
The manufacturer may, on the responsibility of the notified body, affix the
notified body’s identification number during the manufacturing process.
1. For all devices other than those covered by Annex II of the
Directive, which i s s et out in S c hed u le I I , a nd d ev i ces f or
performance evaluation, the manufacturer shall, in order to affix
the CE marking, follow the procedure referred to in Annex III of
the Directive, which is set out in Schedule III, and draw up the EC
declaration of conformity required before placing the devices on
the market.
7.1.1.
For all devices for self-testing other than those
covered by Annex II of the Directive, which is set
out in Schedule II, and medical devices for
performance evaluation, the manufacturer shall,
prior to the drawing up of the aforementioned
declaration of conformity, fulfil the supplementary
requirements set out in Annex III, point 6 of the
Directive, which is set out in Schedule III. Instead
of applying this procedure, the manufacturer may
follow the procedure referred to in regulations 7.2
and 7.3.
7.2. For all devices referred to in List A in Annex II of the
Directive, which is set out in Schedule II, other than those intended
for performance evaluation, the manufacturer shall, in order to
affix the CE marking either
7.2.1.
follow the procedure relating to the EC declaration
of conformity set out in Annex IV (full quality
assurance) of the Directive, which is set out in
Schedule IV, or
7.2.2.
follow the procedure relating to EC type-
examination set out in Annex V of the Directive,
which is set out in Schedule V, coupled with the
procedure relating to the EC declaration of
conformity set out in Annex VII (production
quality assurance) of the Directive, which is set out
in Schedule VII.
7.3. For all devices referred to in List B in Annex II of the
Directive, which is set out in Schedule II, other than those intended
for performance evaluation, the manufacturer shall for the purposes
of affixing the CE marking, follow either
7.3.1.
the procedure relating to the EC declaration of
conformity set out in Annex IV (full quality
assurance) of the Directive, which is set out in
Schedule IV, or
7.3.2.
the procedure relating to EC type-examination set
out in Annex V of the Directive, which is set out in
Schedule V, coupled with
7.3.2.1.
the procedure relating to EC verification
set out in Annex VI, which is set out in
Schedule VI, or
7.3.2.2.
the procedure relating to the EC
declaration of conformity set out in
Annex
VII
(production
quality
assurance), which is set out in Schedule
VII.
7.4. In the case of devices for performance evaluation, the
manufacturer shall follow the procedure referred to in Annex VIII
of the Directive, which is set out in Schedule VIII, and draw up the
statement set out in that Schedule before such devices are made
available.
7.4.1.
This provision does not affect national regulations
relating to the ethical aspects of carrying out
performance evaluation studies using tissues or
substances of human origin.
7.5. During the conformity assessment procedure for a device,
the manufacturer and, if involved, the notified body shall take
account of the results of any assessment and verification operations
which, where appropriate, have been carried out in accordance with
these regulations at an intermediate state of manufacture.
7.6. The manufacturer may instruct his authorised
representative to initiate the procedures provided for in Annexes
III, V, VI and VIII of the Directive, which are set out in Schedules
III, V, VI and VIII.
7.7. The manufacturer must keep the declaration of conformity,
the technical documentation referred to in Annexes III to VIII of
the Directive, which are set out in Schedules III and VIII, as well as
the decisions, reports and certificates, established by notified
bodies, and make it available to the national authorities for
inspection purposes for a period ending five years after the last
product has been manufactured. Where the manufacturer is not
established in Malta, the obligation to make the aforementioned
documentation available on request applies to his authorised
representative.
7.8. Where the conformity assessment procedure involves
intervention of a notified body, the manufacturer, or his authorised
representative, may apply to a body of his choice within the
framework of tasks for which the body has been notified.
7.9. The notified body may require, where duly justified, any
information or data, which is necessary for establishing and
maintaining the attestation of conformity in view of the chosen
procedure.
7.10. Decisions taken by the notified bodies in accordance with
Annexes III, IV, and V of the Directive, which are set out in
Schedules III, IV, and V, shall be valid for a maximum of five years
and may be extended on application, made at a time agreed in the
contract signed by both parties, for further periods of up to five
years.
7.11. The records and correspondence relating to the procedures
referred to in regulations 7.1 to 7.4 shall be in an official language.
7.12. By way of derogation from regulations 7.1 to 7.4, the
competent authorities may authorise, on duly justified request, the
placing on the market and putting into service, of individual
medical devices for which the procedures referred to in regulations
7.1 to 7.4 have not been carried out and the use of which is in the
interest of protection of health.
7.13. The provisions of regulation 7 shall apply accordingly to
any natural or legal person who manufactures devices covered by
these regulations and, without placing them on the market, puts
them into service and uses them in the context of his professional
activity.
Based on Annex VII of the Directive
EC DECLARATION OF CONFORMITY
(PRODUCTION QUALITY ASSURANCE)
1. The manufacturer must ensure application of the quality system approved
for the manufacture of the devices concerned and carry out the final inspection, as
specified in section 3 of this Schedule, and is subject to the surveillance referred to
in section 4 of this Schedule.
2. The declaration of conformity is the part of the procedure whereby the
manufacturer who fulfils the obligations imposed by section 1 ensures and declares
that the products concerned conform to the type described in the EC type-
exanunation certificate and meet the provisions of these regulations which apply to
them.
The manufacturer must affix the CE marking in accordance with regulation
12 of these regulations and draw up a declaration of conformity covering the devices
concerned.
3. Quality system
3.1. The manufacturer must lodge an application for assessment of his quality
system with a notified body.
The application must include the technical documentation on the types
approved and a copy of the EC type-examination certificates.
3.2. Application of the quality system must ensure that the devices conform to
the type described in the EC type-examination certificate.
All the elements, requirements and provisions adopted by the manufacturer
for his quality system must be documented in a systematic and orderly manner in the
form of written policy statements and procedures. This quality system
documentation must permit uniform interpretation of the quality policy and
procedures such as quality progranunes, plans, manuals and records.
It must include in particular an adequate description of
(a) the manufacturer’s quality objectives;
(b) the organisation of the business and in particular
-
the organisational structures, the responsibilities of the
managerial staff and their organisational authority where quality
of manufacture of the devices is concerned,
-
the methods of monitoring the efficient operation of the quality
system and in particular its ability to achieve the desired quality
of product, including control of devices which fail to conform;
(c) the inspection and quality assurance techniques at the manufacturing
stage and in particular
-
the processes and procedures which will be used, particularly as
regards sterilisation,
-
the procedures in relation to purchasing,
-
the product identification procedures drawn up and kept up to
date from drawings, specifications or other relevant documents at
every stage of manufacture;
(d) the appropriate tests and trials to be carried out before, during and after
manufacture, the frequency with which they will take place, and the test
equipment used; it must be possible to trace back the calibration.
3.3. The notified body must audit the quality system to determine whether it
meets the requirements referred to in section 3.2 of this Schedule. It must presume
that quality systems which implement the relevant harmonised standards conform to
these requirements.
The assessment team must have past experience of assessments of the
technology concerned. The assessment procedure must include an inspection on the
manufacturer’s premises and, in duly substantiated cases, on the premises of the
manufacturer ’s suppliers and, or subcontractors to inspect the manufacturing
processes.
The decision must be notified to the manufacturer. It must contain the
conclusions of the inspection and a reasoned assessment.
3.4. The manufacturer shall inform the notified body which approved the quality
system of any plan for substantial changes to the quality system. The notified body
must assess the changes proposed and verify whether after these changes the quality
system still meets the requirements referred to in section 3.2 of this Schedule. It
must notify the manufacturer of its decision. This decision must contain the
conclusions of the inspection and a reasoned assessment.
4. Surveillance
The provisions of Annex IV, section 5 of the Directive, which is set out in
Schedule IV, shall apply.
5. Verification of manufactured products covered by Schedule II, List A.
5.1. In the case of devices covered by Annex II, List A of the Directive, which is
set out in Schedule II, the manufacturer shall forward to the notified body without
delay after the conclusion of the controls and tests the relevant reports on the tests
carried out on the manufactured devices or each batch of devices.
Furthermore, the manufacturer shall make the samples of manufactured
devices or batches of devices available to the notified body in accordance with pre-
IN VITRO DIAGNOSTIC MEDICAL DEVICES
agreed conditions and modalities.
5.2. The manufacturer may place the devices on the market, unless the notified
body communicates to the manufacturer within the agreed time-frame, but not later
than thirty days after reception of the samples, any other decision, including in
particular any condition of validity of delivered certificates.
1. Where it is ascertained that the devices referred to in
regulation 6.1, when correctly installed, maintained and used in
accordance with their intended purpose, may compromise the
health and, or safety of patients, users or, where applicable other
persons, or the safety of property, the Medicines Authority shall take
all appropriate interim measures to withdraw such devices from the
market, or prohibit or restrict their being placed on the market or
put into service.
8.1.1.
The Medicines Authority shall immediately inform
Commission of any such measures, indicating the
reasons for the decision and in particular, whether
non-compliance is due to
8.1.1.1.
failure
to
meet
the
essential
requirements referred to in regulation 5;
8.1.1.2.
incorrect application of the standards
referred to in Article 5 of the Directive,
insofar as it is claimed that the standards
have been applied;
8.1.1.3.
shortconungs
in
the
standards
themselves.
8.2. Where a non-complying medical device referred to in
regulation 3 bears the CE marking, the Medicines Authority shall take
appropriate action against whomsoever has affixed the marking or
drawn the declaration and shall so inform the Commission and the
other Member States thereof.
8.3. Any decision taken pursuant to these regulations which
restricts the placing on the market and putting into service of
devices shall state the exact grounds on which it is based.
8.3.1.
Such a decision shall be notified as soon as
possible to the party concerned, who shall at the
same time be informed of the legal remedies
available to him under the laws in force in Malta
and of the time limits to which such remedies are
subject.
8.4. Where the Medicines Authority considers, in relation to a
given product or group of products, that, in order to ensure
protection of health and safety and, or to ensure that public health
requirements are observed pursuant to Article 36 of the Treaty, the
availability of such products should be prohibited, restricted or
made subject to particular requirements, necessary and justified
transitional measures may be taken.
8.5. The Medicines Authority shall immediately inform the
Commission of any measures taken in pursuance of regulations
8.1.1, 8.2 and 8.4.
8.6. In the event of a decision as referred to in regulation 8.2,
the manufacturer or his authorised representative shall have an
opportunity to put forward his point of view in advance, unless
such consultation is not possible because of the urgency of the
measure to be taken as justified in particular by public health
requirements.
Based on Annex VIII of the Directive
STATEMENT AND PROCEDURES CONCERNING DEVICES
FOR PERFORMANCE EVALUATION
1. For devices for performance evaluation the manufacturer or his authorized
representative shall draw up the statement containing the information stipulated in
section 2 of this Schedule and ensure that the relevant provisions of these regulations
are met.
2. The statement shall contain the following information
-
data allowing identification of the device in question,
-
an evaluation plan stating in particular the purpose, scientific, technical
or medical grounds, scope of the evaluation and number of devices
concerned,
-
the list of laboratories or other institutions taking part in the evaluation
study,
-
the starting date and scheduled duration for the evaluations and, in the
case of devices for self-testing, the location and number of lay persons
involved,
-
a statement that the device in question conforms to the requirements of
the regulations, apart from the aspects covered by the evaluation and
apart from those specifically itenused in the statement, and that every
precaution has been taken to protect the health and safety of the patient,
user and other persons.
3. The manufacturer shall also undertake to keep available for the competent
national authorities the documentation allowing an understanding of the design,
manufacture and performances of the product, including the expected performances,
so as to allow assessment of conformity with the requirements of these regulations.
This documentation must be kept for a period ending at least five years after the end
of the performance evaluation.
The manufacturer shall take all the measures necessary for the
manufacturing process to ensure that the products manufactured conform to the
documentation mentioned in the first paragraph.
4. The provisions of regulations 9.1, 9.3 and 9.5 of these regulations shall
apply to devices intended for performance evaluation.
1. Any manufacturer who places devices on the Maltese
market under his own name shall notify the Medicines Authority
9.1.1.
of the address of the registered place of business,
9.1.2.
in the case of an authorised representative,
sufficient evidence that he is the authorised
representative of the manufacturer;
9.1.3.
of information relating to the reagents, reagent
products and calibration and control materials in
terms of common technological characteristics and,
or analytes and of any significant change thereto
including discontinuation of placing on the market;
for other devices, the appropriate indications;
9.1.4.
in the case of devices covered by Annex II of the
Directive, which is set out in Schedule II, and of
devices for self-testing, of all data allowing for
identification of such devices, the analytical and,
where appropriate, diagnostic parameters as
referred to in Annex I, part A, section 3 of the
Directive, which is set out in Schedule I, the
outcome of performance evaluation pursuant to
Annex VIII of the Directive, which is set out in
Schedule VIII, certificates and any significant
change thereto, including discontinuation of
placing on the market.
9.2. For devices covered by Annex II of the Directive, which is
set out in Sched ule I I, and for devices for self-t esting, the
Medicines Authority may request to be informed of the data
allowing identification together with the label and the instructions
for use when such medical devices are placed on the market and, or
put into service within their territory.
9.2.1.
The measures given in regulation 9.2 cannot
constitute a precondition for the placing on the
market and, or putting into service of medical
devices which are in conformity with these
regulations.
9.3. Where a manufacturer who places medical devices on the
market under his own name does not have a registered place of
business in Malta, he shall designate an authorised representative.
The authorized representative shall notify the Medicines Authority
of all paiticulars as referred to in regulation 9.1.
9.4. The notification referred to in regulation 9.1 shall also
include any new device. In addition, where, in the context of such
notification, a device notified, bearing the CE marking, is a "new
product", the manufacturer shall indicate this fact on his
notification.
For the purposes of regulation 9, a medical device is "new"
if
9.4.1.
there has been no such device continuously
available on the Cornmunity market during the
previous three years for the relevant analyte or
other parameter;
9.4.2.
the procedure involves analytical technology not
continuously used in connection with a given
analyte or other parameter on the Community
market during the previous three years.
9.5. The notifications referred to in regulations 9.1 and 9.3 are
to be registered immediately in the databank described in Article 12
of the Directive. The procedures for implementing this regulation
and in particular those referring to the notification and the concept
of significant change shall be adopted in accordance with the
procedure referred to in Article 7 of the Directive.
9.6. Transitionally, pending the establishment of a European
Databank accessible to the competent authorities of the Member
States and containing the data relating to all medical devices
available on the territory of the Comrnunity, the manufacturer shall
give such notification to the competent authorities of each Member
State concerned by the placing on the market.
Based on Annex IX of the Directive
CRITERIA FOR THE DESIGNATION OF NOTIFIED BODIES
1. The notified body, its director and the assessment and verification staff shall
not be the designer, manufacturer, supplier, installer or user of the devices which
they inspect, nor the authorised representative of any of these persons. They may not
be directly involved in the design, construction, marketing or maintenance of the
devices, nor represent the parties engaged in these activities. This in no way
precludes the possibility of exchanges of technical information between the
manufacturer and the body.
2. The notified body and its staff must carry out the assessment and
verification operations with the highest degree of professional integrity and the
requisite competence in the field of medical devices and must be free from all
pressures and inducements, particularly financial, which might influence their
judgment or the results of the inspection, especially from persons or groups of
persons with an interest in the results of the verifications.
Should the notified body subcontract specific tasks connected with the
establishment and verification of the facts, it must first ensure that the subcontractor
meets the provisions of the regulations. The notified body shall keep at the disposal
of the national authorities the relevant documents assessing the subcontractor’s
qualifications and the work carried out by the subcontractor under these regulations.
3. The notified body must be able to carry out all the tasks assigned to such
bodies by one of Annexes III to VII of the Directive, which are set out in Schedules
III to VII, and for which it has been notified, whether these tasks are carried out by
the body itself or on its responsibility. In particular, it must have the necessary staff
and possess the facilities needed to perform properly the technical and
administrative tasks entailed in assessment and verification. This includes the
availability of sufficient scientific staff within the organisation who possess
adequate experience and knowledge necessary to assess the biological and medical
functionality and performance of devices for which it has been notified, in relation to
the requirements of this Directive and, in particular, with the requirements of Annex
I of the Directive, which is set out in Schedule I. The notified body must also have
access to the equipment necessary for the verifications required.
4. The inspection staff must have
-
sound vocational training covering all the assessment and verification
operations for which the body has been designated,
-
satisfactory knowledge of the rules on the inspections which they carry
out and adequate experience of such inspections,
-
the ability required to draw up the certificates, records and reports to
demonstrate that the inspections have been carried out.
5. The impartiality of the inspection staff must be guaranteed. Their
remuneration must not depend on the number of inspections carried out, nor on the
results of the inspections.
6. The body must take out civil liability insurance, unless liability is assumed
by the State under domestic legislation or the Member State itself carries out the
inspections directly.
7. The staff of the inspection body are bound to observe professional secrecy
with regard to all information gained in the course of their duties (except vis-a-vis
the competent administrative authorities of the State in which their activities are
carried out) under these regulations or any provision of national law putting it into
1. The Medicines Authority shall take the necessary steps to
ensure that any information brought to his knowledge, in
accordance with the provisions of these regulations, regarding the
incidents mentioned below involving devices bearing the CE
marking is recorded and evaluated centrally
10.1.1. any malfunction, failure or deterioration in the
characteristics and, or performance of a device, as
well as any inadequacy in the labelling or the
instructions for use which, directly or indirectly,
might lead to or might have led to the death of a
patient, or user or of other persons or to a serious
deterioration in their state of health;
10.1.2. any technical or medical reason in relation to the
characteristics or performance of a device for the
reasons referred to in regulation 10.1.1, leading to
systematic recall of medical devices of the same
type by the manufacturer.
10.2. Where medical practitioners, medical institutions or the
organizers of external quality assessment schemes are required to
inform the competent authorities of any incidents referred to in
regulation 10.1, necessary steps shall be taken to ensure that the
manufacturer of the device concerned, or his authorized
representative, is also informed on the incident.
10.3. After carrying out an assessment, if possible together with the
manufacturer, the Medicines Authority shall, without prejudice to
Article 8, immediately inform the Commission and the other Member
States of the incidents referred to in regulation 10.1 for which
appropriate measures, including possible withdrawal, have been taken
or are contemplated.
10.4. Where, in the context of notification referred to in
regulation 9, a device notified, bearing the CE marking, is a "new"
product, the manufacturer shall indicate this fact on his
notification. The Medicines Authority so notified may at any time
within the following two years and on justified grounds, require the
manufacturer to submit a report relating to the experience gained
with the device subsequent to its being placed on the market.
10.5. The Medicines Authority of the Malta Standards Authority
shall immediately inform the Commission of any measures taken in
pursuance of regulation 10.3 of these regulations.
Based on Annex X of the Directive
CE MARKING OF CONFORMITY
The CE conformity marking shall consist of the initials "CE" taking the
following form
For the avoidance of doubt, it is hereby decdared that the grid providing the
background in the above graduated drawing is not part of the CE marking.
if the marking is reduced or enlarged the proportions given in the above
graduated drawing must be respected,
the various components of the CE marking must have substantially the
same vertical dimension, which may not be less than 5mm. This
minimum dimension may be waived for small-scale devices.
1. The CE marking consists of the initials "CE" in accordance
with the model in Annex X of the Directive, which is set out in
Schedule X.
11.2. Devices, other than medical devices for performance
evaluation, considered to meet the essential requirements referred
to in regulation 5, must bear the CE marking of conformity when
they are placed on the market.
11.3. The CE marking of conformity, as shown in Annex X of
the Directive, which is set out in Schedule X, must appear in a
visible, legible and indelible form on the device, where practicable
and appropriate, and on the instructions for use. The CE marking of
conformity must also appear on the sales packaging.
11.3.1. The CE marking shall be accompanied by the
identification number of the notified body
responsible for implementation of the procedures
set out in Annexes III, IV, VI and VII of the
Directive, which are set out in Schedules III, IV,
VI, and VII.
11.4. No person shall affix on any device, to which these
regulations apply, any markings or inscriptions which are likely to
mislead third parties with regard to the meaning or the graphics of
the CE marking.
11.5. Without prejudice to regulation 11.4, nothing in these
regulations shall prohibit the affixing on device, to the packaging
or to the instruction leaflet accompanying the device, provided that
the visibility and legibility of the CE marking are not thereby
reduced.
11.6. Without prejudice to regulation 8
11.6.1. where it is established that the CE marking has
been wrongly affixed, the manufacturer or his
authorized representative shall be obliged to end
the infringement under conditions laid down by the
Medicines Authority;
11.6.2. where non-compliance continues, the Medicines
Authority shall take all appropriate measures to
restrict or prohibit the placing on the market of the
product in question or to ensure that it is
withdrawn from the market, in accordance with the
procedure laid down in regulation 8.
11.7. The provisions stated in regulation 11.6 shall also apply
where the CE marking has been affixed in accordance with the
procedures in these regulations, but inappropriately, on products
that are not covered by these regulations.
11.8. Subject to regulation 11.9, where the devices are subject to
other directives, concerning other aspects which also provide for
the affixing of the CE marking, the latter shall indicate that the
devices also fulfil the provisions of the other directives.
11.9. Where one or more of the other directives referred to in
regulation 11.8 allow the manufacturer, during a transitional
period, to choose which arrangements to apply, the CE marking
shall indicate that the devices fulfil the provisions only of those
directives applied by the manufacturer. In case, the particulars of
these directives, as published in the Official Journal of the
European Communities, must be given in the documents, notices or
instructions required by the directives and accompanying such
devices.
L.N. 30 of 2004.
Substituted by
L.N. 21 of 2010.
Based on Annex I of Commission Decision 2009/108/EC of 3 February 2009 on common
technical specifications (CTS) for in vitro diagnostic medical devices
1. SCOPE
The common technical specifications set out in this Schedule shall apply for
the purposes of Schedule II, List A.
2. DEFINITIONS AND TERMS
(Diagnostic) sensitivity
The probability that the device gives a positive result in the presence of the
target marker.
True positive A specimen known to be positive for the target marker and
correctly classified by the device.
False negative A specimen known to be positive for the target marker and
misclassified by the device.
(Diagnostic) specificity The probability that the device gives a negative result
in the absence of the target marker.
False positive
A specimen known to be negative for the target marker and misclassified by
the device.
True negative
A specimen known to be negative for the target marker and correctly
classified by the device.
Analytical sensitivity
Analytical sensitivity may be expressed as the limit of detection, i.e. the smallest
amount of the target marker that can be precisely detected.
Analytical specificity
Analytical specificity means the ability of the method to determine solely the
target marker.
Nucleic acid amplification techniques (NAT)
The term ‘NAT’ is used for tests for the detection and/or quantification of
nucleic acids by either amplification of a target sequence, by amplification of a
signal or by hybridisation.
Rapid test
‘Rapid test’ means qualitative or semi quantitative in vitro diagnostic
medical devices, used singly or in a small series, which involve non-automated
procedures and have been designed to give a fast result.
Robustness
The robustness of an analytical procedure means the capacity of an analytical
procedure to remain unaffected by small but deliberate variations in method
parameters and provides an indication of its reliability during normal usage.
Whole system failure rate
The whole system failure rate means the frequency of failures when
the
entire process is performed as prescribed by the manufacturer.
Confirmation assay
Confirmation assay means an assay used for the confirmation of a reactive result
from a screening assay.
Virus typing assay
Virus typing assay means an assay used for typing with already known positive
samples, not used for primary diagnosis of infection or for screening.
Sero-conversion HIV samples
IN VITRO DIAGNOSTIC MEDICAL DEVICES
Sero-conversion HIV samples mean
-
p24 antigen and/or HIV RNA positive and;
-
recognised by all of the antibody screening tests and;
-
positive or indeterminate confirmatory assays.
Early sero-conversion HIV samples
Early sero-conversion HIV samples mean
-
p24 antigen and/or HIV RNA positive and;
-
not recognised by all of the antibody screening tests and;
-
indeterminate or negative confirmatory assays.
3. COMMON TECHNICAL SPECIFICATIONS (CTS) FOR PRODUCTS
REFERRED TO IN SCHEDULE II, LIST A.
3.1 CTS for performance evaluation of reagents and reagent products for the
detection, confirmation and quantification in human specimens of markers of HIV
infection (HIV 1 and 2), HTLV I and II, and hepatitis B, C, D
General Principles
3.1.1 Devices which detect virus infections placed on the market for use as
either screening or diagnostic tests, shall meet the requirements for sensitivity and
specificity set out in Table 1. See also principle 3.1.11 for screening assays.
3.1.2 Devices intended by the manufacturer for testing body fluids other than
serum or plasma, for example urine, saliva, etc shall meet the same CTS
requirements for sensitivity and specificity as serum or plasma tests. The
performance evaluation shall test samples from the same individuals in both the tests
to be approved and in a respective serum or plasma assay.
3.1.3 Devices intended by the manufacturer for self-test, i.e. home use, shall
meet the same CTS requirements for sensitivity and specificity as respective devices
for professional use. Relevant parts of the performance evaluation shall be
carried out (or repeated) by appropriate lay users to validate the operation of the
device and the instructions for use.
3.1.4 All performance evaluations shall be carried out in direct comparison with
an established state of the art device. The device used for comparison shall be
one bearing CE marking, if on the market at the time of the performance
evaluation.
3.1.5 If discrepant test results are identified as part of an evaluation, these
results shall be resolved as far as possible, for example
-
by evaluation of the discrepant sample in further test systems;
-
by use of an alternative method or marker;
-
by a review of the clinical status and diagnosis of the patient; and
-
by the testing of follow-up-samples.
3.1.6 Performance evaluations shall
be
performed
on
a population
equivalent to the European population.
3.1.7 Positive specimens used in the performance evaluation shall be
selected to reflect different stages of the respective disease(s), different
antibody patterns, different genotypes, different subtypes, mutants, etc.
3.1.8 Sensitivity with true positives and sero-conversion samples shall be
evaluated as follows
3.1.8.1 Diagnostic test sensitivity during sero-conversion has to represent the
state of the art. Whether further testing of the same or additional sero-conversion
panels is conducted by the notified body or by the manufacturer the results
shall confirm the initial performance evaluation data (see Table 1).
Seroconversion panels should start with a negative bleed(s) and should have narrow
bleeding intervals.
3.1.8.2 For blood screening devices (with the exception of HBsAg and anti-
HBc tests), all true positive samples shall be identified as positive by the device
to be CE marked (Table 1). For HBsAg and anti-HBc tests the new device shall
have an overall performance at least equivalent to that of the established device
(see 3.1.4).
3.1.8.3 Regarding HIV tests
-
all sero-conversion HIV samples shall be identified as positive; and
-
at least 40 early sero-conversion HIV samples shall be tested. Results
should conform to the state of the art.
3.1.9 Performance evaluation of screening assays shall include 25 positive (if
available in the case of rare infections) "same day" fresh serum and/or plasma
samples (≤ 1 day after sampling).
3.1.10 Negative specimens used in a performance evaluation shall be defined
so as to reflect the target population for which the test is intended, for example blood
donors, hospitalised patients, pregnant women, etc.
3.1.11 For performance evaluations for screening assays (Table 1) blood donor
populations shall be investigated from at least two blood donation centres and
consist of consecutive blood donations, which have not been selected to exclude
first time donors.
3.1.12 Devices shall have a specificity of at least 99.5% on blood donations,
unless otherwise indicated in the accompanying tables. Specificity shall be
calculated using the frequency of repeatedly reactive (i.e. false positive)
results in blood donors negative for the target marker.
3.1.13 Devices shall be evaluated to establish the effect of potential
interfering substances, as part of the performance evaluation. The potential
interfering substances to be evaluated will depend to some extent on the
composition of the reagent and configuration of the assay. Potential interfering
substances shall be identified as part of the risk analysis required by the
essential requirements for each new device but may include, for example
- specimens representing "related" infections;
- specimens from multipara, i.e. women who have had more than
one pregnancy, or rheumatoid factor positive patients;
- for recombinant antigens, human antibodies to components of the
expression system, for example anti E. coli, or anti yeast.
3.1.14 For devices intended by the manufacturer to be used with serum and
plasma the performance evaluation must demonstrate serum to plasma
equivalency. This shall be demonstrated for at least 50 donations (25 positive and 25
negative).
3.1.15 For devices intended for use with plasma the performance
evaluation shall verify the performance of the device using all anticoagulants
which the manufacturer indicates for use with the device. This shall be demonstrated
IN VITRO DIAGNOSTIC MEDICAL DEVICES
for at least 50 donations (25 positive and 25 negative).
3.1.16 As part of the required risk analysis the whole system failure rate
leading to false-negative results shall be determined in repeat assays on low-
positive specimens.
3.1.17 If a new in vitro diagnostic medical device belonging to Schedule II, List
A is not specifically covered by the common technical specification, the
common technical specification for a related device should be taken into account.
Related devices may be identified on different grounds, for example by the
same or similar intended use or by similar risks.
3.2
Additional Requirements for HIV antibody/antigen combined tests
3.2.1 HIV antibody/antigen combined tests intended for anti-HIV and p24
antigen detection which include claims for single p24 antigen detection shall follow
Table 1 and Table 5, including criteria for analytical sensitivity for p24 antigen.
3.2.2 HIV antibody/antigen combined tests intended for anti-HIV and p24
detection which do not include claims for single p24 detection shall follow
Table 1 and Table 5, excluding criteria for analytical sensitivity for p24.
3.3 Additional Requirements for Nucleic Acid Amplification Techniques
(NAT)
The performance evaluation criteria for NAT assays can be found in Table 2.
3.3.1 For target sequence amplification assays, a functionality control for
each test sample (internal control) shall reflect the state of the art. This control
shall as far as possible be used throughout the whole process, i.e. extraction,
amplification/hybridisation, detection.
3.3.2 The analytical sensitivity or detection limit for NAT assays shall be
expressed by the 95% positive cut-off value. This is the analyte concentration where
95% of test runs give positive results following serial dilutions of an international
reference material for example a WHO standard or calibrated reference material.
3.3.3 Genotype detection shall be demonstrated by appropriate primer or probe
design validation and shall also be validated by testing characterised genotyped
samples.
3.3.4 Results of quantitative NAT assays shall be traceable to international
standards or calibrated reference materials, if available, and be expressed in
international units utilised in the specific field of application.
3.3.5 NAT assays may be used to detect virus in antibody negative samples,
i.e. pre sero conversion samples. Viruses within immune-complexes may
behave differently in comparison to free viruses, for example during a
centrifugation step. It is therefore important that during robustness studies,
antibody-negative (pre sero-conversion) samples are included.
3.3.6 For investigation of potential carry-over, at least five runs with alternating
high positive and negative specimens shall be performed during robustness
studies. The high positive samples shall comprise of samples with naturally
occurring high virus titres.
3.3.7 The whole system failure rate leading to false-negative results shall be
determined by testing low-positive specimens. Low positive specimens shall
contain a virus concentration equivalent to 3 times the 95% positive cut-off virus
concentration.
3.4
CTS for the manufacturer’s release testing of reagents and eagent products
for the detection, confirmation and quantification in human specimens of markers of
HIV infection (HIV 1 and 2), HTLV I and II, and hepatitis B, C, D (Immunological
assays only).
3.4.1 The manufacturer’s release testing criteria shall ensure that every batch
consistently identifies the relevant antigens, epitopes, and antibodies.
3.4.2. The manufacturer’s batch release testing for screening assays shall
include at least 100 specimens negative for the relevant analyte.
3.5 CTS for performance evaluation of reagents and reagent products for
determining the following blood group antigens: ABO blood group system ABO1
(A), ABO2 (B), ABO3 (A,B); Rh blood group system RH1 (D), RH2 (C), RH3 (E),
RH4 (c), RH5 (e); Kell blood group system KEL1 (K).
Criteria for performance evaluation of reagents and reagent products for
determining the blood groups antigens: ABO blood group system ABO1 (A),
ABO2 (B), ABO3 (A,B); Rh blood group B 9 system RH1 (D), RH2 (C), RH3 (E),
RH4 (c), RH5 (e); Kell blood group system KEL1 (K) can be found in Table 9.
3.5.1 All performance evaluations shall be carried out in direct comparison with
an established state of the art device. The device used for comparison shall be
one bearing CE marking, if on the market at the time of the performance
evaluation.
3.5.2 If discrepant test results are identified as part of an evaluation, these
results shall be resolved as far as possible, for example
-
by evaluation of the discrepant sample in further test systems;
-
by use of an alternative method.
3.5.3 Performance evaluations shall
be
performed
on
a population
equivalent to the European population.
3.5.4 Positive specimens used in the performance evaluation shall be selected
to reflect variant and weak antigen expression.
3.5.5 Devices shall be evaluated to establish the effect of potential
interfering substances, as part of the performance evaluation. The potential
interfering substances to be evaluated will depend to some extent on the
composition of the reagent and configuration of the assay. Potential interfering
substances shall be identified as part of the risk analysis required by the
essential requirements for each new device.
3.5.6 For devices intended for use with plasma the performance evaluation shall
verify the performance of the device using all anticoagulants which the
manufacturer indicates for use with the device. This shall be demonstrated for at
least 50 donations.
3.6. CTS for the manufacturers release testing of reagents and reagent products
for determining the blood group antigens: ABO blood group system ABO1 (A),
ABO2 (B), ABO3 (A,B); Rh blood group system RH1 (D), RH2 (C), RH3 (E), RH4
(c), RH5 (e); Kell blood group system KEL1 (K).
3.6.1 The manufacturer’s release testing criteria shall ensure that every batch
consistently identifies the relevant antigens, epitopes, and antibodies.
3.6.2 Requirements for manufacturers batch release testing are outlined in Table
10. Table 1: "Screening" assays: anti-HIV 1 and 2, anti-HTLV I and II,
IN VITRO DIAGNOSTIC MEDICAL DEVICES
anti-HCV, HBsAg, anti-HBc
anti-HIV-1/2
anti-HTLV-
anti-HCV
HBsAg
anti-HBc
I/II
Diagnostic
Positive
400 HIV-1 100
300 HTLV-I 400 (positive
400 Including
sensitivity
specimens
HIV-2
100 HTLV-II samples)
subtype-
Including
including 40
consideration
evaluation
Including
non-B-
of other
samples from
subtypes, all
HBV-
different stages
available HIV/
markers
of infection and
1 subtypes
reflecting
should be
different
represented by
antibody
at least 3
patterns.
samples per
subtype
Genotype 1-4: >
20 samples - per
genotype
(including non-a
sub-types of
genotype 4);
5: > 5 samples;
6: if available
Sero-
20 panels
To be
20 panels
20 panels
To be
conversion
10 further
defined
10 further panels
10 further
defined
panels
panels (at
when
(at Notified
panels (at
when
Notified Body
available
Body or
Notified Body
available
or
manufacturer)
or
manufacturer)
manufacturer)
Analytical
Standards
0.130 IU/ml
sensitivity
(Second
International
Standard for
HBsAg,
subtype adw2,
genotype A,
NIBSC code
00/588)
Specificity
Unselected
donors
(including1
st
time
donors)
Hospitalize
d patients
Potentially
cross-
reacting
blood-
specimens
(RF+,
related
viruses,
pregnant
women,
etc)
Table 2: NAT assays for HIV1, HCV, HBV, HTLV I/II (qualitative and
quantitative; not molecular typing)
HIV1
HCV
HBV
HTLV I/II
Accep-
tance
NAT
qualitative
quantitative
qualitative
quantitative
quantitative
qualitative
quantitative
criteria
As for HIV
As for HIV
As for HIV
quantitative
quantitative
quantitative
Sensitivity
According
Detection
According
According
According
Detection
to EP
limit: as
to EP
to EP
to EP
limit
validation
for
validation
validation
validation
Detection
guideline
qualitative
guideline
guideline
guideline
( 1 )
( 1 ): several
( 1 ): several
of
(1)
tests;
analytical
several
Quantific-
several
dilution
dilution
sensitivity
dilution
ation limit
dilution
series into
series into
(IU/ml;
series into
dilutions
series into
borderline
borderline
defined on
borderline
(half-
borderline
concentr-
concentr-
WHO
concentra-
log10 or
concentra-
ation;
ation;
standards
tion;
less) of
tion;
statistical
statistical
or
statistical
calibrated
statistical
analysis
analysis
calibrated
analysis
reference
analysis
(e.g.
(e.g. Probit
reference
(e.g.
prepara-
(e.g.
Probit
analysis)
materials)
Probit
tions,
Probit
analysis)
on the basis
analysis)
definition
analysis)
on the
of at least
on the
of lower,
on the
basis of at
basis of at
upper
basis of at
least 24
replicates;
least 24
quantifi-
least 24
replicates;
calculation
replicates;
cation
replicates;
calculation
of 95% cut-
calculatio
limit,
calculatio
of 95%
off value
n of 95%
precision,
n of 95%
cut-off
cut-off
accuracy,
cut-off
value
value
"linear"
value
measuring
range,
"dynamic
range".
Reproduci
-bility at
different
concentra-
tion levels
to be
shown
Genotype/
At least 10
Dilution
At least 10
As far as
As far as
subtype
samples per
series of
samples
calibrated
calibrated
detection/
subtype (as
all
per
genotype
genotype
quantific-
far as
relevant
genotype
reference
reference
ation
available)
genotypes
(as far as
materials
materials
efficiency
/subtypes,
available)
are
are
preferabl
available
available
y of
reference
materials,
as far as
available
IN VITRO DIAGNOSTIC MEDICAL DEVICES
HIV1
HCV
HBV
HTLV I/II
Accep-
tance
NAT
qualitative
quantitative
qualitative
quantitative
quantitative
qualitative
quantitative
criteria
As for HIV
As for HIV
As for HIV
quantitative
quantitative
quantitative
Cell culture
Transcrip
supernatant
ts or
s (could
plasmids
substitute
quantified
for rare
by
HIV-1
appropria
subtypes)
te
According
meethods
to EP
may be
validation
used
guideline
According
According
According
( 1 ) as far as
to EP
to EP
to EP
calibrated
validation
validation
validation
subtype
guideline
guideline
guideline
reference
( 1 ) as far as
( 1 ) as far as
( 1 ) as far
materials
calibrated
calibrated
as
are
subtype
subtype
calibrated
available;
reference
reference
subtype
in vitro
materials
materials
reference
transcripts
are
are
materials
could be an
available;
available;
are
option
available;
in vitro
in vitro
transcripts
transcripts
in vitro
could be an
could be an
transcripts
option
option
could be
an option
Diagnosti
500 blood
500 blood
500 blood
500 blood
c
donors
blood
donors
donors
donors
specificit
donors
y
negative
samples
Potential
By
As for
By assays
By assays
By assays
cross
suitable
qualitative design and/
design and/
design
reactive
assay
tests
or testing
or testing of
and/or
markers
design
of at least
at least 10
testing of
evidence
10 human
other DNA-
at least 10
(e.g.
flavivirus
virus
human
sequence
(e.g. HGV,
positive
retrivirus
compari-
YFV)
samples
(e.g. HIV-)
son) and/
positive
positive
or testing
samples
samples
of at least
10 human
retrovirus
(e.g.
HTLV)-
positive
samples
Robustness
As for
qualitativ
e tests
Cross-
At least 5
At least 5
At least 5
At least 5
contami-
runs using
runs using
runs using
runs using
nation
alternatin
alternating
alternating
alternatin
g high
high
high
g high
positive
positive
positive
positive
(known to
(known to
(known to
(known to
occur
occur
occur
occur
naturally)
naturally)
naturally)
naturally)
and
and
and
and
negative
negative
negative
negative
samples
samples
samples
samples
Inhibition
Internal
Internal
Internal
Internal
control
control
control
control
preferably
preferably
preferably
preferably
to go
to go
to go
to go
through
through the
through the
through
the whole
whole NAT
whole NAT
the whole
NAT
procedure
procedure
NAT
procedure
procedure
HIV1
HCV
HBV
HTLV I/II
Accep-
tance
qualitative
quantitative
qualitative
quantitative
quantitative
qualitative
quantitative
criteria
As for HIV
As for HIV
As for HIV
quantitative
quantitative
quantitative
At least
At least
At least
At least
99 / 100
assays
samples
samples
samples
samples
positive
virus-
virus-
virus-
virus-
spiked with
spiked
spiked
spiked
3 x the
with 3 x
with 3 x
with 3 x
95% pos
the 95%
the 95 %
the 95 %
cut-off
pos cut-off
pos cut-off
pos cut-off
concentra-
concentra-
concentra-
concentr-
tion
tion
tion
ation
( 1 ) European Pharmacopoeia guideline
Acceptance criteria for ‘whole system failure rate leading to false-neg results’ is 99/100
assays positive.
For quantitative NATs a study shall be performed on at least 100 positive specimens
reflecting the routine conditions of users (e.g. no pre-selection of specimens). Comparative
results with another NAT test system shall be generated in parallel.
For qualitative NATs a study on diagnostic sensitivity shall be performed using at least 10
sero-conversion panels.
Comparative results with another NAT test system shall be generated in parallel.
Table 3: Rapid tests: anti-HIV 1 and 2, anti-HCV, HBsAg, anti-HBc, anti-
HTLV I and II
anti-HIV 1/2
anti-HCV
HBsAg
anti-HBc
anti-HTLV I/
Acceptance
II
criteria
Positive
Same criteria
Same criteria
Same criteria
Same criteria
Same criteria
Same criteria as
specimens
as for
as for
as for
as for
as for
for screening
screening
screening
screening
screening
screening
assays
assays
assays
assays
assays
assays
Sero-
Same criteria
Same criteria
Same criteria
Same criteria
Same criteria
Same criteria as
conversion
as for
as for
as for
as for
as for
for screening
panels
screening
screening
screening
screening
screening
assays
assays
assays
assays
assays
assays
99 % (anti-
Negative
1000 blood
1000 blood
1000 blood
1000 blood
1000 blood
HBc: 96 %)
specimens
donations 200
donations
donations
donations
donations
clinical
200 clinical
200 clinical
200 clinical
200 clinical
specimens
specimens 200
specimens 200 specimens
specimens
200 samples
samples from
samples from
200 samples
from pregnant
pregnant
pregnant
from pregnant
women
women
women
women
100 potentially 100 potentially 100
interfering
interfering
potentially
potentially
potentially
samples
samples
interfering
interfering
interfering
samples
samples
samples
IN VITRO DIAGNOSTIC MEDICAL DEVICES
Table 4: Confirmatory/supplementary assays for anti-HIV 1 and 2, anti-HTLV
I and II, anti-HCV, HBsAg
anti-HIV
anti-HTLV
HCV
HBsAg
Acceptance
Confirmatory
Confirmatory Supplementary
Confirmatory
criteria
Assay
Assay
Assay
Assay
Diagnostic Positive
200 HIV-1 and 200 HTLV-I
300 HCV
300 HBsAg
Correct
sensitivity specimens
100 HIV-2
and 100
(positive
identification
HTLV-II
samples)
as positive (or
indeterminate),
not negative
Including
Including
Including
samples from
samples from
samples from
different
different
different stages
stages of
stages of
of infection 20
infection and
infection and
“high pos”
reflecting
reflecting
samples (> 26
different
different
IU/ml); 20
antibody
antibody
samples in the
patterns
patterns.
cut-off range
Genotypes 1 -
4: > 20
samples
(including
non-a sub-
types of
genotype 4);
5: > 5 samples;
6: if available
Sero-con-
15 sero-
version
conversion
seroconversion
seroconversion
panels
panels/ low
panels/ low
panels/ low
titre panels
titre panels
titre panels
Analytical
Standards
Second
sensitivity
International
Standard for
HBsAg,
subtype adw2,
genotype A,
NIBSC code
00/588
anti-HTLV
HCV
HBsAg
Acceptance
anti-HIV
Confirmatory
Confirmatory Supplementary
Confirmatory
criteria
Assay
Assay
Assay
Assay
Diagnostic
Negative
200 blood
200 blood
200 blood
10 false
No false-
specificity
specimens
donations
donations
donations
positives as
positive
available from
results/ (1) no
the
neutralisation
performance
evaluation of
the screening
assay. (1)
200 clinical
200 clinical
200 clinical
samples
samples
samples
including
including
including
pregnant
pregnant
pregnant
women
women
women
50 potentially
50 potentially
potentially
potentially
interfering
interfering
interfering
interfering
samples,
samples
samples,
samples,
including
including
including
samples with
samples with
samples with
indeterminate
indetermin-
indeterminat
results in
ate results in
e results in
other
other
other
confirmatory
confirmatory
confirmatory
assays
assays
assays
Table 5: HIV 1 Antigen
HIV-1 Antigen Assay
Acceptance criteria
Diagnostic
Positive specimens
50 HIV-1 Ag-positive
Correct identification (after
sensitivity
50 cell culture supernatants
neutralisation)
including different HIV-1
subtypes and HIV-2
Sero-conversion panels
20 sero-conversion panels/low
titre panels
Analytical
Standards
HIV-1 p24 Antigen, 1st
≤ 2 IU/ml
sensitivity
International Reference
Reagent, NIBSC code: 90/636
Diagnostic
200 blood donations 200
>99.5% after neutralisation
specificity
clinical samples 50 potentially
interfering samples
Table 6: Serotyping and Genotyping Assay: HCV
HCV Serotyping and
Acceptance criteria
Genotyping Assay
Diagnostic
Positive specimens
(positive
samples)
> 95% agreement between
sensitivity
Including
samples
from
serotyping and genotyping
different stages of infection and
> 95% agreement between
reflecting different antibody
genotyping and sequencing
patterns. Genotypes 1 - 4: > 20
samples (including non-a sub-
types of genotype 4);
5: > 5 samples;
6: if available
IN VITRO DIAGNOSTIC MEDICAL DEVICES
HCV Serotyping and
Acceptance criteria
Genotyping Assay
Diagnostic
Negative specimens
specificity
Table 7: HBV Markers: anti-HBs, anti HBc IgM, anti-HBe, HBeAg
anti-HBs
anti-HBc IgM
anti-HBe
HBeAg
Diagnostic
Positive
100 vaccinees 200 Including 200 Including
200 Including
sensitivity
specimens 100 naturally samples from samples from
samples from
infected
different stages different stages
different
persons
of
infection of
infection
stages
(acute/chronic (acute/chronic
infection
etc.)
etc.)
(acute/chronic
etc.)
The
acceptance
criteria should
only
be
applied
on
samples from
acute infection
stage
Sero-con-
follow- When available
version
ups or anti-
panels
HBs
sero-
conversions
Analytical
Standards
WHO
1st
HBe
sensitivity
International
Referenzan-
Reference
tigen 82; PEI
Preparation
Germany
1977;
NIBSC,
United
Kingdom
Diagnostic
No
blood
blood
specificity
negative
Including
donations
donations
donations
specimens
clinical
samples
clinical
clinical
200 clinical
samples
samples
samples
50 potentially
50 potentially
50 potentially
interfering
interfering
interfering
samples
samples
samples
Table 8: HDV markers: anti-HDV, anti-HDV IgM, Delta Antigen
anti-HDV
anti-HDV IgM
Delta Antigen
Diagnostic
Positive
sensitivity
specimens
Specifying
HBV- Specifying HBV-
markers
markers
Diagnostic
Negative
specificity
specimens
Including
clinical Including clinical Including
clinical
samples
samples
samples
potentially 50
potentially 50
potentially
interfering samples interfering samples interfering samples
Table 9: Blood group antigens in the ABO, Rh and Kell blood group systems
Specificity
Number of tests per
Total number of samples
Total number of samples
recommended
to be tested for a launch
to be tested for a new
method
product
formulation, or use of
well-characterized
reagents
Anti-ABO1(anti-A),anti-
Anti-ABO2 (anti-B), Anti-
ABO3 (anti-A,B)
Anti-RH1 (anti-D)
Anti-RH2 (anti-C ), anti-
RH4
(anti-c),
anti-RH3 (anti-E)
Anti-RH5 (anti-e)
Anti-KEL1 (anti-K)
Acceptance criteria
All of the above reagents shall show comparable test results with
established reagents with acceptable performance with regard to claimed reactivity
of the device. For established reagents, where the application or use has been
changed or extended, further testing should be carried out in accordance with the
requirements outlined in column 1 (above).
Performance evaluation of anti-D-reagents shall include tests against a range of
weak RH1 (D) and partial RH1 (D) samples, depending on the intended use of the
product.
Qualifications
Clinical samples
10% of the test population
Neonatal specimens
> 2% of the test population
ABO samples
> 40% A, B positives
‘weak D’
> 2% of RH1 (D) positives
Table 10: Batch release criteria for reagents and reagent products to
determine blood group antigens in the ABO, Rh and Kell blood group systems
Specificity Testing Requirements on each reagent
1. Test reagents
Blood Group Reagents
Minimum number of control cells to be tested
Positive reactions
Negative reactions
A2B
Ax
B
Anti-ABO1 (anti-A)
2*
B
A1B
Anti-ABO2 (anti-B)
Ax
B
Anti-ABO3 (anti-A,B)
R1r
R2r
Weak D
r’r
r’’r
rr
Anti-RH1 (anti-D)
2*
R1R2
R1r
r’r
R2R2
r’’r
rr
Anti-RH2 (anti-C)
R1R2
R1r
r’r
R1R1
IN VITRO DIAGNOSTIC MEDICAL DEVICES
Blood Group Reagents
Minimum number of control cells to be tested
Positive reactions
Negative reactions
Anti-RH4 (anti-c)
R1R2
R2r
r”r
R1R1
r’r
rr
Anti-RH 3 (anti-E)
R1R2
R2r
r”r
R2R2
Anti-RH5 (anti-e)
Kk
kk
Anti-KEL1 (anti-K)
(*) Only by recommended techniques where reactivity against these antigens is claimed
Note: Polyclonal reagents must be tested against a wider panel of cells to confirm specificity
and exclude presence of unwanted contaminating antibodies.
Acceptance Criteria
Each batch of reagent must exhibit unequivocal positive or negative results by all
recommended techniquesin accordance with the results obtained from the performance
evaluation data.
2. Control Materials (red Cells)
The phenotype of red cells used in the control of blood typing reagents listed
above should be confirmed using established device.
1. Without prejudice to national law and practice on medical
secrecy, it shall be ensured that all the parties involved in the
application of these regulations are bound to observe
confidentiality with regard to information obtained in carrying out
their tasks. This does not affect the obligations of the persons
concerned to provide information under criminal law.
12.97, p. 19).
†Council Directive 88/379/EEC of 7 June 1988 on the approximation of the laws, regulations and
administrative provisions of the Member States relating to the classification, packaging and labelling of
dangerous preparations (OJ No. L 187, 16.07.88, P. 14). Directive as last amended by Commission Directive
96/65/EC (OJ No. L 265, 18.10.96 p. 15).
The provisions of the aforementioned Directives on the safety data sheet
shall apply, unless all relevant information as appropriate is already made available
by the instructions for use.
8.4. The label must bear the following particulars which may take the form of
symbols as appropriate
(a) the name or trade name and address of the manufacturer. For devices
imported into the Community with a view to their distribution in the
Community, the label, the outer packaging, or the instructions for use
shall contain in addition the name and address of the authorised
representative of the manufacturer;
(b) the details strictly necessary for the user to uniquely identify the device
and the contents of the packaging;
(c) where appropriate, the word "STERILE" or a statement indicating any
special microbiological state or state of cleanliness;
(d) the batch code, preceded by the word "LOT", or the serial number;
(e) if necessary, an indication of the date by which the device or part of it
should be used, in safety, without degradation of performance,
expressed as the year, the month and, where relevant, the day, in that
order;
(f)
in case of devices for performance evaluation, the words "for
performance evaluation only";
(g) where appropriate, a statement indicating the in vitro use of the device;
(h) any particular storage and, or handling conditions;
(i)
where applicable, any particular operating instructions;
(j)
appropriate warnings and, or precautions to take;
(k) if the device is intended for self-testing, that fact must be clearly stated.
8.5. If the intended purpose of the device is not obvious to the user, the
manufacturer must clearly state the intended purpose in the instructions for use and,
if appropriate, on the label.
8.6. Wherever reasonable and practicable, the devices and separate components
must be identified, where appropriate in terms of batches, to allow all appropriate
action to detect any potential risk posed by the devices and detachable components.
8.7. Where appropriate, the instructions for use must contain the following
particulars
(a) the details referred to in point 8.4 of this section with the exception of
points (d) and (e);
(b) composition of the reagent product by nature and amount or
concentration of the active ingredient(s) of the reagent(s) or kit as well
as a statement, where appropriate, that the device contains other
ingredients which might influence the measurement;
(c) the storage conditions and shelf life following the first opening of the
primary container, together with the storage conditions and stability of
working reagents;
(d) the performances referred to in point 3 of part A of this Schedule;
(e) an indication of any special equipment required including information
necessary for the identification of that special equipment for proper use;
(f)
the type of specimen to be used, any special conditions of collection,
pre-treatment and, if necessary, storage conditions and instructions for
the preparation of the patient;
(g) a detailed description of the procedure to be followed in using the
device;
(h) the measurement procedure to be followed with the device including as
appropriate
-
the principle of the method,
-
the specific analytical performance characteristics (e.g.
sensitivity, specificity, accuracy, repeatability, reproducibility,
limits of detection and measurement range, including information
needed for the control of known relevant interferences),
limitations of the method and information about the use of
available reference measurement procedures and materials by the
user,
-
the details of any further procedure or handling needed before the
device can be used (for example, reconstitution, incubation,
dilution, instrument checks, etc.),
-
the indication whether any particular training is required;
(i)
the mathematical approach upon which the calculation of the analytical
result is made;
(j)
measures to be taken in the event of changes in the analytical
performance of the device;
(k) information appropriate to users on
-
internal quality control including specific validation procedures,
-
the traceability of the calibration of the device;
(l)
the reference intervals for the quantities being determined, including a
description of the appropriate reference population;
(m) if the device must be used in combination with or installed with or
connected to other devices or equipment in order to operate as required
for its intended purpose, sufficient details of its characteristics to
identify the correct devices or equipment to use in order to obtain a safe
and proper combination;
(n) all the information needed to verify whether the device is properly
installed and can operate correctly and safely, plus details of the nature
and frequency of the maintenance and calibration needed to ensure that
the device operates properly and safely; information about safe waste
disposal;
(o) details of any further treatment or handling needed before the device
can be used (for example, sterilisation, final assembly, etc.);
(p) the necessary instructions in the event of damage to the protective
packaging and details of appropriate methods of resterilisation or
decontamination;
(q) if the device is reusable, information on the appropriate processes to
allow reuse, including cleaning, disinfection, packaging and
resterilisation or decontamination, and any restriction on the number of
reuses;
(r) precautions to be taken as regards exposure, in reasonably foreseeable
environmental conditions, to magnetic fields, external electrical
influences, electrostatic discharge, pressure or variations in pressure,
acceleration, thermal ignition sources, etc.;
(s) precautions to be taken against any special, unusual risks related to the
use or disposal of the device including special protective measures;
where the device includes substances of human or animal origin,
attention must be drawn to their potential infectious nature;
(t)
specifications for devices for self-testing
-
the results need to be expressed and presented in a way that is
readily understood by a lay person; information needs to be
provided with a device to the user on action to be taken (in case of
positive, negative or indeterminate result) and on the possibility
of false positive or false negative result,
-
specific particulars may be omitted provided that the other
information supplied by the manufacturer is sufficient to enable
the user to use the device and to understand the result(s) produced
by the device,
-
the information provided must include a statement clearly
directing that the user should not take any decision of medical
relevance without first consulting his or her medical practitioner,
-
the information must also specify that when the device for self-
testing is used for the monitoring of an existing disease, the
patient should only adapt the treatment if he has received the
appropriate training to do so;
(u) date of issue or latest revision of the instructions for use.