"Official Gazette of the RS", No.

3/2019

Pursuant to article 99, para 8 of the Law on medicines and medical devices
(Official Gazette of the RS, No. 105/17),

the Minister of health enacts this

RULEBOOK

on vigilance

I INTRODUCTORY PROVISIONS

1. Content of the Rulebook

 Article 1

This Rulebook regulates in greater detail terms and manner of

implementing the vigilance system.

2. Definitions

Article 2

Terms used in the Law on medical devices (hereinafter: the Law) and
this Rulebook shall have the following meaning:

1) medical device vigilance is a set of activities that assure the collection,

assessment, understanding and response to knowledge of the risks
arising from the use or application of a medical device, in particular
with regard to reporting incidents in order to improve and protect the
health and safety of patients, users and other persons and, if
necessary, provide information that reduces the likelihood of the
incident being repeated or alleviating the consequences of the incident
(hereinafter: vigilance);

2) Person responsible for the vigilance and monitoring of the medical

device on the market is a full-time employee at the manufacturer or
an authorized representative of the manufacturer who performs
vigilance tasks and has completed medical, dental, pharmaceutical,
technological, electro-technical, mechanical, chemical or other
appropriate faculty depending on the type of medical device, as well
as additional education in the field of vigilance (hereinafter: person
responsible for vigilance);
3) Improper use is the act or omission by a person who handles a
medical device or by the user, the consequence of which is the
behavior of a medical device that is beyond any risk control by the
manufacturer;

4) authorized representative of a foreign medical device manufacturer

(hereinafter: authorized representative of a manufacturer) is a legal
or natural person with a head office in the Republic of Serbia who is
solely authorized by the foreign manufacturer in writing to act on their
behalf and to conduct the procedures prescribed by this Law and who
is responsible for the safety and performance of a particular medical
device in the same way as the manufacturer of that medical device;

5) corrective action is the activity undertaken by the manufacturer, or the

authorized representative of the manufacturer in the event of a
potential or established non-conformity of a medical device or other
unwanted situation. There may be more than one non-conformity.
Corrective action is taken to prevent repetition, while preventive ones
are taken to prevent such an event (Corrective and Preventive Action -
CAPA);

6) product that is a combination of a medicine and a medical device is a

medical device the integral part of which is a medicine or a substance
acting as a supplement to the medical device;

7) EUDAMED is a European database for medical devices that centralizes

registration data of manufacturers, or authorized representatives of
manufacturers and medical devices placed on the market of the
European Union, data on issued, amended, supplemented, as well as
certificates that have ceased to be valid, which are withdrawn or
rejected, data obtained in accordance with the procedure for the
vigilance of medical devices and data on clinical trials;

8) Field Safety Corrective Action (FSCA) is a measure taken by the

manufacturer or an authorized representative of the manufacturer
to reduce the risk of death or serious deterioration of a health
condition associated with the use of the medical device placed on
the market. Such measures, regardless of whether they are related
to direct or indirect damage, are reported and recorded through the
Field Safety Notice;

9) Field Safety Notice (FSN) is a notice for customers, i.e. users sent
from by the manufacturer, or an authorized representative of the
manufacturer in relation to the Field Safety Corrective Action;
10)damage is a physical injury or damage to the health of people,
animals or damage to property or the environment;

11)without delay is the method of urgent action, that is, the treatment
whose postponement cannot be justified;

12)incident is any malfunction or deterioration of the characteristics or

performance of a medical device, as well as the inadequacy in the
labelling or in the instruction for use which, directly or indirectly, led
or could have led to the death of a patient, user or other person or
to serious deterioration of his health;
13)Indirect harm is a harm that in most cases can arise through the
application/administration of diagnostic devices, in vitro diagnostic
medical devices, medical devices for in vitro fertilization and assisted
reproduction technology which, due to the nature of their intended
use do not lead directly to a physical harm or damage to individuals.
Typically, such medical devices lead to indirect rather than to direct harm.
Harm may occur as a consequence of the medical decision, action
taken/not taken on the basis of information or result(s) provided by the
device or as a consequence of the treatment of cells (e.g. gametes and
embryos in the case of IVF/ART devices) or organs outside of the human
body that will later be transferred to a patient. Indirect harm can be for
instance, misdiagnosis, delayed diagnosis, delayed treatment, inappropriate
treatment, absence of treatment, transfusion of inappropriate materials.
Indirect harm can also be caused by imprecise results, inadequate quality
controls, inadequate calibration, false positive or false negative results. In
case of in vitro diagnostic medical devices for self-testing, a medical decision
can be taken also by the user thereof who is also a patient;

14)intended purpose is the use for which the medical device is

intended in accordance with the information supplied by the
manufacturer on the labelling, in the instructions and/or in
promotional materials;

15)medical device manufacturer (hereinafter: manufacturer) is a legal of

natural 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;

16)medical device (in general) means any instrument, apparatus,

appliance, software, implant, reagent, material and other product
used alone or in combination, including software provided by the
manufacturer for diagnostic or therapeutic purposes and which is
software support necessary for its proper use in people intended by
the manufacturer, and is used for:

(1)diagnosis, prevention, monitoring, prediction, prognosis, treatment

or alleviation of disease,

(2)diagnosis, monitoring, treatment, alleviation or compensation of

injury or disability,

(3)investigation, replacement or modification of the anatomy or

physiological or pathological process and state,
(4)providinginformation by means of in vitro examination of
specimens derived from the human body, including organ, blood
and tissue donations,

(5)control or support of conception,

(6)products intended for cleaning, disinfection or sterilization of medical

devices.
 The medical device referred to in paragraph 1 of this item 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;

17) operator is a person handling equipment;

18)Periodic Safety Report is a method of reporting agreed between

the Agency and the manufacturer or the authorized representative
of the manufacturer for reporting similar incidents with the same
device or device type in a consolidated way where the root cause is
known or an Field Safety Corrective Action has been implemented;

19)serious public health threat is any event that can lead to

immediate danger of death, serious deterioration of health or
serious illness requiring prompt remedial actions. This would
include:

(1) events that are of significant and unexpected nature such that they
become alarming as a potential public health hazard, e.g. human
immunodeficiency virus (HIV) or Creutzfeldt-Jacob Disease (CJD).
These concerns may be identified by either the Ministry, the Agency
or the manufacturer, or the authorized representative of the
manufacturer,

(2)the possibility of multiple deaths occurring at short

intervals;

20)Trend reporting is a type of reporting used by the manufacturer, i.e.,

the authorized representative thereof, uses when there is a significant
increase in the number of events normally not considered to be
incidents, for which pre-defined levels, i.e., “triggers” are used to
determine the threshold for reporting;

21)unanticipated deterioration in state of health is a deterioration

leading to the event that was not considered in a risk analysis.
Documented evidence in the design file is needed that such analysis
was used to reduce the risk to an acceptable level, or that this risk is
well known by the intended user;

22)error in use/use error is an act or omission the result of which

is different from the one intended by the manufacturer or
expected by the operator;
23)user is a health institution, private practice, healthcare worker or a
patient using or maintaining a medical device;

24)Adverse event in a clinical trial is any unpleasant medical occurrence,

accidental illness or injury or an unfavorable clinical symptom
(including an unfavorable laboratory finding) in a patient, user or other
person, whether or not related to the medical device that is clinically
studied. This definition includes events related to a medical device that
is clinically studied or a medical device to compare with, as well as
events related to the procedures involved. For users or other persons,
this definition is limited to events relating to a medical device that is
clinically studied;
25)Serious adverse event in a clinical trial is an unwanted event that led
to or may lead to death or serious deterioration of the patient's
health, resulting in life-threatening illness or injury or permanent
damage to the body's structure or function, hospitalization of the
patient, or the extension of existing hospital treatment, medical or
surgical interventions to prevent illness or injury that is life-
threatening or permanent damage to the structure or function, and
which may lead to fetal distress, fetal death or congenital anomalies,
or effect. Planned hospitalization for the pre-existing condition or
procedure required by the Clinical Investigation Plan, without serious
harm to health, is not considered a serious adverse event;

26)Adverse effect in a clinical trial is an adverse event in relation to the

use of a medical device that is clinically studied. This definition
includes adverse effects arising from insufficient or inadequate
instructions for use, development, implantation, installation or
operation or any malfunctioning of the medical device being clinically
studied. This definition includes any event resulting from an error in
use or from the deliberate misuse of a medical device that is clinically
studied;

27)Serious adverse effect in a clinical trial is an adverse effect the result

of which is on a par with any of the outcomes of a serious adverse
event;

28)Unexpected serious adverse effect in a clinical trial is a serious

adverse effect which, by its nature, incidence, seriousness or
outcome is not described in the applicable version of the risk
analysis;

29)Device deficiency is any inadequacy of a medical device in relation

to identity, quality, durability, reliability, safety or performance.
Defects of a medical device include failures, malfunctions and
inadequate labelling.

II VIGILANCE SYSTEM

Article 3
The manufacturer, i.e., the authorized representative of the manufacturer
investigates the incident and the Agency supervises the investigation and
undertakes measures necessary to amend or supplement the measures
taken by the manufacturer, i.e., the authorized representative of the
manufacturer. Depending on the results of the survey, the Agency
provides all the information needed to prevent incidents or to limit their
consequences after the placing of medical devices on the market and into
service (hereinafter: the vigilance system), in accordance with the Law.

The vigilance system is a set of activities that assure the collection,

assessment, understanding and response to knowledge of the risks arising
from the use or application of a medical device, in particular with regard
to reporting incidents in order to improve and protect the health and
safety of patients, users and other persons and, if necessary, provide
information that reduces the likelihood of the incident being repeated
elsewhere or alleviating the consequences of the incident.
In addition, the vigilance system is intended for facilitating a direct.
Timely and harmonized implementation of a Field Safety Corrective
Action, wherever the medical device was in use, across the entire
territory of the Republic of Serbia.

Corrective actions include but are not limited to: medical device recall,
issuance of the Field Safety Notice, additional supervision, modification of
a medical device in use, modification of the medical device design or a
part of the manufacturing process, modification of labelling or user
instruction manual.

1. Field Safety Corrective Action

Article 4

The Field Safety Corrective Action may include:

1) The return of the medical device to the supplier;

2) modification of the medical device;

3) replacement of the medical device;

4) destruction of the medical device;

5) retrofit by purchaser of manufacturer's modification or design

change;
 6) manufacturer’s advice regarding the use of the device and/or the
follow up of patients, users or others (e.g. where the device is no
longer on the market or has been withdrawn but could still possibly
be in use e.g. implants or change in analytical sensitivity or
specificity for diagnostic devices).

Article 5

The manufacturer can as part of ongoing quality assurance or an

investigation at the manufacturing site identify a failure of a device to
perform according to the characteristics specified in the information for
use.

If the failure might lead to or might have led to death or serious

deterioration in the state of health associated with the use of a medical
device and has an impact on a product that has already been placed on
the market the manufacturer must initiate a Field Safety Corrective
Action.

Examples of failure modes may include software anomalies (e.g. incorrect

correlation between patient sample and the obtained result), invalid
controls, invalid calibrations or reagent failures (e.g. contamination,
transcription errors and reduced stability).

Article 6

A device modification can include:

1) permanent or temporary changes to the labeling or instructions for

use:
 (1) advice pertaining to a change in the way the device is used (for
inst. the manufacturer advises revised quality control procedure
such as use of third party controls or more frequent calibration
or modification of control values for the device),

(2) changes to storage conditions for sample to be used

with an in vitro diagnostic medical device,

(3) advice given to users relating to a change in the stated shelf life of
medical devices for in vitro fertilization and assisted reproduction
technology (for inst. the manufacturer informs the users of an
error on the labelling of their device which indicates a shelf life
longer than the validated shelf life for the product);

2)software upgrades following the identification of a fault in the software

version already in the field. (This must be reported regardless of
whether the software update is being implemented by customers, field
service engineers or by remote access).

Manufacturer’s advice may include modification to the clinical

management of patients/samples to address a risk of death or serious
deterioration in state of health related specifically to the
characteristics of the device. For example:

1) for implantable devices it is often clinically unjustifiable to explant

the device. Corrective action taking the form of special patient
follow-up, irrespective of whether any affected un-implanted
devices remain available for return, constitutes FSCA;

2) in case of diagnostic medical devises (for inst. in vitro diagnostic

devices and equipment, or medical devices for screening), a
corrective measure in the form of returning patients or their samples
for re-examination/re-testing or in the form of revision of previous
results constitutes a Field Safety Corrective Action.

2. Reporting by the manufacturer, i.e., manufacturer’s

authorized representative

Article 7
The manufacturer, i.e., the authorized representative of the manufacturer
shall report to the Agency or Ministry each and every incident and Field
Safety Corrective Action if the reporting criteria foreseen by this Rulebook
are met.

The manufacturer, i.e., the authorized representative of the

manufacturer investigates the incidents and takes all necessary
corrective measures.

If the incident occurs as a consequence of the combined use of two or

more separate devices(and/or accessories) made by some other
manufacturer, each manufacturer, i.e., authorized representative thereof
shall report this to the Agency and the Ministry.

The manufacturer, i.e., the authorized representative of the manufacturer

shall notify the body authorized for conformity assessment of the
problems arising in the post-production phase affecting the certification,
including relevant changes derived from the vigilance system.

The act of reporting an incident is not to be construed as an admission of

liability for the incident and its consequences. Written reports may carry
a disclaimer to this effect.

In case of replacement of the manufacturer, i.e., manufacturer’s

authorized representative, if the vigilance obligation and market
supervision are being transferred to another legal entity, it is important
that post market surveillance activities continue and that Agency and the
Ministry are appraised of the implications and provided with new contact
details as soon as possible, so that any detrimental effects on the
functioning of the vigilance system are minimized.
.

3. Obligations of manufacturers of medical devices that are not

intended to act directly on the individual

Article 8
In case of medical devices which do not generally come into contact with
patients (most diagnostic devices, in vitro diagnostic and medical devices
for in vitro fertilization and assisted reproduction technology), if a direct
harm to the patient is difficult to prove (unless the device itself causes
deterioration in state of health) the harm is considered to be indirect –
the result of an act or omission based on incorrect results obtained
through the use of a diagnostic device, in vitro diagnostic medical device
or the consequence of the treatment of cells (e.g. gametes and embryos
in the case of medical devices for in vitro medical fertilization and
assisted reproduction technology) or organs outside of the human body
that will later be transferred to a patient. Indirect damage can also be
caused by a software considered to be a medical device. Incidents and
events leading to indirect harm must be reported to both the Agency and
the Ministry.

If the manufacturer, i.e., the authorized representative of the

manufacturer of the medical device referred to in para 1 of this article
identifies an event that has led or may lead to indirect harm to the patient
and that has led or may lead to death or serious deterioration of the
patient’s health, such an incident must be reported to both the Agency
and the Ministry.
Any action taken by the manufacturer, i.e., the authorized
representative of the manufacturer to reduce the risk of death or
serious deterioration of patient’s health associated with the use of a
medical device already placed on the market are reported through a
Field Safety Notice. The action is reported in adherence with the provisions
of this Rulebook, regardless of whether it is undertaken in connection with
direct or indirect harm.

It may be difficult to determine whether a serious deterioration of

patient’s health was or can be the consequence of an erroneous result
obtained through the use of an in vitro diagnostic or diagnostic medical
devise, the consequence of an inappropriate treatment with reproductive
cells using a medical device for in vitro fertilization or assisted
reproduction technology or the consequence of an error made by the
user or a third party. In case of doubt, a report must be submitted in
adherence with the provisions of this Rulebook.

In case of the error made by either the user or a third person, the
labelling and the user instruction manual shall be closely examined for
inadequacy, especially in connection with devices intended for self-testing
where the medical decision can be taken solely by the patient.
Inadequacies in the information provided by the manufacturer that led or
could have led to harm to the user, patient or a third party shall be
reported in adherence with this Rulebook.

4. Agency’s Activities

article 9

The Agency shall supervise incident investigations conducted by the

manufacturer, i.e., the authorized representative of the manufacturer
and take necessary actions in addition to those undertaken by the
manufacturer, i.e., the authorized representative of the manufacturer, in
accordance with the Law.

The Agency shall post, on its webpage, all the information necessary to
prevent future incidents or limit the consequences thereof, depending on
the investigation conducted by the manufacturer, i.e., the authorized
representative of the manufacturer.
The Agency shall be responsible for raising awareness of the
organizations and individuals included in the health protection system in
charge of purchasing medical devices about the importance of their
cooperation as well as for ensuring the first step actions within the
vigilance system.

For the purpose of increasing the efficiency of the vigilance system, the
Agency shall encourage incident reporting by the users and professionals
included in the distribution, supply or putting medical devices into use.
This includes organizations and individuals responsible for ensuring calibration
and maintenance of the medical devices. Such reports are to be submitted to the
manufacturer, i.e., the authorized representative of the manufacturer as well as
to the Agency.

The Agency shall keep the information on the vigilance system as

confidential, pursuant to the Law. Upon request, the Agency shall
submit incident reports to the Ministry’s department in charge of
inspection.
 5. Reporting by the User

Article 10

The users shall report incidents involving a medical device to the

manufacturer, i.e., the authorized representative of the manufacturer as
well as to the Agency.

If a corrective or other measure is identified, the vigilance coordinator, a

healthcare professional, i.e., a representative of the user responsible for
maintenance and safety of the medical device, a person in charge of
calibration and maintenance of the medical device, i.e., a person in
charge of vigilance shall take appropriate actions. The actions, if feasible,
shall be taken in cooperation with the manufacturer, i.e., the authorized
representative of the manufacturer.

The report template for reporting incidents associated with medical

devices by health institutions and healthcare professionals is given in
Annex 8 attached to this Rulebook as an integral part thereof.

The report template for reporting adverse reactions to medical devices by

other users, i.e., patients is given in Annex 9 attached to this Rulebook
as an integral part thereof.

III VIGILANCE SYSTEM OF THE MANUFACTURER, I.E., THE AUTHORIZED

REPRESENTATIVE OF THE MANUFACTURER

1. Incident Reporting System

Article 11
The manufacturer, i.e., the authorized representative of the
manufacturer shall submit the initial report on the incident to the
Agency, recording and evaluation purposes. Each and every initial
report shall lead to a final report unless they are combined into a single
report, however not all incident reports will lead to a corrective action.
As a general principle, there should be a pre-disposition to report rather than
not to report in case of doubt on the reportability of an incident..

Reference to the following considerations may be made in the report, or

should be kept on file by the manufacturer, i.e., the authorized
representative of the manufacturer, in the case of a decision not to
report.

1) incidents which happened outside the Republic of Serbia, EEA,

Switzerland and Turkey that do not lead to a Field Safety Corrective
Action relevant to these geographical areas are do not need to be
reported;

2) incidents which happened outside the Republic of Serbia, EEA,

Switzerland and Turkey that led to a Field Safety Corrective Action
relevant for these geographical areas are reported as a Field Safety
Corrective Action.

Where appropriate, the manufacturer shall notify its authorized

representative, persons in charge of placing the medical device on the
market and any other agents (for inst. distributers) authorized to act on
its behalf of the incident and the Field Safety Corrective Action reported
under the Medical Device Vigilance System.
If the manufacturer’s head office is located outside the republic of Serbia,
EEA, Switzerland and Turkey, it is necessary to appoint the contact
person. This person may be the manufacturer’s authorized
representative, the person in charge of placing the medical device on the
market, the person responsible for vigilance or any other agent
authorized to act on their behalf for purposes relating to Medical Devices
Vigilance.

1.1. Reporting criteria applicable for incidents that the

manufacturer, i.e., the authorized representative of the
manufacturer is obliged to report to the Agency

Article 12

Any event which meets all of the basic reporting criteria listed below is
considered as an incident and must be reported to the Agency:

1) an event including situations where testing performed on the

device, examination of the information supplied with the device or
any scientific information indicates some factor that could lead or
has led to an event. Typical events of this nature include but are
not limited to:

(1) malfunction or deterioration of the characteristics or performances

of a medical device (malfunction or deterioration should be
understood as a failure of a device to perform in accordance with
its intended purpose, provided it is used in strict compliance with
the manufacturer’s instructions),

(2) for in vitro diagnostic medical devices, where there is a risk that an
erroneous result may cause indirect damage to the patient,
consequentially leading to life-threatening illness of the tested individual
or to the individual’s offspring or to death or severe disability to the
individual or fetus being tested, or to the individual’s offspring, all false
positive or false negative results shall be considered to be incidents. For
all other IVDs, false positive or false negative results falling outside the
declared performance of the test shall be considered as events.

(3) Unanticipated adverse reaction or unanticipated side effect,

(4) interaction with other substances or products,

(5) degradation, i.e., destruction of a medical device (for inst. in fire),

(6) inappropriate therapy,

(7) An inaccuracy in the labelling, instructions for use and/or

promotional materials. Inaccuracies include omissions and
deficiencies. Omissions do not include the absence of information
that should generally be known by the intended users.
 See ISO TS 19218 on adverse event type and cause/effect coding for
further details on events;

2) The manufacturer’s device is suspected to be a contributory cause of

the incident. When assessing whether the incident is associated with
a medical device, the manufacturer, i.e., the authorized
representative of the manufacturer shall take into account:

(1) the
opinion of the healthcare professionals based on available
evidence,

(2) the result of manufacturer’s preliminary assessment of the incident,

(3) evidence of previous, similar incidents,

(4) other evidence held by the manufacturer.

This judgement may be difficult when there are multiple devices and
drugs involved in the event that has led on the incident. In that case,
it should be assumed that the device may have caused or contributed
to the incident and the manufacturer should err on the side of
caution;

3) the event led or might have led to one of the following outcomes:

(1) death of a patient, user or a third person,

(2) serious deterioration in state of health of a patient, USER or other

person

A serious deterioration in the state of health referred to in para 1,

item 3) subitem (2) of this article includes, also:
1) lift-threatening illness;

2) permanent impairment of a body function or permanent damage to

a body structure;

3) a condition necessitating medical or surgical intervention to prevent

the consequences referred to in items 1) and 2) of this paragraph
(for inst. a clinically relevant prolongation of a surgical procedure; a
condition requiring hospitalization or a significant prolongation of
existing hospitalization;

4) any indirect harm that is a consequence of an incorrect diagnostic or

IVD test result or as a consequence of the use a medical device for
in vitro fertilization or assisted reproduction technology when used
within manufacturer´s instructions for use (errors in use that are
subject to reporting in accordance with the provisions of this
Rulebook);

5) fetal distress, fetal death or any congenital abnormality or birth

defects.
 Not all incidents result in death or serious deterioration of health
condition, owing to favorable circumstances or interventions of
healthcare professionals. For that reason, it would suffice that the
incident is associated with a medical device and that the nature of the
incident was such that it could have led to death or serious deterioration of
health condition, i.e., that if repeated, it can lead to the death or serious
deterioration of the patient’s health condition. Examples of incidents and
Field Safety Corrective Actions reported by the manufacturer, i.e., the
authorized representative of the manufacturer are given in Annex 1
attached to this Rulebook as an integral part thereof.

1.2. Conditions for the Submission of the Periodic Safety Report

Article 13

The Agency may request the manufacturer, i.e., the authorized

representative of the manufacturer, to submit to it a Periodic Safety Report
or a Trend Report following the submission of one or more initial reports
that the two sides have jointly assessed. This type of reporting must be
agreed between the manufacturer, i.e., the authorized representative of
the manufacturer and the Agency and the report must be submitted in
the agreed format and within time periods set for each particular type of
medical device and incident.

A Periodic Safety Report template is given in Annex 2 attached to this

Rulebook as an integral part thereof.

Incidents Described in a Field Safety Notice

Article 14
Incidents specified in the Field Safety Notice that occur after the
manufacturer, i.e., the authorized representative of the manufacturer has
issued the Field Safety Notice and conducted the Field Safety Corrective
Action are not to be reported individually. The manufacturer, i.e., the
authorized representative of the manufacturer and the Agency shall
agree upon the frequency and content of the Periodic Safety Report (for
inst. the manufacturer issued a Periodic Safety Report and implemented
a Field Safety Corrective Action for a coronary stent that migrated due
inadequate inflation associated with the balloon mechanism. Subsequent
examples of stent migration were summarized in quarterly reports
concerning the Field Safety Corrective Action and individual incidents did
not have to be reported).

Common and well-documented incidents

Article 15

Common and well-documented incidents (identified as such in the risk

analysis of the device and which have already led to incident reports
assessed by the Agency and the manufacturer) may be exempted from
reporting individually and changed to Periodic Safety reporting.

The Agency shall be in charge of supervising the incidents referred to in

para 1 of this Article and responsible for determining trigger levels Trigger
levels for interim reporting should also be agreed the manufacturer, i.e., the
authorized representative of the manufacturer. An interim report should be
made whenever trigger levels are exceeded.

1.3. Conditions where reporting under vigilance system is not

usually required

Deficiency of a device found by the user prior to its use

Article 16
Medical device deficiencies that are always detected (that could not go
undetected) by the user prior to use shall not be reported under the
vigilance system, regardless of the provisions printed in the
manufacturer’s instruction manual (for inst., the packaging of a sterile
single use device is labelled with the caution 'do not use if the packaging
is opened or damaged'. Prior to use, obvious damage to the packaging
was observed, and the device was not used; intravenous
administration set tip protector has fallen off the set during distribution
resulting in a non-sterile fluid pathway. The intravenous administration
set was not used; a vaginal speculum has multiple fractures. Upon
activating the handle, the device fell apart. The device was not used; in
an in vitro diagnostic test kit, a bottle labelled lyophilized is found to be
fluid, this is discovered by the USER prior to use).

In cases referred to in para 1 of this Article, the user shall notify the
manufacturer, i.e., the authorized representative of the manufacturer
accordingly prior to the use of the medical device.

Event caused by patient conditions

Article 17

When the manufacturer, i.e., the authorized representative of the

manufacturer has information that the root cause of the event is the
patient’s condition, the event does not need to be reported. These
conditions could be pre- existing or occurring during device use (for inst.
early revision of an orthopedic implant due to loosening caused by the
patient developing osteolysis, which is not considered a direct
consequence of the implant failure. This conclusion would need to be
supported by the opinion of a medical expert; a patient died after
dialysis treatment. The patient had end-stage-renal disease and died of
renal failure, the manufacturer’s investigations revealed the device to be
functioning as claimed and the INCIDENT was not attributed to the
device).

To justify the non-reporting of the event referred to in para 1 of this

Article, manufacturer, i.e., the authorized representative of the
manufacturer concludes that the device performed as intended and did
not cause or contribute to death or serious deterioration in state of
health.
This conclusion needs to be accepted by a person qualified to undertake a
medical assessment. The manufacturer, i.e., the authorized representative
of the manufacturer includes a clinical physician in the decision-making
process.

Service life or shelf-life of the medical device exceeded

Article 18

When the only cause for the event was that the device exceeded its
service life or shelf-life as specified by the manufacturer and the failure
mode is not unusual, the incident does not need to be reported (e.g.,
loss of sensing after a pacemaker has reached end of life. Elective
replacement indicator has shown up in due time according to device
specification. Surgical explantation of pacemaker required; insufficient
contact of the defibrillator pads to the patient was observed. The patient
could not be defibrillated due to insufficient contact to the chest. The
shelf life of the pads was labelled but exceeded; a patient is admitted to
hospital with hypoglycemia based on an incorrect insulin dosage following
a blood glucose result. The investigation found that the test strip was
used beyond the expiry date specified by the manufacturer).

The service life or shelf-life must be specified by the device manufacturer

and included in the master record [technical file] and, where appropriate,
the instructions for use (IFU) or labelling, respectively. Service life or
shelf-life can include e.g.: the time or usage that a device is intended to
remain functional after it is manufactured, put into service, and maintained
as specified. Reporting assessment shall be based on the information in
the master record or in the IFU.

Protection against a fault functioned correctly

Article 19
Events which did not lead to a serious deterioration in state of health or
death, because a design feature protected against a fault becoming a
hazard (in accordance with relevant standards or documented design
inputs) shall not be subject to reporting. As a precondition, there must be
no danger for the patient to justify not reporting. If an alarm system is
used, the concept of this system should be generally acknowledged for
that type of product (e.g. an infusion pump stops, due to a malfunction,
but gives an appropriate alarm in compliance with relevant standards and
there was no injury to the patient; microprocessor-controlled radiant
warmers malfunction and provide an audible appropriate alarm in
compliance with relevant standards and there was no deterioration in
state of health of the patient; during radiation treatment, the automatic
exposure control is engaged. Treatment stops. Although patient receives
less than optimal dose, patient is not exposed to excess radiation; a
laboratory analyzer stops during analysis due to a malfunction of the sample
pipetting module, but the appropriate error message was provided for the user.
An intervention by the user or an immediate remote intervention by
manufacturer allowed the analyzer to resume the analysis, resulting in correct
results).
 Expected and foreseeable adverse effects

Article 20

Expected and foreseeable adverse effects that, are not ordinarily

reportable, shall be considered to be the effects that are:

1) clearly identified in the manufacturer’s labelling, i.e., in the

instructions for use of the medical device;

2) clinically well known as being foreseeable and having a certain

qualitative and quantitative predictability when the device is used
and performs as intended;

3) documented in the technical documentation (master record) along

with the appropriate risk assessment prior to the occurrence of the
incident;

4) clinically acceptable in terms of the individual benefit to the patient.

The manufacturer, i.e., the authorized representative of the

manufacturer shall include a clinical physician in the process of making
decision referred to in para 1 of this article.

The manufacturer, i.e., the authorized representative of the manufacturer

shall consider any change in the risk-benefit ratio (for inst. increase of
frequency, i.e., severity) based on the report on expected and
foreseeable adverse effects that led or might lead to death or serious
deterioration of state of health, as a deterioration in the characteristics of
the performance of the device.

In the case referred to in para 2 of this article, manufacturer, i.e., the

authorized representative of the manufacturer shall file a trend report
with the Agency.
An adverse effect shall not be considered to be an incident except when
the change in the risk-benefit ratio is deemed to be worsening of the
performances of a medical device.

Expected and foreseeable adverse effects are those that are well-known
in medical, scientific or technological sense and are clearly identified
during clinical trials or clinical practice and listed on the label or in the
manufacturer’s user manual.

The conditions that lead to an adverse effect may be clearly described

and predicted numerically, if feasible.

Adverse effects which were not documented and foreseeable or which

were not clinically acceptable in terms of individual patient benefit should
continue to be reported to the Agency.
 Negligible likelihood of occurrence of death or serious
deterioration in state of health

Article 21

The incident for which the risk of a death or serious deterioration in state
of health is quantified and found to be negligibly low shall not be subject
to reporting unless it resulted in death or serious deterioration in state of
health, provided the risk has been described and documented as
acceptable within a comprehensive risk assessment (for inst., the
pacemaker manufacturer placed on the market identifies a software error
and quantifies the probability of serious deterioration of health within the
set environment as negligible and no adverse effects upon the patient’s
health were recorded).

If the consequence of an incident is death or serious deterioration in

state of health, the incident must be reported and the risk reassessed. If
the reassessment results in the confirmation that the risk remains
exceptionally low, the prior incidents of the same type shall not be subject to
retroactive reporting. The decision not to report subsequent failures of the
same type must be documented. Changes in trend (typically increases) of
these non-serious outcomes must be reported.

1.4. Trend reporting

Article 22

The manufacturer, i.e., the authorized representative of the manufacturer

shall file a report with the Agency on any significant increase or trend of
events that are usually not included in individual reporting. To that end,
the manufacturer, i.e., the authorized representative of the manufacturer
should have suitable systems in place for proactive scrutiny of claims and
incidents associated with the medical device in question.

The manufacturer, i.e., the authorized representative of the

manufacturer, shall file a trend report with the Agency in case of a
significant increase in the rate of:

1) incidents already subject to reporting;

2) incidents typically not subject to reporting;

 3) events typically not subject to reporting irrespective of whether
periodic Safety reporting has been agreed.

A trend report template is given in Annex 3 attached to this Rulebook as

an integral part thereof.

1.5. Reportable errors in use and abnormal uses

Article 23
The manufacturer, i.e., the authorized representative of the
manufacturer shall evaluate all events, potential errors in use and
abnormal uses as well as other claims pertaining to the medical device.
Such an evaluation shall be governed by risk management, engineering,
usability, design validation and corrective and preventive action
processes.

Results of the assessment referred to in para 1 of this article shall be

submitted to the Agency upon demand.

Errors in use subject to reporting

Article 24

The manufacturer, i.e., the authorized representative of the manufacturer

shall report to the Agency errors in the use of a medical device resulting
in death or serious deterioration of patient’s health or serious threat to
public health.

The errors in use referred to in para 1 of this article shall be reported if

the manufacturer, i.e., the authorized representative of the
manufacturer:

1) notices a significant trend change (typically, increased incidence) or

in case of a significant change in the pattern of events that might
lead to the death or serious deterioration of health or serious threat
to public health;

2) initiates a Field Safety Corrective Action to prevent death or

serious deterioration of health or serious threat to public health.

Errors in use typically not subject to reporting

 Article 25

The manufacturer, i.e., the authorized representative of the manufacturer

shall not report to the Agency the errors in use that do not result in death
or serious deterioration in state of health or serious threat to public
health. Such events are handled within the quality and risk management
systems. Any decision to not report such errors must be justified and
documented.

Abnormal use

Article 26

The manufacturer, i.e., the authorized representative of the manufacturer

shall not report to the Agency cases of abnormal use. If a cases of
abnormal use becomes known, health institutions, i.e., healthcare workers
can be notified accordingly.
 1.6. Data on incidents

Article 27

Data on incident stated in each and every report the manufacturer, i.e.,
the authorized representative of the manufacturer submits to the Agency
and used for the initial, follow-up and the final report shall be submitted
as a report by manufacturer, i.e., the authorized representative of the
manufacturer on the incident given as a template in Annex 4 attached to
this Rulebook as an integral part thereof.

Reporting referred to in para 1 of this article shall be performed in

electronic form via the Agency’s own portal.

If the initial report is submitted orally (over the phone, for inst.), the
manufacturer, i.e., the authorized representative of the manufacturer
shall, without delay file a written report as well.

A report by the manufacturer, i.e., the authorized representative of the

manufacturer on the incident may also include a statement to the effect
that the report is made by the manufacturer without prejudice and does
not imply any admission of liability for the incident or its consequences.

The initial, follow-up and final reports shall be filed using a template given
as Annex 3 to this Rulebook.

1.7. Timescale for the submission of the initial incident report

Article 28

As soon as it becomes aware of an event and of the fact that the medical
device caused or contributed to the event, the manufacturer, i.e., the
authorized representative of the manufacturer shall proceed with
determining whether or not it was an incident.
The manufacturer, i.e., the authorized representative of the manufacturer
shall report to the Agency each and every serious public health threat
without delay, however within two calendar days at the latest from the
day of becoming aware of the threat.

The manufacturer, i.e., the authorized representative of the manufacturer

shall report the Agency each case of death or unanticipated deterioration
in state of health without delay, after he established a link between the
medical device and the event, within ten calendar days at the latest from
the day of becoming aware of the event.

The manufacturer, i.e., the authorized representative of the

manufacturer shall report to the Agency any and all other incidents
without delay, after he has established the link between the medical
device and the event, within 30 calendar days at the latest from the day
of becoming aware of the event.

If, after becoming aware of a potentially reportable incident there is still

uncertainty about whether the event is reportable, the manufacturer
shall submit to the Agency a report within the timeframe set for the
type of incident in question as referred to in paras 2, 3 and 4 of this
article.

2. Agency’s actions upon users’ reports

 Article 29

If the Agency submits a user’s report to the manufacturer, i.e., the

authorized representative of the manufacturer, it is obliged to verify it in
line with the criteria listed in article 12 of this Rulebook and to submit to the
agency its own initial, follow-up or final incident report, provided the event
meets the relevant criterion. If the manufacturer, i.e., the authorized
representative of the manufacturer is of the opinion that the event does
not meet the said criteria, it shall submit to the Agency an explanation
including the information on how the manufacture intends to use the
information received (for inst., it will include the information in the claims
documentation).

3. Investigations by the manufacturer, i.e., the authorized

representative of the manufacturer

Article 30

The manufacturer, i.e., the authorized representative of the manufacturer

shall undertake an investigation of the incident and the Agency shall
supervise such an investigation. The manufacturer, i.e., the authorized
representative of the manufacturer shall define the time period necessary
for monitoring, i.e., time period necessary for the completion of the
investigation and, if needed, it shall submit monitoring reports as well as
the final report.

If the manufacturer, i.e., the authorized representative of the

manufacturer is unable to conduct the incident investigation, it shall
notify the Agency accordingly, without delay.

The Agency may intervene in the investigation or initiate an independent

investigation, if necessary. Whenever feasible, the Agency shall proceed
in agreement with the manufacturer, i.e., the authorized representative
of the manufacturer.

Access to the medical device suspected to be involved in the

incident

Article 31
The manufacturer, i.e., the authorized representative of the manufacturer
may consult with the user on a particular, reported incident before a
report is made to the Agency.

The manufacturer, i.e., the authorized representative of the manufacturer

may also need to have access to the device suspected to have contributed
to the incident for the purpose of deciding whether the incident should be
reported to the Agency. I such cases the manufacturer, i.e., the
authorized representative of the manufacturer should make reasonable
efforts to gain access to the device so that a technical inspection can be
performed as soon as possible. Any delay can result in loss of evidence
(e.g. loss of short term memory data stored in the device software;
degradation of certain devices when exposed to blood) rendering future
analysis of the root cause impossible.

If the manufacturer, i.e., the authorized representative of the

manufacturer gains access to the device, and his initial assessment (or
cleaning or decontamination process) will involve altering the device in a
way which may affect subsequent analysis, then the manufacturer should
inform the Agency before proceeding.
The Agency may then consider whether to participate in the assessment.
Due to the frequency of these requests, a statement introduced in the
Initial Vigilance report should cover this requirement, (e.g. “The
manufacturer will assume destructive analysis can begin 10 days
following issuance of this Initial incident Report, unless the Agency
contacts the manufacturer within this time frame opposing a destructive
analysis of the medical device).

The provisions of paras 1, 2 and 3 of this article shall apply also to

samples of the medical device and any other useful information
associated with the incident.

4. Outcome of an investigation and follow-up

Article 32

The manufacturer, i.e., the authorized representative of the manufacturer

shall take the action necessary following the investigation, including
consultation with the Agency and performing any Field Safety Corrective
Action.

The Agency may take any further action it deems appropriate, consulting
with the manufacturer, i.e., the authorized representative of the
manufacturer.

Follow-Up Report

Article 33

The manufacturer, i.e., the authorized representative of the

manufacturer shall provide a follow-up-report to the Agency if the
investigation time reaches the time line given to the Agency within the
initial report.
 Final Report

Article 34

The manufacturer, i.e., the authorized representative of the manufacturer

shall submit to the Agency a final report which is a written statement of
the outcome of the investigation and of any action (e.g. no action,
additional surveillance of medical devices in use, preventive action on
future production, a Field Safety Corrective Action).

If the Agency performs the investigation then the manufacturer, i.e., the
authorized representative of the manufacturer shall be informed of the
result.

Field Safety Corrective Action

 Article 35

The manufacturer, i.e., the authorized representative of the

manufacturer shall report to the Agency any technical or medical
reason leading to a systematic recall of medical devices of the same
type by the manufacturer, i.e., the authorized representative of the
manufacturer. Those reasons are any malfunction or deterioration in the
characteristics and/or performance of a medical device, as well as any
inadequacy in the instructions for use which might lead to or might have led to
the death of a patient or the user or to a serious deterioration in his state of
health. The Field Safety Corrective Measure rfers to also to recall or
withdrawal of a medical device from the market.

Removals from the market for purely commercial non-safety related

reasons shall not be considered to be the reasons referred to I para 1 of
this article.

In assessing the need for the Field Safety Corrective Measure , the
manufacturer, i.e., the authorized representative of the manufacturer
shall use the methodology described in the harmonized Risk
Management standard EN ISO 14971.

In case of doubt, there should be a predisposition to report and to

undertake a Field Safety Corrective Measure.

Field Safety Corrective Action should be notified to the customers via a

Field Safety Notice.

Where a Body in charge of conformity assessment was involved in the

conformity assessment procedure of the device, it is recommended to
inform them about the Field Safety Corrective Action, in accordance with
the Law.

Notifying the Agency of the Field Safety Corrective Action

Article 36

The manufacturer, i.e., the authorized representative of the

manufacturer shall submit to the Agency a report by manufacturer, i.e.,
the authorized representative of the manufacturer of the Field Safety
Corrective Action – using the format given in Annex 5 attached to this
Rulebook as an integral part thereof.
This notification should include all relevant documents necessary for the
Agency to monitor the Field Safety Corrective Action, in particular:

1) Exact name of the medical device, along with the group of generic
medical devices it belongs to;

2) Relevant parts from the risk analysis;

3) Background information and reason for the Field Safety Corrective

(including description of the device deficiency or malfunction,
clarification of the potential hazard associated with the continued use
of the device and the associated risk to the patient, USER or other
person and any possible risks to patients associated with previous
use of affected devices);

4) Description and justification of the action (corrective/preventive);

5) Advice on actions to be taken by the distributor and

the User;

6) method of recovery, disposal or modification of the medical device;

7) recommended patient follow up, (if needed);

8) a request to pass the Field Safety Notice to all those who need to be
aware of it within the organization and to maintain awareness over
an appropriate defined period;

9) a request for the details of any affected devices that have been
transferred to other organizations and a copy of the Field Safety
Notice to be passed on to the organization to which the device has
been transferred;
 10) affected medical devices and serial / lot / batch number range

11)In the case of an action concerning lots or parts of lots an

explanation why the other devices are not affected;

12) Identity of the manufacturer, i.e., the authorized representative of

the manufacturer. .

Along with the information referred to in para 1 of this article, the

Agency should also receive a copy of the Filed Safety Notice before the
issuance of the Field Safety Corrective Action as well as a draft version
of the FSCA .

Normally, the manufacturer, i.e., the authorized representative of the

manufacturer should allow a minimum of 48 hours for receipt of
comment on the Field Safety Notification unless the nature of the FSCA
dictates a shorter timescale (for inst. for serious public health threat).

It is recommended to copy the Field Safety Corrective Measure to the

Body in charge of conformity assessment if, indeed it was involved in
the conformity assessment procedure of that medical device.

Content of the Field Safety Notice

Article 37

The manufacturer, i.e., the authorized representative of the

manufacturer should use a distribution means ensuring the appropriate
organizations have received the Field Safety Notice (e.g. by confirmation
of receipt).
The Field Safety Notice should be on a company letterhead, be written in
the Serbian language and include the following:

1) a clear title, with “Urgent Field Safety Notice ” followed by the

commercial name of the affected product, a Field Safety
Corrective Measure identifier (e.g. date) and the type of action;

2) Specific details to enable the affected product to be easily identified

(e.g. type of device, model name and number, batch/lot or serial
numbers of affected devices and part or order number);

3) A factual statement explaining the reasons for the Field Safety

Corrective Action, including description of the device deficiency or
malfunction, clarification of the potential hazard associated with the
continued use of the device and the associated risk to the patient,
user or other person and any possible risks to patients associated
with previous use of affected devices;

4) Advice on actions to be taken by the user, including:

(1) identifying and quarantining the device,

(2) method of recovery, disposal or modification of device,

(3) recommended review of patients previous results or patient

follow up, (e.g. implants, in vitro diagnostic medical devices,

(4) timelines;

5) a request to pass the Field Safety Notice to all those who need to be
aware of it within the organization and to maintain awareness over
an appropriate defined period;

6) if relevant, a request for data on each affected medical device that

has been sent to other organizations to be forwarded to the
manufacturer, i.e., the authorized representative of the manufacturer
along with a copy of the Field Safety Notice that will be forwarded to
the organization to which the medical device has been sent;
7) If relevant, a request that the recipient of the Field Safety Notice
alerts other organizations to which incorrect test results from the use
of the devices have been sent (for example failure of diagnostic tests);

8) Confirmation that the Agency has been advised of the Field Safety
Corrective Action;

9) Any comments and descriptions that attempt to:

(1) serve to play down the level of risk in an inappropriate manner,

(2) advertise products or services should be omitted;

10) Contact point for customers how and when to reach the
designated person.

An acknowledgment form for the receiver of the Field Safety Notice might
also be included especially useful for Manufacturer’s control purposes.

A template for a Field Safety Notice is provided in Annex 6 attached to

this Rulebook as an integral part thereof.

IV RESPONSIBILITIES OF THE AGENCY

Article 38

The Agency should send an acknowledgement of receipt of the report to

the sender.

The Agency shall evaluate the report in consultation with the

manufacturer i.e., the authorized representative of the manufacturer,
advise as appropriate and intervene if necessary.

1. Actions on a report from users or other systems

Article 39
A report which appears to meet the criteria of article 12 of this Rulebook,
received by the Agency from a user reporting system or other source,
shall be copied by the Agency to the manufacturer, i.e., the authorized
representative of the manufacturer without delay or translation. In
doing so, patient confidentiality should be maintained pursuant to the
Law.

In the case referred to in para 1 of this article, the manufacturer, i.e., the
authorized representative of the manufacturer shall act in line with article
11-37 of this Rulebook.

2. Risk evaluation and subsequent actions

Risk evaluation by the Agency

Article 40

The risk assessment of an incident or Safety Corrective Measure

reported may include where relevant:

1) Acceptability of the risk, taking into account criteria such as: causality,
technical/other cause, probability of occurrence of the problem,
frequency of use, detectability, probability of occurrence of harm,
severity of harm, intended purpose and benefit of the product,
requirements of harmonized European, i.e., Serbian standards, the
Medical Device safety principles foreseen by the law and by-law
governing the basic requirements pertaining to medical devices,
potential users, affected populations, etc.;

2) Need for (what) corrective action

3) Adequacy of measures proposed or already undertaken by the

manufacturer, i.e., the authorized representative of the
manufacturer.
 Monitoring of subsequent measures by the manufacturer,
i.e., the authorized representative of the manufacturer

Article 41

The Agency normally monitors the investigation being carried out by the
manufacturer, i.e., the authorized representative of the manufacturer
and it may intervene at any time in consultation with the manufacturer
where practicable.

Aspects of the manufacturer's investigation which may be

monitored by the Agency include, for example:

1) course (direction the investigation is taking);

2) conduct (how the investigation is being carried out);
3) progress (how quickly the investigation is being carried out);
4) outcome (whether the results of device analysis are satisfactory).
Facts which may be needed in monitoring referred to in para 1 of this
article are:
1) the number of devices involved;

2) the length of time they have been on the market;

3) details of design changes which have been made.

In the course of the monitoring referred to in para 1 of this article, liaison

may be needed with:

1) the Body in charge of conformity assessment (involved in the

attestation leading to the CE marking);

2) users;

3) other Competent Authorities in the country and abroad;

4) other independent bodies, test houses, etc.

The Agency may also monitor experience with the use of devices of the
same kind (for instance, all defibrillators or all syringes), but made by
different manufacturers. It may then be able to take harmonized
measures applicable to all devices of that kind (for example, initiating
user education or suggesting re-classification).
 Agency actions

Article 42

For drug device combination products regulated under the medical device
regulations, pursuant to the Law, the Agency receiving the incident report
should establish a link with any other relevant bodies in the country and
abroad, if required .

The Agency should take coordinating action to ensure that an

investigation is carried out if several manufacturers, i.e., authorized
representatives thereof, are involved.

The Agency’s actions as a result of a report of the manufacturer or the

authorized representative of the manufacturer may include, for example:

1) no further action;

2) gathering more information (for example by commissioning

independent reports);

3) making recommendations to manufacturers (for example to improve

information provided with the device);

4) keeping other Competent Authorities in the country and abroad

informed (for example on FSCA and other actions to be taken);
5) consulting with the relevant Body competent for conformity
assessment on matters relating to the conformity assessment
of the medical device;

6) consulting the Ministry if it is considered that re-classification of

the device is necessary;

7) further user education;

8) further recommendations to users;

9) any other action to supplement the actions of the manufacturer

or the authorized representative of the manufacturer.

3. Dissemination of information by the Agency

 Article 43

The Agency gives careful consideration to the mode of communication,

the drafting and the dissemination of information within the vigilance
system.

The possible positive and negative effects of the information to be

disseminated should be considered when drafting advisory notifications
and when selecting the means and medium by which the message is
transmitted.

When the manufacturer has informed the Agency in advance of the start
of an FSCA this information should be held confidential by the Agency
until the information becomes public.

In general, preference should be given to notification communicated

directly to medical practitioner or health-care facilities concerned, over
communication to the public.

In some cases dissemination of information directly to the public may be

needed e.g. to suggest that patients contact their medical practitioner for
further, more specific advice.

Where appropriate, it is recommended that the Agency’s communication

includes a statement indicating that medical practitioners or other health-
care professionals should be consulted and that the information is
intended for medical professionals only.

The Agency pays special attention to the preparation of press statements.

The provisions of paras 1-7 of this article apply also to dissemination

of information by the manufacturer or the authorized representative of
the manufacturer in consultation with the Agency.

Interfaces with communication media should be coordinated wherever

practicable between the manufacturer or the authorized representative
of the manufacturer and the Agency.
 4. Completion of investigation

Article 44

The Agency shall place the final report by the manufacturer or the
authorized representative of the manufacturer on file and make any
other observations necessary. The files investigation may then be
endorsed as "complete”.

If the Agency itself conducts an investigation, the manufacturer or the

authorized representative of the manufacturer shall be informed of
progress and of the results.

The Agency should inform the manufacturer or the authorized

representative of the manufacturer when the investigation is complete, or
if no investigation is required by the Agency which does not preclude the
investigating as part of their ongoing quality assurance procedures.
Records of incident reports shall be retained by the Agency and the
manufacturer, i.e., the authorized representative of the manufacturer to
enable the investigation to be reopened if necessary, and to facilitate
systems for trend analysis.

5. The role of the Body in charge of conformity

assessments

Article 45

Even though the Body in charge of conformity assessments does not play
a key operational role in the Medical Device Vigilance System, the overall
performance of the Medical Device Vigilance System is supported by the
Body’s activity in the following areas:

1) Assessment of vigilance procedures;

2) Audit of the implementation of the vigilance procedures, and link

with other systems (e.g. Corrective and Preventive Action (CAPA) ,
FSCA);

3) Assessment of the impact of vigilance issues on the certification

granted;

4) Liaise with the Agency if required, (e.g. specific

investigations/audits based on a request of the National Competent
Authority).

6. The role of the user

 Article 46

There is no legal requirement obliging users to have an active role in the

Vigilance System, yet for the successful operation of the vigilance
system their involvement is vital.

The manufacturer, i.e., the authorized representative of the manufacturer

shall closely cooperate with the users in gathering data on suspected
incidents as well as in the implementation of any Field Safety Corrective
Action.

The Agency shall promote and encourage relationships between the

manufacturer, i.e., the authorized representative of the manufacturer and
his customers/users. The method of promotion is given in the Guide for the
manufacturer, i.e., the authorized representative of the manufacturer
which integrates the users into the vigilance system as given in Annex 7
attached to this Rulebook as an integral part thereof.
The Agency may also strengthen its promotional activities by offering
individual advice.

V Reporting serious adverse events in a clinical trial involving a

medical device

Article 47
If a serious adverse event occurs in the course of a clinical trial, the
sponsor, i.e., its authorized representative (hereinafter: sponsor) is
obliged to immediately notify the Agency of:

1) the serious adverse event;

2) the deficiency of the medical device that could lead to a serious

adverse event in the course of clinical trial in the absence of
appropriate action or intervention or under unfavorable conditions;

3) any new finding in connection with an already reported event.

In case of a multicenter clinical trial, the sponsor is obliged to report to

the Agency events referred to in para 1 of this article that have occurred
at any of the clinical trial locations, in line with this Rulebook.

Reports, i.e., incidents in connection with post-marketing, non-

interventional clinical trials of a medical device shall be subject to the rules
applicable within the vigilance system.

Article 48

The sponsor shall report to the Agency any serious adverse event that
may lead to immediate danger of death, serious injury or illness, thus
requiring urgent corrective actions for the benefit of other respondents,
users or third persons resulting in a new finding in connection to such a
serious adverse event, within two calendar days from the day the
sponsor becomes aware of the event or the finding that is subject to
reporting.

The sponsor shall report to the Agency any other events referred to in
article 47 para 1 of this Rulebook within seven calendar days from the day
the sponsor becomes aware of the event or the finding that is subject to
reporting.

The sponsor of a clinical trial is obliged to provide and maintain a system

for receiving reports on adverse events from the researcher.
The healthcare professional participating in a clinical trial in the capacity
of a researcher shall report the events referred to in article 47 para 1 of
this Rulebook to the sponsor, in accordance with the approved Clinical
Trial Protocol within three calendar days at the latest from the day he
becomes aware of the event or the finding that is subject to reporting.
Exceptionally, other deadline may apply if so stipulated in the approved
Clinical Trial Protocol.

Article 49

A form for reporting the event referred to in article 47 para 1 of this

Rulebook shall be posted on the Agency’s website. The form shall be
filled out in line in accordance with the instructions the Agency shall also
post on its webpage. Other forms or formats may be used as well,
provided they contain the elements listed in the instructions.
.

VI TRANSITIONAL AND FINAL REMARKS

Article
50

On the day this Rulebook enters into force the Rulebook on the method
of reporting, gathering and monitoring adverse reactions to medical
devices (Official Gazette of the RS No. 64/11 and 21/14) shall cease to
apply.

Article
51

This Rulebook shall enter int force on the day it is published in the
“Official Gazette of the Republic of Serbia”.

No. 110-00-450/2018-06
In Belgrade, 14 January 2019

Minister,
Dr. Zlatibor Lončar, in person