workers shall register to the National Materiovigilance Center by b1w565l3

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									                                MINISTRY OF HEALTH
Pursuant to Article 138 of the Law on Medicinal Products and Medical Devices (Official
  Gazette of the Republic of Macedonia No. 106/2007), the Minister of Health hereby
                                       adopts a
  RULEBOOK ON THE MANNER OF REPORTING ADVERSE EFFECTS
 DURING THE USE OF MEDICAL DEVICE, TYPES OF REACTIONS THEY
CAUSE, THE ACTIONS OF HEALTH WORKERS AND SUPPLIERS, AS WELL
  AS THE MANNER OF ORGANIZING THE SYSTEM OF MONITORING
     ADVERSE EFFECTS AND REACTIONS TO MEDICAL DEVICES
                                I. GENERAL PROVISIONS
                                          Article 1
This Rulebook shall stipulate the manner of reporting adverse effects during the use of
medical device, types of reactions they cause, the actions of health workers and suppliers,
as well as the manner of organizing the system of monitoring adverse effects and reactions
to medical devices.


                                          Article 2
Certain terms used in this Rulebook shall have the following meanings:
    1) “Adverse reactions(effects)” to medical device shall mean any adverse and
harmful response caused by the medical device that occurs when using a medical device
under the prescribed conditions of use or application of medical device during the clinical
trial;
   2) “Serious adverse reaction” to medical device shall mean any adverse reaction that
results in death, is life-threatening, requires patient hospitalization or prolongation of
existing hospitalization, results in persistent or significant disability or incapacity, or in
congenital anomaly/birth defect;
   3) “Unexpected adverse reaction” to medical device shall mean any unexpected and
adverse reaction whose nature, weight and outcome are not consistent with the described
characteristics of the medical device or they are not described in the brochure of the
examiner;
   4) “Adverse event” shall mean adverse reaction that occurred during the use of the
medical device and for which a cause-and-effect relation with the use of medical devices
need not be proven;
   5) “Serious adverse event” shall mean any adverse reaction that results in death, is life-
threatening, requires inpatient hospitalization or prolongation of existing hospitalization,
results in persistent or significant disability or incapacity, or in congenital anomaly/birth
defect;
   6) “Interaction” shall mean change in the properties of medical device caused by the
simultaneous use of other medical device and/or drug, food or other substances;
   7) “Suspected medical device” shall mean any medical device for which there is a
reasonable doubt that it has caused adverse reaction or interaction;
   8) “Clinical trial of medical device” shall mean a trial that is performed on people in
order to determine or verify the clinical, pharmacological, pharmacodynamical effects of
one or more tested medical devices, or the identification of each effect to one or more
tested medical devices, in order to establish its/their safety or efficiency;
   9) “Interventional postmarketing clinical trial of medical device” shall mean a trial
in which medical device is used according to the conditions of the marketing
authorisation for that medical device and for which additional diagnostic procedures and
monitoring procedures defined in the protocol for clinical trials of medical devices are
needed;
   10) “Non-interventional postmarketing clinical trial of medical device” shall mean
a trial in which medical device is used according to the conditions of the marketing
authorisation for that medical device, where the selection of patients is not determined in
advance in the protocol for clinical trial and belongs to the routine practice of regular
manner of treating, the medical device being clearly separated from the patient's decision
to join the trial. Additional diagnostic procedures or monitoring procedures are not
applied, and the obtained results are analysed using the epidemiological methods;
   11) “International day of release of medical device” (hereinafter: IBDs) shall mean
the date of first marketing authorisation for the new medical device, and every holder of
the authorization in any country in the world should possess that authorization;
   12) “Data entry termination” (hereinafter: DLP) shall mean the date of termination
of data entry processed for the periodical report on the medical device safety that is based
on IBDs and usually refers to a period of six months;
   13) “Abuse of medical device” shall mean any permanent or periodical, intentional
excessive use of medical device, accompanied by harmful physical or psychic effects;
  14) “Disapproved application of medical device” shall mean any use of medical
device in therapeutic indication or manner of use which is not listed in the properties of
medical device or which is not approved;
   15) “Spontaneous reporting” shall mean voluntary reporting of adverse reactions to
the medical device placed on the market that occurred during the use of that medical
device by health institutions and health workers;
   16) “Mandatory reporting” shall mean reporting of serious adverse reactions to the
medical device, reported during the clinical trial or in the period after gaining the
authorisation by the manufacturer of that medical device, the sponsor of the clinical trial,
the researcher, the competent institution in which the clinical trial is conducted
(hereinafter: the applicant for mandatory packaging), and the holder of the authorisation;
  17) “New medical device” shall mean medical device used less than five years, or
medical device used in a while and which has a new manner of use or new indication;
   18) “Protocol of the clinical trial” shall mean a document which contains the
objectives, plan, methodology of the trial, method of data processing and organization of
clinical trials in accordance with the principles of good clinical practice.


                                         Article 3
The reporting adverse effects during the use of medical device, types of reactions they
cause, the actions of health workers and suppliers, as well as the manner of organising the
system of monitoring adverse effects and events of medical devices is accomplished
through the National Centre for Medical Devices Adverse Reactions/Events Monitoring
(hereinafter: National Materiovigilance Centre) and the Agency for Medicinal Products
(hereinafter: the Agency).


      II. MATERIOVIGILANCE IN CLINICAL TRIAL OF MEDICAL DEVICE
                                          Article 4
The applicant for clinical trial of medical device (hereinafter: the applicant) for which an
authorization for conducting clinical trial or interventional postmarketing clinical trial is
gained, shall apply to the National Materiovigilance Center:
   1) serious, unexpected adverse reactions to medical devices that occurred during the
clinical trial;
   2) serious, expected adverse reactions to medical devices that occurred during the
clinical trial, which have an increased incidence of appearance (which is clinically
significant);
  3) serious, unexpected adverse reactions to medical device which is used as active
control, for which the holder of the authorization for medical devices marketing in the
Republic of Macedonia is notified.
If multicentre clinical trial is conducted in the Republic of Macedonia, the applicant shall
report the adverse reactions to medical devices referred to in paragraph 1 of this Article
that appeared in any of the countries in which the clinical trial is implementing.


                                          Article 5
For serious, unexpected adverse reactions that occurred during the clinical trial of
medical devices which result in death or life-threatening, the applicant shall immediately
report the Agency, the National Materiovigilance Centre and Ethics Commission, at least
24 hours from the initial awareness (hereinafter: the initial application).
The application by the applicant is done by submitting a complete form, no later than
seven days from the date of submission the initial application to the National
Materiovigilance Centre.
Serious, unexpected adverse reactions which do not result in death or which are not life-
threatening, are reported by the applicant no later than 15 days from the date of first
reporting for such adverse reaction, to the National Centre for pharmacovigilance.
The applicant shall annually submit to the National Centre for pharmacovigilance
periodical report for all adverse reactions noticed during the clinical trial of medical
devices, and after the clinical trial he/she shall submit completed report for the safety of
tested medical devices.


                                          Article 6
The initial application shall contain information especially for:
1) patient’s identification designation (the examinee) and his/hers initials;
2) name and catalogue designation of medical devices;
3) manifested adverse reaction;
4) identification designation for clinical trial and
5) name and address of the applicant.


                                           Article 7
The complete report shall contain data for:
  1) the clinical trial: the identification designation for the clinical trial (protocol
  number), the most important data for clinical trial (ex. phase and purpose of the trial,
  medical devices that are tested, indication), number of the authorisation for medical
  devices marketing;
  2) the patient i.e. the examinee: initials, identification designation (code), age, sex,
  weight, height, country;
  3) the suspected medical device: name and catalogue designation of the medical
  devices, number of series, indication, manner of application, date and starting and
  ending time for the use of medical device;
  4) the adverse reactions;
  5) the simultaneous use of other medical devices and/or medicinal products, including
  dietary and other products with the same data as well as the suspected medical device;
  6) the examiners: name and surname, telephone number, occupation and specialisation,
  signature and date of the application and
  7) the applicant: name and address, date of first reporting of serious unexpected adverse
  reactions to the sponsor.


                                           Article 8
For adverse reactions of Article 7, item 4 of this Rulebook the following information
shall be indicated:
  1) detailed description of all reactions (signs and symptoms) indicating the site of
  manifestation, the severity of the manifestation, and the criteria on the basis of which
  the reaction is considered serious;
  2) date and time of beginning and end of the reaction;
  3) symptomatic therapy and other measures taken due to manifested adverse reaction;
  4) information for the presence or absence of adverse reactions after termination of the
  use of medical device and reuse that medical device;
  5) information for the outcome of the manifested reaction (fatal outcome data for the
  cause of death, comment of the cause-and- effect relation with the suspected medicinal
  product and the findings “post-mortem” - when available, permanent damage, inpatient
  hospitalisation or prolongation of existing hospitalisation, risk to life or recovery
 without consequences) and
 6) information significant for assessment of adverse reaction (ex. history of disease,
 laboratory findings and results of diagnostic tests, allergies, pregnancy, abuse of drugs
 or alcohol, family anamnesis.


       III. MATERIOVIGILANCE OF MEDICAL DEVICES IN CIRCULATION


                                           Article 9
Health institutions and health workers shall register to the National Materiovigilance
Center:
 1) adverse reactions or events of new medical devices or in case of suspicion for
 adverse reactions or events and reactions/events that are not serious;
 2) serious and unexpected adverse reactions to medical devices (even if not of a serious
 nature) that are in use for more than five years or in case of suspicion of these reactions;
 3) information about the increased incidence of manifestation of the expected response,
 clinically significant interactions, abuse of medical devices, drug overdose, use during
 pregnancy and lactation, lack of efficiency as well as information for medical error.
In the cases of paragraph 1, item 3 of this Article, it is efficient to exist suspicion that the
used medical device probably caused adverse reaction or event to the patient.


                                          Article 10
The reporting of adverse reactions or events relating to materiovigilance of medical
devices in public can be made by the holder of the authorisation after the approval by the
Agency.
The reporting of materiovigilance of paragraph 1 of this Article should be objective.


                                          Article 11
Adverse reactions to medical devices or suspicion of the adverse reaction of medical
devices by health institutions and health workers are reported by submission of an
application for adverse reactions to medical devices, which is given in Appendix 1, which
is an integral part of this Rulebook.


                                          Article 12
The application of adverse reactions to medical devices shall contain data on:
   1) the patient (initials, age and sex) and adverse reaction (date of starting the reaction,
description of clinical manifestation, outcome and possible treatment, association
between adverse reaction and suspected medical device);
  2) suspected medical device and the course of adverse reaction during termination
and/or reuse of suspected medical device;
  3) simultaneous use of other medical device or drug with the starting date of the use
and the history of the patient;
  4) the manufacturer of suspected medical device (name and country, number of series)
and the applicant (date of registration, origin and type of application, name and surname,
contact telephone number, occupation).


                                        Article 13
The data for the applicant for reporting adverse reaction to the medical device and the
data for the patient in accordance with the Law are considered as classified information.


     IV. MANNER OF ORGANISING THE SYSTEM OF MATERIOVIGILANCE
                                        Article 14
The system for collecting new data on the safety of medical device, assessment of
adverse reactions and events, information and interactions and abuse of medical device
and proposing appropriate measures to be taken in the period the authorization validation
for medical device marketing or during the clinical trial of that medical device is
performed by the National Materiovigilance Center, which establishes and maintains a
system of materiovigilance in accordance with the Law.


                                        Article 15
The National Materiovigilance Centre shall carry out the following activities, in
performing the activities of Article 14 of the Rulebook:
  1) collecting, processing and evaluating the data for adverse reactions to medical
devices and adverse events relating to the use of medical devices during clinical trial or
medical devices marketing i.e. interventional postmarketing clinical trial of medical
device;
   2) processing and evaluating of periodical reports on medical devices safety, which are
obtained from the holder of the authorization for medical devices marketing;
    3) collecting, processing and assessing data from interventional postmarketing clinical
trial of medical device which are obtained from the holder of the authorization for
medical devices marketing;
   4) immediately reporting of the holder of the authorization for medical devices
marketing for serious drug adverse reactions, no later than 15 days from the date of
receipt of this information;
   5) immediately reporting of the Agency and health workers for serious adverse
reactions to the medical device and for significant changes in the safety of medical
devices, no later than 15 days from the date of receipt of this information;
  6) encourage health professionals to report adverse events and adverse reactions to
medical devices i.e. the suspicion for that medical device;
  7) maintaining a database of information collected in the system of materiovigilance
which are available to the public and the authorities in the country and abroad;
  8) exchange of information collected in the system of materiovigilance with the
competent authorities for materiovigilance in other countries.
The National Center shall submit to the Agency a report on the reported adverse reactions
to the medical device every three months and an annual report on reported adverse drug
reactions.


                                          Article 16
On the basis of the collected data on adverse reactions to medical devices during the
clinical trial of medical device, the National Materiovigilance Center can propose the
following measures:
1) changes in the protocol of clinical trial of medical device;
2) implementation of control over the clinical trial of medical device;
3) termination of clinical trial of medical device.


                                          Article 17
The holder of the authorisation for medical devices marketing, according to the Law for
implementing the system of materiovigilance, shall determine a person responsible for
materiovigilance which:
   1) shall organize and maintain the system of collecting, processing, assessment and
storage of data on all adverse events or reactions to the medical device reported to the
manufacturer of medical device, to the holder of the authorization irrespective of the
geographical origin of the data source;
   2) shall propose to the National Materiovigilance Center measures to be implemented
for security reasons, shall provide complete and timely responses and required
information for safety assessment of the medical device and health risk during its use;
  3) shall notify the National Materiovigilance Center for all serious adverse reactions to
medical device i.e. suspected adverse reactions that occurred in the territory of the
Republic of Macedonia or that have been reported outside the territory of the Republic of
Macedonia;
   4) shall report all serious adverse reactions to medical devices during interventional
postmarketing clinical trial (pharmacoepidemiological examination), according to item 3
of this Article;
   5) shall notify the National Materiovigilance Center for all abuse and uncontrolled use
of medical device that have an impact on the assessment of the risk/benefit;
   6) shall submit periodical report on the safety of medical device to the National
Materiovigilance Center in which are outlined all other adverse reactions suspected to be
associated with the use of medical device;
    7) shall prepare a report to the National Materiovigilance Center for activities referred
to in items 1 - 6 of this Article in accordance with the Law and this Rulebook;
   8) shall provide additional information at the request of the Agency that are necessary
to assess the safety of medical device and health risk that needs to be given in its entirety
and on time, accompanied by the information on the quantity sold and prescribed medical
devices to which the information refers to.


                                        Article 18
The person responsible for manufacturer’s pharmacovigilance, during the renewal of the
medical device marketing to the Agency should submit all data on adverse reactions
and/or events that are registered as medical device within a time period of gaining the
authorisation for marketing in the Republic of Macedonia.
The report referred to in paragraph 1 of this Article shall contain data on adverse
reactions and/or events to medical device that is registered in the Republic of Macedonia
and in all countries in which the device is approved for marketing.


                                        Article 19
Upon receipt of an application for a serious adverse reaction to medical devices that can
have serious consequences for human health, the holder of the authorization for medical
device marketing shall immediately submit to the Agency proposal for emergency safety
measures.
If the Agency does not respond within 24 hours of receipt of the application referred to in
paragraph 1 of this Article, the holder of the authorization shall impose emergency safety
measures in accordance with the regulations which stipulate the receipt of the
authorization for medical devices marketing.
The emergency safety measures in paragraph 1 of this Article shall apply to:
 1) temporary or permanent withdrawal of medical devices from the market;
 2) change in the instructions for use of medical device, and introduction of
 contraindications, warnings or precautions, narrowing of the indication area and
 3) informing the health workers and patients about the newly discovered risk during the
 use of medical device.


                                        Article 20
This Rulebook shall enter into force on the eighth day from the date of its publication in
the Official Gazette of the Republic of Macedonia.
No. 15-5035/1
4 June 2009                                                     Minister,
     Skopje                                                     Dr Bujar Osmani

								
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