EUROPEAN COMMISSION
DIRECTORATE GENERAL for HEALTH and CONSUMERS
Consumer Affairs
Cosmetics and Medical Devices
MEDDEV 2.7/3
December 2010
GUIDELINES ON MEDICAL DEVICES
CLINICAL INVESTIGATIONS:
SERIOUS ADVERSE EVENT REPORTING
UNDER D IRECTIVES 90/385/EEC AND 93/42/EEC.
The prent guidelines are part of a t of guidelines relating to questions of application of EU-Directiv
es on MEDICAL DEVICEs. They are legally not binding. The guidelines have been carefully drafted through a process of intensive consultation of the various interested parties (competent authorities, Commission rvices, industries, other interested parties) during which intermediate drafts were circulated and comments were taken up in the document. Therefore, this document reflects positions taken by reprentatives of interested parties in the medical devices ctor.
The guidelines incorporate changes introduced by Directive 2007/47/EC amending Council Directive 90/385/EEC and Council Directive 93/42/EEC.
1. OBJECTIVE
This guidance defines Serious Adver Event (SAE) reporting modalities and includes a summary tabulation reporting format1. Its objective is to contribute to the notification of SAEs to all
concerned National Competent Authorities (NCAs2) in the context of clinical investigations in
line with the requirements of Annex 7 of Directive 90/385/EEC and Annex X of Directive
93/42/EEC, as amended by Directive 2007/47/EC.
According to annex 7 of Directive 90/385/EEC and to annex X of Directive 93/42/EEC: “All
rious adver events must be fully recorded and immediately notified to all competent
authorities of the Member States in which the clinical investigation is being performed."
2. SCOPE
The reporting modalities and format t out in this guidance apply to pre-market3 clinical
investigations4-5 conducted with:
a.Non-CE marked devices,
a.b.C E marked devices ud outside the intended u(s) covered by the CE marking.
The tabular format featured in the Appendix needs to be updated for each reportable event or for new findings/updates to already reported events. It shall be transmitted to all NCAs where the
clinical investigation is being performed.
3. DEFINITIONS (from ISO/FDIS 14155)
Adver Device Effect (ADE)
Adver event related to the u of an investigational medical device.
NOTE 1- This includes any adver event resulting from insufficiencies or inadequacies in the
instructions for u, the deployment, the implantation, the installation, the operation, or any
malfunction of the investigational medical device.
NOTE 2- This includes any event that is a result of a u error or intentional misu.
Adver Event (AE)
Any untoward medical occurrence, unintended dia or injury or any untoward clinical signs
(including an abnormal laboratory finding) in subjects, urs or other persons whether or not
related to the investigational medical device.
1 A template for individual reporting of SAEs is under preparation to harmonize individual SAE forms in ca NCAs require individual reporting for the SAEs occurring within their jurisdictions. Further revisions of the template documents may become necessary in line with the forthcoming correspo
nding GHTF-Guidance.
2 For the purpo of this guidance," NCAs" encompass the National Competent Authorities of the EU, the EEA and of Switzerland and Turkey.
3 A specific guidance on Post Market Clinical Follow-Up Studies is in preparation.
4 - This includes pre-market clinical investigations:
which started prior to 21 March 2010 and are continued after that date. [Note: reporting of SAE as covered in this guidance only started on 21 March 2010 with the implementation of Directive 2007/47/EC and is SAEs that occurred prior to 21 March 2010].
- For pre-market clinical investigations involving CE marked comparator devices, SAEs occurring in or to subjects that are in the comparator arm of an investigation shall also be reported in accordance with the guidelines.
5 Where the right to bear the CE marking has been obtained before the end of the clinical investigation, the SAE reporting continues until completion of the investigation, according to the clinical investigation plan.
NOTE 1: This includes events related to the investigational device or the comparator.
NOTE 2: This includes events related to the procedures involved (any procedure in the clinical
investigation plan).
NOTE 3: For urs or other persons this is restricted to events related to the investigational
medical device.
Device deficiency
什么报国Inadequacy of a medical device related to its identity, quality, durability, reliability, safety or
performance, such as malfunction, misu or u error and inadequate labeling.
Investigational medical device
Medical device being assd for safety or performance in a clinical investigation NOTE: This includes medical devices already on the market that are being evaluated for new intended us, new populations, new materials or design changes.
Serious Adver Device Effect (SADE)
Adver device effect that has resulted in any of the conquences characteristic of a rious
adver event.
Serious Adver Event (SAE)
Adver event that:
中国励志人物素材
a) led to a death,
b) led to a rious deterioration in health that either:
1) resulted in a life-threatening illness or injury, or
2) resulted in a permanent impairment of a body structure or a body function, or
3) required in-patient hospitalization or prolongation of existing hospitalization, or
4) resulted in medical or surgical intervention to prevent life threatening illness or injury
or permanent impairment to a body structure or a body function.
山洞探险c) led to fetal distress, fetal death or a congenital abnormality or birth defect.
NOTE 1: This includes device deficiencies that might have led to a rious adver event if a)
suitable action had not been taken or b) intervention had not been made or c) if circumstances had been less fortunate. The are handled under the SAE reporting system.
NOTE 2: A planned hospitalization for pre-existing condition, or a procedure required by the
Clinical Investigation Plan, without a rious deterioration in health, is not considered to be a
rious adver event.
Unanticipated Serious Adver Device Effect (USADE)
Serious adver device effect which by its nature, incidence, verity or outcome has not been
identified in the current version of the risk analysis report.
NOTE: Anticipated: an effect which by its nature, incidence, verity or outcome has been
previously identified in the risk analysis report多汁牧草
4. REPORTABLE EVENTS UNDER ANNEX 7 AND ANNEX X OF DIRECTIVES 90/385/EEC AND 93/42/EEC RESPECTIVELY.
For the purpo of this guidance and bad on the definitions above, the following events are
considered reportable events in accordance with Annex 7, ction 2.3.5 and Annex X, ction 2.3.5 of the above mentioned Directives:
-any SAE,
-any Investigational Medical Device Deficiency that might have led to a SAE if a) suitable action had not been taken or b) intervention had not been made or c) if circumstances had
been less fortunate
-new findings/updates in relation to already reported events.
Reportable events occurring in Third Countries6 in which a clinical investigation is performed under the same clinical investigation plan, have to be reported in accordance with this guidance.
5. REPORT BY WHOM.
Reportable events have to be reported by the sponsor of the clinical investigation, which could be the manufacturer (MFR), the authorized reprentative (AR) or another person or entity7-8.
6. REPORT TO WHOM.
Reportable events must be reported at the same time to all NCAs where the clinical investigation has commenced9-10 using the summary tabulation featured in the Appendix.
A list of clinical investigation contact points within the NCAs is published at the Commission's
homepage.
7. REPORTING TIMELINES
7.1 Report by sponsor to NCAs.
The sponsor must report to the NCAs where the clinical investigation has commenced: • a SAE which indicates an imminent risk of death, rious injury, or rious illness and that requires prompt remedial action for other patients/subjects, urs or other persons11 or a new
finding to it: immediately, but not later than 2 calendar days after awareness by sponsor of a张继的资料
new reportable event or of new information in relation with an already reported event.
惠崇拼音•any other reportable events as described in ction 4 or a new finding/update to it: immediately, but not later than 7 calendar days following the date of awareness by the sponsor
of the new reportable event or of new information in relation with an already reported event.
6 Countries other than Switzerland, Turkey and tho belonging to the EU and the EEA.
7 Note: Member States may also require parate reporting by clinical investigators/medical professionals.
8 Note: SAEs concerning CE marked devices (e.g. comparators) which meet the vigilance reporting criteria may also need to be handled under the post-market surveillance/vigilance system.
9 For the purpo of this guidance, an investigation is considered to have commenced in an individual Member State when the sponsor is authorid to start the investigation in accordance with the notification procedures in that Member State.
10 Note: Member States may also require parate reporting to the Ethics Committee(s) and/or parate reporting to the other clinical investigators/study centers involved in the clinical investigation.
11This includes:
•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 Dia (CJD). The concerns may be
identified by either the NCA or the MFR.
•the possibility of multiple deaths occurring at short intervals.
7.2 Report by the investigator to the sponsor
The sponsor shall implement and maintain a system to ensure that the reporting of the reportable events will be provided by the investigator to the sponsor in acceptable timely conditions, but not later than within 3 calendar days after the occurrence of the event.
In some cas, a different periodicity or different modalities12 may be agreed by the participating
NCAs according to the investigational design and to the pathology under clinical investigation. This would allow adequate provision for clinical investigations (e.g. palliative oncology…) in which SAE frequency is expected to be high due to progression of the dia. This needs to be agreed between the sponsor and relevant NCAs.
8. REPORTING FORM
九女山The reporting form template for the summary SAE tabulation is given in the Appendix of this
document.
The table gives a cumulative overview of the reportable events per clinical investigation and will be updated and transmitted to participating NCAs each time a new reportable event or a new
finding to an already reported event is to be reported. More detailed information has to be
provided on request of an NCA.
The sponsor shall identify the new/updated information in the status column of the tabular form featured in the Appendix as:
a = added = new reportable event;
m = modified = new finding/update to an already reported event;
u = unchanged.洋跃进
Changes in a line should be highlighted in bold and/or color in the respective column.
The reporting form is study specific and covers only a given clinical investigation, defined by a distinct clinical investigation plan. English is the recommended language for the reporting form.
The report should be nt by email preferably in Excel or equivalent format to the participating
NCAs.
R EFERENCES:
1.Council Directive 90/385/EEC of 20 June 1990 on the approximation of the laws of the Member States relating
to active implantable medical devices, last amended by Directive 2007/47/EC.
2.Council Directive 93/42/EEC of 14 June 1993 concerning medical devices, last amended by Directive
2007/47/EC.
3.ISO/FDIS 14155:2010 Clinical investigation of medical devices for human subjects – Good clinical practice 12 in line with Annex 7.2.3.5 of Directive 90/385/EEC and Annex X.2.3.5 of Directive 93/42/EEC
