Guidelines on Notification for Clinical Investigation of Medical
Devices in Norway
December 2005
Contents:
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Introduction
Purpose of the Clinical Investigation
The Legal Framework and Standard pertaining to the Clinical Investigation of
Medical Devices
Terminology
Procedure for Notification
Further Information concerning the submission
Contents of a Notification
1.
2.
3.
4.
Information about the manufacturer
Information on the medical device
Information on the conditions under which the investigation is to be carried out
Information on the clinical investigation
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Introduction
Being a signatory to the EEA agreement, Norway has the same rights and obligations
concerning medical devices as other member states of the European Union. The Act and
Regulation relating to medical devices implement the provisions of the Active
Implantable Medical Devices Directive 90/385/EEC, the Medical Devices Directive
93/42 EEC and Directive 98/79/EC on in vitro Diagnostic Medical Devices. These sets
of regulations establish systems under which manufacturers must submit to the
Norwegian Competent Authority information about clinical investigations carried out in
Norway.
A key principle of the legal framework concerning medical devices is to ensure that each
medical device in use is appropriate, which entails making certain that the medical device
shall achieve its intended purpose as designated by the manufacturer, and that its use does
not entail an unacceptable risk to the patient, health personnel or to any other.
Medical devices shall bear the CE marking of conformity to indicate that their
manufacture conformed to the Regulations, and that they complied with all relevant
Essential Requirements for items in their category.
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Certification of most medical devices require a Notified Body to carry out verifications,
investigations and evaluations on such devices in accordance with the Regulations. Such
Bodies are independent Bodies having the necessary competence, and are designated by
the Competent Authorities of each individual country.
In order to demonstrate compliance with the relevant Essential Requirements, it will
sometimes be necessary to provide data in form of specifically designed clinical
investigations.
According to §§ 4-5, 5-6 of the Regulations of December 15th 2005 No. 1690 relating to
medical devices, notifications for clinical investigations of medical devices shall be sent
to the Directorate for Health and Social Affairs, P.O.Box 7000 St. Olavs plass, N-0130
Oslo.
It must be noted that some clinical investigations may also require assessment/approval
by or notifications to other authorities. Further information on this issue may be found at
the homepage of the Regional Medical Research Ethics Committee:
http://www.etikkom.no/E/index.htm
Purpose of the Clinical Investigations
The purpose of conducting clinical investigations of a medical device, is to ascertain and
record that the performance claimed by the manufacturer can be adequately
demonstrated, and that the device is judged by a clinical expert to be safe to use on
patients, taking into account any risks associated with the use of the device when
weighed against the expected benefits.
A clinical investigation may be undertaken only when necessary documentation
concerning performance and safety can not be obtained by other means than investigating
the device in human subjects.
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The Legal framework and Standards pertaining to the Clinical
Investigation of Medical Devices
Clinical investigations are subject to:
 Act of 12 January 1995 No. 6 relating to medical devices
 Regulations of December 15th 2005 No. 1690 relating to medical devices
 NS-EN ISO 14155 Clinical investigation of medical devices for human subjects
 The Helsinki Declaration of 1964 and revisions thereof.
Clinical activities involved in such investigations are subject to
Act of 30 March 1984 No. 15 relating to public inspection of health services.
Satisfactory provisions for compensation shall be made against possible injuries that may
result from clinical investigations to the patients and/or volunteers, on whom such
investigations of medical devices are carried out (ref. NS-EN ISO 14155).
For further information on the requirements such clinical investigations should meet,
please refer to: Directive 90/385/EEC relating to active implantable medical devices and
Directive 93/42/EEC concerning most other medical devices. These documents may be
viewed at the homepage of the Directorate for Health and Social Affairs:
http://www.shdir.no/
Terminology
In the present document, the following technical terms are used as defined in NS-EN ISO
14155 Standard, concerning the clinical investigations of medical devices in human
subjects:
Clinical Investigation: any designed and planned systematic study in human subjects
undertaken to verify the safety and/or performance of a specific device
Clinical Investigator: individual and/or institution responsible for the conduct of a
clinical investigation who and/or which takes the clinical responsibility for the well-being
of the subjects involved
Principal Clinical Investigator: clinical investigator responsible for the organization of
the clinical investigation at one site
Subject: individual who participates in a clinical investigation, either as a recipient of the
device under investigation or as a control
Sponsor: individual or organisation who or which takes responsibility for the initiation
and/or implementation of a clinical investigation
Monitor: individual appointed by the sponsor responsible for assessing the investigator’s
compliance with the clinical investigation plan and for performing source-data
verification
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Procedure for notifications
Notifications for clinical investigations of medical devices should accord with Directive
90/385/EEC Article 10 and Annex VI and Directive 93/42/EEC Article 15 and Annex
VIII (ref. Regulation relating to medical devices, §§ 4-5, 5-6).
Such a notification should include all the relevant information about the clinical
investigation to be undertaken, as described in NS-EN ISO 14155 Clinical investigation
of medical devices for human subjects. The notification should be accompanied by a
favourable opinion of the proposed clinical investigation by the relevant Regional
Medical Research Ethics Committee (ref. Regulation relating to medical devices, § 4).
If in the view of the Directorate for Health and Social Affairs there are reasons to raise
grounds for objection to the investigation in question (ref. medical devices Act §4), the
manufacturer/sponsor and the Clinical Investigator will be notified of the Competent
Authority’s objections within sixty days (of having received the duly completed
notification) (ref. Regulation relating to medical devices §§ 4-5, 5-6). The Directorate for
Health and Social Affairs may raise objections if there are reasonable grounds to suspect
that risks to public health or safety are unjustifiable, e.g:
 a device does not satisfy relevant Essential Requirements
 the clinical investigation is not subject to controls equivalent to the requirements of
the relevant European Standard NS-EN ISO 14155
 there exists professional opinion on the proposed clinical investigation that the riskbenefit analysis given by or on behalf of the manufacturer is inaccurate and that the
investigation would represent a significant safety hazard to the patient or user
 where insufficient information has been submitted to enable a proper assessment to be
made
An objection by the Directorate for Health and Social Affairs to commence a clinical
investigation is appealable as provided in Act of 10 February 1967 No. 00 relating to
procedure in administrative cases, and as amended by Act of 19 June 1969 No. 54.
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Further Information concerning Submission of a Notification
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A notification for a clinical investigation of a medical device should be sent to the
Directorate for Health and Social Affairs , either by the manufacturer, or his
authorised representative in the EEA
The manufacturer or his representative should first seek the formal opinion of the
proposed clinical investigation by the Regional Medical Research Ethics Committee
for the region where the Clinical Investigator, or the Principal Clinical Investigator is
located. On requesting such formal opinion, in addition to a notification set up as
shown below, one should also send in a duly completed application form available
from the Regional Medical Research Ethics Committee. For further information, do
please visit: http://www.etikkom.no/E/index.htm
The Regional Medical Research Ethics Committee will assess the points 3 and 4 of
the notification as described below, in the light of information provided by the points
1 and 2
The notification, together with the recommendation of the Regional Medical
Research Ethics Committee should be sent to the Directorate for Health and Social
Affairs. If deemed necessary, the Directorate for Health and Social Affairs may
request further information
The Sponsor and the Clinical Investigator of the proposed clinical investigation shall
be informed of the decision of the Directorate for Health and Social Affairs within
sixty days after the receipt of the notification.
Contents of a Notification
To facilitate dealing with your notification, do please base it on the template given below.
Indicate whether the applicant wishes to withhold certain information from the public.
Openness in Public Administration Act of 19 June 1970 No. 69 generally applies.
Notifications should preferably be in Norwegian or in English. However, all the clinical
information patients are legally entitled to know (the written “patient information form”),
must be in Norwegian.
1. Information about the manufacturer
a. Date of the submission, and whether there has been previous submissions for clinical
investigations in Norway of the same device
b. Name, address, etc. of the applicant; please indicate whether the applicant is the
Manufacturer or his Authorised Representative in the EEA area
c. Name, address, etc. of the Sponsor
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d. Information on any certificates the present medical device has received, or the
modifications thereto, issued by a competent third party, such as a Notified Body
e. Information on the person who is in charge of the clinical investigation at the
Manufacturer
f. Information on the person who is in charge of the clinical investigation at the
Sponsor.
2. Information on the medical device
a. Generic and type-specific information about the medical device, and its risk category
(I, IIa, IIb, III or active implantable; for further information on the classification, do
please see the Annex IX to Directive 93/42/EEC)
b. All relevant information about the medical device;
1. A complete and illustrated technical description of the device
2. A description of its components
3. List of materials used in construction of the device; particulars of the material
used on its surfaces, as well as reference to standards for materials coming into
contact with the body
4. Technical details of its mode of action
5. Function of the medical device, and its mode of action
6. Technology the medical device represents
7. General method of production, specific method of sterilisation, if relevant
8. Description of packaging required to keep the device sterile, and to protect its
fragile components, if relevant
9. A risk-analysis, together with an account of measures taken to minimise any
existing risks (for details on risk-analysis, please see Standard NS- EN ISO 14971
10. Reference to the standards used for conformity assessments; standards or parts
thereof, that have not been used for such assessments, and an account on how the
Essential Requirements are met in the latter case
11. Identification of any tissues of animal origin incorporated within the device,
together with information of sourcing and collection of such tissue and details
with regard to standards or validation of manufacturing procedures employed for
the reduction or inactivation of unconventional agents
12. Identification of any pharmacological components which are part of the medical
device, with description of intended purpose and available clinical experience
c. An assessment of the technical performance of the medical device, carried out by an
independent expert
d. An assessment of the clinical performance of the medical device, carried out by an
expert, whose affiliation with the manufacturer or the Sponsor should be stated.
3. Information on the conditions under which the clinical
investigation is to be carried out
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a. A description of the medical condition involved, and of the generally recognised
methods of observation, diagnosis or treatment relevant for the present clinical
investigation
b. A brief description of clinical aspects considered to be well documented, areas open
to further research, and specific areas the proposed clinical investigation is intended
to investigate
c. A brief account of the theoretical framework of the proposed investigation
d. The number of patients required to take part in the clinical investigation with a
statistical justification
e. Criteria for patient selection, inclusion and exclusion criteria and justification for
including a control group, if relevant
f. Information on remuneration if any, to the participants in the clinical investigation
and the Clinical Investigator
g. Duration of study (please include the proposed start- and end dates), and proposed
follow-up period (with justification)
h. Description of data-collection methods, analytical procedures and criteria for a
possible interruption of the investigation
i. A declaration by which the applicant undertakes to inform the Directorate for Health
and Social Affairs of any adverse events during the clinical investigation
j. A declaration by which the applicant undertakes to inform the Directorate for Health
and Social Affairs of any amendments to the study protocol.
It should be noted that alterations or changes of the device in use, set of indications,
method of treatment, etc., may require a new submission
k. Description of how patient insurance is to be provided.
4. Information on the Clinical Investigation
a. Name of the Clinical Investigator; if the clinical investigation is carried out in several
localities, include the name of the Principal Clinical Investigator. The investigation
protocol should be signed by the Clinical Investigator, as well as the Head of the
medical unit where it is to be carried out
b. Description of the clinical investigation, its aims and objectives
c. A description of the Essential Requirements which are to be addressed by the
proposed investigation (ref. Annex I of the relevant directive)
d. A declaration that all other Essential Requirements have been duly fulfilled and how,
and if not, justification for the omission
e. Declaration affirming that the clinical investigation shall conform to the NS-EN ISO
14155 Standard. Any deviation therefrom should be given and justified
f. A declaration affirming that necessary measures are taken to ensure the patients’
health and safety during the clinical investigation
g. A list of countries where the present medical device is planned to be tested clinically
h. A copy of the duly signed investigation protocol (se point 4a.).
i. An information brochure for the Subjects to be included , and a “Declaration of
Consent” form to participate in the clinical investigation; both of these should be in
Norwegian. The former should fulfil the requirements embodied in NS-EN ISO
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14155, including giving the reader a description of the purpose of the investigation,
the possible risks and discomfort it may entail, and informing the reader that
participation is voluntary, and that one may withdraw from the clinical investigation
at any time. For further information on the content of such a brochure, do please visit
the home-page of the Regional Ethics Committee in Medical Research:
http://www.etikkom.no/E/index.htm
j. A declaration to affirm that a final report will be written by the Clinical Investigator,
and will be available to the Directorate for Health and Social Affairs on request.
Directorate for Health and Social Affairs
PO Box 7000 St Olavs plass
N-0130 Oslo, Norway
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