EUROPEAN COMMISSION

DG ENTERPRISE
Directorate G
Unit 4 - Pressure Equipment, Medical Devices, Metrology

MEDICAL DEVICES: Guidance document

MEDDEV 2.12-2

May 2004

GUIDELINES

ON POST MARKET CLINICAL FOLLOW-UP

The present Guidelines are part of a set of Guidelines relating to questions of application
of EC-Directives 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 services, 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
representatives of interested parties in the medical devices sector.

Page 1
CEC CLINICAL EVALUATION TASK FORCE. May 18, 2004

POST MARKET CLINICAL FOLLOW-UP OF

MEDICAL DEVICES UNDER
THE MEDICAL DEVICES DIRECTIVES

Foreword : Rationale and Goals of PMCF

This document is intended to be a guide for manufacturers and notified bodies on how to
carry out PMCF in order to fulfill post market surveillance obligation according to point 3.
1 of annex II, point 3. of annex IV, point 3 of annex V, point 3.1 of annex VI or point 4 of
annex VII of medical device directive (add ref. AIMDD)

While clinical evidence is an essential element of the premarket conformity assessment

process, it is important to recognize the limitations inherent to these premarket clinical
investigations. The extent of the data that can be gathered in the premarket phase does
not enable the manufacturer to detect infrequent complications or problems only
apparent after widespread use, or /long term performance issues. As part of the
manufacturer’s quality system, a program of appropriate post market surveillance is key
to identifying and investigating risks associated with the use of medical devices placed
on the market.

Manufacturers should have general systems in place to cover PMS as well as having a
defined PMS strategy for each of their products/product ranges

Therefore, PMCF appears as a method of choice for this purpose. It will, for instance,
enable patients' access to new therapies while establishing a review process for long
term safety follow-up and detection of possible emergent risks that cannot be adequately
detected by relying solely on pre-market clinical investigations (given the relatively short
follow up required) or product experience /vigilance.
Implementation
Post market surveillance may include a number of strategies in addition to complaint
handling and vigilance :

¾ active supervision by customer surveys,

¾ inquiries of users and patients,
¾ literature reviews,
¾ Post market Clinical Follow-up, etc..

Post market clinical follow-up (PMCF) through clinical studies and registries has a great
importance among these strategies.

Post Market Clinical Follow-up (PMCF) should always be considered for devices where
identification of possible emerging risks and the evaluation of long term safety and
performance are critical. In identifying such emerging risk, the following criteria should
be taken into account :
Page 2
 • innovation, when the design of the device, the material, the principles of
operation, the technology, or the medical indication is new
• severity of the disease,
• sensitive target population
• risky anatomical location
• well known risk from the literature
• well known risk of similar marketed devices
• Identification of an acceptable risk during pre-CE clinical evaluation, which
should be monitored in a longer term and/or through a larger population.
• Obvious discrepancy between the premarket follow up timescales and the
expected life of the product

All PMCF should be planned. The PMCF plan can take the form of extended follow-up of
patients enrolled in the pre-market trials, and / or a prospective study of a representative
subset of patients after the device is placed on the market. It can also take the form of
open registries. This plan will need to take into account :

• Results of the clinical investigation including Adverse events identified

• Average life expectancy of the device
• The claims made by the manufacturer for the device
• Performances for which equivalence is claimed
• New information becoming available

PMCF, when carried out, must always be performed for the use of the product within its
intended indications according to Instructions for use. National regulations on post
market clinical studies must be taken into account.

The involved Notified Body should review the appropriateness of the manufacturer's
general PMS procedures, incorporating PMCF, as relevant, as well their PMCF plan(s)
and results for specific products as part of conformity assessment procedures and
quality management system auditing

The follow up duration should take into account the average life expectancy of the
product in its indication. Therefore, in case of a device subject to short term premarket
follow up and intended to stay in the patient for its lifetime, a longer follow up will be
required.

PMCF will not be required for products for which the long term clinical performance and
safety is already known from previous use of the device. In the case the assessment of a
product is performed through the concept of equivalence , PMCF should always be
considered .

Post Market clinical Requirements (Risk based matrix)

The following table sets out a ‘triage approach’ and suggests general advice for the
evaluation of products under different circumstances.

Notified bodies should be part of the decision making with the manufacturer if applicable.

Page 3
PMCF Product specificities Required actions
no PMCF Products for which the • All received complaints and adverse events data shall be
medium/long term clinical systematically reviewed, and all product related adverse
performance and safety is events such as those described in Annex II 3.1 of the
already known from MDD must be notified to the relevant Competent
previous use of the device Authority (ies). This includes all sources of information
, or from fully transferable known by the manufacturer, including published
experience with equivalent literature.
devices (except **)
• Monitoring of postmarket performance should take into
account relevant data publicly available with similar
devices especially when the CE marking was based on
equivalence.

PMCF Always considered for

devices where • Same as above ,
identification of possible ¾ Plus
emerging risks and the
evaluation of long term • Post-Market Clinical Follow-up (PMCF) in the form of
safety and performance follow up of all or a justifiable subset of patients already
are critical enrolled in pre-marketing Clinical Investigations; or on
specific sub-groups and/or prospective study or registry
of a sample of products. A formal protocol should
describe the duration of PMCF; identify patient
(**)Products quoted as population and data to be collected.
"equivalent" devices where
reference product is (NOTE: The manufacturer must justify the design,
subjected to PMCF nature, and duration of post-marketing follow-up, having
regard to any published standards)
PMCF report to be provided to the relevant NB for
review and to competent authority if requested.

*Equivalence has been precisely defined and should be demonstrated according

to the criteria described in the document “Evaluation of clinical data: A guide for
manufacturers and notified bodies” (see annex 1 of this document).

Page 4
 ANNEX 1 : The Demonstration of equivalence

From MEDDEV.2.7.1 : guidelines on medical devices Evaluation of clinical data : a guide

for manufacturers and notified bodies -Section 4.3.1 d)relevance of data

• The manufacturer must demonstrate equivalence in all the following essential

characteristics with the device, which is the subject of the published reports.
Equivalence means :

¾ Clinical:
-used for the same clinical condition or purpose;
-used at the same site in the body;
-used in similar population (including age, anatomy, physiology);
-have similar relevant critical performance according to expected
clinical effect for specific intended use.

¾ Technical:
-used under similar conditions of use;
-have similar specifications and properties (e.g. tensile strength,
viscosity, surface characteristics)
-be of similar design;
-use similar deployment methods (if relevant);
-have similar principles of operation

¾ Biological:
-use same materials in contact with the same human tissues or
body fluids;

To be equivalent, the devices should have similarity with regard to the clinical,
technical and biological parameters with special attention to the performance,
principles of operation and materials; or if there are differences identified, an
assessment and demonstration of the significance these might have on safety
and performance must be documented.

For example, where the device under consideration and the device referred to in
the published study has a new principle of operation, then the two devices cannot
be considered equivalent. A new mechanism and action does not necessarily
result in a new clinical benefit and therefore a specifically designed clinical
investigation will be needed to provide data to demonstrate (or otherwise) the
clinical benefit of the new device

Page 5