A
Regulatory Primer (Part 5):
An Important Post-Market
Requirement
In
the first part of this series, Roger Gray of Donawa
Consulting explained how device classification can
play an important role in determining not only the
quickest route to market, but also, potentially, in
which of the major markets, United States (U.S.) or
Europe (EU), the product is likely to achieve first
clearance for sale. The second article looked in more
detail at classification issues in the U.S., the third
provided detail on the European classification system,
and the fourth focused on quality system (QS) requirements.
This article will look at the post-market requirements in
the United States and Europe.
It may be useful first of all to define what we mean
by "post-market requirements."
This
is a term that covers activities
that manufacturers should undertake during the post-production
phase, including
the proper management of adverse incidents involving
one of their devices, and carrying out appropriate corrective
and preventive actions related to devices that have
already been sold.
Various terms are used to describe
such activities, and the vocabulary itself varies between
the United States and Europe.
IN THE UNITED STATES
MDR (Medical Device Report): reporting
of a qualifying adverse incident to the US Food
and Drug Administration.
Recall: Used to describe any "removal
or "correction" of
devices that do not meet regulatory requirements.
Correction:
Modification, adjustment, relabeling, destruction,
or inspection (including patient monitoring) of
a product without its physical removal to some other
location.
Removal: The physical removal of a
device from its point of use to some other location
for repair, modification, adjustment, relabeling,
destruction, or inspection.
Advisory notice: Communication to customers advising
of the need for post-market action.
IN EUROPE
Medical Devices Vigilance System: The system
that applies in Europe to both adverse event reporting
and post-market corrective action.
Vigilance report: A report to a European
Competent Authority providing details of an adverse incident.
FSCA (Field Safety Corrective Action): Any
post-market activity that concerns devices that
have already been sold, in order to reduce a risk of
death or serious deterioration in the state of health.
FSN (Field Safety Notice): Communication to
customers in relation to a Field Safety Corrective Action.
U.S. Requirements
The actions that manufacturers must
take in the United States, should there be a need
to report an adverse incident or undertake other types
of post-market activities, are covered by federal
laws.
The principal ones are:
21 CFR Part 7: Recalls
21 CFR Part 803: Medical Device Reporting
21 CFR Part 806: Medical Devices; Reports of Corrections
and Removals
MDRs
What Is a Serious Injury?
Serious injury means
an injury or illness that --
is life threatening, even if temporary in
nature;
results in permanent impairment of a body
function or permanent damage to a body structure;
or
necessitates medical or surgical intervention
to preclude permanent impairment of a body function
or permanent damage to a body structure.
The
basic adverse event reporting requirement in the US
is that a report is required when a manufacturer becomes
aware of information that reasonably suggests that
one of its marketed devices may have caused or contributed
to a death or serious injury, or has malfunctioned,
and that the device or a similar device marketed by
the manufacturer would be likely to cause or contribute
to a death or serious injury if the malfunction were
to recur.
In this context, ‘becomes aware’,
means when any employee of the manufacturer becomes
aware of a reportable event, from any information
source. A ‘malfunction’ is a failure of
a device to meet its performance specifications or
otherwise perform as intended; malfunctions are not
reportable if they are not likely to result in death
or serious injury.
Manufacturers must report using a specified
format (Form FDA 3500A), although it is likely that
on-line reporting will take over from the paper system
within the next year.
Class I: Reasonable probability that the
use of, or exposure to, the device will cause
serious adverse health consequences or death.
Class II: Use of, or exposure to, the device
may cause temporary or medically reversible
adverse health consequences, or where the probability
of serious adverse health consequences is remote.
Class III: Use of, or exposure to, the device
is not likely to cause adverse health consequences.
The word recall, when used
in the context of U.S. medical device post-market activity,
does not just refer to the physical removal of the product
and its return to the manufacturer’s location,
but also covers on-site and off-site modification, adjustment,
relabeling, inspection or destruction.
Generic requirements, that apply to any
FDA-regulated products, for the voluntary
recall of items, are provided in 21 CFR
Part 7. Device-specific requirements for reporting
corrections and removals are contained in 21 CFR 806.
For example, if an action was taken to reduce a risk to
health posed by a device, the correction or removal of
that device is required to be reported to FDA by the
manufacturer.
Once FDA is notified of a recall, it classifies it
into Class I, II, or III to indicate the relative degree
of health hazard presented by the product being recalled,
with Class I representing the highest risk (see box).
FDA recommends that the manufacturer develops a recall
strategy that it shares with FDA, addressing the following
elements of the recall:
Depth of recall. Depending on the degree of hazard
and extent of distribution, the level in the distribution
chain to which the recall is to extend.
Public warning. The purpose of a public warning is
to alert the public that a product being recalled
presents a serious hazard to health. This is reserved
for urgent situations where other means for preventing
use of the recalled product appear inadequate.
Effectiveness checks. The purpose of effectiveness
checks is to verify that all consignees (at the
specified recall depth) have received notification about
the recall and have taken appropriate action.
The three European medical device directives (for
active implantable devices, "general" medical
devices and in vitro diagnostic devices) all include
articles requiring post-market surveillance on the
part of device manufacturers. All mandate that manufacturers
establish systematic procedures to review experience
gained from devices in the post-production phase,
implement appropriate means to apply any necessary
correction, and conduct reviews of the post-production
experience. In addition, they must notify the competent
authorities should there be --
any malfunction or deterioration in the characteristics
and/or performance of a 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 user or
a serious deterioration in his state of health; or
any technical or medical reason connected with
the characteristics or performance of a device leading
for the reasons referred to above to systematic
recall of devices.
See the document, Guidelines
on a Medical Devices Vigilance System (MEDDEV
2.12-1 rev. 5, updated in April 2007), for
comprehensive guidelines on the application of the
directives' requirements
for vigilance.
This document not only covers adverse incident reporting,
but also the need to keep the relevant competent authorities
up-to-date with any post-market actions the manufacturer
may decide to take, as a result of either an adverse
incident report or information from some other source,
such as a service report.
Such actions are referred to as Field Safety Corrective
Actions (FSCA), which may include --
the return of a medical device to the manufacturer;
device modification;
device exchange;
device destruction;
retrofit by purchaser of manufacturer's modification
or design change; and
advice given by manufacturer regarding the use of
the device.
In this context, device modification can include
--
permanent or temporary changes to the labelling
or instructions for use;
software upgrades, including those carried out by
remote access;
modification to the clinical management of patients
to address a risk of death or serious deterioration
in state of health related specifically to the characteristics
of the device; and
advice relating to a change in the way the device
is used.
The MEDDEV also includes a template for Field Safety
Notices (FSN), which are the means of communicating
the required FSCA to users.
Generic report forms for
initial and final reports are also included in the
guidance, although many European competent authorities
either have their own versions of the form, or have
on-line reporting systems.
Conclusion
The types of adverse events that
need to be reported to the regulatory authorities
in the U.S. and Europe are very similar, and the type
of information to be provided is also comparable.
The forms to be used have a number of significant
differences however, so separate forms will need to
be used if parallel reports are required.
Regulatory
authorities around the globe now also exchange adverse
incident and FSCA information, so reports sent to
one authority will often result in enquiries from
authorities in other parts of the world, wanting to
know if suspect devices have also been sold in their
market.
In addition, filing an incident
or field action report with a regulatory authority
may also trigger an on-site inspection, to allow the
authority the opportunity of assessing the manufacturer’s
competence in dealing with such problems effectively.
Despite
an understandable reluctance on the part of manufacturers
to admit any failings in design or manufacture by
submitting a vigilance report, this must not delay
or halt reporting, as the later discovery by a regulatory
authority of information that should have been reported
is likely to become a much more serious issue than making
the initial report.
About the author:Roger
Gray holds a B.Sc. in mechanical engineering and
is Director, Global Regulatory Affairs at Donawa
Consulting (Rome, Italy), where he is responsible for assisting
medical technology clients obtain marketing clearance
for both Europe and the USA, in addition to managing
the company’s
European Authorized Representative portfolio. He has
over 25 years' experience in the device industry and
was involved with the development of the Medical Devices
Directive during its formative stages.
