A
Regulatory Primer (Part 2): Up Close:
U.S. FDA Classes
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.
In this article, Roger looks at
classification issues in the United States in greater detail.
His first words of advice: Determine device classification as early
as possible.
Class I: General
controls are deemed sufficient to demonstrate
safety and effectiveness
General controls include
--Manufacturer establishment registration (which currently
costs $1,706 per annum)
--Listing of devices
--Compliance
with the quality system requirements in Title 21 of the
U.S. Code of Federal Regulations (CFR), Part 820 (21 CFR
820 or QSR)
--Labeling in accordance with 21 CFR 801 or
809
--Submission of a premarket notification [otherwise
known as a 510(k)].
Class II:General
controls and special controls are deemed sufficient to demonstrate
safety and effectiveness
Special controls may include
--Additional
labeling requirements
--Conformity with mandatory or voluntary
standards or FDA guidance documents
--Requirement
to conduct specified postmarket surveillance activities
Class III: General
controls and premarket
approval are required to demonstrate
safety and effectiveness
Premarket approval (PMA)
--Process
of detailed scientific review, carried out by FDA,
of data submitted by the manufacturer, to ensure device
safety and effectiveness
Class I & the Important Exception to the
(Regulatory) Rule
Well-Documented Exceptions
As with most
regulatory rules, there are exceptions in each case.
This overview will not concern itself with many of
these, except to say that all the exceptions
are well-documented on the FDA website.
One very important exception, that I do want to mention,
however, is that the majority of Class I devices
(around 75%) are exempt from the 510(k) requirement.
This means that bringing one of these 510(k) exempt Class
I devices to the U.S. market is relatively easy and inexpensive
-- all that is needed is a quality system meeting
the requirements of QSR.
Many Class I devices are
also exempt from the design control aspects (Section 820.30)
of the regulation.
Furthermore, there is no certification
or prior quality system inspection required from FDA or
a third party --
compliance with the QSR is self-imposed, but may be subject
to FDA inspection once the device is on the market.
Class II and the 510(k): Notification, Timelines
& Guidelines
Follow the FDA Format
There is no specific format required by law
for a 510(k), but FDA publishes guidelines on
what should be included. It suggests the submission
should have 20
chapter headings, even if some of these are
indicated as being "not
applicable."
Every 510(k) must include the following: --detailed
description of the devices
--comparison with one
or more existing devices already on the U.S.
market (predicate devices)
The purpose of the 510(k) is
to establish that the new device is "substantially
equivalent" to the predicate(s).
When a 510(k) is required, mainly for Class
II devices, in addition to requiring compliance with
the QSR, including design controls, a notification has
to be made to FDA at least 90 days before the company
intends to introduce the device to the U.S. market.
Assembling the 510(k) Data: Allow the
Necessary Time
Assembling the data for a 510(k) can take
many weeks.
What it includes: In addition to a device description and
comparison with predicate devices, results
of bench tests, animal tests and clinical data. results of
Submission fee: $3,404,
reduced to $1,702 for "small businesses." The
discount is available to non-U.S. companies and
domestic U.S. organizations.
FDA response time: FDA is required to respond
to a 510(k) within 90 days, but may seek clarification
of certain aspects, or require additional data, in which
case, officially, the 90-day clock starts again.
In
practice, however, FDA reviewers adopt an "interactive"
relationship with the submitter, to reduce to a minimum
any delays in clearing the device for sale, or establishing
that the product is not "substantially equivalent" to
the selected predicate(s).
Class III : A Process All on Its Own
Class III devices are, with only
a few exceptions, required to go through the pre-market
approval (PMA) process.
What it includes: A very detailed
submission must be assembled. It will necessarily
include the provision of clinical data to demonstrate
safety and effectiveness, with the likelihood that specific
clinical studies will have to be planned and carried
out in compliance with a study protocol that has been
agreed by FDA.
Submission fee: $185,000, reduced to
$46,250 for companies meeting the "small business" criteria.
There
is, however, an important waiver of the fee for the
first PMA submitted by a company, as long as its turnover
is less than $30 million, which is very useful for start-ups
with high-risk devices.
FDA response time: Although there is no regulatory time
limit on PMA review, FDA is targeted with completing
its review with 180 working days from receipt if it
is approved as received, or 320 days if additional information
is required.
Prior to giving approval of a device via the PMA process,
FDA may schedule an inspection of the manufacturer’s
facility to check compliance with the QSR, and marketing
approval will not be forthcoming until an acceptable
response to any observed nonconformities has been lodged
with FDA.
Class Distinctions
So it can be seen that the difference
between the marketing authorization processes for Class
I, Class II, and Class III devices is considerable in
terms of both timescale and cost.
Classification is
based on the "intended use" of the
device, so it may be possible to achieve initial market
clearance under a lower classification if the intended
use is restricted at first, to allow more rapid market
access, with income from initial sales then being used
to support additional claims that may push the device
into a higher classification.
Recommended Reading on the FDA Site
The FDA website is very comprehensive.
If a manufacturer seeks to establish the
classification of its device, the best place
to start is on the "Classify
Your Medical Device" page.
In the next article: Equivalent
details of the European classification system under
the Medical Devices Directive (93/42/EEC) and the various "conformity
assessment routes"
available for each
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.
