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FEDERAL REGULATORY ISSUES:
US Food and Drug Administration
Medical Device Amendments
M. Spect
Spector, Ph.D.
2.782 FDA REPORT
• 10% of grade
• Total length: 8 pages
– Includes text, all images and all
references
• Line spacing: 1.5
• Minimum font: 12
Page 1
GOVERNMENT REGULATION OF
MEDICAL DEVICES
US
Canada
Mexico
Europe
China
India
FDA
Health Canada
Health Ministry (uses US FDA)
European Union “CE Mark”
Chinese FDA
None
INDIA
• India does not regulate the sale of medical
medica
devices.
• India accepts non-U.S. Food & Drug
Administration-approved as well as nonCE-marked medical devices
– however, in accordance with U.S. FDA
requirements, U.S. manufacturers may only
export to India and to other countries medical
devices that have been approved either by the
US FDA
www.ita.doc.
gov/td/mdequip/indiar
quip/indiareegs.html
ita.doc.gov/td/mde
s.html
Page 2
US FDA ORGANIZATION
Center for Biologics Evaluation and Research (CBER)
Center for Devices and Radiological Health (CDRH)
Center for Drug Evaluation and Research (CDER)
Center for Food Safety and Applied Nutrition
(CFSAN)
Center for Veterinary Medicine (CVM)
National Center for Toxicological Research (NCTR)
Office of the Commissioner (OC)
Office of Regulatory Affairs (ORA)
Which center to review
review your application?
FDA
Center for Devices and
Radiologi
Radiologiccal
al Health
http://www.fda.gov/cdr
h/index.html
Page 3
FDA APPROVAL PROCESS
Classification of Product as I, II, or III
TE products
I. General
Controls
II. Special
Controls
III. Premarket
Approval (PMA)
Good Manuf.
nuf.
Practice
GMP
GMP
FDA APPROVAL PROCESS
Classification of Product as I, II, or III
TE products
I. General
Controls
II. Special
Controls
No approval of
FDA prior to
selling the
product.
Good Manuf.
nuf.
Practice
GMP
GMP
Page 4
III. Premarket
Approval (PMA)
FDA APPROVAL PROCESS
Classification of Product as I, II, or III
TE products
I. General
Controls
II. Special
Controls
III. Premarket
Approval (PMA)
No approval of Equival
ent to Market
ed
Equivalent
Marketed
FDA prior to
Device?;
Device?;
selling the
Premar
Premarket Notification
product.
510 (k)
Good Manuf.
nuf.
Practice
GMP
GMP
FDA APPROVAL PROCESS
Classification of Product as I, II, or III
TE products
I. General
Controls
II. Special
Controls
III. Premarket
Approval (PMA)
No approval of Equival
ent to Market
ed
Equivalent
Marketed
FDA prior to
Device?;
Device?;
selling the
Premar
Premarket Notification
product.
510 (k)
Good Manuf.
nuf.
Practice
GMP
GMP
Analysis of composition
and properties, and in vitro
and in vivo studies
Page 5
Good Lab Pract.
Pract.
GLP
FDA APPROVAL PROCESS
Classification of Product as I, II, or III
TE products
I. General
Controls
II. Special
Controls
No approval of Equival
ent to Market
ed
Equivalent
Marketed
FDA prior to
Device?;
Device?;
selling the
Premar
Premarket Notification
product.
510 (k)
Good Manuf.
nuf.
Practice
GMP
GMP
Analysis of composition
and properties, and in vitro
and in vivo studies
III. Premarket
Approval (PMA)
Human Trial
Investigational
Device
Exemption IDE
PMA
Good Lab Pract.
Pract.
GLP
FDA History
http://www.fda.gov/oc/opacom/fda101/sld017.html
• In 1906,
906, Pres
President Theodore
Theodore Roosev
Roosevelt
elt signed
signed into la
law the Food and
and Drugs
Drugs
Act.
Act. The 1906 law's
law's relevant
relevant backg
backgrround in Am
America star
starts with col
colonial
nial food
statut
statutes concer
concerned with brea
bread and
and meat.
meat. The firs
first na
national law ca
came in
in 1848
1848
during
an War.
during the Mexic
Mexica
War. It bann
banned the impor
importtatio
ation of adulterated
adulterated drugs
drugs,, a
chronic public health proble
m.
problem.
• In 1937, a public
th disa
public heal
health
disaster demo
demonstrated
trated the need for a strong
rongeer federal
ral
law. Sulfani
lamide, the firs
ve
Sulfanilamide,
first "wonder drug
drug" and
and a popular
pular and effecti
fectiv
trea
rrhea,, was
ulat
ateed into an
treatment for diseases
diseases like strep throat and gono
gonorrhea
was form
formul
Elixir
eted
d for use in
Elixir of Sulfanilamide and mark
markete
in chil
children
dren. But the
the liquid
formulat
aineed a pois
on, the same chemica
eeze,
e, and it
rmulatiion cont
contain
poiso
chemical used in antifr
antifreez
killed 107
107 people, most of them chil
children. The earlier
earlier la
law did not
not require the
drug's
on for safety
drug's manufact
manufacturer to test
test the form
formulati
ulatio
safety before it was
was sold.
sold.
• Congress
s
co
o
rrected
ected
this
weakness
in
the
la
a
w
in
1938
38
when
en
it
pass
sse
e
d
t
he
Congres c rr
l
19 wh
pa
Federal Food, Drug
Drug, and Cosmet
Cosmetic Act
Act. This la
law, for the
the firs
first time,
time, required
required
compan
ies to prove the safety
companies
fety of new drug
drugs before
before putting
putting them on
on the
the
market. The new act also
also added the
the re
regul
gulation
tion of cosmeti
metics and therapeutic
herapeuti
devices,
ion
n.
devices, and generally
generally updated the law to improve
improve consumer
consumer protect
protectio
• 1976 Medica
Medical Devices
Devices Amendment
• Cong
ress continues
Congress
continues to give FDA new responsibilities.
responsibilities.
Page 6
FDA STAFFING
• To carry out its mission, FDA employs some
9,000 staff who work in locations around the
country.
• The network of 167 field offices is generally the
first point of contact for the public and regulated
manufacturers. The employees in these offices
focus on inspection and surveillance, laboratory
work, and public and industry education.
• The FDA staff who work in the greater
Washington, D.C., area focus on product review
revie
and regulatory policy.
CDRH Advisory Committees
•
•
The Center for Devices and Radiological
Radiological Heal
Health has
established advisory committees
committees to provide independent,
professional
professional expertise and
and technical
technical assist
assistance on the
development, safety and
ess, and regulation of
and effectiven
effectiveness,
medical devices and electronic products that produce
radiation. Each committee consists of experts wi
with
recogniz
ed expertise and
recognized
and judgment in a specific field. The
committees are advisory
nd
advisory -- they provide their expertise aand
recommendations
recommendations -- but final decisions are made by FDA.
The Center has four advisory committees, including a
Medical Devices Advisory Committee which consists of 18
panels that cover the medical
medical specialty
specialty areas.
areas. These advisory
committee
committee meet
meetings are open to the public, and
and time is
provided for public comment on the topic under
consideration.
Page 7
CDRH Advisory Committees
• Medical Devices Advisory Committee
– Consists of 18 Panels
• Devices Good Manufacturing Practice
(GMP) Advisory Committee
• National Mammography Quality Assurance
Advisory Committee
• Technical Electronic Product Radiation
Safety Standards Committee
FDA ADVISORY PANELS
• Anesthesiology and Respiratory Therapy
Devices
• Circulatory System Devices
• Clinical Chemistry and Clinical Toxicology
Devices
• Dental Products
• Ear, Nose, and Throat Devices
• Gastroenterology and Urology Devices
• General and Plastic Surgery Devices
• General Hospital and Personal Use Devices
• Hematology and Pathology Devices
Page 8
FDA ADVISORY PANELS
•
•
•
•
•
•
•
•
•
Immunology Devices
Medical Devices Dispute Resolution
Microbiology Devices
Molecular and Clinical Genetics
Neurological Devices
Obstetrics and Gynecology Devices
Ophthalmic Devices
Orthopaedic and Rehabilitation Devices
Radiological Devices
FDA ADVISORY PANELS
Current Role in the Regulatory Process
• Each Panel is made up of experts in the field including
physicians, surgeons, scientists and engineers, a
consumer representative, and an industry
representative (non-voting member)
• FDA staff requests that the Panel review certain
submissions to FDA and make a recommendation to
FDA regarding the acceptance or rejection of the
documentation with respect to sufficient evidence to
support safety and efficacy; the Panel takes a vote to
determine the recommendation
• At the Panel meeting, the company makes a
presentation to the Panel to support its documentation
• FDA may choose to accept or reject the Panel
recommendation
Page 9
FDA ADVISORY PANELS
Initial Role in the Regulatory Process
• Each Panel reviewed every medical device in
i
its specialty to determine of the classification
of the device should be I, II, or II.
• The Panels currently make recommendations
about the “down-classification” of devices;
e.g., hip replacement prostheses were downclassified from II to II.
CDRH
Overview of Regulations
• The CDRH is responsible for regulating firms who
manufacture, repackage, relabel, and/or import
medical devices sold in the United States.
• Medical devices are classified into Class I, II, and III.
A description of device classification and a link to the
Product Classification Database can be found at:
ttp://www.fda.gov/cdrh/devadvice/313.html.
Regulatory control increases from Class I to Class III.
The device classification regulation defines the
regulatory requirements for a general device type.
– Most Class I devices are exempt from Premarket
Premarke
Notification 510(k)
– Most Class II devices require Premarket Notifi
cation
on
Notificati
510(k);
510(k);
– Most Class III devices require Premarket
Premarket Approval.
Approval.
Page 10
CDRH
Overview of Regulations
• The basic regulatory requirements that
manufacturers of medical devices distributed in
the U.S. must comply with are:
– Premar
Premarket Notification 510(k), unless exempt, or
Premar
Premarket Approval (PMA),
– Establishment
Establishment regist
registrration on form
form FDAFDA-2891,
– Medical Device Listing on form FD
FDA-2892,
– Quality System (QS) regulation,
– Labeling requirements, and
– Medical Device Reporting (MDR)
Is My Product Regulated by FDA's Center
for Devices and Radiological Health?
• The FDA regulates medical devices to assure their safety and effectiveness.
The CDRH is the component within the FDA that is responsible for this
program. To fulfill the provisions of the FD&C Act that apply to medical
devices and radiation-emitting products, the FDA develops, publishes and
implements regulations. These regulations are initially published in the
Federal Register (FR) for public comment. The FR is a compilation of the
daily government activities including proposed and final regulations. Final
regulations are subsequently placed or codified into the Code of Federal
Regulations (CFR) on an annual basis.
• One of the most important aspects of getting a medical device to market is to
know where to begin. The starting point is determining whether the product
you plan to market is a medical device, as defined in section 201(h) of the
FD&C Act. If your product meets the definitions, it will be subject to the
provisions of the FD&C Act, that is, there are FDA regulatory requirements
that must be met before a product can be marketed in the U.S. The purpose
of Device Advice is to help you decide whether your product is subject to
FDA regulations, and if so, to identify what these regulatory requirements
are and help you comply with them.
Page 11
Medical Device Definition
• Medica
Medical device
devices range from simple
simple tongue depress
depressors and
and bedp
bedpans to
complex program
mable pacemakers
ogy and la
programm
pacemakers with micro-c
micro-chip technol
technolo
laser
se
surgical devic
oted or used
devicees. If a produc
productt is
is labeled,
beled, prom
promoted
used in a man
manner th
that
meets the following
on in section 201(h) of the Federal Food Drug &
following definiti
definition
Cosm
ated by the FDA as a medic
medical dev
device
Cosmetic (FD&
(FD&C) Act
Act it
it will be regul
regula
and is subjec
ng and
ry cont
rols.
ls.
subjectt to prem
premarketi
arketing
and postma
postmarrketing
eting regulato
latory
contro
• A device
an instru
ement, ma
device is:"
is:"a
instrument, appara
apparatus, impl
implement,
machine, contrivance,
contrivance,
implan
t, in vit
ent,
t, or other
cle, incl
plant,
vitro reag
reagen
other similar
similar or related
related arti
article,
including
uding a
componen
ory
y which is
component part, or access
accessor
is:
– recogniz
ed in the
recognized
the offici
official Nation
National Formul
Formulary, or the
the United
United States
Pharmac
opoei
armaco
poeia, or any
any supplem
supplement to them
them,
– intende
d for use in the diagnosis of disease or other conditions
intended
conditions, or in the
the cure
cure,,
mitigation, treatment,
treatment, or prevention
prevention of disease, in man or
or other animals, or
– inten
ded to affect
intend
affect the
the st
structu
ructurre or any
any function of the body of man or other
animals, and which
which does
does not achieve
achieve any
any of it's
it's primary intended purpose
purposess
through chemical acti
action within or on the body of man or other animals
animals and
which
nt upon be
vement of any
ich is not depende
dependent
being metaboliz
metabolizeed for the achie
achiev
any of its
primary
d purpose
s."
"
primary intende
intended
purposes.
Medical Device Definition
• The definition provides a clear di
distinction between
between a medical
medical
device and other FDA regulated products
products such as drugs. If the
primary intended use of
of the product is achieved through
chemical action or by being metabolize
metabolized by th
the body, the
product is usually a drug. Human drugs are regulated by
FDA's Center for Drug Evaluation and Research (CDER).
Biological pr
products wh
which include
include blood and blood products,
and blood banking equipment are regulated by FDA's Center
for Biologics Evaluation and Research (CBER).
• FDA's Center for
for Veterinary Medicine (CVM) regulat
regulates
products used
used wi
with animals.
• If your product is not a medical device but regulated by
another Center in the FDA, each component of the FDA has an
office to assist wi
with questions about the products they re
regulate.
late.
• In cases wh
where it is not clear wh
whether a product is a medical
device there are proc
procedures in place
place to use DSMICA Staff
Directory to assist you in making a determination.
Page 12
FDA DEVICE CLASSIFICATION
• The FDA has established classifications for approximately
approximately 1,700
different ge
generic types of devices and grouped them into 16
medical specialties
specialties referred to as panels. Each of these gene
generic
ri
types of devices is assigned to one of three regu
regulatory classes
classes
based on the level of control
control necess
necessary to assure
assure the safety
safety and
an
effectivenes
effectivenesss of the device:
– Class
Class I Genera
General Cont
Controls
– Class
ral Cont
Class II Gene
General
Controls and Sp
Special Contro
Controls
– Class
al
Class III General
General Cont
Controls and Premarke
Premarkett Approv
pproval
• The class to which your device is assigned determines, among
other things
things, the type of
of premarketing submission/applica
submission/applicattion
required for
for FDA clearance to market.
market.
– If your
your devi
device is cla
classified
sified as Class II a 510k will be required
required for
fo
marketin
marketing.
– For Clas
Classs III devices,
devices, a prem
premarke
arket approval
approval applicat
applicatiion (PMA) will be
required.
FDA DEVICE CLASSIFICATION
• Device classification depends on th
the intended
intended us
use of the device
and also upon indicatio
ns for use.
indication
use. For exampl
example, a scalpel's
intended use is to cut tissue. A su
subset of intend
intended use arises when
when
a more specia
lized
ed indication is added in the device's labeling
specializ
such as, "for making incisions
incisions in the
the cornea." Indications for use
use
can be found in the device's labeling,
labeling, but may also be conv
conveyed
orally during sale of the product.
• In addition, classification is risk
risk based, that is, the risk the
the device
poses to the patient and/or the user
user is a major factor in the class
class
it is assigned. Class I includes devices wi
with the lowe
lowest risk and
and
Class III includes those wi
with the greatest risk.
• As indicated above all classes of devices as subject to General
Controls. General
General Controls are
are the baseline requirements of the
Food, Drug and Cosmetic (FD&C) Act that apply to all medical
devices, Class
Class I, II, and III.
Page 13
How to Determine Classification
• To find the classification of your device you need to find the regulation
number that is the classification regulation for your device. There are two
methods for accomplishing this: go directly to the classification database and
search for a part of the device name, or, if you know the device panel
(medical specialty) to which your device belongs, go directly to the listing for
that panel and identify your device and the corresponding regulation.
• If you already know the appropriate panel you can go directly to the CFR
and find the classification for your device by reading through the list of
classified devices, or if you're not sure, you can use the keyword directory in
the PRODUCT CODE CLASSIFICATION DATABASE. In most cases this
database will identify the classification regulation in the CFR. You can also
check the classification regulations below and the Precedent Correspondenc
for information on various products and how they are regulated by CDRH.
• Once you have identified the correct classification regulation go to What are
the Classification Panels below and click on the correct classification
regulation or go to the CFR Search page. Some Class I devices are exempt
from the premarket notification and/or parts of the good manufacturing
practices regulations. Approximately 572 or 74% of the Class I devices are
exempt from the premarket notification process. These exemptions are listed
in the classification regulations of 21 CFR and also has been collected
together in the Medical Device Exemptions document.
DEVICE CLASSES
Class I - General Controls
Controls
Class II - Special Controls
Class III - Premarket Approval
Page 14
DEVICE CLASSES
Class I - General Controls
• Class I devices are subject to the
the least regulat
regulatory control.
control. They
They
present minimal potential for harm to the user and are often
simpler in design than Class II or Class III devices.
devices. Class I devices
devices
are subject to "General Controls" as are Class II and Class III
devices.
• Genera
Generall controls
controls incl
include:
– Establis
hmen
nt Regis
on of co
Establishme
Registrati
ration
companies
mpanies which are required
required to regis
registter
kages
under 21 CFR Part
20, su
such as ma
manufact
nufacturers,
urers, dis
distributors
butors, repac
repack
Part 807.
807.2
and relabeler
relabelerss.
– Medical
Form 2892
2892)) wi
with FDA of devices
devices to be
cal De
Device List
Listing
ing (use FDA Form
marketed
marketed.
– Manufac
tice
ces
Manufactturing
uring device
devicess in accordance
accordance with
with Good Ma
Manuf
nufacturin
uring Prac
Practi
(GMP
(GMP).
– Labeling
Labeling devices
devices in acco
accordance with labeli
labeling regulatio
regulations.
– Submiss
n [510
(k)] before
Submissiion of a prem
premarket
arket notif
notifiicatio
cation
[510(k)]
before ma
market
rketing a device.
• Examples of Class I devices include
include elastic bandages, examination
examination
gloves, and handhand-held surgical
surgical instruments.
instruments.
DEVICE CLASSES
Class II - Special Controls
• Class II devices are those for which general
controls alone are insufficient to assure safety and
effectiveness, and existing methods are available to
provide such assurances. In addition to complying
with general controls, Class II devices are also
subject to special controls.
• Special controls may include special labeling
requirements, mandatory performance standards
and postmarket surveillance.
• Examples of Class II devices include powered
were
wheelchairs, infusion pumps, and surgical drapes.
Page 15
DEVICE CLASSES
Class III - Premarket Approval
• Class
nt regulatory category
Class III is the
the mo
most stringe
ringen
category for devices.
devices. Clas
Classs III
III
devices
devices are those for which insufficient
insufficient informat
information exists
exists to assu
ssure safe
safety
and effect
effectiveness sole
solely through general
general or special
special contro
controls.
ls.
• Clas
ces are usually those
ain hum
Classs III devi
devices
those that suppor
supportt or sust
susta
human life
life,, are
of subs
tantia
al importance in preve
nting im
substanti
preven
impairment of human
human health,
health, or
which present a potentia
potential, unreaso
unreasonable
nable risk
risk of illness
illness or injury.
injury.
• Premarket approval
ss of scientif
approval is the re
required proce
process
scientific review
review to ensure
ensur
the safety
ces
fety and effect
effectiveness
eness of Clas
Classs II
III devices
devices.. Not all Class
Class III devi
devices
require an approved premarket
on to be market
premarket approval
approval applicati
applicatio
rketed.
ed.
Class
ces which are equivalent
y market
Class III devi
devices
equivalent to devices
devices legall
legally
marketed before
May 28, 1976 may be market
fica
ation
rketed through the prem
premarket
arket noti
notific
[510(k)] proce
ss until FDA has publishe
d a requirement
turers
process
published
requirement for manufac
nufacturers
of that
that generi
genericc ty
type of devic
device to subm
submit PMA dat
data.
• Class
ces which require
Class III devi
devices
require an approved
approved premarke
premarkett approval
pproval
applicati
on to be ma
applicatio
market
rketed are those:
– regulated as new drugs prior
tional devices.
prior to
to May
May 28,
28, 1976,
1976, also called
called transi
transitional
– devic
devicees found not substantially equivalen
quivalent to device
devices mark
marketed prior to May
May 28,
28,
1976.
– Class III preamend
on in 21 CFR, require a
reamendment
ent devic
devicees which,
ich, by
by regulati
regulation
premarke
remarket appr
approval application.
application.
DEVICE CLASSES
Class III - Premarket Approval
• Examples of
of Class III devices wh
which require a premarket
premarke
approval include
include replacement heart valves, silicone gelgel-filled
breast implants, and implanted cerebella stimulators.
• Class III devices
devices which can be marketed wi
with a premarket
notification 510(k) are those:
– post
nt (i.e.,
oduced
uced to the U.
postamendme
amendmen
(i.e., intr
introd
U.S. ma
market
rket after
after May 28,
28, 197
1976)
Class
ces which are substan
nt
Class III devi
devices
substanttially
lly equivalent
quivalent to preamendme
preamendmen
(i.e.,
ed to the U.S. market bef
(i.e., introduc
introduced
before May
May 28,
28, 1976)
1976) Class III
devices
ation ca
devices and for which the regul
regula
calling
lling for the premarke
premarkett approval
pproval
applicati
on has no
d in 21 CFR.
applicatio
not been
been publishe
published
• Examples of
of Class III devices wh
which currently require a
premarket notification include implantable
implantable pa
pacemak
cemaker pulse
generators
generators and endoss
endosseous implan
implants.
Page 16
What is Premarket Notification [510(k)]
• Each person who wants to market Class I, II and some
III devices intended for human use in the U.S. must
submit a 510(k) to FDA at least 90 days before
marketing unless the device is exempt from 510(k)
requirements.
• A 510(k) is a premarketing submission made to FDA to
demonstrate that the device to be marketed is as safe
and effective, that is, substantially equivalent (SE), to a
legally marketed device that is not subject to premarket
premarke
approval (PMA). Applicants must compare their 510(k)
510(k
device to one or more similar devices currently on the
U.S. market and make and support their substantial
equivalency claims.
What is Premarket Notification [510(k)]
• A legally marketed device is
– a device that wa
was legally marketed prior to May 28, 1976
(preamendments device), or
– a device which has been reclassified from Class III to Class II
or I,
– a device which has been found to be substantially
substantially equivalent
to such a device through the 510(k) process.
• The legally marketed device(s) to which equivalence is
drawn is known as the "predicate" device(s).
Page 17
What is Premarket Notification [510(k)]
• Applicants must submit descriptive data and,
when necessary, performance data to
establish that their device is SE to a predicate
device. Again, the data in a 510(k) is to show
comparability, that is, substantial equivalency
(SE) of a new device to a predicate device.
What is Substantial Equivalence
• Unlike PMA, which requires demonstration of
reasonable safety and effectiveness, 510(k) requires
demonstration of substantial equivalence. SE means
that the new device is as safe and effective as the
predicate device(s).
• A device is SE if, in comparison to a predicate device it:
– has the same intended use as the predicate device; and
– has the same technological characteristics
characteristics as the predicate
device; or
– has different technological characteristics,
characteristics, that
that do not raise
new question
eness, and the sponsor
questions of safety and effectiv
effectiveness,
demonstrates that the device
device is as safe and effective as the
legally marketed device.
Page 18
IDE Overview
• An in
ce exemp
tio
on (IDE)
invest
vestigati
ational devi
device
exempti
(IDE) all
allows the in
invest
vestigational
onal devic
device
to be used in a clinical
clinical study in order to collect safety
safety and effec
effecttiveness
eness data
required to suppor
al (PMA
supportt a Premar
emarket Approv
pproval
(PMA)) appli
application or a
Premarket Notification
cation [510(k)]
510(k)] submission to FDA
FDA.
• Clinical
ortt a PM
Clinical studies
studies are
are mo
most often conducted
conducted to supp
suppor
PMA.
• Only
ortt the
Only a small
small percentage of 510(k)’
510(k)’s re
require
quire clinical
clinical data to supp
suppor
applicati
on.
applicatio
• All clini
ationa
inical eva
evaluat
uations of inve
investig
stiga
ionall devices, unless exempt,
pt, must have
hav
an appro
ved IDE before the stu
study is ini
initiated.
approv
• Cli
Clinical evalu
aluation of devi
devicces that
that have not been cle
cleared
red fo
for market
rketing
requires:
requires:
– an IDE approve
d by an institut
approved
institutional
ional review board
board (IRB). If th
the study
study involve
involves a
significant risk device, the IDE must also be appr
oved
d by FDA;
approve
FDA;
– informed
informed cons
consent from
from all patients;
– labeling for
for inve
investigational use only
– monitori
monitoring of the study and;
– requ
required record
recordss and
and reports
reports..
Premarket Approval (PMA)
• PMA is
y review
uate the
is the FDA proces
processs of scientif
scientific and regulator
regulatory
review to eval
evalu
the
safety
cal devices.
safety and effectiv
ffectiveness
eness of Class
Class III medi
medical
devices.
– Class III devic
devicees are
are those that support
support or sustain
sustain human life, are
are of substantia
substantial
impo
g impa
entt a
importance
rtance in preventin
reventing
impairment
ment of human health,
health, or which
ich pres
presen
potential,
potential, unre
unreasonable risk of illness
illness or injury
injury.
– Due to the level
level of risk associ
associated
ated with Class III devic
devicees, FDA has determine
termined
that
that general
general and
and special cont
controls
rols alone
alone ar
are ins
insufficient
fficient to ass
assure the safety
safety and
and
effec
ffectiven
iveness of class III devic
devicees.
– Therefore
Therefore,, thes
thesee de
devices
vices require a prem
premarke
arkett approval (PMA) application
under section
section 515 of the
the FD&C Act in order to obtain marketing clea
clearrance.
ance.
• PMA is the most
most stringe
ringent typ
type of device
device marketin
marketing applicatio
application required
required by
FDA. Th
ve FDA
val of its PM
The appl
applicant
ant must
must recei
receive
FDA appro
approv
PMA appl
applicatio
ation
prior to marketin
g the devi
ce. PMA approval
ina
ation
marketing
device.
approval is based on a determ
determin
io
by FDA that
icient va
that the PMA co
contains suff
sufficient
valid scientif
scientific evi
evidence
ence to assure
assure
tha
ved
that the devi
device is safe
safe and ef
effective
fective for its
its intended
intended use(
use(s). An appro
approv
PMA is,
tin
ng the appl
is, in effec
effect, a priva
ivate lic
license gran
granti
appliicant
ant (o
(or owner)
permiss
rize
permission to market the device.
device. The PMA owner, howe
however, can autho
authorize
use of its data by another.
another.
Page 19
PMA Data Requirements
• A PMA applicat
atory docume
application is
is a scie
scientif
ntific,
ic, regul
regula
documentation to FDA
FDA to
t
demonstr
ate the safety and effect
demonstrate
effectiven
iveness
ess of the class III
III device.
device. Good science
and scientific
val of PMA appli
scientific writing is a key to the appro
approv
pplicati
ation. If a PMA
PM
applicati
on lacks valid clinic
on and scientif
pplicatio
clinical informati
formatio
scientific analysis
ysis on so
sound
und
scientif
ew and
al.. PMA
scientific reas
reasoning,
ing, it will delay FDA’
FDA’s revi
review
and approv
approval
PMA
applications
te,, inc
al
ions tha
that are inc
incompl
mplete, inaccura
curate
inconsist
istent, om
omit critic
critica
informati
on, and po
informatio
poorly organiz
organizeed have
have result
resulted in delays
delays in ap
approval
roval or
denial of PMA applic
ations.. Manu
urers
roll
applications
Manufact
factu
ers sho
should perform a qu
quality cont
contro
audit
ation before sendin
audit of a PM
PMA applic
application
sending it to FDA to assure
assure tha
that it is
scient
y sound
scientificall
ically
und and presented
presented in a well organiz
organizeed form
format.
g data and
• Technical Sect
technical sect
sections cont
containin
aining
and in
inform
formatio
ation
Sections:
ns: The technical
should allo
mine whet
allow FDA to deter
determ
whether to approve
approve or disa
disapprove
pprove the
the
applicatio
n. Thes
lly divi
clinical la
torry
ication.
Thesee sections
ections are usua
usually
divided into non
non--clinical
labora
borato
studies and cl
clinical inves
investtigatio
gations.
ns.
• Non-clin
ical Labo
ratory
ry Stud
ies’’ Sect
Non-clini
inical labo
laborratory
tory stud
studiies’
Non-clinical
Laborato
Studies
Section: Non-c
sectio
on on microbiology,
gy,
section includes
includes informati
informatio
microbiology, to
toxicol
cology,
gy, immunolo
immunolog
biocom
patibil
biliity, st
biocompati
stress,
ress, wear, shelf
shelf life,
life, and other laboratory
boratory or anim
animal tes
tests.
Non-cli
nical st
on must
nce
Non-clin
studies for safety
safety ev
evaluati
aluation
must be co
conducted
nducted in complia
compliance
with
Laboratory
tory Practice
actice for Nonclinical
Nonclinical Labo
Laborratory
with 21C
21CFR Part
Part 58 (Good Labora
Stud
Studies)
ies).
PMA Data Requirements
• Clinical Inve
Investigat
stigations’
ions’ Section: Clinical investigations’
investigations’ section
includes study protocols, safety and effectiveness
effectiveness data, adverse
advers
reactions and complications, device failures
failures and
and replacements,
patient information,
laints, tabulations of data
information, patient comp
complaints,
from all individual subjects, results
results of statistical analyses, and
and
any other information from the clinical investigations. Any
investigation conducted under an Investigational Device
Exemption (IDE) must be identified
identified as such.
• Like ot
other sc
scientific reports, FDA has observed problems wi
with
study designs, study conduct,
conduct, data analyses, presentations, and
conclusions. Investigators should always
always consult
consult all applicable
FDA guidance documents
(http://www.accessdata.fda.gov/scripts/cdrh
/cfdocs/cfGGP/Sear
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfGGP/Sea
ch.cfm).
ch.cfm).
Page 20