Food and Drug Administration
Michael Jordan and Jeff Beegle
October 23nd, 2013
An Overview of the FDA

Regulates more than $1 trillion worth consumer
goods.

25 cents of every dollar spent by Americans

Regulates cosmetics, food, blood supply,
medicines, biological, medical devices, radiationemitting products, and feed & drugs for animals

Performs surveillance of regulated products

Makes sure products are labeled truthfully

Employs 9,000 employees

95,000 FDA-regulated businesses
An Overview of the FDA
(cont)
Visits to 15,000 facilities/yr
 collect 80,000 domestic & imported product
samples
 Violations of FDA laws & regulations
 encourage firm to voluntarily correct the
problem
 recall a faulty product from the market


about 3,000 products recalled/yr
FDA can go to court to force a company to stop
selling a product, can seize and destroy products
 Also criminal penalties against manufacturers and
distributors

Example of Product Recall
OASYS Midline Occiput Plate
 On May 30, 2013, Stryker issued an Urgent
Medical Device Recall requesting medical
facilities to examine their inventory and
immediately stop distributing or using the
recalled lots.
 Stryker has received reports indicating postoperative fracture of the pin that connects
the tulip head to the plate body. This may
cause serious adverse health consequences
including blood loss, nerve injury, and the
need for revision surgery to replace the
fractured implant.

Major Centers at FDA


FDA is an agency of the Public Health Service
which is part of the Department of Health and
Human Services
Center for Biologics Evaluation & Research


Center for Drug Evaluation and Research


regulates biologically produced products such as blood,
vaccines, biological therapeutics
regulates the safe and effective use of drugs
Center for Devices and Radiological Health

regulates the safe and effective use of medical devices
and eliminates unnecessary exposure to man-made
radiation from medical, occupational, and consumer
products
Latest Major Medical Device
Law

The Medical Device User Fee and Stabilization Act
(MDUFSA) of 2005.

The MDUFSA amends the user-fee system created by the
original Medical Device User Fee and Modernization Act of
2002, which allows the FDA to charge a fee for medical
device product reviews.
The History of
the FDA
History of the FDA
Oldest comprehensive consumer protection
agency in the U. S. federal government
 Appointment of Lewis Caleb Beck to the US
Patent Office in 1848


Job of carrying out chemical analysis of
agricultural products
1906 Pure Food and Drugs Act (The Jungle)
 Began as Division of Chemistry, then the
Bureau of Chemistry, then the Food, Drug,
and Insecticide Administration (1927), then
the FDA (1930)

History of the FDA



Federal Food, Drug, and Cosmetic Act (FD&C Act) 1938

Following the death of the 1906 act

Tennessee “wonder sulfa drug”

US Congress for the first time addressed issues related to medical
devices and drugs
Radiation Control & Health Safety Act of 1968

Both medical and nonmedical applications

Performance standards for x-ray systems, computed tomography,
laser-based devices, and ultrasonic diagnostic and therapeutic
products
Cooper Committee Report 1970

Requires premarket clearance of risky devices

Based on 10,000 device-related injuries over a 10 yr period

Classified medical devices into 3 groups: Class I, Class II, Class III
History of the FDA (cont)


Bureau of Medical Devices (BMD) 1974
◦
Began classifying medical devices
◦
Created Office of Small Manufacturers Assistance to help manufacturers
understand the law
Medical Device Amendments 1976
◦
Made into law the tripartite medical device classification scheme
◦
Manufacturers had to notify FDA prior to marketing any device, unless the
device was exempt
◦
Introduced concept of substantial equivalence to pre-amendment devices
◦
Certain products previously classified as drugs were reclassified as class III
devices
◦
Required registration of medical device establishments
◦
Authorized what became Good Manufacturing Practices (GMP)
◦
Expanded FDA enforcement authority
History of the FDA (cont)

Good Manufacturing Practices Regulation (GMP) 1978


Comprehensive set of requirements on

Facilities

Methods

Controls for manufacturing, packaging, and storage of medical
devices
Medical Device Reporting Regulation (MDR rule) 1984

Requires manufacturer to submit a report to FDA whenever
a device they marketed might have caused an adverse
event resulting in death or serious injury

Must file a report whenever 1 device was known to have
failed and a repeat occurrence would be likely to lead to
death or serious injury
History of the FDA (cont)


FDA Plan of Action (first) 1985
◦
Response to criticism of FDA’s implementation of the 1976
amendments
◦
Maintain regulatory control without putting up roadblocks
to innovation
◦
Provided guidelines for functional substantial equivalence
rather than technological equivalence
◦
Allowed premarket notifications (PMN or 510 (k) s) rather
than premarket approvals (PMA)
FDA Plan of Action (second) 1987
◦
FDA would focus on risk assessment for informed judgments
on device safety
◦
Emphasize post-market surveillance of devices
◦
FDA focus on user education
History of the FDA (cont)



FDA reviewer Guidance for Computer-controlled Medical
Devices undergoing 510(k) review 1991

Applies to medical products having software as part of the device

Ensures uniform review of such devices
FDA Regulatory Procedures Manual Revision 1991

Replaced older enforcement system of notices of adverse findings
and regulatory letters

Now a single type of FDA communication - warning letter
Medical Device Amendments of 1992

Refined medical device tracking regulations

Made noncompliance with postmarket surveillance a civil or
criminal penalty

FDA can require repair, replacement, or refund for devices not
designed or made properly
History of the FDA (cont)


Temple Report 1993

Found deficiencies in the design, conduct, and analysis of
clinical trials in support of PMA’s and 510(k)’s

Expressed a need for better scientific rigor, called for
controlled, randomized, and masked trials when feasible
Medical Device Reporting regulation for
Manufacturers 1995


Requires device manufacturers to provide FDA with more
information about adverse events with substantially more
specificity
Revised GMP Regulation 1996

FDA rules for GMP now include preproduction quality
control
History of the FDA (cont)

FDA Modernization Act of 1997

Device industry’s efforts to reform FDA


their view, FDA is inefficient, unfair, needs
reform
Became effective February 19, 1998
What is a Medical Device?

Medical Device (section 201 of Federal Food, Drug, &
Cosmetic Act)

Instrument, apparatus, implement, machine, contrivance,
implant, in vitro reagent, or other similar or related article
including any component, part, or accessory which is:

recognized in the official National Formulary, or the United States
Pharmacopeia (USP), or any supplement to them;

intended for the use in the diagnosis of disease or other conditions,
or in the cure, mitigation, treatment, or prevention of disease, in
man or animals; or

intended to affect the structure of any function of the body of man
or other animals; and which does not achieve its primary intended
purposes through chemical action within or on the body of man…
and which is not dependent upon being metabolized for the
achievement of its primary purposes (i.e. not a drug).
Which Class is my Device?

Depends mainly on intended use and indications for use
Classification of Medical Devices

Class I Medical Devices “General Control”

Not life sustaining, no risk to life

Least risk of injury to either the operator or the patient

Only general controls such as adulteration/misbranding,
registration and listing, repair, replacement, refund, and
banned products are needed to ensure safety and
effectiveness

Some class I devices can be exempt from PMN (Pre-Market
Notification) and/or GMP (Good Manufacturing Practice)

Examples: manual stethoscopes, surgical scalpels, forceps,
wheelchairs, elastic bandages, exam gloves, hand-held
surgical instruments

Class II Medical Devices “General and Special Control”

Not life sustaining, no risk of life

Need additional controls such as performance standards,
post market surveillance, special labeling, patient
registries, guidelines, recommendations

Usually exempt from proving safety and efficacy,
however FDA may require additional laboratory or
clinical studies

Never exempt from PMN or GMP

Examples: endoscopes for viewing body cavities, surgical
lasers, powered wheelchairs, infusion pumps, surgical
drapes, physiological monitoring

Class III Medical Devices “General and Premarket Approval”
◦
General and special controls not sufficient to establish safety and
efficacy
◦
Used to support or sustain life or present a potential unreasonable risk
of injury or illness
◦
Generally requires an approved premarket approval (PMA) application
(PMAA), unless:

equivalent to devices marketed before 5/28/76 in which case you follow
premarket notification (PMN or 510(k)) process unless FDA has already made
that type of device follow the PMA process

PMA can take several years
◦
Failure mode analysis, animal tests, toxicology, human clinical trials
(IDE and IRB) are required
◦
Examples: indwelling gas analyzers, implanted cardiac pacemakers,
balloon catheters, stents, cardiac arrhythmia alarms, heart valves,
breast implants
Types of Class III Devices


Preamendment Device

Device that was in commercial distribution before May 28, 1976,
the date the Medical Device Amendments were signed into law.

Require a PMA only after FDA publishes a regulation calling for
PMA submissions.
Postamendment Devices


Device that was first distributed commercially on or after May
28, 1976. Subject to same requirements as equivalent
preamendment devices.
Transitional Devices

Device that was regulated as a new drug before May 28, 1976.

Any Class III device that was approved by a New Drug Application
(NDA) is now governed by the PMA regulations.

Some of the transitional devices were down-classified to Class II.
Types of Devices

In Vitro Diagnostics (IVD)

Medical devices that test for diseases, conditions, or infections.

Can be used in a laboratory setting, a professional healthcare setting, or even
for at home use.

Includes reagents, instruments, kits, or systems used to examine body
specimens such as blood or tissue.

Examples:

Common tests include blood tests for glucose, liver enzymes, levels of
electrolytes such as calcium, sodium, and potassium, and tests for drugs.

‘Specimen receptacles’ - devices specifically intended by their
manufacturers for the primary containment and preservation of specimens
derived from the human body for the purpose of in vitro diagnostic
examination.

Exempt: General lab equipment not specifically
intended for in vitro diagnostic examination.
Types of Devices

Combination Devices

A product that is a combination of a drug, device, and/or
biologic.

Includes products that are physically or chemically combined,
products that are packaged together as one unit, and any other
products that are intended for use specifically with another
product.

Office of Combination Products (OCP) assigns which center has
the primary responsibility for these types of devices.

Examples:

Device coated with
drug or biologic

Drug delivery
system
Types of Devices

Custom Devices

Devices ordered by a physician or dentist for
his or her own use or for a specific patient and
that are not generally available.

These devices cannot be labeled or advertised
for commercial distribution.

Currently being scrutinized by the FDA since a
complete DHF and FDA submission is not
required.
 Doctors
must sign waivers saying that they
release the company from all liabilities.
FDA Approval Process

Registration

Medical device manufacturers, US importers, distributors,
repackers, and relabelers must register with the FDA.

Exempt from registration:

Licensed practitioners such as physicians, dentists, and
optometrists who manufacture or alter devices solely
for their own use or practice.

Retail outlets, research manufacturers with no
commercial products, warehouse operators provided
they do not alter the devices, delivery people, people
who dispense such as audiologists, optometrists, etc.
FDA Approval Process

Device Listing
 After
being cleared for commercial
distribution, the owner/operator must
list the device with the FDA.
 Identifies the owner/operator and all
others involved in the manufacturing,
repacking, relabeling, specification
development, distribution, or
importation of the device.

Responsibility of the device is now listed
FDA Approval Process

Device Labeling

FDA requires following information on a
label:

Common name of device and accurate statement of its principal
intended actions.

Adequate directions for use:
 Indications,
dose, frequency of
administration, duration of
administration, time of
administration, route of
administration, preparation for use

Declaration of its net quantity of contents.

Name and address of the manufacturer, packer, or distributor.
FDA Approval Process

Premarket Approval (PMA)
 PMA is the FDA process of scientific and
regulatory review to evaluate the safety and
effectiveness of Class III medical devices.
 PMA’s must contain sufficient scientific evidence
to ensure it is safe and effective for its intended
use.
 FDA regulations provide 180 days to review the
PMA and must decide that the device is safe and
effective for PMA approval which may use
advisory committees
 If there is not an effective date listed for the
PMA then a Class III 510(k) should be submitted.
FDA Approval Process

Premarket notification (PMN or 510(k) )
◦
◦
Any Class I, II or III device intended for human use that does not
require a PMA must submit a 510(k) unless:

the device is exempt from PMN

was marketed before May 28, 1976

requires premarket approval (PMA)
This is a premarket submission to the FDA that demonstrates that
the device is as safe and effective as a legally marketed device
which is not subject to PMA (aka equal).

◦
The legally marketed device to which equivalence is drawn is known
as the predicate device.
This allows the FDA to decide whether the device is substantially
equivalent to a legally marketed Class I or Class II device, or to a
predicate Class III device not requiring a PMA
FDA Approval Process

Premarket notification (PMN or 510(k) )
(cont)


To say the device is substantially equivalent means it need
to be AT LEAST as safe and effective as the predicate
device therefore it:

Has the same intended use as the predicate and as the same
technological characteristics as the predicate OR

Has the same intended use as the predicate and has different
technological characteristics and information submitted to the FDA
A device may not be marketed until the device is declared
substantially equivalent. If it is not then the submitter
may

Resubmit a 510(k) with new data

Submit a PMA

Or reclassify the device
FDA Approval Process

Good Manufacturing Practices (GMP)

Part of a quality system covering the manufacture and
testing of pharmaceuticals, food and medical devices.

Includes clearly defined and controlled processes to
validate a process for consistent testing and results.

Must provide assurance that the device is manufactured
under regulated conditions and controls that ensure it is
safe and effective for the intended use.


6o
Needs a quality assurance program (QA)

Refers to a program with systematic monitoring and
evaluation to ensure the quality of the system/product is met.

Quality Departments
FDA Approval Process

Investigational Device Exemptions (IDE)

Section 520 of the FD&C Act provides manufacturers the
authority to ship devices solely for investigational use if
they obtain approval for an IDE as part of a Pre Market
Approval

get the clinical data needed for the PMA

Unless exempt, all clinical evaluations of investigational
devices must have an approved IDE before starting the
study.

If evaluation is not cleared for marketing requires:

An IDE approved by an institutional review board (IRB) and if there is a risk
with the device then FDA approval is also needed.

Consent from patients

Labeling for investigational use only

Monitoring of the study as well as records and reports.
FDA Approval Process

Investigational Device Exemptions (IDE) (cont)

the IDE application must include

device description

prior investigations

investigational plan

facility where the device was made

investigator agreements

institutions where the study will be conducted

proposed labeling

description of clinical evaluation and IRB supervision

informed consent from human subjects
Example In Industry (Pharmaceuticals)
Example in Industry (Medical Devices)
New Development Product (i.e. at US Endoscopy)
Production Level
Device is Ready
In Vitro Testing
on Animal Parts
Testing acceptable
Bench Testing (Age,
Output Verification, etc.)
Testing acceptable
Formal
Application to
the FDA
Design Limited Market
Release (Clinical Testing
on Patients)
Testing acceptable
90 or 180 days
Full
Market
Release
redesign
FDA Consent Decree

What is it?



An agreement between the FDA and a company that
outlines steps to return a product to full production
Aligns FDA’s vision of GMP’s with the companies
Company has to stop marketing and manufacturing the
product that is not in compliance

Unless the device is life saving
FDA Consent Decree


What causes it?

Recall of product due to manufacturing defect

Failed audit results in “serious” warning letter

Series of “less serious” warning letters

Failure to comply to inspection reporting in a timely
manner
What should a company do?

Reconfigure their compliance procedures to meet FDA
requirements