Food and Drug Administration
Kevin Bedal, Lisa Carlin, Matt Carroll, Erin Nichols
October 24th, 2011
An Overview of the FDA
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Regulates $1 trillion worth of products
◦ 25 cents of every dollar spent by Americans
Regulates cosmetics, food, blood supply, medicines,
biological, medical devices, radiation-emitting products,
and feed & drugs for animals
Performs surveillance of regulated products
Makes sure products are labeled truthfully
Employs 9,000 employees
◦ cost is $3 / person/yr
◦ 95,000 FDA-regulated businesses
An Overview of the FDA (cont)
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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
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2010 Infant Formula Recall
◦ On September 22, 2010, Abbott issued a voluntary
recall of certain Similac powdered infant formula after
identifying a common warehouse beetle (both larvae
and adults) in the finished product at their Sturgis,
Michigan plant.
◦ The company said it was voluntarily recalling just shy
of 5 million units of Similac, the top-selling baby
formula, in United States, Guam, Puerto Rico and
other Caribbean markets.
Major Centers at FDA
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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
◦ regulates biologically produced products such as blood, vaccines,
biological therapeutics
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Center for Drug Evaluation and Research
◦ regulates the safe and effective use of drugs
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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
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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.
History of the FDA
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Federal Food, Drug, and Cosmetic Act (FD&C Act) 1938
◦ 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
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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)
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Bureau of Medical Devices (BMD) 1974
◦ began classifying medical devices
◦ created Office of Small Manufacturers Assistance to help manufacturers
understand the law
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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)
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Good Manufacturing Practices Regulation (GMP) 1978
◦ comprehensive set of requirements on
 facilities
 methods
 controls for manufacturing, packaging, and storage of medical devices
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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)
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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)
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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
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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
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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)
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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
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Medical Device Reporting regulation for Manufacturers
1995
◦ requires device manufacturers to provide FDA with more
information about adverse events with substantially more
specificity
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Revised GMP Regulation 1996
◦ FDA rules for GMP now include preproduction quality control
History of the FDA (cont)
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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?
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Medical device (section 201 of the Federal F,D, & C 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).
Difference in Roles/ Responsibilities
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Medical Device Manufacturer
◦ Any person who manufactures, fabricates, assembles, or
processes a finished device, including any repacker and/or
relabeler.
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Medical Device Distributor
◦ Any person who furthers the marketing of a device from the
original place of manufacture, whether domestic or imported, to
the person who makes final delivery or sale to the ultimate
consumer or user, but who does not repackage or otherwise
change the container, wrapper, or labeling of the device or the
device package.
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Medical Device Company Owner/Operator
◦ The name of the corporation, subsidiary, affiliated company,
partnership, or proprietor.
Classification of Medical Devices
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Class I Medical Devices
◦ 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
◦ examples include manual stethoscopes, surgical scalpels, forceps,
wheelchairs, elastic bandages, exam gloves
◦ some class I devices can be exempt from PMN and/or GMP
Classification of Medical Devices
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Class II Medical Devices
◦ also not life sustaining
◦ need additional controls such as performance standards,
postmarket surveillance, special labeling, patient registries,
guidelines, recommendations
◦ examples include endoscopes for viewing body cavities, surgical
lasers, powered wheelchairs, infusion pumps, surgical drapes
◦ usually exempt from proving safety and efficacy, however FDA
may require additional laboratory or clinical studies
◦ class II devices are never exempt from PMN or GMP
Classification of Medical Devices
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Class III Medical Devices
◦ 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 a
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 include indwelling gas analyzers, implanted cardiac
pacemakers, balloon catheters, stents, cardiac arrhythmia alarms,
heart valves, breast implants
Types of Class III Devices
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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.
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Postamendment Devices
◦ Device that was first distributed commercially on or after May 28, 1976.
Subject to same requirements as equivalent preamendment devices.
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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.
Which Class is my Device?
Types of Devices
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In Vitro Diagnostics
◦ 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 (cont)
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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 (cont)
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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
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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
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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.
FDA Approval Process
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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
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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
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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
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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
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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.
◦ 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.
FDA Approval Process
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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
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Investigational Device Exemptions (IDE) (cont)
◦ the IDE application must include
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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