The Medical Device Approval Process and Related Legislative Issues
Congressional research reportMar 20, 2010
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The Medical Device Approval Process and
Related Legislative Issues
Erin D. Williams
Specialist in Public Health and Bioethics
March 20, 2010
Congressional Research Service
7-5700
www.crs.gov
RL32826
CRS Report for Congress
Prepared for Members and Committees of Congress
c11173008
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The Medical Device Approval Process and Related Legislative Issues
Summary
The central medical device issue for Congress is how best to help speed medical devices to
consumers if they are safe and effective, and correct them or keep them from consumers if they
are not. A medical device may be anything from a tongue depressor to a pacemaker. In order to be
legally marketed in the United States, medical devices must be approved by the Food and Drug
Administration (FDA), the agency responsible for protecting the public health by assuring the
safety, efficacy, and security of human medical devices and other products. FDA’s Center for
Devices and Radiological Health (CDRH) is primarily responsible for medical device review. The
regulation of medical devices can affect their cost, quality, and availability in the health care
system.
During reviews, FDA classifies devices according to the risk they pose to consumers. If a
premarket review is warranted by the potential risk, a manufacturer must demonstrate that its
device is safe and effective, or substantially equivalent to a device already on the market. FDA
requires product manufacturers to register their facilities, list their devices with FDA, and follow
general controls requirements. Manufacturers of FDA-approved devices are required to report
serious adverse events associated with the use of their devices to FDA. In addition, tracking is
required for some medical devices.
The medical device approval process is currently funded through direct FDA appropriations from
Congress, and increasingly through user fees collected from applicants. FDA’s authority to collect
user fees, originally authorized in 2002 (P.L. 107-250), has been reauthorized in five-year
increments. It will next expire on October 1, 2012, under the terms of the FDA Amendments Act
of 2007 (P.L. 110-85).
A number of medical device-related topics are of interest to Members of the 111th Congress, and
have prompted the introduction of legislation with pertinent provisions. Three such topics are
included in major health reform bills: medical device-related taxes as a source of revenue for
health reform (House-passed H.R. 3962; Senate-passed H.R. 3590; and the accompanying
reconciliation bill, Amendment in the Nature of a Substitute to H.R. 4872, as amended by a
manager’s amendment); a national medical device registry (House-passed H.R. 3962); and
reporting requirements for gifts to physicians (House-passed H.R. 3962 and Senate-passed H.R.
3590).
Device-related topics addressed in other legislation include liability and preemption, as
highlighted by Riegel v. Medtronic and Wyeth v. Levine (S. 540/H.R. 1346, H.R. 1086, S. 45, and
S. 1324); the 501(k) clearance and device approval processes (H.R. 1321/S. 391); importation and
inspection (H.R. 759 and S. 882); advertising (S. 301/H.R. 3138 and H.R. 3261); use of
unapproved devices (H.R. 3261); laboratory test (in vitro diagnostic, or IVD) regulation; (H.R.
1699 and H.R. 1452); issues specific to certain devices, situations, diseases, or conditions (S. 717,
S. 819, H.R. 1878, S. 586/H.R. 1483, H.R. 1380, H.R. 1236, H.R. 1142, S. 422/H.R. 1032, H.R.
1021, H.R. 554, S. 332, S. 254/H.R. 574, S. 236, H.R. 463, S. 21, H.R. 2088, H.Res. 577, and S.
1746); and certain other issues (H.R. 1531/S. 1089, H.R. 1737, S. 1733, S. 1591/H.R. 3560, H.R.
2454/S. 2998, H.R. 3012, H.R. 3090, H.R. 3242, and H.R. 3932).
This report contains the legislative history of medical device regulation, describes FDA’s
approval process for medical devices, and provides an overview of the medical device-related
legislative issues facing Congress.
This report will be updated as events warrant.
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The Medical Device Approval Process and Related Legislative Issues
Contents
Introduction ................................................................................................................................1
Medical Devices and Their Manufacturers...................................................................................3
The History of Laws Governing Medical Device Regulation ......................................................4
The Medical Device Approval Process: Premarket Review Requirements....................................5
Fundamental Concepts and Terms of Art ...............................................................................6
Safety and Effectiveness .................................................................................................6
Approval and Clearance ..................................................................................................6
Device Classification ......................................................................................................7
Medical Device Marketing Applications................................................................................9
Before a Marketing Application Is Submitted ................................................................ 10
Marketing Applications for Medical Devices................................................................. 11
In Vitro Diagnostic (IVD) Products................................................................................ 16
The Medical Device Approval Process: Post-Approval Requirements and Issues ...................... 18
Labeling........................................................................................................................ 18
Manufacturing .............................................................................................................. 19
Postmarket Surveillance................................................................................................ 20
Adverse Event Reporting .............................................................................................. 20
The Sentinel Initiative ................................................................................................... 21
Medical Device Tracking .............................................................................................. 21
Unique Device Identification......................................................................................... 22
Compliance and Enforcement........................................................................................ 22
Legislative Issues ...................................................................................................................... 25
Proposals in Health Reform Legislation .............................................................................. 25
Device-Related Taxes.................................................................................................... 25
National Medical Device Registry................................................................................. 27
Gifts to Physicians and Other Health Providers ............................................................. 27
Liability and Preemption ..................................................................................................... 28
510(k) Clearance and Device Approval ............................................................................... 28
Importation and Inspection.................................................................................................. 29
Unapproved Devices ........................................................................................................... 29
Advertising ......................................................................................................................... 29
IVD Regulation................................................................................................................... 30
Device-Specific Legislation ................................................................................................ 30
Other Issues ........................................................................................................................ 31
Tables
Table 1. Appropriations for the FDA Devices and Radiological Health Program (DR&H),
Medical Device User Fees, and Medical Device User Fees as a Percentage of Total
DR&H Program Level Appropriations, FY2003-FY2011 .........................................................2
Table 2. Medical Device Approval Basics....................................................................................9
Table 3. CDRH, FDA Foreign and Domestic Inspections, FY2004 – FY2008 ............................ 22
Table 4. CDRH Warning Letters Issued, FY2000-FY2009......................................................... 24
Table 5. CDRH Class I, II, and III Product Recalls, FY2004 - FY2008 ...................................... 25
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Contacts
Author Contact Information ...................................................................................................... 31
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The Medical Device Approval Process and Related Legislative Issues
Introduction
There are many dimensions to the central medical device issue confronting Congress: how to
speed medical devices to consumers if they are safe and effective, and correct them or keep them
from consumers if they are not. The goals of device availability and device safety may exert
opposite pulls, with implications for consumers, the health care system, and the economy.
Investment in medical device development reportedly reached a high of $3.790 billion in 2007.
However, investment has slowed considerably since then, reaching only $3.337 billion in 2008,
and $1.197 billion in the first three quarters of 2009.1 The products generated by the nation’s
venture capital-backed biotechnology and medical devices and equipment sectors supported
nearly 494,000 high-skilled, high-wage jobs in 2006.2
Manufacturers make decisions about pursuing new devices based in part on the cost of their
development. Additional regulatory requirements may escalate these costs, while other incentives,
such as tax breaks or market exclusivity extensions, may diminish them. If the device
development cost is too high, the eventual result may be that consumers are denied access
because new products are not developed or brought to market. Access problems have led to
proposals for and the enactment of incentives to develop medical devices for rare diseases and
pediatric populations. However, if the regulation and oversight of device development are not
stringent enough, unsafe or ineffective products may reach the market and cause harm to
consumers.
Troubles related to medical devices can have serious consequences for consumers. Problems with
the procedures and equipment for HIV (human immunodeficiency virus) and hepatitis C
laboratory tests have led to hundreds of incorrect test results.3 Defects in other types of medical
devices, such as pacemakers, defibrillators, and coronary stents, have caused patient deaths.4
Consequences such as these have raised questions as to whether adequate enforcement tools,
resources, and processes are in place to ensure that marketed devices are safe.
The federal agency primarily responsible for ensuring the safety and effectiveness of medical
devices and certain other products (drugs and biologics, for example) is the Food and Drug
Administration (FDA)—one agency within the Department of Health and Human Services
(HHS). A manufacturer must receive FDA permission before its device can be legally marketed in
the United States. FDA’s Center for Devices and Radiological Health (CDRH) is primarily
responsible for medical device review. One other center, the Center for Biologics Evaluation and
Research (CBER), regulates some devices—specifically those associated with blood collection
and processing procedures, as well as with cellular therapies (e.g., stem cell treatments).
1
PriceWaterhouseCoopers/ National Venture Capital Association, “Medical Devices and Equipment,” Money Tree
Report, data provided by Thomson Reuters, at http://www.pwcmoneytree.com, searched January 26, 2010.
2
Global Insight, “Venture Impact: The Economic Importance of Venture Capital Backed Companies to the U.S.
Economy, Fourth Edition” (2008), at http://www.nvca.org/pdf/NVCA_VentureCapital07-2nd.pdf. (Note: the fifth
edition, published 2009, did not contain information about jobs and the device industry.)
3
See “Maryland Hospital Officials Resign After Patients Receive Incorrect HIV, Hepatitis C Test Results Processed in
Lab,” Kaiser Network, Across The Nation (April 22, 2004), at http://www.kaisernetwork.org/daily_reports/
rep_index.cfm?DR_ID=23322.
4
Information on recalls is available by searching the database at FDA, Medical Device Recalls, Database,
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRES/res.cfm.
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Jurisdiction of the centers’ medical device review is governed by the FDA Intercenter Agreement
between CBER and CDRH (October 31, 1991).5
FDA’s medical device review process is funded through a combination of public money (direct
FDA appropriations from Congress) and private money (user fees collected from device
manufacturers), which together comprise FDA’s total program level.6 Since they were first
collected in FY2003, the medical device user fee amounts have risen more quickly than direct
appropriations for device-related activities (see Table 1).7 Congress has reauthorized in five-year
increments FDA’s collection of medical device user fees. The authority will next expire on
October 1, 2012.
Table 1. Appropriations for the FDA Devices and Radiological Health Program
(DR&H), Medical Device User Fees, and Medical Device User Fees as a Percentage of
Total DR&H Program Level Appropriations, FY2003-FY2011
(dollars in thousands)
Total Program Level
Medical Device User Fees
MDUFA /Total
FY2003 Actual
$217,285
$14,838
6.8%
FY2004 Actual
$221,506
$23,875
10.8%
FY2005 Actual
$244,282
$27,161
11.1%
FY2006 Actual
$255,041
$32,069
12.6%
FY2007 Actual
$267,543
$35,202
13.2%
FY2008 Actual
$275,284
$36,422
13.2 %
FY2009 Actual
$345,311
$47,304
13.7%
FY2010 Appropriation
$368,342
$57,014
15.5%
FY2011 Request
$384,815
$61,860
16.1%
Sources: Food and Drug Administration tables for FY2005 - FY2011, “ALL PURPOSE TABLE - Total Program
Level,” at http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/BudgetReports/default.htm.
Notes: (1) Devices and Radiological Health (D&RH) total program level is the sum of budget authority and fees
allocated from the MDUFA and MQSA authorities. The FY2011 request for the D&RH program includes $3.2
million in proposed reinspection user fees. (2) The numbers contained in this table were compiled by Susan
Thaul, Specialist in Drug Safety and Effectiveness, CRS (sthaul@crs.loc.gov, 7-0562).
Medical device issues confronting the Congress arise in the context of a variety of concerns about
FDA and CDRH.8 Chief among these is that, in September of 2007, Congress passed the most
5
FDA, Devices Regulated by the Center for Biologics Evaluation and Research, January 8, 2010, http://www.fda.gov/
BiologicsBloodVaccines/DevelopmentApprovalProcess/510kProcess/ucm133429.htm.
6
For more information on FDA’s budget, See CRS Report RL34334, The Food and Drug Administration: Budget and
Statutory History, FY1980-FY2007, coordinated by Judith A. Johnson; CRS Report RL34638, FDA FY2009
Appropriations, coordinated by Susan Thaul.
7
For more information about medical device user fees, see CRS Report RL34571, Medical Device User Fees and User
Fee Acts, by Erin D. Williams, and CRS Report RL33981, Medical Device User Fee and Modernization Act
(MDUFMA) Reauthorization, by Erin D. Williams. FDA also funds some device and radiological health activities with
fees collected under the Mammography Quality Standards Act (MQSA, P.L. 102-539), and some device user fees fund
non-device specific activities at FDA.
8
See CRS Report RS22946, Food and Drug Administration (FDA): Overview and Issues, by Erin D. Williams.
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comprehensive FDA reform legislation in almost a decade: the Food and Drug Administration
Amendments Act of 2007 (FDAAA; P.L. 110-85).9 The impact of FDAAA for medical device
regulation is discussed below in the “The History of Laws Governing Medical
Device Regulation” section. In the wake FDAAA, issues related to medical devices and other
products remain. These exist both in areas that FDAAA did not comprehensively address, and in
areas raised by its implementation. Such issues are discussed in the “Legislative Issues” section
of this report.
In order to fully understand the medical device related legislative issues that Congress faces,
some background information is illustrative. This report provides an overview of the following:
medical devices and their manufacturers, the history of FDAAA and other laws governing
medical device regulation, and the medical device approval process. The final section surveys the
device-related legislative issues of interest to Congress.
Medical Devices and Their Manufacturers
Medical device regulation is complex, in part because of the wide variety of items that are
categorized as medical devices. They may be simple tools used during medical examinations,
such as tongue depressors and thermometers. They may be high-tech life-saving implants like
pacemakers and coronary stents. They may be machines used for diagnostic purposes, like CAT
scans and EEG machines. They may even be test kits used in laboratories or by consumers at
home, such as tests for pregnancy or blood glucose levels.
According to law, a medical device is an instrument, apparatus, implement, machine, contrivance,
implant, in vitro reagent, or other similar or related article, including any component, part, or
accessory, that (1) does not achieve its primary intended purposes through chemical action within
or on the body of humans or other animals, (2) is not dependent upon being metabolized for the
achievement of its primary intended purposes, and (3) is one of the following:
•
recognized in the official National Formulary, or the United States Pharmacopeia,
or any supplement to them;
•
intended for use in the diagnosis of disease or other conditions, or in the cure,
mitigation, treatment, or prevention of disease, in humans or other animals; or
•
intended to affect the structure or any function of the body of man or other
animals.10
The medical device market is highly fragmented: surgical and medical supplies make up the
largest sector, followed by in vitro diagnostic products (IVDs, which are laboratory tests),
cardiovascular devices, orthopedic devices, and diagnostic imaging. 11 Although the largest
companies dominate the market for devices in terms of sales, it is often the small companies that
make a significant contribution to early innovation. Small companies often partner with larger
9
See CRS Report RL34465, FDA Amendments Act of 2007 (P.L. 110-85), by Erin D. Williams and Susan Thaul.
Federal Food, Drug and Cosmetic Act §201(h), (21 U.S.C. 321).
11
The Lewin Group, for AdvaMed, The Impact of Regulation and Market Dynamics on Innovation: The State of the
Industry (Washington, DC, 2001).
10
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companies to bring products to market, because they often lack access to capital, and the
resources to conduct clinical trials and navigate the regulatory and reimbursement hurdles.
These characteristics of the medical device industry distinguish it from the drug industry, which is
less fragmented, larger, and dominated by larger companies. The U.S. medical device industry as
a whole is much smaller than the U.S. pharmaceutical industry. For example, the Centers for
Medicare and Medicaid Services reports that the 2008 annual national health expenditures were
$234.1 billion for prescription drugs, and $26.6 billion for durable medical equipment.12 As a
result, device companies often do not have the economic or financial resources of multi-billion
dollar drug companies. These distinctions between device and drug manufacturers may be
relevant in some regulatory discussions. Incentives and requirements placed on drug
manufacturers are sometimes applied to device manufacturers as well, on which they may have a
markedly different impact.
The History of Laws Governing Medical
Device Regulation
Though food has been regulated since early colonial times, and drugs since the Drug Importation
Act of 1848, medical devices did not come under federal scrutiny until Congress passed the
Federal Food, Drug and Cosmetic Act (FFDCA) of 1938 (P.L. 75-717). At that time, few medical
devices existed. In 1966, the Fair Packaging and Labeling Act (P.L. 89-755) required all
consumer products in interstate commerce to be labeled accurately and truthfully, with FDA
enforcing the provisions on regulated medical products, including medical devices.
The Medical Device Amendments of 1976 (MDA; P.L. 94-295) was the first major legislation
passed to ensure safety and effectiveness of medical devices, including diagnostic products,
before they could be marketed. The amendments required manufacturers to register with FDA and
follow quality control procedures in their manufacturing processes. Some products were required
to undergo premarket review by FDA, while others had to meet performance standards before
marketing. Devices already on the market in 1976 (preamendment or grandfathered devices) did
not have to undergo retrospective approval for marketing. Instead, they were to be broadly
classified by FDA into one of three regulatory classes based on the risk they posed to the patient.
Devices coming to market after 1976 had to undergo premarket review (unless they were
exempt). Devices could be cleared by FDA if they were substantially equivalent to a
preamendment device. If the device (or its use) were truly novel, it could be approved if it was
proven safe and effective on its own merits.
In 1990, the Safe Medical Devices Act (SMD Act; P.L. 101-629) established postmarket
requirements for medical devices. The SMD Act required facilities that use medical devices to
report to FDA any incident that suggested that a medical device could have caused or contributed
to the death, serious illness, or injury of a patient. Manufacturers of certain permanently
implanted devices were required to establish methods for tracking the patients who received them
12
Centers for Medicare and Medicaid Services, NHE Web Tables (Historical), Table 2. National Health Expenditures
Aggregate Amounts and Average Annual Percent Change, by Type of Expenditure: Selected Calendar Years 19602008, Washington, DC, p. 2, http://www.cms.hhs.gov/NationalHealthExpendData/downloads/tables.pdf. [Note that the
definition of durable medical equipment (DME) (Social Security Act sec. 1861(n)), is not identical to that for medical
devices (FFDCA 201(h)), but is the most similar type of expenditure tracked by CMS.]
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and to conduct postmarket surveillance to identify adverse events. The act authorized FDA to
carry out certain enforcement actions, such as device product recalls, for products that did not
comply with the law.
In 1997, the Food and Drug Administration Modernization Act (FDAMA; P.L. 105-115)
mandated the most wide-ranging reforms in FDA practice since 1938. For medical devices,
provisions included measures to accelerate premarket review of devices and to regulate company
advertising of unapproved uses of approved devices.
In 2002, the Medical Device User Fee and Modernization Act (MDUFMA; P.L. 107-250)
amended the FFDCA to enact three significant provisions for medical devices: (1) it established
user fees for premarket reviews of devices; (2) it allowed establishment inspections to be
conducted by accredited persons (third parties); and (3) it instituted new regulatory requirements
for reprocessed single-use devices. MDUFMA was amended and clarified by two laws: the
Medical Device Technical Corrections Act (MDTCA, P.L. 108-214), and the Medical Device
User Fee Stabilization Act of 2005 (MDUFSA, P.L. 109-43), and had its user fee provisions
reauthorized by the Medical Device User Fee Act of 2007 (MDUFA; Title II of FDAAA). 13
In 2007, FDAAA amended the FFDCA and the Public Health Service Act to reauthorize several
expiring programs (including the medical device user fee act) and to make agency-wide changes,
several of which have implications for the regulation of medical devices. 14 FDAAA created
incentives as well as reporting and safety requirements for manufacturers of medical devices for
children; required that certain clinical trials for medical devices and some other products be
publicly registered and have their results posted;15 created requirements to reduce conflicts of
interest in advisory committees for medical devices and other products;16 and made certain other
amendments to the regulation of devices.
The Medical Device Approval Process: Premarket
Review Requirements
In order for medical devices to be marketed in the United States, manufacturers17 must register
and list the devices that they commercialize with FDA, and for most devices, must obtain the
agency’s prior and continuing permission.18 FDA grants this permission when a manufacturer
13
See CRS Report RL34571, Medical Device User Fees and User Fee Acts, by Erin D. Williams; For historical
background, see CRS Report RL33981, Medical Device User Fee and Modernization Act (MDUFMA)
Reauthorization, by Erin D. Williams.
14
See CRS Report RL34465, FDA Amendments Act of 2007 (P.L. 110-85), by Erin D. Williams and Susan Thaul.
15
See the Clinical Trials Databases section of CRS Report RL34465, FDA Amendments Act of 2007 (P.L. 110-85), by
Erin D. Williams and Susan Thaul.
16
FDA uses advisory committees to gain independent advice from outside experts. See CRS Report RS22691, FDA
Advisory Committee Conflict of Interest, by Erin D. Williams.
17
The term manufacturer is used throughout this report for simplicity, but regulations also apply to any person,
organization, or sponsor that submits an application to FDA to market a device.
18
Certain medical devices that present only a minimal risk, such as plastic bandages and ice bags, can be legally
marketed upon registration alone. These low-risk devices are deemed exempt from premarket review, and
manufacturers need not submit an application to FDA prior to marketing them. Manufacturers of exempt devices are
still typically required to comply with other regulations, known as general controls. (21 CFR 862-892).
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meets regulatory premarket and postmarket requirements. The premarket requirements, which are
the subject of this section, vary according to a the risk that a device presents. IVDs have their own
unique premarket requirements.
FDA may grant a manufacturer permission to market a device after conducting a premarket
review, based on an application from the manufacturer. There are numerous types of applications
a manufacturer can submit to obtain such permission, which are described later in this section.
First, however, this section presents some fundamental concepts and terms of art that will help
readers to understand the details of the various application processes. These include safety and
effectiveness, approval and clearance (including substantial equivalence to a predicate device),
and device classification (including types of controls).
Fundamental Concepts and Terms of Art
Safety and Effectiveness
FDA has as a part of its mission to ensure that medical devices are safe and effective. The
evidence required to meet the safe and effective standard varies according to the characteristics of
the device, its conditions of use, the existence and adequacy of warnings and other restrictions,
and the extent of experience with its use.19 FDA considers there to be reasonable assurance of
safety when it can be determined that the probable benefits to health that result from use of the
device as directed by the manufacturer outweigh any probable risks. 20 Investigations for safety
can include animal studies, human studies, and/or laboratory studies.21
FDA considers there to be reasonable assurance of effectiveness when valid scientific evidence
suggests that the target population’s use of the device (according to the manufacturer’s
instructions) provides clinically significant results.22 Valid scientific evidence includes that from
controlled clinical trials, other carefully defined clinical investigations, case histories, and other
reports of significant human experience. Evidence can be collected by the manufacturer or a
representative, and can be abstracted from medical literature.
Approval and Clearance
There are two paths that manufacturers can use to bring their medical devices to market with
FDA’s permission. One path consists of conducting clinical studies comparable to those required
for new prescription drugs. This process, generally used for novel and high-risk devices, is
typically lengthy and expensive. It results in a type of FDA permission called approval.
The other path is to demonstrate that the device is substantially equivalent to a device that is
already on the market (a predicate device).23 This type of process is unique to medical devices. It
19
21 CFR § 860.7(c)(2).
21 CFR § 860.7(d)(1).
21
21 CFR § 860.7(d)(2).
22
21 CFR § 860.7(e)(1).
23
To be a predicate, a device must have either been on the market before 1976 when the MDA took effect, or it could
have been cleared for marketing after 1976, but must have the same intended use as a device classified in the CFR.
20
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is typically used for new devices that make incremental improvements or modifications to
previous versions. It results in FDA clearance, and tends to be much less expensive and less timeconsuming than seeking FDA approval.
Substantial equivalence is determined by comparing the performance characteristics of a new
device with those of a predicate device. To be considered substantially equivalent, FDA must
determine that the new device has the same intended use (also called indication(s) for use) as a
predicate device.24 In addition, the new device must either (1) have the same technological
characteristics as the predicate, (2) have different technological characteristics that do not raise
new questions of safety and effectiveness, or (3) be least as safe and effective as the predicate.
The manufacturer selects which predicate device to compare with its new device. However, FDA
has the ultimate discretion in determining whether a comparison is appropriate.
Here is an example of how a device might be cleared through a determination of substantial
equivalence. If a manufacturer wanted to market a blood glucose test for diabetes, it could apply
to FDA for a determination that the new device is substantially equivalent to a blood glucose test
for diabetes that was sold in 1972. FDA has classified these devices in the Code of Federal
Regulations (CFR) as follows (note, the device classification process is described at the start of
the next section):
21 CFR 862.1345 Glucose test system.
(a) Identification. A glucose test system is a device intended to measure glucose
quantitatively in blood and other body fluids. Glucose measurements are used in the
diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus,
neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.
(b) Classification. Class II.
The manufacturer would likely ask FDA to clear the new device based on evidence that it was
substantially equivalent to the device described in the CFR, rather than based on a large-scale
clinical study. To obtain FDA clearance, the manufacturer would need to demonstrate two things.
First, that the new device did not present new questions of safety and effectiveness. Second, that
it had the same intended use as the older device (i.e., “intended to measure glucose quantitatively
in blood and other body fluids”). If, based on the evidence, FDA determined that the new device
was substantially equivalent to the predicate, the agency could clear the new device, and the
manufacturer could market it.
Device Classification
Under the terms of the MDA, FDA has created three broad categories to describe the risk that
each medical device poses to its intended patients (the target population) when it is used or
misused. 25 The risk categories (known as classifications) are Class I, II , and III, which represent
24
The statement of intended use is a general description of the diseases or conditions that the device will diagnose,
treat, prevent, cure, or mitigate, including a description, where appropriate, of the patient population for which the
device is intended. (21 CFR § 807.92(a)(5), and § 814.20 (b)(3)(I))
25
Preamendment medical devices (those on the market prior to the passage of the MDA in 1976) were presumed to be
marketable. They did not need to undergo premarket review, and could be legally unless and until FDA required their
removal. As required by the MDA, FDA classified the preamendment devices and used them as the basis for creating
(continued...)
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low-, moderate-, and high-risk categories, respectively. (See Table 2.) Since the MDA was
enacted, the agency has classified over 1,700 distinct types of devices and organized them in the
Code of Federal regulations (CFR) in 16 medical specialties (referred to as classification panels),
such as “cardiovascular devices” or “ear, nose, and throat devices.”26
FDA can classify a new device based on comparison with a legally marketed device, by
regulation, or by recognizing that if falls into a classification panel. If unsure what classification a
product would receive, a manufacturer may make a formal request for classification to FDA.
A device’s classification determines the type of regulatory requirements that a manufacturer must
follow. These regulatory requirements, known as controls, are described in more detail in the
descriptions of Class I, II, and II devices that follow.
Class I
Devices in Class I are those for which general controls are sufficient to ensure their safe and
effective use (21 CFR § 860.3(c)(1)). General controls, the minimum regulations that apply to all
FDA regulated medical devices, include five elements:27
•
establishment registration—registration with FDA of companies required to do
so under 21 CFR 807.20 (such as manufacturers, distributors, repackagers and
relabelers, and foreign firms);
•
device listing—listing with FDA of all devices to be marketed;
•
good manufacturing practices (GMP)—manufacturing of devices in accordance
with the Quality Systems Regulation (QSR) in 21 CFR 820;
•
labeling—labeling of devices in accordance with 21 CFR 801 or 809; and
•
premarket notification—submission to FDA of a premarket notification 510(k)
(described in detail in the Types of Device Marketing Applications section
below).
Many Class I devices are exempt from the premarket notification and/or the QSR requirements,
though they still have to comply with the other general controls. A device is exempt if FDA
determines that it presents a low risk of illness or injury to patients. (See 21 CFR 862 to 892).
Class II
Devices in Class II are those for which general controls alone are not sufficient to provide
reasonable assurance of safety and effectiveness. Class II includes devices that pose a moderate
risk to patients, and may include new devices for which information or special controls are
(...continued)
the classification panels and as the first cadre of predicate devices that could be used to demonstrate substantial
equivalence.
26
FDA, Device Classification, June 18, 2009, http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/
Overview/ClassifyYourDevice/default.htm.
27
FFDCA 513(a)(1)(A); also see FDA, General and Special Controls, April 30, 2009, http://www.fda.gov/
MedicalDevices/DeviceRegulationandGuidance/Overview/GeneralandSpecialControls/default.htm.
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available to reduce or mitigate risk. Most Class II devices require premarket review; however,
some are exempt by regulation (21 CFR 860.3(c)(2)).
Special controls are requirements beyond general controls that FDA deems necessary to assure
safe and effective use of a medical device (FFDCA 513(a)(1)(B)). They might include, for
example, performance standards, postmarket surveillance requirements, or patient registries, or
the development and dissemination of guidelines.
Class III
Class III medical devices include those for which general and/or special controls are not sufficient
to assure safe and effective use of the device, and which require premarket approval (PMA;
described in detail in the Medical Device Marketing Applications section below; FFDCA
513(a)(1)(C)). Class III includes devices which are life-supporting or life-sustaining, and devices
which present a high or potentially unreasonable risk of illness or injury to a patient. New devices
that are not classified as Class I or II by another means, are automatically designated as Class III
unless the manufacturer files a request or petition for reclassification under FFDCA 513(f)(2).
(Also see 21 CFR 860.3(c)(3).)
Table 2. Medical Device Approval Basics
Device
Classification
Examples
Safety / Effectiveness
Controls
Required Submissiona
Class I
elastic bandages, examination gloves,
and hand-held surgical instruments
General Controls
-Registration only unless
510(k) specifically required
Class II
powered wheelchairs, infusion pumps,
and surgical drapes
General Controls &
Special Controls
-510(k) clearance
unless exempt
-IDE possibleb
Class III
heart valves, silicone gel-filled breast
implants, and implanted cerebella
stimulators
General Controls &
Premarket Approval
-PMA approval
unless 510(k) specifically
permitted
-IDE probable
a.
Each type of required submissions is described in the Types of Device Marketing Applications section that
follows.
b.
IDE means investigational device exemption, as described below in the “Before a Marketing Application Is
Submitted” section.
Medical Device Marketing Applications
As stated above, a manufacturer can market a device if FDA determines that the device is safe
and effective. The agency makes that determination based on information the manufacturer
submits. The information that is required—in other words, the type of marketing application the
manufacturer must make (if any)—is determined based on the risk of that the device poses, if
used according to the manufacturer’s instructions. Under the terms of MDUFA, manufacturers
must pay a fee for most types of submissions.28
28
See CRS Report RL34571, Medical Device User Fees and User Fee Acts, by Erin D. Williams.
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Generally speaking, according to the FFDCA, manufacturers
•
are prohibited from selling an adulterated product;29
•
are prohibited from misbranding a product;30
•
must register their facility with FDA and list all of the medical devices that they
produce or process (a process which now requires a fee under the terms of
FDAAA);
•
must file the appropriate premarket submission with the agency at least 90 days
before introducing a non-exempt device onto the market; and
•
must report to FDA any incident that they are aware of that suggests that their
device may have caused or contributed to a death or serious injury.
Very few applications are actually denied approval. Instead, an application may be deemed “not
approvable” in its current form (typically because the data that the manufacturer provides are not
sufficient to demonstrate safety and effectiveness). Applications that are “not approvable” are
usually withdrawn by the manufacturer before a denial is rendered.
Before a Marketing Application Is Submitted
FDAMA gave FDA the authority to establish procedures for meeting with manufacturers prior to
preparing a submission. 31 The procedures aim to speed the review process by giving FDA and a
manufacturer the opportunity to address questions and concerns about the device and/or the
planned studies that will be used to support the marketing application before the studies are
initiated and the application is submitted. For example, the “pre-IDE” process (an IDE is an
investigational device exemption that allows a manufacturer to conduct a clinical trial on a
medical device) is an informal “pre-submission” process. The “pre-IDE” process is so-called in
name only; submitting a pre-IDE does not mean that manufacturers are required to submit
subsequently an IDE application.32 The pre-IDE process is simply a means for FDA and industry
to engage in dialogue about a new device, before a study is initiated or a marketing application is
submitted.
The pre-IDE process may involve sending analytical or clinical protocols to FDA for review and
comment before proceeding with studies, or meeting with FDA to discuss protocols and/or
possible regulatory pathways. This particular process is strictly voluntary, and not binding on
either FDA or industry. The benefits to manufacturers include an opportunity to begin a dialogue
29
A device is adulterated if it includes any filthy, putrid, or decomposed substance, or if it is prepared, packed, or held
under unsanitary conditions. The FDC Act further states that a device is adulterated if its container contains any
poisonous or deleterious substance, or if its strength, purity or quality varies significantly from what the manufacturer
claims. For higher class devices, a device can be considered adulterated if it fails to meet performance requirements
outlined in its approval, or if it is in violation of other Good Manufacturing Practice requirements.
30
A device is misbranded when all or part of the labeling (i.e., the FDA-approved printed material providing
information about the device) is false, misleading, or missing.
31
For guidance on the procedures established, see Early Collaboration Meetings Under the FDA Modernization Act;
Final Guidance for Industry and CDRH Staff, February 28, 2001, at http://www.fda.gov/MedicalDevices/
DeviceRegulationandGuidance/GuidanceDocuments/ucm073604.htm.
32
For more information on the IDE, please refer to the “Marketing Applications for Medical Devices” section that
immediately follows this discussion.
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with FDA, to promote greater understanding of new technologies, to reduce the cost of research
studies by focusing on the important information needed for FDA approval (or clearance),
eliminating unnecessary or burdensome studies, and to speed the review process for the future
marketing application since FDA will already be familiar with the device.
Marketing Applications for Medical Devices
The following sections describe the types of premarket submissions that FDA reviews for medical
devices. (See Table 2.)
Premarket Notification (510(k))
A 510(k) submission is required for any new, non-exempt low- or moderate-risk medical device
that will be marketed in the United States. A 510(k) could also be used for currently marketed
devices for which the manufacturer seeks a new indication (e.g., a new population, such as
pediatric use, or a new disease or condition), or for which the manufacturer has changed the
design or technical characteristics such that the change may affect the performance characteristics
of the device.
The standard for clearance of a traditional 510(k) is substantial equivalence with a predicate
device. A predicate device can be one of two things. It can be a previously cleared Class I or II
device that does not require a PMA. It can also be preamendment Class III for which the agency
has not issued regulations requiring a PMA. (PMAs, which are more rigorous submissions than
510(k)s, are discussed in the “Premarket Application (PMA)” section.)
There are several types of 510(k)s: traditional, abbreviated, special and de novo. In a traditional
510(k), the manufacturer submits information about the performance of the device under specific
conditions of use. It also contains information about the design of the device, characteristics of
device components, representations of packaging and labeling, a description and summary of the
non-clinical and clinical studies that were done to support the device performance characteristics,
a description of means by which users can assess the quality of the device, and information about
any computer software or additional or special equipment needed. Several administrative forms
are also required. 33
Most of the studies supporting a 510(k) submission are not true clinical studies. While FDA
prefers to see data on performance of the device in the actual intended population, substantial
equivalence in many cases, means only that the device performs in a similar fashion to the
predicate under a similar set of circumstances. As a result, many devices never have to
demonstrate safety and effectiveness through clinical studies.
FDA may take any of the following actions on a 510(k) after conducting its review (21 CFR
§ 807.100(a)): find the device substantially equivalent to the predicate and issue a clearance letter,
find the device not substantially equivalent (NSE) and issue an NSE letter prohibiting marketing,
or request additional information (with the final clearance decision pending review of that
information). A manufacturer generally has 30 days to provide any additional information, or
33
FDA, How to Prepare a Traditional 510(k), September 14, 2009, http://www.fda.gov/MedicalDevices/
DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketNotification510k/
ucm134572.htm#link_4.
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FDA may issue a notice of withdrawal of the application (21 CFR § 807.87(l)). The manufacturer
may, at any time, withdraw its 510(k). FDA has 90 days to review a traditional 510(k). 34
Abbreviated and special 510(k)s were new approaches to premarket notification that came from
FDAMA of 1997, intended to streamline and expedite FDA’s review for routine submissions
meeting certain qualifications, thus leaving more reviewer time for more complicated
submissions. An abbreviated 510(k) uses guidance documents developed by FDA to communicate
regulatory and scientific expectations to industry. Guidance documents have been prepared for
many different kinds of devices, and are available on FDA’s website. All guidance documents are
developed in accordance with Good Guidance Practices (GGP, 21 CFR § 10.115)), and many with
public participation or opportunities for public comment.35
In addition to issuing guidance documents, FDA can either develop performance or consensus
standards or ‘recognize’ those developed by outside parties (21 CFR Part 861). In an abbreviated
510(k), the manufacturer describes what guidance document, special control, or performance
standard was used, and how it was used to assess performance of their device. Other minimum
required elements are the product description, representative labeling, and a summary of the
performance characteristics. FDA typically reviews an abbreviated 510(k) in 60 days.
The Quality System Regulation (QSR; 21 CFR § 820.30) is the regulation that describes the good
manufacturing practice (GMP) requirements for medical devices (see the “Manufacturing”
section of this report for more detail on QSR). A special 510(k) utilizes the design control36
requirement of the QSR and may be used for a modification to a device that has already been
cleared. The modifications should not affect the safety and effectiveness of the device. The
special 510(k) allows the manufacturer to declare conformance to design controls, without
providing the data. This type of submission references the original 510(k) number, and contains
information about the design control requirements. FDA aims to review most special 510(k)s in
30 days.
Under the FFDCA, novel devices lacking a legally marketed predicate would automatically be
designated Class III. FDAMA amended Section 513(f) to allow FDA to establish a new, expedited
mechanism for reclassifying these devices based on risk, thus reducing the regulatory burden on
manufacturers. The de novo 510(k), though requiring more data than a traditional 510(k), often
requires less information than a premarket application (PMA), discussed below.
In a de novo 510(k) process, the manufacturer submits a traditional 510(k) for its device.
However, because there is no predicate device or classification, the agency will return a decision
of not substantially equivalent. Within 30 days, the manufacturer submits a petition requesting
reclassification of its device into Class II or I, as appropriate. Within 60 days, FDA will render a
decision classifying the device according to criteria in 513(a)(1) of FFDCA. With approval, FDA
34
The FDA time clock (i.e., review cycle) begins when FDA receives the 510(k) and ends with the date that FDA
issues either a request for additional information or a decision. More than one cycle may occur before FDA issues its
final decision.
35
FDA continually accepts public comment on any draft or final guidance document.
36
Design controls are a series of predetermined checks, verifications, and specifications that are built into the
manufacturing process to validate the quality of the product throughout the process. These can include defining the
personnel responsible for implementing steps in the development and manufacturing process, defining specifications
and standards for assessing the quality of the materials that go into making the product, designing specifications for
accepting and rejecting different batches or lots of final product, and requirements for maintaining appropriate records.
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issues a regulation that classifies the device. If the device is Class II, a special controls guidance
document is also developed that then allows subsequent manufacturers to submit either traditional
or abbreviated 510(k)s.37
Premarket Application (PMA)
A PMA is the most stringent type of device marketing application required by FDA for new
and/or high-risk devices. PMA approval is based on a determination by FDA that the application
contains sufficient valid scientific evidence to assure that the device is safe and effective for its
intended use(s) (21 CFR Part 814). A PMA must contain the following information (among other
things): administrative requirements; summaries of non-clinical and clinical data supporting the
intended use and performance characteristics; detailed information on the design of the device
and a description of the device components; instructions for use; representations of packaging and
labeling; a description of means by which users can assess the quality of the device; information
about any computer software or additional or special equipment needed; literature about the
disease and the similar devices; information on the manufacturing process; and assurance of
compliance with QSR.
In contrast to a 510(k), PMAs generally require some clinical data, but can also use studies from
the medical literature (a “paper PMA”). Approval is based not only on the strength of the
scientific data, but also on inspection of the manufacturing facility to assure that the facility and
the manufacturing process are in compliance with the quality systems regulations (QSR: 21 CFR
Part 820). FDAMA made it easier for manufacturers to submit the required sections of a PMA in
a serial fashion as data are available (“modular PMA”).
When a PMA is first received, FDA has 45 days to make sure the application is administratively
complete. If so, FDA formally files the application. If not, the application is returned. FDA then
has 75 days to complete the initial review and determine whether an advisory committee meeting
will be necessary.
Advisory committees, comprised of scientific, medical, and statistical experts, and industry and
consumer representatives, can be convened to make recommendations on any scientific or policy
matter before FDA.38 They allow for interested persons to present information and views at an
oral public hearing before the advisory committee (21 CFR Part 14). FDA typically accepts
advisory committee recommendations for an application (approvable, approvable with conditions
or non-approvable); however, there have been cases where the decision has not been consistent
with the recommendation (e.g., where the conditions for approval are so burdensome as to
practically present a non-approvable situation). CDRH will hold joint advisory committee
meetings with other centers where necessary.
After FDA notifies the applicant that the PMA has been approved or denied, a notice may be
published on the Internet (1) announcing the data on which the decision is based, and (2)
providing interested persons an opportunity to petition FDA within 30 days for reconsideration of
37
FDA, New Section 513(f)(2) - Evaluation of Automatic Class III Designation, Guidance for Industry and CDRH
Staff, February 19, 1998, http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/
ucm080195.htm..
38
For further information, see CRS Report RS22691, FDA Advisory Committee Conflict of Interest, by Erin D.
Williams.
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the decision. Though FDA regulations allow 180 days to review the PMA and make a
determination (21 CFR § 814.40), in reality the review time could be much longer. Pursuant to
MDUFA performance goals have been established to reduce the review time for PMAs.
Supplements to 510(k)s and PMAs
Once a device has been cleared through a 510(k) process or approved through the PMA process,
the manufacturer can market the device only for the intended use that FDA cleared or approved.
For example, a device, such as a stent, approved to treat coronary artery disease may not be
marketed for treatment of blocked biliary ducts unless the manufacturer files additional
information with FDA to demonstrate that the device is safe and effective for the new use. The
information can be filed as a supplement to the original application. Supplements are required not
only for new uses of a cleared or approved device, but also for design or manufacturing changes
that may impact safety and effectiveness (e.g., changing the type of metal or plastic on a device,
or using a different antibody for diagnosis of a disease).
Investigational Device Exemption (IDE)
An IDE allows an unapproved device (most commonly an invasive or life-sustaining device) to
be used in a clinical study to collect data required to support a submission, most commonly a
PMA, at some later point in time. 39 Investigational use can also include clinical evaluation of
certain modifications to or new intended uses of legally marketed devices (e.g., supplemental
application). All clinical evaluations of investigational devices, unless they are exempt, must have
an IDE and be approved by an institutional review board (IRB), before the study is initiated. 40
The IDE permits a device to be shipped lawfully for investigation of the device without requiring
that the manufacturer comply with other requirements of the FFDCA, such as registration and
listing. Manufacturers of devices with IDEs are also exempt from the quality systems regulations
(QSR), except for the requirements for design control.
While under investigation, manufacturers, sponsors, clinical investigators and IRBs must comply
with Good Clinical Practices, including all regulations that govern the conduct of clinical studies:
•
Investigational Device Exemptions (21 CFR Part 812) covering the procedures
for the conduct of clinical studies with medical devices including application,
responsibilities of sponsors and investigators, labeling, records, and reports;
•
Protection of Human Subjects (21 CFR Part 50) providing the requirements and
general elements of informed consent;
•
Institutional Review Boards (21 CFR Part 56) covering the procedures and
responsibilities for IRBs that approve clinical investigations protocols;
39
FDA, Device Advice: Investigational Device Exemption (IDE), July 9, 2009, http://www.fda.gov/MedicalDevices/
DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/default.htm..
40
An IRB is a group, generally comprised volunteers, that examines proposed and ongoing scientific research to ensure
that human subjects are properly protected. For further information, see CRS Report RL32909, Federal Protection for
Human Research Subjects: An Analysis of the Common Rule and Its Interactions with FDA Regulations and the HIPAA
Privacy Rule, by Erin D. Williams.
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•
Financial Disclosure by Clinical Investigators (21 CFR Part 54) covering the
disclosure of financial compensation to clinical investigators which is part of
FDA’s assessment of the reliability of the clinical data; and
•
Design Controls of the QSR (21 CFR Part 820 Subpart C) providing the
requirement for procedures to control the design of the device in order to ensure
that the specified design requirements are met.
Devices are exempt from IDE requirements when testing is noninvasive, does not require
invasive sampling, does not introduce energy into a subject, and is not stand alone (i.e., is not
used for diagnosis without confirmation by other methods or medically established procedures)
(21 CFR § 812.2(c)(3)).
Humanitarian Device Exemption (HDE)
An HDE is an application that is similar to a PMA, but exempt from the effectiveness
requirements. An approved HDE authorizes marketing of a humanitarian use device. A
humanitarian use device is intended to benefit patients in the treatment and diagnosis of diseases
or conditions that affect fewer than 4,000 individuals in the U.S. per year. The exemption from
proving effectiveness is designed to encourage manufacturers to develop medical devices for
these small markets, assisting patients with rare diseases and conditions who might otherwise not
be served.
Before submitting an HDE application, the manufacturer submits a request for a humanitarian use
device designation to FDA’s Office of Orphan Products Development (OOPD). The request
includes (1) a statement that they are requesting a humanitarian use device designation for a rare
disease or condition; (2) the name and address of the manufacturer; (3) a description of the rare
disease or condition for which the device is to be used; (4) a description of the device; and (5)
documentation, with appended authoritative references, to demonstrate that the device is designed
to treat or diagnose a disease or condition that affects or is manifested in fewer than 4,000 people
in the United States per year (see 21 CFR § 814.102(a)). In order for a device to receive
marketing approval under this regulation, there should not be another legally marketed device
available to treat or diagnose the disease or condition. Once a device with the same intended use
as the humanitarian use device is approved or cleared, an HDE cannot be granted for the
humanitarian use device.
The agency has 75 days from the date of receipt to review an HDE application. This includes a
30-day filing period during which the agency determines whether the HDE application is
sufficiently complete to permit substantive review. FDA does require that a manufacturer comply
with the QSR that the agency deems most relevant to the safety of the device. Alternatively, the
manufacturer can request an exemption. Supplements, and sometimes even a new HDE, are
required for additional indications.41
41
FDA, Guidance for Industry and FDA Staff - Humanitarian Device Exemption (HDE) Regulation: Questions and
Answers, July 18, 2006, http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/
ucm071473.htm.
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In Vitro Diagnostic (IVD) Products
IVD products (e.g., laboratory tests) are those reagents, instruments, and systems intended for use
in diagnosis of disease or other conditions, including a determination of the state of health, in
order to cure, mitigate, treat, or prevent disease or its sequelae. Such products are intended for use
in the collection, preparation, and examination of specimens taken from the human body.42
IVDs are medical devices as defined in Section 210(h) of the FFDCA (such as equipment used for
genetic testing), and may also be biological products subject to Section 351 of the Public Health
Service Act (such as biological agent diagnostic systems). IVDs may consist of general purpose
reagents,43 analyte specific reagents (ASRs),44 general purpose or specific equipment, sometimes
with computer analysis software. 45
IVDs are different from other medical devices in that they do not act directly on a patient to
produce a result like an implantable, life-sustaining or other device does. Instead, the risk to the
patient is from the generation of inaccurate test results (i.e., wrong answers) that lead to
mismanagement of a patient’s condition.
Most IVD products that are stand-alone items of general purpose equipment, such as automated
clinical analyzers, are exempt Class I devices. However, if the equipment performs a specific test,
equipment plus the test becomes a test system. Test systems are considered combination devices,
and they are classified according to the risk level of the highest of the two device classifications
(i.e., an analyzer may be Class I exempt, but if a manufacturer wishes to market it with an HIV
test kit, the system could be regulated as a Class III device and require a PMA). Most IVD
products are reviewed in CDRH’s Office of In Vitro Diagnostic Device Evaluation and Safety
(OIVD), and CBER’s Office of Blood Research and Review (OBRR). The classification of
existing IVDs can be found in 21 CFR Part 862, 21 CFR Part 864, and 21 CFR Part 866.
Like other medical devices, IVDs are subject to premarket and postmarket controls. But unlike
other devices, IVDs are also subject to the Clinical Laboratory Improvement Amendments
(CLIA) of 1988.46 CLIA establishes quality standards for laboratory testing and an accreditation
program for clinical laboratories that perform testing using IVD products. CLIA requirements
vary according to the technical complexity in the testing process and risk of harm in reporting
42
21 C.F.R. § 809.3.
A general purpose reagent is “a chemical reagent that has general laboratory application, is used to collect, prepare,
and examine specimens from the human body for diagnostic purposes, and is not labeled or otherwise intended for a
specific diagnostic application … [General purpose reagents] do not include laboratory machinery, automated or
powered systems” (21 CFR § 864.4010).
44
Analyte specific reagents (ASRs) are “antibodies, both polyclonal and monoclonal, specific receptor proteins,
ligands, nucleic acid sequences, and similar reagents which, through specific binding or chemical reaction with
substances in a specimen, are intended for use in a diagnostic application for identification and quantification of an
individual chemical substance or ligand in biological specimens” (21 CFR § 864. 4020(a)).
45
In 2006, FDA’s OIVD issued two draft guidance documents on IVDs: FDA, Draft Guidance for Industry and FDA
Staff - Commercially Distributed Analyte Specific Reagents (ASRs): Frequently Asked Questions, September 14,
2007, http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/
UCM071269.pdf; and FDA, Draft Guidance for Industry, Clinical Laboratories, and FDA Staff In Vitro Diagnostic
Multivariate Index Assays, July 26, 2007, http://www.fda.gov/downloads/MedicalDevices/
DeviceRegulationandGuidance/GuidanceDocuments/UCM071455.pdf.
46
FDA, Overview of IVD Regulation, June 18, 2009, http://www.fda.gov/MedicalDevices/
DeviceRegulationandGuidance/IVDRegulatoryAssistance/ucm123682.htm.
43
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erroneous results. The regulations establish three categories of testing on the basis of the
complexity of the testing methodology: (a) waived tests, (b) tests of moderate complexity, and (c)
tests of high complexity.
Manufacturers apply for CLIA categorization (determined by FDA)47 during the premarket
process. Postmarket, the Centers for Medicare and Medicaid Services (CMS) regulates all
laboratory testing (except research) performed on humans in the U.S. through CLIA.48 Under
CLIA, laboratories performing only waived tests are subject to minimal regulation. Laboratories
performing moderate or high complexity tests are subject to specific laboratory standards
governing certification, personnel, proficiency testing, patient test management, quality
assurance, quality control, and inspections.
CLIA categorization (defining regulatory requirements on the laboratory testing process) do not
always match FDA classification (defining regulatory requirements on the tests kits or systems
themselves). For example, a “waived” test under CLIA is the simplest test to perform (usually by
an untrained user), with the smallest margin of error. As such, they receive little to no oversight
under CLIA. However, FDA may designate such a test as Class III, so that it undergoes rigorous
review to insure that it performs as advertised (i.e., with a small margin of error in the hands of an
untrained user).
Most IVDs are exempt from IDE requirements. Because the benefits and risks to the patient from
use of IVDs are indirect (i.e., due to the use of the test result in patient management), FDA
requires that the companies demonstrate analytical test performance in patient samples that would
test along the continuum of positive and negative for the marker of interest. In addition, FDA
requires support for the clinical validity of the test (i.e., evidence that the biological marker that
the test is detecting actually is associated with the disease or condition that the company wishes to
market the test for in a predictable way).
For some of the applications seeking clearance for an IVD, biological markers that the test
purports to measure may be relatively well characterized with respect to a disease and patient
population (such as the link between glucose measurement and diabetes). In these cases,
analytical studies using clinically derived samples (e.g., blood specimens from healthy and
diabetic individuals) suffice to show that the test is actually detecting the marker. Sometimes
clinical samples can be supplemented by carefully selected artificial samples, particularly if a
disease, condition or marker is rare. For example, if FDA were to review a genetic test to measure
genetic markers for drug metabolism, they may require the manufacturer to use actual patient
samples to demonstrate that they can detect common markers. FDA may, however, allow the
company to use artificial or “spiked” samples to test for rare markers so that the company would
not have to test an overly burdensome number of clinical samples. In this type of submission, the
manufacturer could use medical literature to support the clinical validity of the biological marker
to the disease, and would not have to conduct a clinical study to demonstrate that the test
measures the marker and the marker is associated with the disease.
47
See FDA, Find Device CLIA ‘88 Categorization, July 11, 2009, http://www.fda.gov/MedicalDevices/
DeviceRegulationandGuidance/IVDRegulatoryAssistance/ucm124103.htm.
48
CMS, Clinical Laboratory Improvement Amendments (CLIA) Overview, August 26, 2009, http://www.cms.hhs.gov/
CLIA/.
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For other IVDs, the link between analytical performance of the test in its ability to detect a
biological marker and the clinical validity of the marker is not well defined. In these
circumstances, new clinical information may be required. FDA rarely requires prospective
clinical studies for IVDs, but regularly requests clinical samples with sufficient laboratory and/or
clinical characterization to allow an assessment of the clinical validity of a new device. For
example, a company seeking to market a test for a new tumor marker may use well-characterized,
archived patient samples collected as part of a completely separate study to demonstrate that their
test can classify patients in a predictable way. Clinical performance is usually expressed in terms
of clinical sensitivity and clinical specificity (when compared to a disease or health state) or
agreement (when compared to performance of a predicate device or reference method). For most
PMAs, manufacturers identify surrogate endpoints (such as tumor shrinking or reduction in a
tumor marker) and establish the device performance in relation to those rather than to disease
outcome (such as improved survival).
The Medical Device Approval Process:
Post-Approval Requirements and Issues
Once approved or cleared for marketing, manufacturers of medical devices must comply with
regulations on labeling and advertising, manufacturing, on postmarket surveillance, adverse
events, a related new Sentinel Initiative, device tracking, unique device identification, compliance
and enforcement. The requirements for each of these are described below.
Labeling
Like drugs and biological products, all FDA approved or cleared medical devices are required to
be labeled in a way that informs a user of how to use the device in a safe and effective manner.
Section 201(k) of the FFDCA defines a “label” as a “display of written, printed, or graphic matter
upon the immediate container of any article.” Section 201(m) defines “labeling” as “all labels and
other written, printed, or graphic matter upon any article or any of its containers or wrappers, or
accompanying such article” at any time while a device is held for sale after shipment or delivery
for shipment in interstate commerce. The term “accompanying” is interpreted to mean more than
physical association with the product; it extends to posters, tags, pamphlets, circulars, booklets,
brochures, instruction books, direction sheets, fillers, webpages, etc. Accompanying can also
include labeling that is connected with the device after shipment or delivery for shipment in
interstate commerce. According to an appellate court decision, “most, if not all advertising, is
labeling. The term ‘labeling’ is defined in the FFDCA as including all printed matter
accompanying any article. Congress did not, and we cannot, exclude from the definition printed
matter which constitutes advertising.”49
Labeling regulations pertaining to medical devices are found in the following parts of Title 21
CFR:
49
•
General Device Labeling (21 CFR Part 801)
•
In Vitro Diagnostic Products (21 CFR Part 809)
United States v. Research Laboratories, Inc., 126 F.2d 42 (9th Cir. 1942).
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•
Investigational Device Exemptions (21 CFR Part 812)
•
Good Manufacturing Practices (21 CFR Part 820)
•
General Electronic Products (21 CFR Part 1010)
All devices must conform to the general labeling requirements. Certain devices require specific
labeling which may include not only package labeling, but informational literature, patient release
forms, performance testing, and/or specific tolerances or prohibitions on certain ingredients.50
Various sections of the QSR have an impact on labeling: Section 21 CFR § 820.80(b) requires the
inspection and testing of incoming materials including labeling; and 21 CFR § 820.70(f) requires
buildings to be of suitable design and have sufficient space for packaging and labeling operations;
21 CFR § 820.120 deals with specific requirements for the control of labeling. This regulation
applies to the application of labeling to ensure legibility under normal conditions of use over the
expected life of the device; and also applies to inspection, handling, storage, and distribution of
labeling. FDA considers a device to be adulterated if these requirements are not met. These
requirements do not apply to the adequacy of labeling content, except to make sure the content
meets labeling specifications contained in the device master record. However, failure to comply
with GMP requirements, such as proofreading and change control, could result in labeling content
errors. In such cases, the device could be misbranded and/or adulterated.
Manufacturing
Like drug manufacturers, medical device manufacturers must produce their devices in accordance
with Good Manufacturing Practice (GMP). The GMP requirements for devices are described in
the QSR, (FFDCA §520; 21 CFR 820). The QSRs require that domestic or foreign manufacturers
have a quality system for the design, manufacture, packaging, labeling, storage, installation, and
servicing of non-exempt finished medical devices intended for commercial distribution in the
United States. The regulation requires that various specifications and controls be established for
devices; that devices be designed and manufactured under a quality system to meet these
specifications; that finished devices meet these specifications; that devices be correctly installed,
checked and serviced; that quality data be analyzed to identify and correct quality problems; and
that complaints be processed. FDA monitors device problem data and inspects the operations and
records of device developers and manufacturers to determine compliance with the GMP
requirements. 51
Though FDA has identified in QSR the essential elements that a quality system should have,
manufacturers have a great deal of leeway to design quality systems that best cover nuances of
their devices and the means of producing them.
50
21 CFR §§ 801.405 to 801.437. Denture repair kits, impact resistant lenses in sunglasses and eyeglasses, ozone
emission levels, chlorofluorocarbon propellants, hearing aids, menstrual tampons, chlorofluorocarbons or other ozone
depleting substances, latex condoms, and devices containing natural rubber.
51
FDA, Medical Devices: 1. The Quality System Regulation, June 18, 2009, http://www.fda.gov/MedicalDevices/
DeviceRegulationandGuidance/PostmarketRequirements/QualitySystemsRegulations/
MedicalDeviceQualitySystemsManual/ucm122391.htm.
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Postmarket Surveillance
Once their device is approved or cleared, manufacturers must conduct postmarket surveillance
studies to gather safety and efficacy data for certain devices introduced into interstate commerce
after January 1, 1991. This requirement applies to devices that
•
are permanent implants, the failure of which may cause serious adverse health
consequences or death;
•
are intended for use in supporting or sustaining human life; or
•
present a potential serious risk to human health.
FDA may require postmarket surveillance for other devices if deemed necessary to protect the
public health. The primary objective of postmarket surveillance is to study the performance of the
device after clearance or approval as it is used in the population for which it is intended—and to
discover cases of device failure and its attendant impact on the patient.
Manufacturers may receive notification that their device is subject to postmarket surveillance
when FDA files (i.e., accepts) the submission, and again when a final decision is made. If
notified, manufacturers must submit a plan for postmarket surveillance to FDA for approval
within 30 days of introducing their device into interstate commerce.
MDUFMA authorized additional appropriations for postmarket surveillance—$3 million for
FY2003, $6 million for FY2004, and such sums as may be necessary in subsequent years;
however, the money was not appropriated. MDUFA authorized the appropriation of $25 million
per year for Postmarket Studies and Surveillance (21 USC 355 note).
Adverse Event Reporting
Section 519(a) of the FFDCA as amended by the SMDA of 1990 required FDA to establish a
system for monitoring and tracking serious adverse events that resulted from the use or misuse of
medical devices. The Medical Device Reporting (MDR) regulation is the mechanism that FDA
and manufacturers use to identify and monitor significant adverse events involving medical
devices, so that problems are detected and corrected in a timely manner. User facilities (e.g.,
hospitals, nursing homes, clinical laboratories) are required to report suspected medical devicerelated deaths to both FDA and the manufacturers within 10 working days. User facilities may
report medical device related serious injuries only to the manufacturer within 10 days.
Manufacturers must file a summary of all medical device reports to FDA within 30 calendar days.
User facilities must file a summary report annually. Although the FFDCA gives FDA the
authority to impose legal sanctions for not complying with MDR, FDA relies largely on the
goodwill and cooperation of all affected groups to accomplish the objectives of the regulation.
The searchable MDR database for devices is publically accessible at
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmdr/search.CFM.
In August 2009, FDA published notice of a proposed rule, and a related draft guidance document,
that would require manufacturers to submit MDRs to the agency in an electronic format.52
52
FDA, “Proposed Rule, Medical Device Reporting: Electronic Submission Requirements,” 74 Federal Register
42203-42217, August 21, 2009; and FDA, “Draft Guidance for Industry, User Facilities, and Food and Drug
Administration Staff; eMDR—Electronic Medical Device Reporting; Availability,” 74 Federal Register Page 42310,
(continued...)
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According to FDA, the proposed regulatory changes would provide the agency with a more
efficient data entry process that would allow for timely access to medical device adverse event
information and identification of emerging public health issues. The proposal reportedly met with
some resistance from the device industry, which called for a longer timeframe to implement the
changes, among other things.
In October 2009, the HHS Office of Inspector General raised questions about adverse event
reporting for medical devices. 53 The report found that CDRH does not consistently use adverse
event reporting and made several recommendations about how it could better do so.
The Sentinel Initiative
Some provisions related to adverse event reporting were enacted in FDAAA. One requires FDA
to establish an active surveillance system for monitoring drugs, using electronic data from
healthcare information holders. In response, in 2008 FDA launched the Sentinel Initiative. Its goal
is to build and implement a new active surveillance system that will eventually be used to monitor
all FDA-regulated products. According to FDA, the Sentinel Initiative aims to develop and
implement a proactive system that will complement existing systems that the Agency has in place
to track reports of adverse events linked to the use of its regulated products.
Information on the current status of the Sentinel Initiative is available at http://www.fda.gov/
Safety/FDAsSentinelInitiative/default.htm.
Medical Device Tracking
Manufacturers are required to track certain devices from their manufacture through the
distribution chain when they receive an order from FDA to implement a tracking system for a
certain type of device. 54 The purpose of device tracking is to ensure that manufacturers of these
devices can locate them quickly once in commercial distribution if needed to facilitate
notifications and recalls in the case of serious risks to health presented by the devices. FDA may
issue a tracking order for any Class II or Class III device:
•
the failure of which would be reasonably likely to have serious adverse health
consequences;
•
which is intended to be implanted in the human body for more than one year; or
•
which is intended to be a life sustaining or life supporting device used outside a
device user facility. (21 CFR Part 821).
A current list of the devices for which tracking is required can be found at http://www.fda.gov/
MedicalDevices/DeviceRegulationandGuidance/PostmarketRequirements/
MedicalDeviceTracking/default.htm#link_2.
(...continued)
August 21, 2009.
53
Daniel R. Levinson, Adverse Event Reporting for Medical Devices, HHS Office of Inspector General, OEI-01-0800110, October 2009, http://oig.hhs.gov/oei/reports/oei-01-08-00110.pdf.
54
FDA, Medical Device Tracking, May 13, 2009, http://www.fda.gov/MedicalDevices/
DeviceRegulationandGuidance/PostmarketRequirements/MedicalDeviceTracking/default.htm#link_2.
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Unique Device Identification
A provision in FDAAA requires the HHS Secretary to promulgate regulations establishing a
unique device identification (UDI) system (FFDCA 519(f); 21 USC 360i). When implemented,
this new system will require
•
the label of a device to bear a unique identifier, unless an alternative location is
specified by FDA or unless an exception is made for a particular device or group
of devices;
•
the unique identifier to be able to identify the device through distribution and
use; and
•
the unique identifier to include the lot or serial number if specified by FDA.
Information about the current status of the UDI System is available at http://www.fda.gov/
MedicalDevices/DeviceRegulationandGuidance/UniqueDeviceIdentifiers/default.htm.
Compliance and Enforcement
Compliance requirements apply to both the premarket approval process and postmarket
surveillance. When a problem arises with a product regulated by FDA, the agency can take a
number of actions to protect the public health. Initially, the agency tries to work with the
manufacturer to correct the problem on a voluntary basis. If that fails, legal remedies may be
taken, such as: asking the manufacturer to recall a product, having federal marshals seize
products, or detaining imports at the port of entry until problems are corrected. If warranted, FDA
can ask the courts to issue injunctions or prosecute individual company officers that deliberately
violate the law. When warranted, criminal penalties, including prison sentences, may be sought.
Each center has an Office of Compliance (OC) that ensures compliance with regulations while
pre- or postmarket studies are being undertaken, with manufacturing requirements, and with
labeling requirements. The objectives of CDRH’s OC’s Bioresearch Monitoring (BIMO) program
are to ensure the quality and integrity of data and information submitted in support of IDE, PMA,
and 510(k) submissions and to ensure that human subjects taking part in investigations are
protected from undue hazard or risk. This is achieved through audits of clinical data contained in
PMAs prior to approval, data audits of IDE and 510(k) submissions, inspections of IRBs and
nonclinical laboratories, and enforcement of the prohibitions against promotion, marketing, or
commercialization of investigational devices. Any establishment where devices are manufactured,
processed, packed, installed, used, or implanted or where records of results from use of devices
are kept, can be subject to inspection. (See Table 3.)
Table 3. CDRH, FDA Foreign and Domestic Inspections, FY2004 – FY2008
FY
2004
2005
2006
2007
2008
Number of Inspections
2,936
2,694
2,691
2,495
2,353
Source: Prepared by the Congressional Research Service based on FDA, The Enforcement Story , Center for
Devices and Radiological Health Enforcement Statistics, Center for Devices and Radiological Health, FDA
Foreign and Domestic Inspections, Fiscal Years 2004 -2008, 2008, pp. 2-25, http://www.fda.gov/downloads/ICECI/
EnforcementActions/EnforcementStory/UCM129811.pdf.
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The OC also reviews the quality system design and manufacturing information in the PMA
submission to determine whether the manufacturer has described the processes in sufficient detail
and to make a preliminary determination of whether the manufacturer meets the QSR. If the
manufacturer has provided an adequate description of the design and manufacturing process, a
preapproval inspection can be initiated. Inspection is to include an assessment of the
manufacturer’s capability to design and manufacture the device as claimed in the PMA and
confirm that the quality system is in compliance with the QSR. Postapproval inspections can be
conducted within 8 to 12 months of approval of the PMA submission. The inspection is to
primarily focus on any changes that may have been made in the device design, manufacturing
process, or quality systems.
The compliance offices work closely with the Office of Regulatory Affairs (ORA),55 which
operates in the field to regulate almost 124,000 business establishments that annually produce,
warehouse, import and transport $1 trillion worth of medical products. Consumer safety officers
(CSOs) and inspectors typically have conducted about 22,000 domestic and foreign inspections a
year to ensure that regulated products meet the agency’s standards. CSOs also monitor clinical
trials. Scientists in ORA’s 13 laboratories typically have analyzed more than 41,000 product
samples each year to determine their adherence to FDA’s standards.
Section 516 of the FFDCA gives FDA the authority to ban devices that present substantial
deception or unreasonable and substantial risk of illness or injury. Section 518 enables FDA to
require manufacturers or other appropriate individuals to notify all health professionals who
prescribe or use the device and any other person (including manufacturers, importers, distributors,
retailers, and device users) of any health risks resulting from the use of a violative device, so that
these risks may be reduced or eliminated. This section also gives consumers a procedure for
economic redress when they have been sold defective medical devices that present unreasonable
risks. Section 519 of the act authorized FDA to promulgate regulations requiring manufacturers,
importers, and distributors of devices to maintain records and reports to assure that devices are
not adulterated or misbranded. Section 520(e) of the MDA authorized FDA to restrict the sale,
distribution, or use of a device if there cannot otherwise be reasonable assurance of its safety and
effectiveness. A restricted device can only be sold on oral or written authorization by a licensed
practitioner or under conditions specified by regulation.
Warning Letter
A warning letter is a written communication from FDA notifying a responsible individual,
manufacturer, or facility that the agency considers one or more products, practices, processes, or
other activities to be in violation of the laws that FDA enforces. The warning letter informs the
recipient that failure to take appropriate and prompt action to correct and prevent any future
repeat of the violations could result in an administrative or regulatory action. Although serious
noncompliance is often a catalyst for issuance of a warning letter, the warning letter is informal
and advisory. Warning letters are publically available on FDA’s website at http://www.fda.gov/
ICECI/EnforcementActions/WarningLetters/default.htm. (See Table 4.)
55
See ORA at http://www.fda.gov/AboutFDA/CentersOffices/ORA/default.htm.
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Table 4. CDRH Warning Letters Issued, FY2000-FY2009
FY
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
# of Letters
528
498
285
205
198
182
154
155
152
136
Source: Prepared by the Congressional Research Service based on data from FDA’s Office of Legislation.
Product Recall
A recall is a method of removing or correcting products that FDA considers are in violation of the
law. 56 Medical device recalls are usually conducted voluntarily by the manufacturer (21 CFR Part
7), after negotiation with FDA. Under 21 CFR Part 806, manufacturers (including refurbishers
and reconditioners) and importers are required to report to FDA any correction or removal of a
medical device that is undertaken to reduce a health risk posed by the device. A recall may be a
total market withdrawal or may be of a portion of product (such as a single lot). In rare instances,
where the manufacturer or importer fails to voluntarily recall a device that is a risk to health, FDA
may issue a recall order to the manufacturer (21 CFR Part 810).57
When a recall is initiated, FDA performs an evaluation of the health hazard presented taking into
account the following factors, among others:
•
Whether any disease or injuries have already occurred from the use of the
product;
•
Whether any existing conditions could contribute to a clinical situation that could
expose humans or animals to a health hazard;
•
Assessment of hazard to various segments of the population, (e.g., children,
surgical patients, pets, livestock, etc.), who would be exposed to the product;
•
Assessment of the degree of seriousness of the health hazard to which the
populations at risk would be exposed;
•
Assessment of the likelihood of occurrence of the hazard;
•
Assessment of the consequences (immediate or long-range) of occurrence of the
hazard.
Following the health hazard assessment, FDA assigns the recall a classification according to the
relative degree of health hazard. Class I recalls are the most serious, reserved for situations where
there is a reasonable probability that the use of, or exposure to, a product will cause serious
adverse health consequences or death. Class II recalls are for situations where the use of, or
exposure to, a product may cause temporary or medically reversible adverse health consequences
or where the probability of serious adverse health consequences is remote. In a Class III recall
situation, the use of, or exposure to, a product is not likely to cause adverse health consequences.
(See Table 5.)
56
Recall does not include market withdrawal or a stock recovery. A market withdrawal is a firm’s removal or
correction of a distributed product for a minor violation that does not violate the law and would not be subject to legal
action by FDA, e.g., normal stock rotation practices, routine equipment adjustments and repairs, etc. Stock recovery
involves correction of a problem before product is shipped (i.e., is still in the manufacturer’s control).
57
CRS Report RL34167, The FDA’s Authority to Recall Products, by Vanessa K. Burrows.
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Table 5. CDRH Class I, II, and III Product Recalls, FY2004 - FY2008
2004
2005
2006
2007
2008
Class I
36
77
76
45
131
Class II
1,235
1,351
1,252
1,102
2,178
Class III
219
170
222
132
163
Source: Prepared by the Congressional Research Service based on FDA, The Enforcement Story , Center for
Devices and Radiological Health Enforcement Statistics, Center for Devices and Radiological Health Five-Year
Total Product Recall Statistics, Fiscal Years 2004 -2008, 2008, pp. 2-26, http://www.fda.gov/downloads/ICECI/
EnforcementActions/EnforcementStory/UCM129811.pdf.
In addition to a warning letter or recall, FDA may also issue a public notification or safety alert
(e.g., “Dear Doctor” letter), to warn healthcare providers and consumers of the risk of the device
in question. The main page for recalls, market withdrawals, and safety alerts for all FDAregulated products is http://www.fda.gov/opacom/7alerts.html.
Legislative Issues
A number of medical device-related topics are of interest to Members of the 111th Congress. As
described below, these include certain proposals in major health reform legislation, liability and
preemption, 510(k) clearance and device approval, importation and inspection, the use of
unapproved devices, advertising, IVD regulation, device-specific legislation, and some other
issues. Note that appropriations legislation and issues are discussed in other reports.58
Proposals in Health Reform Legislation
Three types of device-related proposals have been included in major health reform legislation.59
One would create device-related taxes to generate revenue for health reform. The second would
require the creation of a national medical device registry. The third would create reporting
requirements certain for gifts to health care providers from device manufacturers and others.60
Device-Related Taxes
Both the House and Senate health reform bills, as well as a reconciliation bill that would amend
the Senate-passed measure, include measures designed to generate revenue by imposing a tax
related to medical devices. These have generated controversy within the device industry, with
device manufacturers voicing their concern that smaller companies may suffer, and that all
58
CRS Report RL34638, FDA FY2009 Appropriations, coordinated by Susan Thaul.
59
For further information about health reform proposals that include device-related provisions, see CRS Report
R40943, Public Health, Workforce, Quality, and Related Provisions in H.R. 3590, as Passed by the Senate, coordinated
by C. Stephen Redhead and Erin D. Williams; and CRS Report R40892, Public Health, Workforce, Quality, and
Related Provisions in H.R. 3962, coordinated by C. Stephen Redhead.
60
It is worth noting that various health reform proposals and certain other bills also address a fourth device-related
topic: Medicare and other federal reimbursement. However, because FDA does not generally consider or regulate the
cost of medical devices, this topic is beyond the scope of this report.
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companies may be less able to capitalize research into the development of future devices.61 There
is currently no special tax on medical devices; however, manufacturers do pay user fees to the
FDA.62
The Patient Protection and Affordable Care Act (H.R. 3590, as passed by the Senate) would
impose an annual fee on device manufacturers and importers, beginning in the calendar year
2011. The total amount of all such fees collected would be $2 billion per year ($3 billion
beginning in 2018). Each manufacturer would pay a portion of the $2 billion equal to its market
share; however, some sales would be excluded from the calculation, based either on the device
type or the amount of gross receipts. Types of devices whose sales would be excluded from the
calculation are Class II devices, typically sold to consumers at retail for $100 per unit or less, and
Class I devices. Amounts of gross receipts that would be excluded are the following: for gross
receipts of market sales that are not more than $5 million, all would be excluded; for gross
receipts more than $5 million, but more than $25 million, half would be excluded. (For gross
receipts more than $25 million, none would be excluded.)
H.R. 3590, as passed by the Senate would also place a 10% tax on indoor tanning services.
The reconciliation bill (the Health Care and Education Affordability Reconciliation Act of 2010;
Amendment in the Nature of a Substitute to H.R. 4872, as amended by a manager’s amendment)
would amend H.R. 3590, as passed by the Senate. It would delete the device tax provisions of
H.R. 3590, instead imposing a 2.3% sales tax on the sale of a medical device by a manufacturer,
producer, or importer. Taxable devices would include those defined in FFDCA Sec. 201(h),
excluding eyeglasses, contact lenses, hearing aids, and any other devices determined by the
Secretary to be of a type the general public typically buys at retail for individual use. Tax
exemptions listed under Internal Revenue Code Sec. 4221(a)(3)-(6) and Sec. 6416(b)(2)(B)-(E)
would not apply, including those for state and local governments, nonprofit educational entities,
and certain others. The tax would apply to sales made after December 31, 2012.
The Affordable Health Care for America Act (H.R. 3962) would place 2.5% tax on certain sales
of certain medical devices. The total revenue that would be generated by this measure is
estimated to be $20 billion over 10 years.63 The tax would be applied to the first taxable sale
(including certain leases and uses) of a medical device. The tax would not apply to devices sold to
(or of the type an quantity typically sold to) consumers by retail establishments. Certain tax
exemptions similar to those in Sec. 4221 and 4222 of the Internal Revenue Code would apply.
These concern devices sold for export, and devices for use by the purchaser for further
manufacture. (Other tax exemptions listed under IRC Sec. 4221(a)(3)-(6) would not apply,
including those for state and local governments, nonprofit educational entities, and certain
others.) Under specified circumstances involving contractually negotiated sales prices, sellers
would be entitled to recover the amount of taxes paid from device producers, manufacturers, or
importers. The tax would apply to sales made after December 31, 2012.
61
See, e.g., Alicia Mundy, “Drug Makers Face Tougher Measures,” The Wall Street Journal, October 30, 2009, p. A4.
For further information about user fees, see CRS Report RL34571, Medical Device User Fees and User Fee Acts, by
Erin D. Williams.
62
63
U.S. Congress, Joint Committee on Taxation, Estimated Revenue Effects of Possible Modifications to the Revenue
provisions of H.R. 3962, the “Affordable Health Care for America Act,” Fiscal Years 2010-2019, 111th Cong., 1st sess.,
October 29, 2009, JCX-43-09 (Washington: GPO, 2009), p. 2.
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National Medical Device Registry
Concern about the safety of certain high-risk medical devices has led Congress to consider
various tracking and postmarket surveillance mechanisms. Sec. 519(e) of the FFDCA permits the
Secretary to order a medical device manufacturer to adopt a method of tracking for certain
devices that may create risks for patients. The FDA Amendments Act of 2007 (P.L. 110-85) added
a new Sec. 519(f), yet to be implemented, which requires medical devices to bear a unique
identifier. 64
Two major proposals for health reform contain provisions that would require the creation of a
national medical device registry. The Affordable Health Care for America Act (H.R. 3962) would
require the HHS Secretary to establish a public national medical device registry to facilitate
analysis of postmarket safety and outcomes data on certain devices. The registry would include
Class III devices and could include, as the HHS Secretary determined appropriate and specified in
regulation, a Class II device that is life-supporting or life-sustaining.
The HHS Secretary would be required to establish a procedure to link specified medical device
data from manufacturers with patient safety and outcomes data from disparate sources, and
integrate the registry activities with certain other postmarket risk and safety activities required by
the FFDCA. In addition, acting through the HHS Office of the National Coordinator for Health
Information Technology, the HHS Secretary would be required to adopt standards for the
electronic exchange and use in certified electronic health records of a unique device identifier.
Gifts to Physicians and Other Health Providers
In recent years, questions have been raised over the propriety of certain financial relationships
between health care professionals (e.g., physicians) and the pharmaceutical and other medical
industries. 65 As part of these relationships, companies may give gifts or make payments to health
care professionals as part of their marketing efforts, or for other purposes. In an effort to promote
transparency and prevent inappropriate relationships, several states and the District of Columbia
have enacted legislation requiring pharmaceutical companies to disclose gifts and payments made
to health care professionals. While companies are free to voluntarily disclose this information,
there is currently no federal requirement to do so.
The Affordable Health Care for America Act (H.R. 3962) would require certain device and other
manufacturers and distributors report to the HHS Secretary of HHS certain gifts to physicians and
other specified health providers. The Patient Protection and Affordable Care Act (H.R. 3590, as
passed by the Senate) would create a similar requirement, but it would not apply to distributors,
and would limit reporting to gifts made to physicians and teaching hospitals. These provisions
also appear in a stand-alone bill, the Physician Payments Sunshine Act of 2009 (S. 301/ H.R.
3138), which is mentioned below in the “Advertising” section of this report.66
64
For information on the implementation status of the unique device identifier, go to http://www.fda.gov/
MedicalDevices/DeviceRegulationandGuidance/UniqueDeviceIdentifiers/default.htm.
65
This paragraph was contributed by Jennifer Staman, Legislative Attorney, CRS (jstaman@crs.loc.gov, 7-2610).
66
For further information about gifts to physicians, see CRS Report R40790, Requiring Disclosure of Gifts and
Payments to Health Care Professionals: A Legal Overview, by Jennifer Staman and Brian T. Yeh.
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Liability and Preemption
Two recent United States Supreme Court cases focus on the question of whether FDA approval
protects a manufacturer from liability under state tort law. 67 The first case, Riegel v. Medtronic,
Inc., involved a Class III medical device with FDA PMA and an express preemption provision in
the FFDCA.68 In Riegel, the Supreme Court held that if the FDA grants PMA for a medical
device, the device manufacturer is immune from suit under state common law claims such as
strict liability, breach of implied warranty, and negligence in design, testing, labeling,
manufacturing, labeling, distribution, sale, inspection, or marketing of the device to the extent
that such state law claims are “different from, or in addition to” federal PMA requirements.69 The
court’s holding in Riegel suggests that to the extent that a lawsuit raises claims that “‘parallel’
rather than add to federal requirements,” such as a state “damages remedy for claims premised on
a violation of FDA regulations,” such suits would not be preempted. 70
By contrast, there was no express preemption statutory provision in the second case, Wyeth v.
Levine, which dealt with implied preemption in the context of an FDA-approved drug label.71 In
Wyeth, the Supreme Court held that FDA’s approval of a drug does not preempt a lawsuit against
the manufacturer alleging that the drug’s label failed to provide an adequate warning against
significant risks. The Court did not find that the FFDCA impliedly preempted such cases. The
Court drew a distinction between Riegel and Wyeth based on differences in congressional action
regarding drugs and devices: “when Congress enacted an express pre-emption provision for
medical devices in 1976, see §521, 90 Stat. 574 (codified at 21 U. S. C. §360k(a)), it declined to
enact such a provision for prescription drugs.”
Some members of Congress have proposed legislation that address what effect, if any, FDA
approval should have on a manufacturer’s liability, among other things. Examples of such
legislation include the Medical Device Safety Act of 2009 (S. 540/H.R. 1346), the HEALTH Act
of 2009 (H.R. 1086), the MCAP Act (S. 45), and the Health Care Freedom Act of 2009 (S. 1324).
510(k) Clearance and Device Approval
FDAAA (the FDA Amendments Act of 2007) required the Government Accountability Office
(GAO) to study and report on the appropriate use of the 510(k) process to determine whether a
new device is as safe and effective as a classified device. 72 The report, released in January 2009,
made one recommendation: that FDA expeditiously take steps to issue regulations for class III
device types currently allowed to enter the market via the 510(k) process (i.e., preamendment
devices) by requiring PMAs or reclassifying them to a lower class. 73 The report has sparked
67
For further information about product liability, see CRS Report RL33423, Products Liability: A Legal Overview, by
Henry Cohen and Vanessa K. Burrows.
68
Riegel v. Medtronic, Inc., 522 U.S. ___ (2008). Riegel v. Medtronic, Inc., 522 U.S. ___ (2008). For a discussion of
this case, please see CRS Report R40534, Riegel v. Medtronic, Inc.: Federal Preemption of State Tort Law Regarding
Medical Devices with FDA Premarket Approval, by Vanessa K. Burrows,
69
21 U.S.C. § 360k(a).
70
Riegel, 522 U.S. ___ (2008); slip op. at 17.
71
Wyeth v. Levine, 555 U.S. ___ (2009).
72
P.L. 110-85, sec. 225.
73
U.S. Government Accountability Office, Medical Devices: FDA Should Take Steps to Ensure That High-Risk Device
Types Are Approved through the Most Stringent Premarket Review Process, GAO-09-190, January 2009,
(continued...)
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The Medical Device Approval Process and Related Legislative Issues
agency action as well as legislative interest in issues related to 510(k) and preamendment
devices. 74
Some legislation has focused on separate approval-related issues. For example, the Healthy
Americans Act (H.R. 1321/S. 391) includes approval provisions related to comparative
effectiveness and device use in subpopulations.
Importation and Inspection
FDA shares its responsibility for ensuring the safety of imported medical devices with other
agencies, including Customs and Border Protection. Questions raised about the safety of imported
medical products have led some members of Congress to propose requiring enhanced registration
for manufacturers and other establishments, the identification of prior transactions in device
production, country of manufacture labeling, the hire of additional foreign inspectors, risk-based
inspection, and other measures.
Examples of legislation that touch on the topics of importation and inspection include the Food
and Drug Administration Globalization Act of 2009 (H.R. 759), and the Drug and Device
Accountability Act of 2009 (S. 882).
Unapproved Devices
Medical devices may not be legally marketed in the United States without FDA’s permission.
Because FDA’s evaluation takes time, there is necessarily a delay between the creation of a new
medical device and FDA’s evaluation of the safety and effectiveness of that device. This delay has
sparked a policy debate about whether consumers and health providers should be allowed use
devices lacking FDA’s approval or clearance, particularly if they treat life-threatening medical
conditions.
An example of legislation aimed at enhancing patient access to unapproved medical devices and
other treatments is the Access to Medical Treatment Act (H.R. 3261).
Advertising
FDA has the authority to regulate the advertising of restricted medical devices, which are the
rough equivalent of prescription drugs (FFDCA 502(r)). (The Federal Trade Commission
regulates the marketing of non-restricted devices.) On one hand, advertising to consumers and
health professionals might serve to educate them about life enhancing products. On the other, it
might bias them, and raise device prices by the amount of advertising costs. Members of
Congress have proposed legislation to regulate how medical device companies should promote
their devices to consumers and physicians, as well as to require disclosure of companies’ gifts to
physicians.
(...continued)
http://www.gao.gov/new.items/d09190.pdf.
74
For an example of agency action, see FDA, “Strengthening the Center for Devices and Radiological Health’s 510(k)
Review Process; Public Meeting; Request for Comments,” 75 Federal Register 4402-4406, January 27, 2010.
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The Medical Device Approval Process and Related Legislative Issues
Examples of legislation that touch on the topic of device promotion to physicians include the
Physician Payments Sunshine Act of 2009 (S. 301/H.R. 3138) and the Access to Medical
Treatment Act (H.R. 3261). The terms of S. 301/H.R. 3138 were incorporated into some health
reform bills, as noted above.
IVD Regulation
FDA claims the authority to regulate all laboratory tests; however, it does not regulate all IVDs.75
Whether FDA regulates a test depends on whether it is a laboratory-developed test (i.e.,
developed in-house, not for commercial distribution, also known as home brews) or a kit intended
for commercial distribution. FDA regulates tests that are kits, and it does not regulate labdeveloped tests in their entirety. (Certain components of lab-developed tests, called analyte
specific reagents, are regulated by the FDA as Class I devices if they are commercially
distributed.) While some argue that less regulation of laboratory developed tests aids consumer
access to rapidly developed personalized tests, others argue that more regulation would help to
ensure that the tests are accurate. Some members of Congress have proposed legislative measures
that address the topic of IVD regulation.
Examples of legislation that touch on the topics of IVD regulation and reimbursement include the
Patient Access to Critical Lab Tests Act (H.R. 1699) and the Medicare Clinical Diagnostic
Laboratory Fee Schedule Modernization Act of 2009 (H.R. 1452).
Device-Specific Legislation
Some proposed legislation would, among other things, promote the development or availability of
medical devices for particular diseases, situations, or types of research. The related legislative
issues vary as widely as the topics addressed. Examples include the 21st Century Cancer ALERT
Act (S. 717); the Autism Treatment Acceleration Act of 2009 (S. 819); the Global Autism
Assistance Act of 2009 (H.R. 1878); the National Neurotechnology Initiative Act (S. 586/H.R.
1483); the Josh Miller HEARTS Act (H.R. 1380); the Compassionate Assistance for Rape
Emergencies Act of 2009 (H.R. 1236); the Alopecia Areata Medicaid Improvement and Parity Act
(H.R. 1142); the HEART for Women Act (S. 422/H.R. 1032); the Access to America’s
Orthopaedic Services Act of 2009 (H.R. 1021); the National Nanotechnology Initiative
Amendments Act of 2009 (H.R. 554); the Lung Cancer Mortality Reduction Act of 2009 (S. 332);
the Medicare Home Infusion Therapy Coverage Act of 2009 (S. 254/H.R. 574); the Longshore
and Harbor Workers’ Compensation Act Amendments of 2009 (S. 236); the Prevention First Act
of 2009 (H.R. 463); the Prevention First Act (S. 21); the Skin Cancer Prevention, Education, and
Consumer Right-To-Know Act (H.R. 2088); a House resolution to recognize the orthopedic
industry for providing devices for active duty armed service members (H.Res. 577); and a bill to
exempt small pharmacies from certain Medicare accreditation requirements for the purpose of
providing diabetic testing strips under part B (S. 1746).
75
For further information, see CRS Report RL33832, Genetic Testing: Scientific Background for Policymakers, by
Amanda K. Sarata.
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The Medical Device Approval Process and Related Legislative Issues
Other Issues
Medical devices are relevant to some other topics of legislative interest as well. For example, the
Promoting American Agricultural and Medical Exports to Cuba Act of 2009 (H.R. 1531/S. 1089)
and the Agricultural Export Facilitation Act of 2009 (H.R. 1737) would ease restrictions the
exportation to Cuba of medical devices and other products.76 The American Clean Energy and
Security Act of 2009 (H.R. 2454/S. 2998) and the Clean Energy Jobs and American Power Act (S.
1733) each have a mechanism for exempting devices from its hydrofluorocarbon requirements.77
The 21st Century Global Health Technology Act (S. 1591/H.R. 3560) would promote investment
in medical devices for maternal and child care. 78 The TRADE Act of 2009 (H.R. 3012) contains a
measure to protect programs that would control the costs of pharmaceuticals or medical devices
in trade agreements.79 The Health Equity and Accountability Act of 2009 (H.R. 3090) and the
Women’s Health Office Act of 2009 (H.R. 3242) would create certain requirements for the
inclusion of minorities and women, respectively, in device clinical trials. The Strengthening of
FDA Integrity Act of 2009 (H.R. 3932) would apply debarment provisions currently applicable to
abbreviated new drug applications to other types of applications, including those for medical
devices.
Author Contact Information
Erin D. Williams
Specialist in Public Health and Bioethics
ewilliams@crs.loc.gov, 7-4897
76
For further information about exportation to Cuba and other related issues, see CRS Report RL33819, Cuba: Issues
for the 110th Congress, by Mark P. Sullivan.
77
For further information about clean air issues, see CRS Report R40145, Clean Air Issues in the 111th Congress, by
James E. McCarthy.
78
For further information about global health, see CRS Report RS22913, Global Health: USAID Programs and
Appropriations from FY2001 through FY2010, by Tiaji Salaam-Blyther
79
For further information on trade policy, see CRS Report RL33944, Trade Primer: Qs and As on Trade Concepts,
Performance, and Policy, coordinated by Raymond J. Ahearn.
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This is a copy of a public record, reproduced as it was published. It is not legal advice, and it may not be the version a court would rely on. Check the official source before you cite it.