The Medical Device Approval Process and Related Legislative Issues
Prepared for Members and Committees of Congress
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
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. These
include the regulation of in vitro diagnostic products (IVDs, which are laboratory tests), liability
and preemption, medicare and other federal coverage, importation, advertising, and some other
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.
Introduc tion ..................................................................................................................................... 1
Medical Devices and Their Manufacturers.....................................................................................3
The History of Laws Governing Medical Device Regulation........................................................4
The Medical Device Approval Process: Premarket Review Requirements.....................................6
Fundamental Concepts and Terms of Art..................................................................................6
Safety and Effectiveness.....................................................................................................6
Approval and Clearance......................................................................................................7
Medical Device Marketing Applications...................................................................................9
Before a Marketing Application Is Submitted..................................................................10
Marketing Applications for Medical Devices....................................................................11
In Vitro Diagnostic Products (IVD)..................................................................................15
The Medical Device Approval Process: Post-Approval Requirements and Issues......................18
Labeli ng ....................................................................................................................... ..... 18
Manufact uring .................................................................................................................. .19
Compliance and Enforcement...........................................................................................21
Legi slation ..................................................................................................................................... 24
Liability and Preemption.........................................................................................................24
Medicare and Other Federal Coverage....................................................................................24
Importati on .............................................................................................................................. 25
Adve rtising .................................................................................................................... .......... 25
Table 1. Funding for the Device Review Process Salaries and Expenses, FY2003-
FY2009 ......................................................................................................................................... 2
Table 2. Medical Device Approval Basics.......................................................................................9
Table 3. CDRH Warning Letters Issued in Total and Under the MQSA, FY2000-FY2008.........22
Author Contact Information..........................................................................................................26
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 new high of $2.934 billion in
considerably in 2008, reaching only $2.85 billion during the first three quarters of the year. The
products generated by the nation’s venture capital backed biotechnology and medical devices and 2
equipment sectors supported nearly 494,000 high-skilled, high-wage jobs in 2006.
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
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 3
laboratory tests led to hundreds of incorrect test results in 2004. Defects in other types of
medical devices, such as pacemakers, defibrillators, and coronary stents, have caused patient 4
deaths. 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 December 29, 2008.
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.
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/
4 See “Medical Device Recalls, Class I Recall: Boston Scientific Express Coronary Stent,” at http://www.fda.gov/cdrh/
recalls/recall-071604.html; “Medical Device Recalls, Class I Recall: Boston Scientific Taxus Express Coronary Stent,”
at http://www.fda.gov/cdrh/recalls/recall-070104.html; and “Medical Device Recalls, Class 1 Recall: Access
CardioSystems Automated External Defibrillators,” at http://www.fda.gov/cdrh/recalls/recall-110304.html.
Jurisdiction of the centers’ medical device review is governed by the FDA Intercenter Agreement 5
between CBER and CDRH (October 31, 1991).
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 6
manufacturers), which together comprise FDA’s device review budget program authority.
Medical device user fees comprise a much greater share of the device budget now than they did 7
when they were first collected in FY2003 (see Table 1). Congress has reauthorized in five-year
increments FDA’s collection of medical device user fees. The authority and will next expire on
October 1, 2012.
Table 1. Funding for the Device Review Process Salaries and Expenses,
(dollars in thousands)
Total Program Level MDUFMA User Fees MDUFMA /Total
FY2003 Actual $217,285 $14,838 6.8%
FY2004 Actual $179,245 $23,875 13.3%
FY2005 Actual $244,282 $27,161 11.1%
FY2006 Actual $255,041 $32,069 12.6%
FY2007 Actual $267,543 $36,861 13.8%
FY2008 Enacteda $283,777 $45,785 16.1%
FY2009 Pres. Budgeta $290,921 $49,040 16.9%
Source: Food and Drug Administration tables for FY2005 - FY2009, “ALL PURPOSE TABLE - Total Program
Level,” at http://www.fda.gov/oc/oms/ofm/budget/documentation.htm.
a. Numbers do not reflect the FY2008 Supplemental appropriation or the FY2009 CR.
Medical device issues confronting the Congress arise in the context of a variety of concerns about 8
FDA and CDRH. Chief among these is that, in September of 2007, Congress passed the most
comprehensive FDA reform legislation in almost a decade: the Food and Drug Administration 9
Amendments Act of 2007 (FDAAA; P.L. 110-85). The impact of FDAAA for medical device
regulation is discussed below in the “History of Laws Governing Medical Device Regulation”
In the wake FDAAA, issues related to medical devices and other products remain both in areas
that FDAAA did not comprehensively address, and in areas raised by its implementation. Most of
5 FDA, “Devices Regulated by CBER,” (updated March 15, 2007), at http://www.fda.gov/cber/dap/devlst.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; and CRS Report RL34638, FDA FY2009
Appropriations, by Susan Thaul et al.
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).
8 See CRS Report RS22946, Food and Drug Administration (FDA): Overview and Issues, by Erin D. Williams.
9 See CRS Report RL34465, FDA Amendments Act of 2007 (P.L. 110-85), by Erin D. Williams and Susan Thaul.
these issues are discussed in this report. However, some FDA-wide issues, which are not
discussed in detail, have consequences for medical device regulation. For example, questions 10
have arisen as to whether FDA’s budget is adequate for the agency to carry out its mission.
Reports have emerged of FDA scientists alleging that politics influenced medical device 11
approvals, and that agency scientists’ morale was declining. In addition, in several well-
publicized instances, FDA representatives failed to respond in a timely and candid manner to 12
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 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 consumer 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;
10 See CRS Report RL34334, The Food and Drug Administration: Budget and Statutory History, FY1980-FY2007,
coordinated by Judith A. Johnson, and CRS Report RL34638, FDA FY2009 Appropriations, by Susan Thaul et al.
11 Union of Concerned Scientists “Voices of Scientists at FDA: Protecting Public Health Depends on Independent
Science,” 2006, available through the FDA Survey Brochure link at http://www.ucsusa.org/news/press_release/fda-
12 For example, Senator Grassley expressed dissatisfaction with FDA’s lack of responsiveness and transparency.
“Grassley questions FDA about risks to children, infants in antibiotic drug trials,” Senator Chuck Grassley Press
Release (June 8, 2008), athttp://grassley.senate.gov/
index.cfm?FuseAction=PressReleases.Detail&PressRelease_id=5092&Month=6&Year=2006. A Congressional report
characterized FDA’s answers to requests for information as haphazard, incomplete, and untimely. United States House
of Representatives Committee on Government Reform Minority Staff, Prescription for Harm: The Decline in FDA
Enforcement Activity, Special Investigation prepared for Representative Henry A. Waxman (June 2006), p. 4, at
• 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.13
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), 14
cardiovascular devices, orthopedic devices, and diagnostic imaging. 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
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, with estimated earnings of $81.6 15
billion in 2007 compared to the drug industry’s estimated $205.8 billion. 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.
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.
13 Federal Food, Drug and Cosmetic Act §201(h), (21 U.S.C. 321), at http://www.fda.gov/opacom/laws/fdcact/
14 The Lewin Group, for AdvaMed, The Impact of Regulation and Market Dynamics on Innovation: The State of the
Industry (Washington, DC, 2001).
15 Frost & Sullivan estimate in Robert Gold, “Healthcare: Products & Supplies, Industry Profile,” Standard and Poor’s
Industry Survey, September 18, 2008; and Herman Saftlas, “Healthcare: Pharmaceuticals, Industry Profile,” Standard
and Poor’s Industry Survey, April 24, 2008.
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
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 16
reauthorized by FDAAA.
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, 17
several of which have implications for the regulation of medical devices. 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 18
publicly registered and have their results posted; created requirements to reduce conflicts of 19
interest in advisory committees for medical devices and other products; and made certain other
amendments to the regulation of devices.
16 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.
17 See CRS Report RL34465, FDA Amendments Act of 2007 (P.L. 110-85), by Erin D. Williams and Susan Thaul.
18 See CRS Report RL32832, Clinical Trials Reporting and Publication, by Erin D. Williams.
19 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.
In order for medical devices to be marketed in the United States, manufacturers20 must register
and list the devices that they commercialize with FDA, and for most devices, must obtain the 21
agency’s prior and continuing permission. FDA grants this permission when a manufacturer
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).
FDA grants its permission to market a device when a manufacturer demonstrates that the device
is 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 22
warnings and other restrictions, and the extent of experience with its use. FDA considers there
to be reasonable assurance of safety when it can be determined that the probable benefits to health 23
that result from use of the device as directed by the manufacturer outweigh any probable risks. 24
Investigations for safety can include animal studies, human studies, and/or laboratory studies.
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 25
instructions) provides clinically significant results. 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.
20 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.
21 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).
22 21 CFR § 860.7(c)(2).
23 21 CFR § 860.7(d)(1).
24 21 CFR § 860.7(d)(2).
25 21 CFR § 860.7(e)(1).
There are two paths that manufacturers can use to demonstrate that their medical devices are safe
and effective, and meet any premarket review requirements FDA may have. 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 prove that a device is safe and effective by demonstrating that it is 26
substantially equivalent to a device that is already on the market (a predicate device). This type
of process is unique to medical devices. It 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 time-consuming 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 27
predicate device. 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
26 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.
27 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))
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.
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 28
misused. The risk categories (known as classifications) are Class I, II , and III, which represent
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.”
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 29
follow. These regulatory requirements, known as controls, are described in more in the
descriptions of Class I, II, and II devices that follows.
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 30
FDA regulated medical devices, include five elements:
• 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).
28 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
the classification panels and as the first cadre of predicate devices that could be used to demonstrate substantial
29 The term “manufacturer” is used throughout this report for simplicity, but also includes any person, organization, or
sponsor that submits a marketing application to FDA for marketing approval for a medical device.
30 FFDCA 513(a)(1)(A); also see FDA, General Controls for Medical Devices, April 16, 1998, at http://www.fda.gov/
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).
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
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 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 (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
Table 2. Medical Device Approval Basics
Device Safety / Effectiveness
Classification Examples Controls Required Submissiona
Class I elastic bandages, examination gloves, General Controls -Registration only unless
and hand-held surgical instruments 510(k) specifically required
Class II powered wheelchairs, infusion pumps, General Controls & b-510(k) clearance
and surgical drapes Special Controls unless exempt
Class III heart valves, silicone gel-filled breast General Controls & -PMA approval
implants, and implanted cerebella Premarket Approval unless 510(k) specifically
a. Each type of required submissions is described in the Types of Device Marketing Applications section that
b. Special controls are described in the Class II section below.
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 MDUFMA and FDAAA, 31
manufacturers must pay a fee for most types of submissions.
Generally speaking, according to the FFDCA, manufacturers:
• are prohibited from selling an adulterated product;32
• are prohibited from misbranding a product;33
• 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.
FDAMA gave FDA the authority to establish procedures for meeting with manufacturers prior to 34
preparing a submission. 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 35
subsequently an IDE application. 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
31 See CRS Report RL34571, Medical Device User Fees and User Fee Acts, by Erin D. Williams.
32 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.
33 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.
34 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/cdrh/ode/guidance/310.pdf.
35 For more information on the IDE, please refer to the “Marketing Applications for Medical Devices” section that
immediately follows this discussion.
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
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.
The following sections describe the types of premarket submissions that FDA reviews for medical
devices. (See Table 2).
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. The standard for clearance of a traditional 510(k) is
substantial equivalence with a predicate device. Though usually for Class I or II devices, an older,
preamendment Class III device may sometimes use a 510(k) submission. 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.
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 36
are also required.
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
36 FDA, “Content of a 510(k),” June 30, 2003, at http://www.fda.gov/cdrh/devadvice/314312.html; and How to Prepare
a Traditional 510(k), January 4, 2005, at http://www.fda.gov/cdrh/devadvice/3143.html#link_4.
FDA may issue a notice of withdrawal of the application (21 CFR § 807.87(l)). The manufacturer 37
may, at any time, withdraw its 510(k). FDA has 90 days to review a traditional 510(k).
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 38
public participation or opportunities for public comment.
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 39
of this report for more detail on QSR). A special 510(k) utilizes the design control 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
issues a regulation that classifies the device. If the device is Class II, a special controls guidance
37 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
38 FDA continually accepts public comment on any draft or final guidance document.
39 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.
document is also developed that then allows subsequent manufacturers to submit either traditional 40
or abbreviated 510(k)s.
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 41
matter before FDA. 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
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
40 Guidance for Industry and FDA Staff, New Section 513(f)(2)—Evaluation of Automatic Class III Designation,
February 19, 1998, at http://www.fda.gov/cdrh/modact/clasiii.pdf.
41 For further information, see CRS Report RS22691, FDA Advisory Committee Conflict of Interest, by Erin D.
MDUFMA and FDAAA performance goals have been established to reduce the review time for
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).
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 42
PMA, at some later point in time. 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 43
an IDE and be approved by an institutional review board (IRB), before the study is initiated.
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 IDE’s 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;
• 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
42 FDA, IDE Overview, July 8, 2003, at http://www.fda.gov/cdrh/devadvice/ide/index.shtml.
43 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.
• 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)).
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
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 44
required for additional indications.
IVD products 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 (21 CFR
§ 809.3). IVDs are medical devices as defined in Section 210(h) of the FFDCA (such as gene
44 CDRH, FDA, Humanitarian Device Exemptions Regulation: Questions and Answers; Final Guidance for Industry,
July 12, 2001, at http://www.fda.gov/cdrh/ode/guidance/1381.html.
chips), and may also be biological products subject to Section 351 of the Public Health Service
Act (such as biological agent diagnostic systems).
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.
IVDs (e.g., laboratory tests) may consist of general purpose reagents,45 analyte specific reagents 4647
(ASRs), general purpose or specific equipment, sometimes with computer analysis software.
Most 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 48
(CLIA) of 1988. 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
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)49 during the premarket
process. Postmarket, the Centers for Medicare and Medicaid Services (CMS) regulates all 50
laboratory testing (except research) performed on humans in the U.S. through CLIA. Under
CLIA, laboratories performing only waived tests are subject to minimal regulation. Laboratories
45 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).
46 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)).
47 In 2006, FDA’s OIVD issued two draft guidance documents on IVDs: “Draft Guidance for Industry and FDA Staff -
Commercially Distributed Analyte Specific Reagents (ASRs): Frequently Asked Questions,” (September 7, 2006), at
http://www.fda.gov/cdrh/oivd/guidance/1590.pdf; and “In Vitro Diagnostic Multivariate Index Assays,” (September 7,
2007), at http://www.fda.gov/cdrh/oivd/guidance/1610.pdf.
48 FDA, Overview of IVD Regulation, March 4, 2003, at http://www.fda.gov/cdrh/oivd/regulatory-overview.html#1.
49 See “Find Device CLIA ‘88 Categorization,” OIVD, FDA website (December 2005), at http://www.fda.gov/cdrh/
50 “Clinical Laboratory Improvement Amendments (CLIA) Overview,” CMS Website (December 18, 2006), at
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
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.
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).
Once approved or cleared for marketing, manufacturers of medical devices must comply with
regulations on labeling and advertising, on production of their device, and on postmarket
surveillance of adverse events associated with the use of their device. The requirements for each
of these are described below.
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 51
matter which constitutes advertising.”
Labeling regulations pertaining to medical devices are found in the following parts of Title 21
• General Device Labeling (21 CFR Part 801)
• In Vitro Diagnostic Products (21 CFR Part 809)
• 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 devices52 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.
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
51 United States v. Research Laboratories, Inc., 126 F.2d 42 (9th Cir. 1942).
52 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.
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.
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 53
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.
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.
53 FDA, Good Manufacturing Practice/Quality Systems, at http://www.fda.gov/cdrh/comp/gmp.html.
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. FDAAA authorized the appropriation of $25 million
per year for Postmarket Studies and Surveillance (21 USC 355 note).
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 device-
related 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.go v/ scri pts/cdrh/cfdocs/cfmdr/sear ch.CFM.
Manufacturers must adopt a method of tracking certain devices. These are devices:
• ●whose failure would be reasonably likely to have serious, adverse health
• which are intended to be implanted in the human body for more than one year; or
• which are life-sustaining or life-supporting devices used outside of a device user
facility (21 CFR Part 821).
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 54
of serious risks to health presented by the devices. A current list of the devices for which
tracking is required can be found at http://www.fda.gov/cdrh/devadvice/353.html.
54 OIVD, which reviews clinical laboratory test kits and equipment, has the capacity for both premarket scientific
review and pre- and postmarket compliance activity.
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) which 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.
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 eight to twelve 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
55 See ORA at http://www.fda.gov/ora/.
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.
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/foi/
A congressional report found the CDRH issued 65% fewer such warning letters in 2005 than in
during field inspections has remained relatively constant. The report suggested that the lack of
enforcement actions may have been due in part to FDA officials rejecting FDA field inspectors
enforcement recommendations. FDA’s Office of Legislation offered an alternative explanation,
referencing a change in policy related to a specific program—the Mammography Quality
Standards Act (MQSA, P.L. 102-539) (see Table 3).
Table 3. CDRH Warning Letters Issued in Total
and Under the MQSA, FY2000-FY2008
Non-MQSA MQSA Total
FY2000 191 337 528
FY2001 105 393 498
FY2002 75 206 285
FY2003 121 84 205
FY2004 193 5 198
FY2005 177 5 182
FY2006 149 5 154
FY2007 146 10 52
FY2008 164 2 166
56 United States House of Representatives Committee on Government Reform Minority Staff, Prescription for Harm:
The Decline in FDA Enforcement Activity, Special Investigation prepared for Representative Henry A. Waxman (June
2006), p. I, at http://oversight.house.gov/Documents/20060627101434-98349.pdf.
Source: FDA Office of Legislation.
Notes: According to FDA’s Office of Legislation, the number of MQSA warning letters has significantly decreased
because of a change in ORA and CDRH policy. Enforcement strategies for violations of the MQSA now focus on
opportunities for correction and re-inspections (fees paid by facilities) prior to issuing warning letters. These
measures have reduced the number of warning letters the program has had to issue.
A recall is a method of removing or correcting products that FDA considers are in violation of the 57
law. 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).
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
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.
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 FDA-
regulated products is http://www.fda.gov/opacom/7alerts.html.
57 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).
A number of medical device related topics are of interest to members of the 111th Congress. As
described below, these include IVD regulation, liability and preemption, medicare and other
federal coverage, importation, advertising, and some other issues.
FDA claims the authority to regulate all laboratory tests, however, it does not regulate all IVDs.58
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 lab-developed
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
In court case Riegel v. Medtronic, Inc., the United States Supreme Court held that if the FDA
grants premarket approval (PMA) to 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. In other words, FDA approval prevents consumers of certain medical
devices from suing the manufacturers in some circumstances. Some members of Congress have 59
proposed legislation on the topic of preemption.
While FDA does not generally consider or regulate the cost of medical devices,60 the way that
medical devices are reimbursed in the public health care system is of interest to many members of 61
Congress. Some members have focused on measures to help keep prices low, such as requiring
the reporting of sales price data for certain devices. Others have sought to enhance access by
amending payment formulas, requiring for Medicare coverage for FDA approved devices, or
eliminating certain preconditions for payment. Issues related to the cost of medical products are
58 For further information, see CRS Report RL33832, Genetic Testing: Scientific Background for Policymakers, by
Amanda K. Sarata.
59 For further information about product liability, see CRS Report RL33423, Products Liability: A Legal Overview, by
Henry Cohen and Vanessa K. Burrows.
60 There are some pricing restrictions for devices HDE devices. For details, see CRS Report RL34571, Medical Device
User Fees and User Fee Acts, by Erin D. Williams.
61 For further information about Medicare, see CRS Report RL33712, Medicare: A Primer, by Jennifer O’Sullivan.
also of potential relevance to legislative discussions focused on health care reform and cost
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, and other
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
Medical devices are relevant to some other topics of legislative interest as well, such as efforts to 62
prohibit the use of live animals for marketing medical devices, or to ease restrictions the 63
exportation to Cuba of medical devices and other products.
62 For further information about the Animal Welfare Act, see CRS Report RS22493, The Animal Welfare Act:
Background and Selected Legislation, by Geoffrey S. Becker.
63 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.
Erin D. Williams
Specialist in Public Health and Bioethics