FDA Legislation in the 110th Congress: A Guide to S. 1082 and H.R. 2900
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FDA Legislation in the 110 Congress:
A Guide to S. 1082 and H.R. 2900
Updated August 6, 2007
Erin D. Williams, Susan Thaul, and Donna V. Porter
Domestic Social Policy Division
FDA Legislation in the 110th Congress:
A Guide to S. 1082 and H.R. 2900
Summary
Both the House and the Senate have passed comprehensive legislation to
reauthorize existing Food and Drug Administration (FDA) programs and expand the
agency’s authority to ensure the safety of prescription drugs, medical devices, and
biologics. The Senate passed the Food and Drug Administration Revitalization Act
(S. 1082) on May 9, 2007. The House passed the Food and Drug Administration
Amendments Act of 2007 (H.R. 2900) on July 11, 2007.
At its core, the legislation renews authority for two key user fee programs that
are set to expire on October 1, 2007: the Prescription Drug User Fee Act (PDUFA;
P.L. 107-188) and the Medical Device User Fee and Modernization Act (MDUFMA;
P.L. 107-250). These account for 87% of FDA’s user fee revenue, and 19% of
FDA’s total FY2008 program level budget. Without the reauthorizations, and absent
a substantial increase in FDA’s annual appropriations, the agency would lose a
significant source of funding. FDA had warned that a failure to reauthorize the user
fee programs before August 1, 2007, would require the agency to issue layoff notices,
but the agency has reportedly forestalled that necessity by switching to reserve funds.
In addition to user fee programs, the bills reauthorize two other FDA authorities
related to prescription drugs for pediatric populations, which are also due to expire
on October 1, 2007: the Best Pharmaceuticals for Children Act (BPCA; P.L.
107-109) and the Pediatric Research Equity Act (PREA; P.L. 108-155). These laws
provide marketing exclusivity incentives and requirements for studying pediatric use
of on-patent and off-patent drugs. S. 1082 and H.R. 2900 also contain provisions
related to drug safety, pediatric medical devices, clinical trial registration, and the
creation of a new nonprofit entity to assist FDA with its mission. The bills’
overlapping provisions are similar, but not identical.
S. 1082 contains some additional provisions that are not present in H.R. 2900,
on the topics of food safety, prescription drug importation, and domestic pet turtle
market access. Attempts to expand the legislation to address several other FDA-
related issues, for example, follow-on biologics and genetic testing, have thus far
been unsuccessful. Differences between the bills may be addressed in conference.
This report contains background information about the FDA relevant to S. 1082
and H.R. 2900. It presents a comparative overview of the bills’ contents, and
contains links to pertinent CRS reports. This report will be updated as further
legislative events warrant.
Contents
In troduction ......................................................1
Drug and Device User Fees..........................................2
Pediatric Drug Research ............................................3
Other FDA Issues..................................................3
Pediatric Medical Devices.......................................3
Drug Safety..................................................3
Clinical Trials Databases .......................................4
Conflicts of Interest............................................4
Reagan-Udall Foundation.......................................4
Importation of Prescription Drugs.................................5
Food Safety..................................................5
S. 1082 and H.R. 2900..............................................6
Prescription Drug User Fees.........................................6
Authorized Uses of Fees........................................7
Authorized Fee Revenue........................................7
New Fees for Advisory Review of Advertisements....................7
Reauthorization and Report Requirements..........................8
Medical Device User Fees...........................................8
User Fee.....................................................8
Device Regulation............................................10
Pediatric Drugs and Devices........................................11
Pediatric Exclusivity Incentives (BPCA Reauthorization).............12
Mandatory Pediatric Assessments (PREA Reauthorization)............12
Pediatric Medical Devices......................................12
Drug Safety.....................................................13
Active Surveillance and Assessment..............................14
Risk Evaluation and Mitigation Strategies.........................14
Postmarket Studies............................................15
Labeling ....................................................15
Advertising ..................................................16
Enforcement .................................................16
Funding ....................................................16
Antibiotic Drugs..............................................17
Anti-Counterfeiting Technologies................................17
Drug Safety Provisions In Only One Bill...........................17
In H.R. 2900 Alone.......................................17
In S. 1082 Alone.........................................17
Clinical Trials Databases...........................................18
Registry ....................................................18
Results Database.............................................19
Coordination, Compliance, and Enforcement.......................20
Conflicts of Interest...............................................20
Reagan-Udall Foundation for the Food and Drug Administration...........22
Office of the Chief Scientist........................................22
Miscellaneous Provisions in S. 1082..................................22
Importation of Prescription Drugs................................22
Food Safety.................................................23
Other Provisions..............................................24
Miscellaneous Provision in H.R. 2900................................24
List of Tables
Table 1. Location of Various Subjects in S. 1082 and H.R. 2900.............6
FDA Legislation in the 110th Congress:
A Guide to S. 1082 and H.R. 2900
Introduction
Both chambers of Congress have passed comprehensive legislation to
reauthorize expiring programs at the Food and Drug Administration (FDA), and to
expand the agency’s authority to help ensure the safety of certain medical products.
The bills are the Food and Drug Administration Revitalization Act (S. 1082), and the
Food and Drug Administration Amendments Act of 2007 (H.R. 2900). S. 1082 and
H.R. 2900 represent the most comprehensive FDA legislation since the Food and
Drug Administration Modernization Act of 1997 (FDAMA; P.L. 105-115).
The primary driver of the legislation is the renewal of FDA’s authority for two
key user fee programs set to expire at the end of FY2007: the Prescription Drug User
Fee Act (PDUFA; P.L. 107-188), and the Medical Device User Fee and
Modernization Act (MDUFMA; P.L. 107-250). FDA had reportedly urged Congress
to complete its reauthorization efforts before August 1, 2007 (rather than by the
program’s termination date of October 1, 2007), because of a requirement that FDA
notify employees at least 60 days in advance of layoffs, which would be necessary
without PDUFA and MDUFMA funds.1 The media report that FDA has switched
to reserve funds to forestall the issuance of layoff notifications, the effect of which
is a hiring freeze at FDA.2 In addition, the FDA Commissioner has reportedly
stressed that the funding uncertainty is harming the morale of employees: 30% of
whom are at a point where they can retire.
The bills also would reauthorize two other expiring authorities, which are
related to pediatric pharmaceuticals: the Best Pharmaceuticals for Children Act
(BPCA; P.L. 105-115; reauthorized in P.L. 107-109), and the Pediatric Research
Equity Act (PREA; P.L. 108-155). In addition, the bills address a number of other
issues of concern to Congress and to the public.
The FDA, an agency within the Department of Health and Human Services3
(HHS), regulates the safety of most human foods, all animal feeds, and certain other
products such as cosmetics. The agency also regulates the safety and effectiveness
1 Joe Reichard, “FDA Running on Budgetary Fumes, Chief Says” CQ Healthbeat News,
August 2, 2007, 4:40 p.m.
2 Anna Edney, “FDA To Avoid Layoff Notices By Dipping Into Reserves,” Congress Daily,
Health, August 2, 2007.
3 The United States Department of Agriculture (USDA) regulates the safety of meat and
poultry products.
of human drugs, biologics (e.g., vaccines), medical devices, and animal drugs.4
Those products regulated for effectiveness must be reviewed and approved by FDA
before they can be placed in commerce, a process called premarket approval. (FDA
is tasked with postmarket surveillance for these products as well.) Products regulated
only for safety may enter commerce with little FDA oversight, though the agency
may inspect production facilities and require that certain good manufacturing
practices be carried out. FDA has the statutory authority to withdraw from commerce
any product it regulates that it determines to be unsafe.
Media coverage of issues related to the safety of food (e.g., spinach), drugs (e.g.,
Vioxx), and medical devices (e.g., cardiac stents) have brought congressional
attention to FDA’s performance and the funding it has available to carry out its
statutory responsibilities. For those products requiring premarket approval, a central
issue for the 110th Congress is how best to balance the need for the agency to help
speed the products it regulates to market if they are safe and effective, and correct
them or keep or remove them from the market if they are not. For human foods,
animal feeds, and other products not requiring premarket approval, key issues relate
to FDA’s ability to assure product safety and protect public health by preventing
health threats from occurring, or by identifying and responding to problems quickly.
Drug and Device User Fees
In order to bring revenue into FDA to help speed products to market, Congress
has passed several measures authorizing FDA to collect user fees from the products’
manufacturers. Some have questioned whether the agency’s reliance on fees it
collects from the companies that it regulates is appropriate, calling instead for greatly
increased appropriations for the agency. Nevertheless, efforts to reauthorize the two
expiring user fee authorities (PDUFA and MDUFMA) are already underway.
Income from PDUFA and MDUFMA represents, by far, the largest proportion
of FDA’s user fee revenue, and a significant proportion of the agency’s overall
budget. According to FDA’s FY2008 budget request, PDUFA will generate
$339,195,000, and MDUFMA will generate $47,500,000. Combined, these fees
would account for 87% of FDA’s user fee revenue, and 19% of its total program
level budget in FY2008.
PDUFA was first enacted in 1992 (P.L. 102-571), and has been reauthorized
twice; once by the Food and Drug Administration Modernization Act of 1997
(FDAMA, P.L. 105-115), and a second time by the Public Health Security and
Bioterrorism Preparedness and Response Act of 2002 (P.L. 107-188). PDUFA
authorizes the FDA to collect fees from companies that produce certain human drugs
and biological products, and to use the revenue for the review of new product
applications. PDUFA also incorporates, by reference, performance goals aimed
primarily at reducing FDA premarket review times.
4 Regulation of biologics for animal use is overseen by the USDA.
MDUFMA, first enacted in 2002, established user fees for FDA’s review of
medical device applications. Like PDUFA, MDUFMA incorporated, by reference,
performance goals for many types of premarket device reviews. MDUFMA also
allowed third-parties to conduct establishment inspections, and added new regulatory
requirements for reprocessed single-use devices. The expiring authorities within
MDUFMA are those related to user fees and the associated performance goals.
Pediatric Drug Research
In part to protect children from the risks of participating in clinical trials,
researchers did not often test drugs on that population. As a result, information about
appropriate dosage levels for and potential side effects of “adult” medications in
children were unknown, frequently leaving clinicians with pediatric patients the
choice of prescribing nothing, or something with an unknown effect. In 1997,
Congress gave FDA a tool, in BPCA, to encourage pediatric drug research —
extended marketing exclusivity in exchange for trials investigating a drug’s effect on
pediatric populations. Meanwhile, FDA’s attempts to require, as part of new drug
applications, assessments of how new drugs would affect pediatric populations were
stopped by the courts until Congress, in 2003, codified that requirement in PREA.
BPCA and PREA provide marketing exclusivity incentives and requirements for
studying pediatric use of both on- and off-patent drugs.
Other FDA Issues
The following topics are addressed in one or both reauthorization bills.
Pediatric Medical Devices
It has been reported that developing medical devices for children is less
profitable and more problematic than developing them for adults. This is because
fewer children need medical devices than adults, and because children have physical
attributes (e.g., size, biochemistry, growth rates), activities, and environmental
influences that vary from those of adults. The result has been characterized as a
critical need for pediatric medical devices that help diagnose and treat diseases and
conditions affecting children. Both S. 1082 and H.R. 2900 contain provisions
offering incentives to manufacturers to create pediatric medical devices, and giving
FDA the authority to require postmarket studies of approved pediatric devices to
ensure their continued efficacy and safety.
Drug Safety
While premarket clinical trials reveal many of the adverse effects of medical
products, others may not become apparent until a product is on the market. This may
be because the adverse effects require a period of years or decades to manifest, or it
may be because the adverse effects are so rare that they require use by a large number
of people for them to be recognized as drug-related. In some instances, only a small
proportion of people who will take the drug are susceptible to a specific effect,
requiring a large swath of the population to use a drug before the adverse effect is
seen. S. 1082 and H.R. 2900 include provisions focused on buttressing FDA’s
system for collecting data on marketed products, sifting through the massive amounts
of information to identify situations that merit FDA action, and providing new
authorities to allow FDA to require manufacturers to take some actions.
Clinical Trials Databases
Medical journals tend only to publish the results of clinical trials demonstrating
a product’s effectiveness, as negative studies do not draw readers in the same way.
Product manufacturers may be reluctant to make unsuccessful results public as well,
to avoid both alerting potential customers to problems and informing competitors of
their activities. However, in 2004, Congress and others raised questions about the
safety and effectiveness of several FDA-approved biomedical products about which
negative trial results had not been publicly disclosed (e.g., antidepressants, cardiac
stents).5 The issue of public access to negative trial results then gained significant
traction. Both S. 1082 and H.R. 2900 contain provisions relating to the public
registration of clinical trials and the public posting of their results.
Conflicts of Interest
FDA uses advisory committees to provide the agency with independent advice
from outside experts on issues related to human and veterinary drugs, biological
products, medical devices, and food. Advisory committees make recommendations
to FDA, which FDA may or may not follow. To be credible and useful, many say
that committees need to be free from or reduce conflicts of interest. However, others
note that the most expert members in the field are often those involved directly or
indirectly in the activities about which FDA is seeking advice, creating the potential
for such conflicts. In 2006 and 2007, the media has reported that FDA advisory
committees are biased in favor of drug approval, and that many committee members
have conflicts of interest.6 Both S. 1082 and H.R. 2900 contain provisions that
would revise FDA’s approach to advisory committee members’ conflicts of interest.
Reagan-Udall Foundation
The year 2000 marked the start of a slowdown in new drug and biologic
submissions to regulatory agencies worldwide. In 2004, puzzled over why, despite
advances in biomedical sciences, there had been a disappointing decline in innovative
medical products submitted for approval, FDA investigated this issue. Its report
noted the rising difficulty and unpredictability of medical product development and
5 Shankar Vedantam, “Antidepressant Makers Withhold Data on Children,” Washington
Post, January 29, 2004, p. A1; and Catherine De Angelis et al., “Clinical Trial Registration:
A Statement from the International Committee of Medical Journal Editors,” New England
Journal of Medicine, vol. 351, no. 12, September 16, 2004, p. 1250.
6 See, for example, Shankar Vedantam, “Group Says FDA, Advisory Panels Show Bias
Toward Drug Approvals,” Washington Post, August 9, 2006, available online at
[ h t t p : / / www.washi n gt onpost . com/ wp-d yn / c ont ent / a r t i c l e / 2006/ 08/ 28/ AR2006082800984
.html].
called for a concerted effort to modernize the scientific tools (e.g., in vitro tests,
computer models, qualified biomarkers, and innovative study designs) and harness
the potential of bioinformation used to evaluate and predict safety, effectiveness, and
manufacturability of candidate medical products.7 S. 1082 and H.R. 2900 propose
the creation of a Reagan-Udall Foundation, a nonprofit corporation that would
support FDA in those tasks.
Importation of Prescription Drugs
The high cost of prescription drugs in the United States has prompted some
consumers to seek medications from foreign sources. Current law permits only the
manufacturer of a prescription drug to import it. Such importation is tightly
regulated by FDA based on law. Because imports acquired outside of this regulated
chain-of-custody may come from foreign sources not subject to the same rigorous
safety and inspection requirements that FDA-regulated manufacturers and importers
face, the law prohibits all other drug importation.
Some lawmakers have tried to find ways to allow access to lower priced
medications — perhaps enabling individuals or commercial importers to purchase
medications from foreign sources — while still ensuring the products’ safety. One
title of S. 1082 was written to allow and regulate some importation of prescription
drugs. An amendment to require the Secretary of HHS (hereinafter referred to as the
Secretary) to certify that the program would be safe and cost-effective effectively
nullifies the detailed drug importation language.
Food Safety
Since 1906, FDA has had responsibility for regulating the safety of most food
products. Its authority has evolved over time to reflect advances in food science and
to address problems that have arisen with either certain categories of food (i.e., infant
formula) or specific food components (i.e., food additives).8 Several recent
widely-reported outbreaks of food borne illness have affected hundreds of
individuals,9 and focused congressional attention on food safety. Many members
have expressed concern with both domestic and imported food products. Food safety
provisions in S. 1082 begin to address some of the larger issues in food safety reform
that Congress may consider.
7 “Stagnation or Innovation,” FDA (March 2004), at [http://www.fda.gov/oc/initiatives/
criticalpath/whitepaper.html ].
8 Infant Formula Act of 1980 (P.L. 96-359) and Food Additives Amendment of 1958 (P.L.
9 CRS Report RL33722, Food Safety: Federal and State Response to the Spinach E. coli
Outbreak, by Donna V. Porter.
S. 1082 and H.R. 2900
The two comprehensive FDA reauthorization and reform bills address many, but
not all of the same topics, though not always in the same way. (See Table 1). The
remaining sections of this report contain descriptions of the key FDA programs
addressed in the bills, certain programs considered but not included in the bills, and
links to relevant CRS reports. Topics include prescription drug user fees, medical
device user fees, pediatric drugs and devices, drug safety, clinical trials databases,
conflicts of interest, importation of prescription drugs, Reagan-Udall Foundation,
office of the chief scientist, food safety, and miscellaneous provisions in one bill or
the other.
Table 1. Location of Various Subjects in S. 1082 and H.R. 2900
SUBJECTS. 1082H.R. 2900
Prescription Drug User FeesTitle ITitle I
Medical Device User FeesTitle III, Subtitle ATitle II, Subtitle A
Medical Device Regulation Title III, Subtitle BTitle II, Subtitle B
Pediatric Exclusivity Incentives (BPCA)Title IV, Subtitle ATitle V
Mandatory Pediatric Assessmts. (PREA)Title IV, Subtitle BTitle IV
Pediatric Medical DevicesTitle IV, Subtitle CTitle III
Drug SafetyTitle II, Subtitle A, ETitle IX
Antibiotic DrugsTitle II, Subtitle FTitle IX
Clinical Trials DatabasesTitle II, Subtitle CTitle VIII
Conflicts of InterestTitle II, Subtitle DTitle VII
Reagan-Udall FoundationTitle II, Subtitle BTitle VI
Importation of Prescription DrugsTitle VIII and Title V***
Food SafetyTitle VI and Title V***
Domestic Pet Turtle Market AccessTitle VII***
Other ProvisionsTitle V***
Prescription Drug User Fees
FDA’s authority to collect user fees pursuant to the Prescription Drug User Fee
Act (PDUFA; Section 735 of the Federal Food, Drug, and Cosmetic Act [FFDCA],
21 U.S.C. 379g) will expire on
October 1, 2007, unlessFor further information, see
Congress reauthorizes theCRS Report RL33914, The Prescription Drug User
program. First enacted in 1992,Fee Act (PDUFA): Background and Issues for
PDUFA gives FDA a revenuePDUFA IV Reauthorization, by Susan Thaul.
source — fees paid by
pharmaceutical manufacturers
— to supplement direct appropriations. At the time, FDA, consumers, and
manufacturers all sought to shorten the time between a manufacturer’s submission
of an application and the agency’s decision on whether to approve the product.
Therefore, PDUFA restricted the use of collected funds to new product review, and
established a mechanism for agency-industry collaboration to create performance
goals that set targets primarily for review times.
As a result of PDUFA, application review times decreased, and the addition of
fee revenue raised the level of the premarket review activities relative to that for
postmarket activities. Congress, therefore, in reauthorizing PDUFA in 1997
(PDUFA II) and 2002 (PDUFA III), gave FDA limited authority to use some of the
fees for postmarket drug safety activities. Due, in part, to recent widely publicized
safety problems with aggressively marketed drugs,10 discussions surrounding a 2007
PDUFA IV reauthorization have included an increased focus on postmarket drug
safety.
Both S. 1082 and H.R. 2900 include, as Title I, the Prescription Drug User Fee
Amendments of 2007. Both bills would reauthorize the assessment, collection, and
use of three types of fees: application, establishment, and product fees. They would
cover applications for both prescription and nonprescription drugs, eliminating the
distinction in current law that covers only some nonprescription drugs.
Authorized Uses of Fees
The bills would add to the list of postmarket safety activities for which the fees
could be used. Both would include adverse event data collection systems and
improved analytical tools; the House bill list extends beyond the Senate’s. Both the
Senate and House bills would increase requirements for adverse event reporting, both
to the HHS Secretary (Secretary) and to the public.
Authorized Fee Revenue
The Senate and House bills would both establish fee revenues, for each fiscal
year, of $393 million with various adjustments. They would amend the adjustment
methods for inflation (to include cost of compension and benefits) and workload
(regarding active investigational new drug applications), and add an adjustment for
rent and rent-related costs. The House, alone, would exempt from product and
facility fees applications for orphan drugs marketed by companies with less than
$100 million in gross worldwide revenue in the preceding year.
New Fees for Advisory Review of Advertisements
Both bills would add a new §736A to the FFDCA to authorize the assessment
and collection of fees to fund the advisory review of certain drug advertisements.
Manufacturer requests for pre-release review of advertisements would be voluntary
and FDA responses would be advisory. Only manufacturers that requested such
10 For example, see Anna Wilde Mathews and Barbara Martinez, “Warning Signs: E-Mails
Suggest Merck Knew Vioxx’s Dangers at Early Stage,” Wall Street Journal, November 1,
reviews would be assessed the new fees, which would include an advisory review fee
and an operating reserve fee.
Reauthorization and Report Requirements
The Senate bill would codify, within FFDCA §735, which it would rename as
Drug Fees, certain core elements of the prescription drug user fee program that,
although included in PDUFA I, II, and III, were never placed into the FFDCA. First,
it would require the Secretary to submit annual performance and fiscal reports to
Congress. Second, it would require the Secretary, in preparation for the next PDUFA
reauthorization, to consult with congressional committees, scientific and academic
experts, health care professionals, representatives of patient and consumer advocacy
groups, and the regulated industry to develop recommendations for what would be
PDUFA V, including goals and plans for meeting the goals. Expanding on PDUFA
III, S. 1082 would require a public hearing and review of the Secretary’s
recommendations following its negotiations with the industry to set performance
goals; and would require the Secretary to include with the submission to Congress
a summary of the public comments and changes made to the recommendations in
response to them.
The House bill would include the same reauthorization and report requirements
but would not amend the FFDCA to include them. The House bill, alone, also would
require that, before presenting recommendations to Congress, the Secretary make
publicly available on the FDA website the minutes of all agency negotiations with
the regulated industry and representatives of patient and consumer advocacy groups.
Medical Device User Fees
User fees were introduced into the medical device review process for the first
time by the Medical Device User Fee and Modernization Act of 2002 (P.L. 107-250;
MDUFMA). MDUFMA 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 third parties; and
(3) it instituted new regulatory requirements for reprocessed single-use devices.
FDA’s authority for the first of these (the collection of user fees) will expire on
October 1, 2007, unless Congress reauthorizes it, as is proposed in S. 1082 (Title III),
and H.R. 2900 (Title II). Both bills also contain certain other provisions related to
the regulation of medical devices.
User Fee
The Medical Device User Fee and Modernization Act of 2002 (MDUFMA; 21
U.S.C. 379i, j) gave FDA the authority to collect user fees from manufacturers
seeking FDA approval or clearance
for their medical devices. As notedFor further information, see
above, that authority, and byCRS Report RL33981, Medical Device User
reference, FDA’s obligation to meetFee and Modernization Act (MDUFMA)
related performance goals, is set toReauthorization, by Erin D. Williams.
expire on October 1, 2007, unless Congress reauthorizes it. Both S. 1082 and H.R.
S. 1082 and H.R. 2900 contain parallel provisions that would lower fee amounts
for FY2008, include a subsequent 8.5% rise per year through FY2012, and add three
new types of fees (annual establishment fees, registration fees, and 30-day fees).
Both bills would except government entities from establishment fees (H.R. 2900
would extend this waiver to Indian tribes). For the newly created establishment fee,
the Secretary could increase the fee amount in FY2010 up to an additional 8.5% over
the annual 8.5% increase if fewer than 12,250 establishments paid the fee in FY2009.
Both bills would extend from FY2007 to FY2012 the requirement that there be
a certain amount of medical device-related direct appropriations (at least
$205,720,000 multiplied by an annual adjustment factor) in order for the Secretary
to assess fees, and be expected to meet performance goals. Both bills would amend
a provision requiring that fees collected for a fiscal year that exceed the authorized
appropriation be subtracted from fees authorized to be collected for the subsequent
year. Instead, fees collected between FY2008 and FY2011 would be considered in
aggregate. A reduction would be made in fees in the final year only if the amount
collected in the four-year period exceeded the amount authorized for the same period.
H.R. 2900 would also authorize the appropriation of specific sums from FY2009
FY2012 for the review of postmarket safety information on medical devices.
The bills would strike a provision that enables the Secretary to adjust the
premarket notification fee amount annually so that, in aggregate, these fees comprise
a target amount. However, H.R. 2900 would maintain a reference to this deleted
provision in the Fee Amounts section (21 U.S.C. 379j(a)(2)(A)).
Regarding reduced or refunded fees, both bills would further reduce the fees
paid by small businesses, remove a provision that the assets of partners and parent
firms be considered in small business qualification, and enable foreign firms to
qualify as small businesses. Both bills would also articulate a new refund policy
specified for modular applications11 withdrawn at different points before final FDA
action is taken. S. 1082 specifies that the Secretary would have the sole authority to
make refund decisions and that they are nonreviewable.
Both bills would require the Secretary to continue to file annual reports through
FY2012. H.R. 2900 would require the reports to include information on postmarket
safety activities. S. 1082 would require information on previous cohorts of medical
device applications, would require that the reports be made public, and would write
the report requirements into the FFDCA.
In FDA’s development of its performance goal recommendations to the
Congress, both bills would require the agency (as did MDUFMA) to consult with an
array of governmental, professional and consumer groups, publish its
recommendations in the Federal Register, provide a public comment period, and hold
11 A modular application is a medical device premarket application submitted to FDA over
time, in parts.
a public meeting. S. 1082 would also specify that the recommendations be revised
upon consideration of public comments, would require the recommendations’
transmittal to Congress, and would write the relevant consultation requirements into
the FFDCA.
H.R. 2900’s user fee provisions would take effect on the bill’s date of
enactment. S. 1082’s provisions would become effective on October 1, 2007, and
the bill also contains a related savings clause to help ensure continuity of fee
collection.
Device Regulation
S. 1082 and H.R. 2900 would make other amendments related to medical device
regulation. The bills generally contain parallel provisions (discussed below), except
that H.R. 2900 would require the Comptroller General to conduct a study on
nosocomial infections12 relating to medical devices.
S. 1082 and H.R. 2900 would extend from FY2007 to FY2012 the authority to
have third parties review premarket notifications. The bills also contain provisions
that would revise the requirements for inspections by accredited third parties in three
ways. First, by reducing administrative requirements associated with qualifying for
the program. Second, by expanding participation in the program. Third, by
permitting device companies to voluntarily submit to FDA reports by third parties
assessing conformance with an appropriate international quality systems standard,
such as those set by the International Standards Organization. FDA would consider
the information in these reports in setting its inspection priorities.
Regarding required registration, both bills would restrict the period within
which device producers must register with the Secretary from any time prior to
December 31 of each year to between October 1 and December 31 of each year. The
bills would also reduce from twice to once per year (between October 1 and
December 31) the requirement that those who register with the Secretary provide a
list of devices on which they perform specific functions.
Both bills would amend electronic registration regulations to require electronic
filing as a default. However, S. 1082 contains a requirement that the Secretary find
that the receipt of electronic information is feasible, which could require additional
rulemaking.
12 A nosocomial infection is one a patient acquires in the hospital, and that was neither
present nor incubating prior to the patient receiving services.
Pediatric Drugs and Devices
FDA has approved for adult use many products never tested in children. Yet
clinicians often prescribe them for children believing that the safety and effectiveness
demonstrated with adults would hold for younger patients. However, this off-label
prescribing can result in children receiving ineffective products, or too much or too
little of a potentially useful drug. Some side effects are unique to children or children
of specific ages, including effects on growth and development. Studies show that,
depending on the maturation and development of a child’s organs and other factors,13
some drugs vary in how long they stay in the body, affecting their usefulness.
With the BetterFor further information, see
Pharmaceuticals forCRS Report RL33986, FDA’s Authority to Ensure That
Children Act (BPCA;Drugs Prescribed to Children Are Safe and Effective,
included in FDAMA ofby Susan Thaul.
1997), CongressCRS Report RL33288, Proprietary Rights in
provided drugPharmaceutical Innovation: Issues at the Intersection of
manufacturers with thePatents and Marketing Exclusivities, by John R. Thomas.
following incentive to
conduct pediatric use
studies on their patented products: if a manufacturer complied with a written FDA
request for a specific pediatric study, FDA would add six months to its market
exclusivity for that product.14 For drugs no longer covered by patent or other
marketing exclusivity agreements, BPCA required the Secretary to list those off-
patent products for which pediatric studies are needed to assess safety and
effectiveness. It also authorized the appropriation of National Institutes of Health
(NIH) funding for these studies. For on-patent drugs whose manufacturers declined
FDA’s written requests for pediatric use studies, BPCA provided for their referral by
FDA to the Foundation for the NIH.15 The Best Pharmaceuticals for Children Act
(also BPCA) reauthorized the exclusivity provisions for another five years. They are
set to expire on October 1, 2007.
In 1998, FDA published the Pediatric Rule, which mandated that manufacturers
submit pediatric testing data, referred to as a pediatric assessment, at the time of all
new drug applications. In 2002, a federal court declared the rule invalid, holding that
FDA lacked the statutory authority to promulgate it. Congress gave FDA that
authority with the enactment of the Pediatric Research Equity Act of 2003 (PREA;
P.L. 108-155). PREA covers drugs and biological products and includes provisions
for deferrals, waivers, and the required pediatric assessment of an approved marketed
13 William Rodriguez, Office of New Drugs, FDA, “What We Learned from the Study of
Drugs Under the Pediatric Initiatives,” June 2006 presentation to the Institute of Medicine,
at [http://www.fda.gov/oc/opt/presentations/whatwelearned.ppt].
14 During that six-month period, FDA would not grant marketing approval to another
identical product (usually a generic).
15 The Foundation supports the research mission of NIH using public-private partnerships
(“The Foundation for the NIH,” at [http://www.fnih.org/aboutus/aboutus.shtml]).
product. PREA did not include a specific sunset date; its provisions remain in effect
as long as BPCA is authorized.
Pediatric Exclusivity Incentives (BPCA Reauthorization)
Both S. 1082 (Title IV, Subtitle A) and H.R. 2900 (Title V) would reauthorize
BPCA (FFDCA §505A) for another five years, through FY2012. The bills also
would encourage research on off-patent products, strengthen the requirements for
labeling changes based on the results of pediatric use studies, and provide for the
reporting of adverse events. A key difference between the Senate and the House bills
concerns the period of exclusivity, which is six months in current law. While H.R.
2900 would leave that provision unchanged, S. 1082 would reduce it to three months
for drugs with over $1 billion in annual gross U.S. sales.
Mandatory Pediatric Assessments (PREA Reauthorization)
S. 1082 (Title IV, Subtitle B) and H.R. 2900 (Title IV) would expand FDA’s
authority under PREA (FFDCA §505B), which requires pediatric assessments of new
drugs and biologics or, for example, new indications of marketed products, by
strengthening standards for requiring tests, explanation of deferrals, labeling, and
publicly accessible information. In one key difference between the two bills, H.R.
2900 would eliminate the provision that ties PREA’s authorities to BPCA
authorization; S. 1082 would maintain that connection.
Pediatric Medical Devices
In addition to reauthorizing BPCA and PREA, both S. 1082 (Title IV, Subtitle
C) and H.R. 2900 (Title III) incorporate legislation that is intended to encourage
medical device manufacturers to develop pediatric products. The Pediatric Medical
Device Safety and Improvement Act of 2007 would amend FFDCA by modifying the
humanitarian device exemption (HDE), which allows a manufacturer with a device
aimed at a U.S. patient population of less than 4,000 to market the product without
having to demonstrate its effectiveness (only its safety), and to have certain
application fees waived. 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. Specifically, the legislation would exempt some manufacturers of pediatric
devices for small populations from the general HDE prohibition on selling a device
for an amount that exceeds its costs of research and development, fabrication, and
distribution. The bills contains similar, though not identical, inspection authorities,
and guidance and reporting requirements related to the new exemption. S. 1082
would extend the new exemption through 2012. H.R. 2900 would extend it through
Regarding funding for research on pediatric medical devices, both bills would
require the NIH Director to designate a contact point or office to help pediatric
medical device developers locate funding. H.R. 2900 would also require the FDA
Commissioner, in collaboration with other agency heads, to submit a plan for
expanding pediatric medical device research and development to relevant
congressional committees.
Both bills would require the Secretary to establish a demonstration project to
promote pediatric device development. The bills’ descriptions of use of grant funds
are not identical, but both focus on possibilities such as connecting innovators with
manufacturers, managing the device development process, connecting innovators to
federal resources, and providing business assistance. Both bills would require
coordination with appropriate points of contact at NIH and FDA. S. 1082 would also
require grantees to report their effectiveness, impact, and device development status
to the Secretary annually. For the demonstration grants, both bills would authorize
$6 million for each of FY2008 through FY2012.
Both bills would amend BPCA to expand the focus of the Office of Pediatric
Therapeutics (OPT) and the Pediatric Advisory Committee to include pediatric
medical devices. S. 1082 would also require the OPT, in collaboration with the
heads of relevant agencies, to deliver a plan for expanding pediatric medical device
research and development to relevant congressional committees.
Finally, both bills would amend the FFDCA to incorporate certain postmarket
surveillance measures. They would expand the Secretary’s authority, enabling
postmarket studies to be required as a condition of approval for pediatric medical
devices that require safety controls (class II or III devices). H.R. 2900 specifies that
such studies may be required for devices indicated for pediatric populations; both
bills indicate they may be required for devices expected to have significant use in
pediatric populations, and that studies may exceed the general 36-month limitation
if necessary to assess the impact of the device on pediatric populations’ growth and
development. H.R. 2900 also includes a dispute resolution provision, entitling a
manufacturer to request a review, during which the device may not be deemed
misbranded except as necessary to protect public health.
Drug Safety
Since the 1938 passage of the Federal Food, Drug, and Cosmetic Act, the
manufacturer of a new drug has had to demonstrate to FDA the product’s safety
before FDA would approve it
for marketing in the UnitedFor further information, see
States. In 1962, the Harris-CRS Report RL32797, Drug Safety and
Kefauver Amendments to theEffectiveness: Issues and Action Options After
FFDCA added productFDA Approval, by Susan Thaul.
effectiveness to the premarket
requirements. The Prescription
Drug User Fee Act of 1992 maintained the focus on premarket review. However, as
previously noted, until a very large number of individuals have taken a drug, a rare
adverse effect may not occur or a very common condition may not be recognized as
drug-associated. FDA, therefore, cannot assert that any drug is completely safe.
Instead, it considers whether, given the available information, the drug is safe enough
when used correctly by the types of individuals and for the diseases or conditions for
which it was tested. FDA and others must remain alert to new information as those
drugs are used more widely. In recent years, researchers revealed that a few widely
used (and advertised) drugs were more dangerous than known or expected. Some felt
that the public health and regulatory problems were compounded by questions about:
(1) industry’s reticence in sharing its knowledge of possible risks; and (2) FDA’s
authority, ability (resources), and willingness to identify and correct postmarket
safety concerns. As a result, FDA asked the Institute of Medicine (IOM) to examine
its handling of drug safety. IOM responded with a 2006 report that addressed the
agency’s organizational culture, science and expertise, regulation, communication,
and resources.16 At the same time, many consumers, health experts, and Members
of Congress looked for ways to enhance FDA’s actions to protect the public.
S. 1082 (Title II, Drug Safety) and H.R. 2900 (Title IX, Enhanced Authorities
Regarding Postmarket Safety of Drugs) reflect those concerns. They would establish
some new authorities and expand others to allow FDA to identify postmarket drug
safety problems and to correct or minimize them.
Active Surveillance and Assessment
Although the Senate and House bills differ on timetables and organization, both
would require that the Secretary establish public-private partnerships to develop a
postmarket risk identification and analysis system using electronic databases.
Risk Evaluation and Mitigation Strategies
Current law allows FDA to require a postmarket study as a condition of its
initial approval of a marketing application. The law does not authorize FDA to add
such requirements after approval, though FDA does recommend that postmarket
studies be conducted for products on the market. Many observers believe that such17
recommendations and requests do not create enough needed postmarket studies.
Thus, the Senate and House bills propose a strengthened authority and set of
procedures to support FDA’s postmarket safety activities.
At the core would be a Risk Evaluation and Mitigation Strategy (REMS). Both
bills would authorize the Secretary to require that the sponsor of a drug or biologic
application or supplement to an application submit a proposed REMS. The bills
differ on the criteria they would require that the Secretary use. The House bill
language calls for pre-approval “to ensure that the benefits of the drug involved
outweigh the risks of the drug.” The Secretary could require a REMS after a product
has been approved if the Secretary “becomes aware of new safety information,”
based, in part, on the sponsor’s required statement as part of the application of
whether it believes a REMS or a postmarket study or clinical trial should be required.
The Senate bill requires that the Secretary’s determination be “based on a signal of
16 Institute of Medicine, Committee on the Assessment of the U.S. Drug Safety System, The
Future of Drug Safety: Promoting and Protecting the Health of the Public, Alina Baciu,
Kathleen Stratton, Sheila P. Burke, Editors, (Washington, DC: National Academies Press,
17 IOM, 2006.
a serious risk with the drug” and that a REMS is necessary “to assess such signal or
mitigate such serious risk.”
This authority also would cover supplemental applications concerning a new
indication for use of an approved product and applications for the marketing of a
generic product.
Both bills call for all REMS to include certain core elements, including
timeframes, and other elements that the Secretary could require. Elements might
include instructions to patients and clinicians, and restrictions on distribution or use
(and a system to monitor their implementation). Both bills would allow a waiver
from REMS restrictions on distribution or use for certain medical countermeasures
in the time of a declared public health emergency. The Senate bill would create a
mechanism to assure access to a drug with a REMS for off-label use for a serious or
life-threatening disease or condition.
Most elements considered in a REMS are part of current FDA practice. The
REMS process proposed by S. 1082 and H.R. 2900 would add authority for
structured follow-through, dispute resolution, and enforcement. Both bills would
require reviews of approved REMS at specified times initially and then as the
Secretary would determine. They lay out detailed procedures for the review of both
proposed REMS and required or voluntary assessments or modifications. Both the
Senate and the House bills would establish a Drug Safety Oversight Board, made up
of federal government scientists and health care practitioners, which would
participate in resolving disputes between the Secretary (through FDA scientists) and
a product’s sponsor.
The bills would require the Secretary, through the Drug Safety and Risk
Management Advisory Committee, to evaluate whether the various REMS elements
assure safe use of a drug; and whether they limit patient access or place an undue
burden on the health care system.
Postmarket Studies
Both bills would authorize the Secretary to require postapproval studies or
clinical trials, but they differ on the criteria for determining whether they are
necessary. According to the Senate bill, the Secretary, in addition to routine active
surveillance and other requirements, would have “to assess a signal of a serious risk
with use of a drug; or to identify, based on a review of a demonstrated pattern of use
of the drug, unexpected serious risks in a domestic population....” The House bill,
unlike S. 1082, addressing this outside of the REMS process, would authorize the
Secretary to require, based on scientific information, a postapproval study to assess
a known risk, assess signals of serious risk, or to identify a serious risk.
Labeling
The Senate bill would require the sponsor and the Secretary to notify each other
upon acquiring new safety information that they think should be included in a drug’s
labeling. For times when a sponsor disagrees with the Secretary’s request to prepare
a supplemental application to change the labeling, the bill would set up a multi-level
process, with defined time limits, involving meetings, dispute review and
recommendations by the Drug Safety Oversight Board, and, if the Secretary
determines necessary, an order to make the safety labeling change. If the sponsor
continues to disagree, the Secretary may deem the drug to be misbranded.
The House bill would authorize the Secretary, based on new safety information,
to order a labeling change. Both bills include time limits for sponsor and Secretary;
the labeling provisions also include a dispute resolution procedure.
Advertising
Both bills would authorize the Secretary to require submission of certain
advertisements to the Secretary for review before dissemination, although they set
different criteria for the Secretary’s decision. The House bill refers to television ads
and specifies that the Secretary could recommend but not require changes. The
Senate bill refers to advertisements, not distinguishing among the media. Both bills
would require a “clear and conspicuous presentation of side effects and
contraindications.”
Enforcement
By allowing the Secretary to impose civil monetary penalties for violations of
certain requirements, both bills would give FDA a new enforcement tool. For
violating a REMS, both bills would authorize fines of up to $250,000 (the Senate
also would set a $15,000 minimum) per violation, and up to $1 million for violations
adjudicated in a single proceeding. The House bill would include additional civil
penalties if a violation were to continue after the Secretary had provided notice: $10
million per violation, not to exceed $50 million for all violations adjudicated in
single proceeding. For a violation that is continuing in nature and poses a substantial
threat to public health, the Secretary could fine the sponsor up to $1 million per day.
Both bills would allow the Secretary to consider a drug not in compliance with
certain elements of its REMS to be misbranded. The House bill explicitly states that
a sponsor could not market a product with a REMS if it is not in compliance with
REMS.
The Senate and House bills would establish separate civil penalty authority for
the dissemination of a false or misleading direct-to-consumer (DTC) ad for a
prescription drug. The House bill fine for a first violation would be up to $250,000,
with fines for subsequent violations not to exceed $500,000 each. The Senate bill
would authorize lower fines: up to $150,000 for a first violation and up to $300,000
for subsequent violations.
Funding
Both bills would authorize increased appropriations to support components of
the proposed drug safety provisions. For the surveillance and assessment activities,
both would authorize the Secretary to use $25 million of PDUFA fees each year to
carry out those activities. For REMS and other drug safety activities in this title, the
Senate bill would increase the revenue allowed under PDUFA by $225 million over
FYs 2008 through 2012, and designate its use for drug safety activities. The House
bill would authorize appropriations of $125 million for that five-year period (i.e., $25
million annually).
Antibiotic Drugs
The House bill would require the Secretary to issue guidance for the conduct of
clinical trials of antibiotic drugs, and require the Secretary to convene a public
meeting regarding orphan antibiotic products. It would also authorize appropriations
of $30 million for each of the next five FYs for grants and contracts to develop
orphan drugs. The Senate bill would consider antibiotics as orphan products and
authorize $35 million for each of those fiscal years. The Senate bill includes other
provisions regarding antibiotic access and innovation; one would provide incentives
(extended marketing exclusivity) for the development of certain antibiotics.
Anti-Counterfeiting Technologies
The Senate bill would require, within a specified timeframe, that the packaging
of any prescription drug incorporate a standardized numerical identifier and overt
optically variable counterfeit-resistant technologies. The House bill would require
the Secretary to develop standards and evaluate technologies to secure the
distribution system against prescription drugs that are counterfeit, diverted, or
substandard or damaged.
Drug Safety Provisions In Only One Bill
Some drug safety provisions appear in only one or the other bill. Many are
reports to Congress on the implementation of a provision, or studies of options or
effectiveness regarding drug safety.
In H.R. 2900 Alone. The House bill would require that any DTC ad include
the following statement: “You are encouraged to report adverse effects of
prescription drug medication to the FDA. Log onto [http://www.fda.gov/medwatch]
or call 1-800-FDA-1088.”
In S. 1082 Alone. Within the “drug safety” title of the Senate bill, provisions
would require that the Secretary establish an Advisory Committee on Risk
Communication; and develop and maintain website content to include an extensive
range of drug safety information, including summaries of surveillance data, and
documents from drug approval and biologics licensing applications such as a
summary of conclusions from all reviewing disciplines and staff disagreements and
recommendations.
The Senate bill would also require that state-legalized medical marijuana be
subject to FDA’s full regulatory requirements. In addition, upon the approval of a
neglected or tropical disease product, it would require the Secretary to award to its
sponsor a priority review voucher, which that sponsor may transfer (including by
sale) to a sponsor of a new drug application; the recipient of the voucher would then
be eligible for priority review of a new drug application. It would require the FDA
Commissioner to create and publish on the FDA website a list of all authorized
generic drugs, and set up a procedure to prevent certain citizen petitions from
delaying agency decisions without review by the Secretary.
Clinical Trials Databases
Federal registration requirements for clinical trials were created by §113 of the
Food and Drug Administration Modernization Act of 1997 (FDAMA), which
amended §402 of the Public Health Service Act (42 U.S.C. 282; PHSA).
Registration is currently
required for clinical trials ofFor further information, see
drugs (but not biologics orCRS Report RL32832, Clinical Trials Reporting
medical devices) intended toand Publication, by Erin D. Williams.
treat serious or life-threatening
diseases and conditions. The
current registry is available online at clinicaltrials.gov. S. 1082 (Title II, Subtitle C)
and H.R. 2900 (Title VIII) contain proposals to expand both the types of trials and
types of information about the trials in the registry (either expanding or supplanting
clinicaltrials.gov). They also contain provisions requiring the publication of the
results of many clinical trials.
Registry
S. 1082 and H.R. 2900 would require the registration of most clinical trials
involving drugs, devices and biologics — not just those involving treatments for life-
threatening conditions — and would include international trials on products with or
seeking FDA approval. However, H.R. 2900 would forestall the public release of
registry-submitted medical device information until after FDA had cleared or
approved the device. S. 1082 would exempt newly created pediatric postmarket
surveillance clinical trials from registry requirements, and would allow the voluntary
registration of clinical trials that are not required to be submitted. Both bills would
link the timing of certain requirements to the trial’s completion date. H.R. 2900
would link the definition of completion date to the collection of data relevant to
primary and secondary outcomes.
Both bills would require the responsible party (RP) for a trial — the trial
sponsor or possibly principal investigator — to comply with the bills’ provisions.
Both bills articulate certain requirements for when a principal investigator might
serve as RP; however, only H.R. 2900 would require that a principal investigator
have control over the data and a right to publish trial results in order to serve as RP.
Both bills would expand the type of information that must be included in the
registry and made public via the Internet, would dictate that it be searchable in
specific ways, and would require that no item or fact submitted be false or
misleading. Both bills would require submitted information to include the elements
of the World Health Organization’s International Clinical Trials Registry Platform
registration data set and other elements.18 H.R. 2900 would require a few elements
not required by S. 1082, including the disclosure of agreements that restrict non-
employees from discussing or publishing trial results.
H.R. 2900 would require that updates, reflecting the dates of any changes, be
submitted to the registry once every six months until the results of the trial were
submitted to the results database. S. 1082 specifies a few more criteria than does
H.R. 2900 by which the registry must be searchable, including, for example, the age
group studied in the trial. S. 1082 also specifies a timeline by which the NIH
Director must make registry information public, and would require the registry to link
to certain public clinical trial results information, for example from FDA and NIH.
Results Database
Both H.R. 2900 and S. 1082 have provisions related to the establishment of a
public database containing the results of clinical trials. However, only H.R. 2900
provides specific instructions on the creation of the results database. S. 1082, in
contrast, would require the Secretary to create a database through rulemaking, based
on the recommendations of the NIH Director. H.R. 2900 specifies for the results
database certain searchable categories, the timing of required submissions and their
public posting, and that the information submitted be truthful and regularly updated.
A requirement that results summaries be non-promotional was removed from an
earlier draft of the bill, and replaced by a requirement that the Comptroller General
conduct a study and report to Congress on whether information in the results database
is promotional.
Regarding the timing of posting into the results database, H.R. 2900 would
require that the results of pre-approval studies be made public within 30 days of a
number of possible events, including the Secretary issuing a not substantially
equivalent (NSE) letter regarding a medical device.19 The issuance of an NSE letter
does not necessarily mark the conclusion of an FDA application for a device
manufacturer; a manufacturer may opt to apply to FDA for premarket approval.20
Thus, the timing provision could result in clinical trial information being made public
regarding a device for which FDA action was still pending. A parallel provision
regarding studies pertinent to a new use of a drug or device already on the market
does raise the same issue. It would allow for a posting delay of up to two years if the
18 “The World Health Organization announces new standards for registration of all human
medical research,” World Health Organization website, May 19, 2006, at
[http://www.who.int/mediacentre/news/releases/2006/pr25/en/index.html], visited July 18,
19 The least rigorous pathway that a manufacturer may use to gain FDA permission to market
a medical device is to demonstrate that it is very similar to — or substantially equivalent
(SE) to — a product already on the market. FDA will issue an NSE letter if it finds that a
product is different from, not substantially equivalent to, one on the market.
20 An application for premarket approval is more rigorous than an application to
demonstrate SE, and is required for devices that are novel and/or require certain safety
controls.
manufacturer certified to the Secretary that a filing with FDA for a new use would
soon be made.
Coordination, Compliance, and Enforcement
Both bills include coordination, compliance, and enforcement provisions. H.R.
2900’s compliance provisions would apply to registry and results database
requirements, whereas parallel provisions in S. 1082 would only apply to registry
provisions. H.R. 2900 contains provisions regarding enforcement of results database
requirements and coordination between registry and results database, and would
prohibit the Secretary from filing, approving, or clearing FDA applications with
noncompliant trials. S. 1082 would require FDA applications to include certification
of registry requirement compliance. One controversial provision that was dropped
from H.R. 2900 (and was never present in S. 1082) specified that the act would not
have had any legal effect on — and thus would have allowed — causes of action for
damages under state law.
Current law does not specify penalties or enforcement mechanisms related to
registry requirements. General mechanisms for enforcing compliance with FDA
requirements may be applicable, but have not been applied by the FDA. Both H.R.
2900 and S. 1082 contain specific penalties for noncompliance. In its enforcement
provisions, H.R. 2900 refers to but would not amend relevant FFDCA sections,
allowing penalties of $10,000 per day, and capping penalties at $15,000 for
individuals and nonprofits. S. 1082 would amend relevant FFDCA sections and
would allow penalties of $10,000 for a first violation, and up to $20,000 for
subsequent violations.
Conflicts of Interest
Both S. 1082 (Title II, Subtitle D) and H.R. 2900 (Title VII) contain provisions
that would affect FDA’s treatment of conflicts of interest in its advisory committees.
Current law generally requires that committee members be free from conflicts of
interest, but allows for
exceptions to that rule under
specific circumstances. UnderFor further information, see
FDA’s current approach, aCRS Report RS22691, FDA Advisory Committee
conflict of interest may requireConflict of Interest Reform Efforts in the 110th
a potential committee memberCongress, by Erin D. Williams.
to disclose the conflict, refrain
from voting, and/or not
participate in a committee, depending on the nature of the conflict. The law is
articulated primarily in three sources: (1) the Federal Advisory Committee Act (5
U.S.C. Appendix; FACA); (2) the FDA advisory committee policy (21 U.S.C.
355(n)); and (3) a law governing special government employees — which advisory
committee members are — Acts Affecting Personal Financial Interest (18 U.S.C.
chapter 11, §208).21 S. 1082 and H.R. 2900 would both insert a new provision into
Chapter VII Subchapter A of the FFDCA, effective October 1, 2007, that would
change both the process of recruiting advisory committee members, as well as some
circumstances under which and processes by which conflict-of-interest waivers may
be granted. The new provisions would also cause some requirements currently only
applicable to drug and biologic advisory committees to apply to committees
providing advice on all topics.
Both bills define advisory committee as a FACA-covered entity that provides
the Secretary with advice and recommendations regarding activities of the FDA, and
define financial interest as defined under 18 U.S.C. 208(a). This definition covers
activities such as a person’s or their family members’ current or future employment,
trusteeship, or directorship. On its face, it does not apply to activities such as stock
ownership, former employment, or receipt of a grant or contract, although FDA’s
regulations do require disclosure of these types of activities. An alternative
definition, offered in 21 U.S.C. 355(n), has been interpreted to require disclosure
relating to a broad range of activities, including those listed above. However, as
encoded in statute, this definition applies only to drug and biologics committees, not
to medical device committees.
S. 1082 and H.R. 2900 would require advisory committee member recruitment
mechanisms, generally focused on reaching experts from areas such as academia,
medical research institutions, public interest and consumer groups. Both contain
provisions to discourage financial conflict waivers. H.R. 2900 contains a section that
would specifically permit the participation of a non-voting guest expert with financial
interest if the Secretary determined that the guest had particular required expertise.
S. 1082 and H.R. 2900 would require advisory committee members’ full
financial disclosure prior to a meeting on a related matter. They would preclude
voting by a member with a conflict of interest unless exempted by the Office of
Government Ethics. The bills would allow a waiver of the voting restriction if
necessary to provide the committee with essential expertise. H.R. 2900 would only
allow one such waiver per meeting.
The bills would require public disclosures for conflict-of-interest
determinations, certifications, and waivers, and would require the Secretary to submit
annual reports regarding advisory committee membership, and conflict-of-interest
waivers. Both bills would require the Secretary to review and update FDA conflict-
of-interest guidance not less than once every five years.
21 For more information, see CRS Report RL30260, Federal Advisory Committees: A
Primer.
Reagan-Udall Foundation for the
Food and Drug Administration
S. 1082 (Title I, Subtitle B) and H.R. 2900 (Title VI) would establish a nonprofit
corporation to advance FDA’s mission regarding product development, innovation,
and safety. The initial Board of Directors (the FDA Commissioner, and the directors
of NIH, CDC, and AHRQ) would select the appointed members from a National
Academy of Sciences-provided candidate list and then resign from the board. The
ongoing board would include representatives from industry, academic research
organizations, government agencies, patient or consumer advocacy organizations,
and health care providers. The Foundation would establish goals and priorities
relating to unmet needs and then coordinate with federal programs, and award grants,
contracts, and other agreements with public and private individuals and entities to
advance those goals. The House and Senate bills would direct the Commissioner to
transfer between $500,000 and $1,250,000 to the Foundation.
Office of the Chief Scientist
The Senate and House bills would require the Secretary to establish an Office
of the Chief Scientist within the FDA Office of the Commissioner. Among the duties
of the Secretary-appointed Chief Scientist would be to oversee, coordinate, and
ensure quality and regulatory focus of FDA’s intramural research programs.
Miscellaneous Provisions in S. 1082
S. 1082 contains a number of provisions that are not present in H.R. 2900, as
described below.
Importation of Prescription Drugs
Current law prohibits the importation of a prescription drug by anyone other
than its manufacturer. S. 1082 (Title VIII, the Pharmaceutical Market Access and
Drug Safety Act of 2007)
would allow commercial
and personal-useFor further information, see
importation. The provisionCRS Report RL32511, Importing Prescription Drugs:Objectives, Options, and Outlook, by Susan Thaul.
would create a detailed setCRS Report RS22660, Prescription Drug Importation:
of procedures to addressHow S. 242 / H.R. 380 Would Change Current Law, by
concerns relating to theSusan Thaul.
safety and effectiveness ofCRS Report RL32191, Prescription Drug Importation and
imported drugs, costInternet Sales: A Legal Overview, by Vanessa K. Burrows.
savings to U.S. consumers,
and administration of the
program. The Senate voted to add the provision to the bill during Senate
consideration. However, the Senate also added a second-degree amendment,
specifying that the title would become effective only if the HHS Secretary certified
to Congress that its implementation would: (1) pose no additional risk to the public’s
health and safety; and (2) result in a significant reduction in the cost of covered
products to the American consumer. The addition of the second-degree amendment
effectively nullified the language of the rest of the title, as both the current and
former Administration have refused to make such a certification.
Food Safety
The topic of food safety is addressed in S. 1082 in both Title VI — Food Safety,
and in several sections of Title V — Other Provisions. H.R. 2900 contains no food
provisions.
Title VI of S. 1082 would require that regulations be established on the
processing and ingredient standards for pet food, animal waste and ingredient
definitions, and on updated standards for nutrient and ingredient information on pet
food labels. It would also require that an early warning and surveillance system be
established to identify
adulteration of the pet
food supply andFor further information, see
outbreaks of diseaseCRS Report RS22600, The Federal Food Safety System:A Primer, by Geoffrey S. Becker and Donna V. Porter.
associated with pet food.CRS Report RL33559, Food Safety: National Uniformity
During a recall of eitherfor Food Act, by Donna V. Porter.
human or pet food, the
Secretary would be
required to collect and aggregate information on the recall, use existing
communication networks to effectively alert the public, and post recall information
on the FDA website. The Secretary also would be directed to coordinate activities,
provide assistance and support staff training for states to improve food safety
programs for fresh and processed produce, including attention to retail commercial
food establishments, and establish procedures and requirements for processed
produce.
Title VI of S. 1082 would also amend §417 of the FFDCA, by requiring the
creation of a registry on adulterated food in which instances of reportable adulterated
food may be listed. The Secretary would be required to review and determine the
validity of the information received before submitting them to the registry and
exercising any other food authority action to protect the public. Alerts would be
issued to the public for food that either had been associated with repeated, separate
outbreaks of illness or adulteration, or that was a reportable adulterated food. The
responsible party or importer of an adulterated food would be responsible for
maintaining records on the problem and reporting to FDA once a determination of
adulteration was reached. Any situation in which the Secretary determined that a
deliberate adulteration had occurred would also have to be reported to the
Department of Homeland Security.
The Secretary would be required to promulgate regulations and establish
standards and thresholds for reporting instances of suspected reportable food
adulteration and notification procedures. The bill would also require an annual report
to Congress on the number and amount of food imports, food import inspectors and
inspections, and the violations and enforcement actions taken. Nothing in the
provisions would affect the regulation or the adverse event reporting system for
dietary supplements under the Dietary Supplement Health and Education Act of 1994
(P.L. 103-417) or the Dietary Supplements and Nonprescription Drug Consumer
Protection Act (P.L. 109-462), respectively.
Certain provisions in S. 1082 Title V would require the preparation of reports
on the following food issues: pesticide residue monitoring program; whether
substances used to preserve the appearance of fresh meat pose health hazards or
mislead consumers; the color additive certification program’s performance and
financial status; any environmental risks associated with genetically engineered
seafood products; the marketing of certain crustaceans; the detection and assessment
of risks; and the authorization of appropriations as needed to implement an
inspection regime for aquaculture and seafood. An additional food provision in this
title includes the prohibition on importing from any foreign food facility that denies
access to U.S. inspectors. Finally, authorization would be provided for enhancing the
FDA inspection regime for aquaculture and seafood through partnerships.
Other Provisions
S. 1082 includes a number of additional provisions that are not present in H.R.
2900. For example, S. 1082 has a title (Title VII — Domestic Pet Turtle Market
Access) that would enable the sale of pet turtles if specific requirements are met for
sanitization and information disclosure to buyers. Other provisions would require an
Institute of Medicine report on genetic test safety and quality, and an FDA report on
indoor tanning device labeling, and the link between tanning device use and skin
cancer.
S. 1082 includes two provisions expressing the sense of the Senate. One states
that legislation should be passed that allows the FDA appropriate flexibility in the
regulation of follow-on biologics. The second would express the Senate’s sense that
the Trade Representative should use all available tools to address violations and other
concerns with intellectual property, and develop and submit to Congress a strategic
plan to address the problem of countries that infringe upon American pharmaceutical
intellectual property rights and/or engage in price manipulation.
Miscellaneous Provision in H.R. 2900
A provision considered only in the House bill addresses another public-private
partnership. The House bill would require the Secretary, through the FDA
Commissioner, to enter into collaborative agreements (Critical Path Public-Private
Partnerships) with educational or tax-exempt organizations to implement the FDA
Critical Path Initiative “by developing innovative, collaborative projects in research,
education, and outreach for the purpose of fostering medical product innovation,
enabling the acceleration of medical product development, and enhancing medical
product safety;” and authorizes to be appropriated $5 million for FY2008 and such
sums as may be necessary for each of FYs 2009 through 2012.