FDA Amendments Act of 2007 (P.L. 110-85)






Prepared for Members and Committees of Congress



On September 27, 2007, the Food and Drug Administration Amendments Act of 2007 (FDAAA;
H.R. 3580) was signed into law (P.L. 110-85). The comprehensive law reauthorizes four expiring
Food and Drug Administration (FDA) programs and expands the agency’s authority to regulate
the safety of prescription drugs and biologics, medical devices, and foods. Understanding the way
in which FDAAA changed the law governing the agency informs policy discussions aimed at
additional FDA reform and reorganization, as well as health care reform efforts that touch upon
the quality, availability, and cost of medical products.
At its core, FDAAA renews the authority for two key user fee programs that were 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). In FY2007, the year in
which FDAAA was enacted, these programs accounted for 91% of FDA’s user fee revenue and
18% of FDA’s total budget. Without the reauthorizations, and absent a substantial increase in
FDA’s annual appropriations, the agency would have lost a significant amount of funding.
In addition to user fee programs, FDAAA reauthorizes two other FDA authorities related to
prescription drugs for pediatric populations, which were 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 drugs. FDAAA also contains provisions related to drug
safety, pediatric medical devices, clinical trial databases, the creation of a new nonprofit entity to
assist FDA with its mission, and food safety.
This report presents a detailed summary of provisions in FDAAA. Each section of the report
begins with background information about the FDA relevant to the passage of FDAAA and some
references, if appropriate, to the two bills that formed its basis (S. 1082 and H.R. 2900), and a law
that amended it (P.L. 110-316); describes FDAAA’s contents; and analyzes how FDAAA changed
the law. The report also contains links to pertinent CRS reports. This report, which is intended for
reference use, will not be updated other than to reflect any technical changes that Congress might
enact.






Introduc tion ..................................................................................................................................... 1
Food and Drug Administration Basics......................................................................................1
Legislative Background: S. 1082 and H.R. 2900......................................................................2
Report Roadmap........................................................................................................................3
Title I. Prescription Drug User Fee Amendments of 2007..............................................................3
Title II. Medical Device User Fee Amendments of 2007..............................................................12
Subtitle A. Fees Related to Medical Devices..........................................................................12
Subtitle B. Amendments Regarding Regulation of Medical Devices.....................................14
Title III. Pediatric Medical Device Safety and Improvement Act of 2007....................................20
Title IV. Pediatric Research Equity Act of 2007............................................................................26
Title V. Best Pharmaceuticals for Children Act of 2007................................................................34
Title VI. Reagan-Udall Foundation...............................................................................................49
The Reagan-Udall Foundation for the FDA............................................................................49
Office of the Chief Scientist....................................................................................................49
Critical Path Public-Private Partnerships................................................................................49
Title VII. Conflicts of Interest.......................................................................................................51
Title VIII. Clinical Trial Databases...............................................................................................56
Regi stry ................................................................................................................................... 56
Result s ..................................................................................................................................... 57
Coordination, Compliance, and Enforcement.........................................................................58
Other Items..............................................................................................................................59
Title IX. Enhanced Authorities Regarding Postmarket Safety of Drugs.......................................68
Subtitle A. Postmarket Studies and Surveillance....................................................................68
Postapproval Studies and Clinical Trials..........................................................................68
Labeling Changes..............................................................................................................68
Risk Evaluation and Mitigation Strategies........................................................................69
Enforcement ...................................................................................................................... 69
Television Advertising......................................................................................................69
Active Surveillance and Assessment.................................................................................70
Information Dissemination...............................................................................................70
Funding ........................................................................................................................ ..... 70
Subtitle B. Other Provisions to Ensure Drug Safety and Surveillance....................................70
Title X. Food Safety......................................................................................................................79
Title XI. Other Provisions.............................................................................................................79
Subtitle A. In General..............................................................................................................79
Subtitle B. Antibiotic Access and Innovation..........................................................................80
Table 1. Origins of FDAAA: Topics Addressed in S. 1082, H.R. 2900, and FDAAA....................2
Table 2. Comparison of Prescription Drug User Fee Amendments of 2007 (FDAAA Title
I) with Previous Law....................................................................................................................6





Table 3. Comparison of Medical Device User Fee Act 2007, Subtitle A (FDAAA Title II,
Subtitle A) with Previous Law....................................................................................................16
Table 4. Comparison of Medical Device User Fee Act 2007, Subtitle B (FDAAA Title II,
Subtitle B) with Previous Law....................................................................................................18
Table 5. Comparison of Pediatric Medical Device Safety and Improvement Act of 2007
(FDAAA Title III) with Previous Law.........................................................................................22
Table 6. Comparison of Pediatric Research Equity Act of 2007 (FDAAA Title IV) with
Previous Law..............................................................................................................................28
Table 7. Comparison of Best Pharmaceuticals for Children Act of 2007 (FDAAA Title V,
Section 502(a)) with Previous Law............................................................................................36
Table 8. Comparison of Best Pharmaceuticals for Children Act of 2007 (FDAAA Title V,
Sections 502(b-f) and 503) with Previous Law..........................................................................44
Table 9. Law Created by Reagan-Udall Foundation (FDAAA Title VI)........................................50
Table 10. Comparison of Conflicts of Interest (FDAAA Title VII) with Previous Law..................53
Table 11. Comparison of Clinical Trial Databases (FDAAA Title VIII) with Previous Law.........60
Table 12. Law Created by Enhanced Authorities Regarding Postmarket Safety of Drugs,
Subtitle A (FDAAA Title IX, Subtitle A)......................................................................................72
Table 13. Law Created by Enhanced Authorities Regarding Postmarket Safety of Drugs,
Subtitle B (FDAAA Title IX, Subtitle B)......................................................................................77
Table 14. Comparison of Other Provisions, Subtitle A (FDAAA Title XI, Subtitle A) with
Previous Law..............................................................................................................................82
Table 15. Law Created by Antibiotic Access and Innovation (FDAAA Title XI, Subtitle B).........84
Table A-1. Appropriations Authorized in FDAAA, FY2008-FY2012..........................................85
Table B-1. FDAAA Action Items with Deadlines for Government Officials, by Title and
Date ........................................................................................................................... ................. 87
Table C-1. FDAAA Authorities with Sunset Dates.......................................................................93
Appendix A. Authorized Appropriations.......................................................................................85
Appendix B. Action Items with Deadlines for Government Officials...........................................86
Appendix C. Authorities with Sunset Dates..................................................................................93
Appendix D. Alphabetical List of Acronyms................................................................................94
Author Contact Information..........................................................................................................95






The Food and Drug Administration Amendments Act (FDAAA; P.L. 110-85) was signed into law
on September 27, 2007. The law reauthorizes four expiring Food and Drug Administration (FDA)
programs and expands the agency’s authority to ensure the safety of prescription drugs and
biologics, medical devices, and foods. FDAAA represents the most comprehensive FDA
legislation since the Food and Drug Administration Modernization Act of 1997 (FDAMA; P.L.

105-115).


The primary impetus for the legislation was the renewal of FDA’s authority for two key user fee
programs that were set to expire at the end of FY2007: the Prescription Drug User Fee Act
(PDUFA, last reauthorized in 2002; P.L. 107-188), and the Medical Device User Fee and
Modernization Act (MDUFMA, enacted in 2002; P.L. 107-250). The law also reauthorizes two
other expiring authorities, which are related to pediatric pharmaceuticals: the Best
Pharmaceuticals for Children Act (BPCA, last reauthorized in 2002; P.L. 107-109), and the
Pediatric Research Equity Act (PREA, enacted in 2002; P.L. 108-155).
In addition to the reauthorizations, FDAAA contains several other FDA-related provisions. These
include provisions designed to enhance drug safety, spark the development of pediatric medical
devices, expand the types of trials and the substance of information in clinical trial databases,
create a new nonprofit entity to assist FDA with its mission, improve food safety, and affect a
number of other areas related to public health. Several of FDAAA’s provisions contain the
authorization to appropriate funding; these are listed in Appendix A. Many create additional
responsibilities with deadlines for federal agency personnel; see Appendix B. In addition, several
of the authorities have sunset dates in 2012 or early 2013; see Appendix C.
FDAAA’s impact on FDA is important to two ongoing policy discussions. One discussion centers
around the possibility of additional legislation to refine or restructure the agency’s regulatory role.
Understanding current law, as amended by FDAAA, is a good starting point for any such
discussion. The second discussion is about health care reform. The agency plays a critical role in
bringing medical products to market, which is described below. In performing that role, as refined
by FDAAA, FDA’s regulation of medical products affects their quality, availability, and cost.
The FDA, an agency within the Department of Health and Human Services (HHS), regulates the 12
safety of most human foods, all animal feeds, and certain other products such as cosmetics. The
agency also regulates the safety and effectiveness of human drugs, biologics (e.g., vaccines), 3
medical devices, and animal drugs. 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.
1
The United States Department of Agriculture (USDA) regulates the safety of meat and poultry products.
2 For more information on Public Health Service agencies, see CRS Report RL34098, Public Health Service (PHS)
Agencies: Background and Funding, coordinated by Pamela W. Smith.
3 The regulation of biologics for animal use is overseen by the USDA.





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) has 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 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 them from entering or staying on 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.
Prior to the introduction of H.R. 3580, the bill enacted as FDAAA, each chamber of Congress had
passed its own version of comprehensive FDA reauthorization and reform legislation. These were
the Food and Drug Administration Revitalization Act (S. 1082), and the Food and Drug
Administration Amendments Act of 2007 (H.R. 2900). While most of the bills’ provisions were
similar, S. 1082 contained some provisions that were not present in H.R. 2900 on the topics of
food safety, prescription drug importation, and domestic pet turtle market access. Of those, only
the food safety provisions were adopted in FDAAA. See Table 1 for a listing of major topics
covered in each bill.
For background information on the two bills that formed the basis of H.R. 3580, see the archived CRS reports:
CRS Report RL34089, FDA Legislation in the 110th Congress: A Guide to S. 1082 and H.R. 2900, by Erin D.
Williams, Susan Thaul, and Donna V. Porter.
CRS Report RL34102, FDA Legislation in the 110th Congress: A Side-by-Side Comparison of S. 1082 and H.R. 2900,
by Erin D. Williams et al.


Table 1. Origins of FDAAA: Topics Addressed in S. 1082, H.R. 2900, and FDAAA
Subject S. 1082 H.R. 2900 FDAAA
Prescription Drug User Fees X X X
Medical Device User Fees X X X
Medical Device Regulation X X X
Pediatric Exclusivity Incentives (BPCA) X X X
Mandatory Pediatric Assessments (PREA) X X X
Pediatric Medical Devices X X X
Drug Safety X X X
Antibiotic Drugs X X X
Clinical Trials Databases X X X



Subject S. 1082 H.R. 2900 FDAAA
Conflicts of Interest X X X
Reagan-Udall Foundation X X X
Importation of Prescription Drugs X
Food Safety X — X
Domestic Pet Turtle Market Access X
Other Provisions X — X
The remaining sections of this report contain descriptions of the key FDA programs addressed in
FDAAA. FDAAA includes eleven titles, each of which is discussed below in its own section of
this report. Each section introduces the topic, surveys the ways in which new provisions changed
the law, provides links to relevant CRS reports, and presents a detailed table comparing FDAAA-
enacted provisions to any existing previous law. The one exception is Title X, Food Safety, which 4
is described briefly in this report, but addressed in more detail in a separate CRS report. In the
text and tables, the Commissioner means the FDA Commissioner, and the Secretary means the
HHS Secretary. The report uses several other acronyms as well, all of which are spelled out at
their first point of use and in Appendix D.
For clarity, the tables comparing FDAAA with previous law have the following attributes. Table
provisions are cited to their location in FDAAA. Where applicable, cites are also included for the
Federal Food, Drug, and Cosmetic Act (FFDCA), the Public Health Service Act (PHSA), and the
United States Code (USC). The USC citations vary in specificity to match the citations listed in
FDAAA. When table text extends across previous and current law fields, this indicates one of two
things. If an FDAAA cite is present, FDAAA is reauthorizing or restating portions of provisions
identical to those of the prior law. If no FDAAA cite is present, a preexisting law interacts with
and is fundamental to interpreting FDAAA, but has not been amended by it.


Title I of FDAAA, the Prescription Drug User Fee Amendments of 2007 (referred to as PDUFA
IV), provides a five-year extension of FDA’s authority to collect user fees from manufacturers of 5
drug and biological products and expands the authorized uses of fee revenue. User fee revenue
has provided an increasing proportion of FDA funding since PDUFA was first enacted in 1992. In
FY1994, the first year FDA noted PDUFA revenue use in its budget justification documents, the
fees contributed 9.7% of the human drug program’s budget. At the time of FDAAA’s passage, the
4
CRS Report RS22779, Food Safety: Provisions in the Food and Drug Administration Amendments Act of 2007, by
Donna V. Porter.
5 PDUFA was first enacted in 1992 in P.L. 102-571. It was reauthorized (PDUFA II) in 1997 as Title I of the Food and
Drug Administration Modernization Act (FDAMA, P.L. 105-115); and again (PDUFA III) as Title V of the Public
Health Security and Bioterrorism Preparedness and Response Act of 2002 (P.L. 107-188).





FY2007 budget showed that PDUFA fees made up 44.7% of the agency’s human drug program 6
budget.
For further information, see CRS Report RL33914, The Prescription Drug User Fee Act (PDUFA): History, Reauthorization in
2007, and Effect on FDA, by Susan Thaul.


In the years leading to PDUFA’s enactment in 1992, 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. FDA lacked the funding for staff to review
those products quickly. With PDUFA, Congress gave FDA a revenue source to supplement direct
appropriations. Congress also structured PDUFA to restrict 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.
PDUFA has had a range of effects. New application review times decreased from 29 months in 7
1987 to 17 months in 1994. PDUFA’s restriction of the use of fee revenue to premarket review
created what many saw as an imbalance between resources available to premarket and postmarket
activities. In its 1997 and 2002 reauthorizations, Congress gave FDA limited authority to use
some of the fees for postmarket safety activities.
During 2004 discussions in preparation for PDUFA IV, several safety problems with aggressively
marketed drugs—such as Vioxx—received wide publicity. This heightened the ongoing concern
over the balance of attention between premarket review and postapproval safety monitoring.
FDAAA reflects that increased focus on postapproval drug safety throughout, but especially in
this title, described below, and in Title IX (Enhanced Authorities Regarding Postmarket Safety of
Drugs), discussed later in this report.
Title I of FDAAA addresses types of fees, authorized fee revenue, authorized uses of fees, new
fees for the advisory review of direct-to-consumer television advertisements, reauthorization and
report requirements, and effective dates, as summarized in the following material.
Types of Fees. FDAAA reauthorizes the assessment, collection, and use of three types of fees
from manufacturers of drugs and biological products. These are application fees, establishment
fees, and product fees.
Authorized Fee Revenue. FDAAA establishes fee revenues, for each fiscal year, of
$392,783,000, with various adjustments for inflation, workload, rent and rent-related expenses,
and final-year adjustments. Congress added to that base amount fee revenues for drug safety
totaling $225 million over the five-year reauthorization.
Authorized Uses of Fees. The new law expands the list of postmarket safety activities for which
the fees could be used. These include developing and using adverse-event data-collection
systems, including information technology systems; developing and using improved analytical
tools to assess potential safety problems, including access to external data bases; and
6
CRS Report RL34334, The Food and Drug Administration: Budget and Statutory History, FY1980-FY2007,
coordinated by Judith A. Johnson.
7 FDA, Third Annual Performance Report: Prescription Drug User Fee Act of 1992, Fiscal Year 1995, Report to
Congress, December 1, 1995, at http://www.fda.gov/ope/pdufa/report95.html.



implementing and enforcing new FFDCA requirements relating to postapproval studies and
clinical trials, labeling changes, risk evaluation and mitigation strategies, and adverse event
reports and postmarket safety activities.
FDAAA also removes the calendar and time limitations on postapproval activities. When
Congress first allowed PDUFA revenue use on postmarket activities in 2002, it set a three-year
limit from the time of a drug’s approval.
New Fees for Advisory Review of Advertisements. FDAAA creates a new user fee to support
FDA’s advisory review of prescription-drug television advertising. The program calls for a
manufacturer to pay a fee if it voluntarily submits an advertisement for pre-dissemination review.
The review is to be advisory. The law authorizes FDA to assess fees only on manufacturers that
request such reviews. It further directs that if the Secretary has not received at least $11.25
million in fees by 120 days after enactment, the DTC advisory review user fee program shall not
commence and all collected fees shall be refunded.
Reauthorization and Report Requirements. FDAAA codifies 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. One is the requirement for annual performance and fiscal reports to
Congress. The others relate to the Secretary’s interaction and communication with various
stakeholders. These include public hearings regarding the Secretary’s negotiations with industry
regarding performance goals; and the requirement that the Secretary, in preparation for the next
PDUFA reauthorization, 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 PDUFA V, including goals and plans for
meeting the goals.
Effective Dates. The amendments in this title took effect on October 1, 2007. Authority to assess,
collect, and use drug fees ceases to be effective October 1, 2012. The reporting requirements
cease to be effective January 31, 2013.




Table 2. Comparison of Prescription Drug User Fee Amendments of 2007 (FDAAA Title I) with Previous Law
Topic Previous Law FDAAA Title I
Types of Fees There are three types of fees—application, establishment, and product—and certain exceptions. [FFDCA 736(a); 21 USC 379h]
A human drug application fee is assessed for an application for which clinical data with respect to safety or effectiveness are required for approval. An Application Fee
application that does not require clinical data or for a supplement is assessed half the application fee. The fee is due at the time of application or
supplement submission.
Exceptions are made for a previously filed application or supplement under certain conditions and for a designated orphan drug or indication. There is a
75% fee refund if an application is refused for filing. [FFDCA 736(a)(1); 21 USC 379h]
The refund provision includes an application withdrawn without a waiver before filing.
[FDAAA 103(a)(2); FFDCA 736(a)(1)(D); 21 USC 379h(a)]
An application or supplement that is resubmitted following an earlier refusal or
withdrawal is required to pay the full fee, unless the fee otherwise is waived or
reduced. [FDAAA 103(a)(2); FFDCA 736(a)(1)(E); 21 USC 379h(a)]
A prescription drug establishment fee is assessed annually for each establishment listed as manufacturing the prescription drug product named in an Establishment Fee
iki/CRS-RL34465approved human drug application. [FFDCA 736(a)(2); 21 USC 379h]
g/w The annual establishment fee regarding an approved human drug application for a
s.orcompounded positron emission tomography (PET) drug is one-sixth the annual
leakestablishment fee. A not-for-profit medical center that produces PET drugs and uses at
least 95% of them within the facility is excepted from the drug establishment fee.
://wiki[FDAAA 103(a)(3); FFDCA 736(a)(2)(C); 21 USC 379h(a)]
httpCertain applications for orphan drugs are exempted from facility fees. [FDAAA 103(f);
FFDCA 736(k); 21 USC 379h]
A prescription drug product fee is assessed annually for each prescription drug product named in an application (except for a product whose Product Fee
manufacturer has had no pending application since September 1992). [FFDCA 736(a)(3); 21 USC 379h]
Certain applications for orphan drugs are exempt from product fees. [FDAAA 103(f);
FFDCA 736(k); 21 USC 379h]




Topic Previous Law FDAAA Title I
The law authorizes FDA to use the fees for “the review of human drug applications.” It defines the term “process for the review of human drug Authorized Uses of
applications” as: activities necessary for the review of human drug applications and supplements; the issuance of action letters; inspection of prescription Fees
drug establishments and other facilities; activities necessary for the review of applications for licensure of biological product establishments and for the
release of lots of biologics; and monitoring of research conducted in connection with the review of human drug applications. [FFDCA 735(6); 21 USC
379g]
For drugs approved after Oct. 1, 2002, the collecting, The list of postmarket safety activities for which the fees could be used also includes:
developing, and reviewing of safety information on the drugs, adverse event data collection systems and improved analytical tools, increased
including adverse event reports, during a period of time after requirements for adverse event reporting both to the Secretary and to the public, and
approval of such applications or supplements, not to exceed enforcement of study and label-change requirements.
three years. There are no longer calendar and time limitations on postapproval activities. [FDAAA
102; FFDCA 735(6)(F); 21 USC 379g]
The term “costs of resources allocated for the process for the review of human drug applications” is defined as expenses and costs for: FDA officers,
employees, contractors, and advisory committees; information management; computer resources; facilities, furniture, equipment, materials and supplies;
and collecting user fees and accounting for resources. [FFDCA 735(7); 21 USC 379g]
Fee Revenue The law established revenue amounts, subject to specified FDAAA establishes total prescription drug user fee revenues, for each fiscal year, of
iki/CRS-RL34465Amounts adjustments, that each type of fee would generate for each of $392,783,000, with various adjustments. It requires that each fee type provide one-
g/wFY2003 through FY2007. For FY2007, the total fee revenue authorized was $259,300,000, evenly divided among third of the total revenue. [FDAAA 103(b); FFDCA 736(b)(1,2); 21 USC 379h(b)]
s.orApplication, Establishment, and Product fees, as required.
leak
Additional Fee No provision. The law directs that, in addition to the adjusted revenue value based on $392,783,000,
://wikiRevenues for Drug Safety there be fee revenues collected and used for drug safety in specific amounts summing to $225 million from FY2008 through FY2012. [FDAAA 103(b); FFDCA 736(b)(4); 21
httpUSC 379h(b)]
Inflation Adjustment The inflation adjustment was based on the Consumer Price The adjustment for inflation method includes the average annual cost per FDA
Index (all U.S. urban) for the previous year or the total percent employee of all personnel compensation and benefits. [FDAAA 103(c)(1); FFDCA
change in the previous year in General Schedule basic pay, as 736(c)(1); 21 USC 379h(b) and 379h(c)]


adjusted by DC-area locality pay. The adjustment was to be
compounded to the sum of all adjustments made each fiscal
year.


Topic Previous Law FDAAA Title I
Fee revenues are adjusted to reflect changes in FDA’s workload for the process for the review of human drug applications. [FFDCA 736(c)(2); 21 USC Workload
379h] Adjustment
The calculation was based on a weighted average of the change The calculation now counts commercial IND applications as the number that were
in the total number of human drug applications, commercial active during the preceding year. [FDAAA 103(b); FFDCA 736(b)(3); 21 USC 379h(b)]
investigational new drug (IND) applications, efficacy
supplements, and manufacturing supplements submitted.
The workload adjustment was prohibited to result in fee The number of human drug applications is adjusted for changes in review activities.
revenues for a fiscal year that were less than those established The adjustment for changes in review activities may not result in more than an
as the total fee revenue for that fiscal year, adjusted for additional 2% increase. [FDAAA 103(c)(2); FFDCA 736(c)(2); 21 USC 379h(c)]
inflation.
No provision. The Secretary must contract with an independent accounting firm to study the
adjustment for changes in review activities and make any warranted recommendations.
The Secretary may not make changes unless the study has been completed, and, once
the study has been completed, must make any appropriate changes. [FDAAA
103(c)(2); FFDCA 736(c)(2)(C); 21 USC 379h(c)]
iki/CRS-RL34465Rent and Rent-No provision. The law directs the Secretary to decrease (up to $11.7 million) the fee revenue total if
g/wRelated Cost Adjustment actual costs paid for rent and rent-related expenses are less than estimates made for such year in FY2006. [FDAAA 103(c)(3); FFDCA 736(c)(3); 21 USC 379h(c)]
s.or
leakThe Secretary may increase total fee revenue if necessary to provide for up to three months of operating reserves for the process of human drug Final Year
application review for the first three months following sunset. [FDAAA 103(c)(4); FFDCA was 736(c)(3), now 736(c)(4)(A); 21 USC 379h(c)] Adjustment
://wikiNo provision. The final year adjustment may decrease fee revenue if FY2009 or FY2010
httpappropriations for both FDA and the review of human drug applications exceed the
amounts appropriated for those activities for FY2008—a “reverse trigger.” This
decrease is limited to a maximum of $65 million. [FDAAA 103(c)(4); FFDCA
736(c)(4)(B); 21 USC 379h(c)]




Topic Previous Law FDAAA Title I
The Secretary must grant a waiver or reduction of fees if necessary to protect the public health, if the fee would be a significant barrier to innovation, if Fee Waiver or
the fee would exceed the cost of the process of review, or if the applicant is a small business that is submitting its first human drug application. [FDAAA Reduction
103(d); FFDCA 736(d); 21 USC 379h]
FDAAA specifies that the Secretary grants a waiver or reduction of fees to a person
who is named as the applicant, and that, in deciding whether to grant a waiver or
reduction, the Secretary may consider only the circumstances and assets of the
applicant and any affiliate of the applicant. [FDAAA 103(d)(3); FFDCA 736(d)(2); 21
USC 379h]
A small business is an entity with fewer than 500 employees, including employees of affiliates. [FDAAA 103(d); FFDCA 736(d); 21 USC 379h]
Regarding waivers and reductions of fees, the definition of a small business is expanded
to narrow eligible businesses to those that do not have a drug product that has been
approved under a human drug application and introduced or delivered for
introduction into interstate commerce. [FDAAA 103(d); FFDCA 736(d); 21 USC
379h]
There were authorized to be appropriated prescription drug There are authorized to be appropriated, for each of FY2008 through FY2012, Crediting and
iki/CRS-RL34465user fees of $222,900,000 for FY2003; $231,000,000 for prescription drug user fees in the amount determined in FDAAA 103(b), as adjusted. Availability of Fees
g/wFY2004; $252,000,000 for FY2005; $259,300,000 for FY2006; and $259,300,000 for FY2007, as adjusted.
s.or
leakThe amount of fees collected in excess of the amount specified in appropriations acts is to be (1) credited to FDA’s appropriation account, and (2)
subtracted from the amount that would otherwise have been authorized to be collected during subsequent fiscal years. [FDAAA 103(e); FFDCA
://wiki736(g)(4); 21 USC 379h]
http The calculation of excess collections was done for each fiscal The amount of excess collections is based on a cumulative calculation of fees collected
year and the offset reflected in the subsequent fiscal year’s in FY2008, FY2009, and FY2010 and those estimated to be collected in FY2011. The
authorization. offset must be reflected in the amount authorized to be collected in FY2012. [FDAAA
103(e); FFDCA 736(g)(4); 21 USC 379h]




Topic Previous Law FDAAA Title I
User Fees for the No provision. The law authorizes the assessment and collection of fees relating to advisory review of
Advisory Review of certain drug advertisements. Manufacturer requests for pre-dissemination review of
Advertisements direct-to-consumer (DTC) television drug advertisements would be voluntary, and
FDA responses would be advisory. Only manufacturers that request such reviews
would be assessed the new fees, which would include an advisory review fee and an
operating reserve fee. The law authorizes $6.25 million in revenue for each of FY2008
through FY2012, adjusted for inflation and workload, and requires the Secretary to
establish an operating fund.
If, by the later of November 1, 2007, or 120 days after enactment, the Secretary has
not received at least $11.25 million in advisory review fees and operating reserve fees
combined, the DTC television advertisement advisory review user fee program shall
not commence and all collected fees shall be refunded. [FDAAA 104; FFDCA 736A; 21
USC 379h-1]
The Secretary is required to submit to congressional committees letters that propose performance goals and user fee amounts for the next round of Reauthorization
PDUFA reauthorization legislation. Previous PDUFA legislation required the letters but did not direct that the provision become part of USC Title 21.
FDAAA codified this provision. [FDAAA 105; FFDCA 736B(a),(b); 21 USC 379h-2]
iki/CRS-RL34465The proposals result from negotiations, required by FFDCA, The Secretary must, in preparation for the next PDUFA reauthorization, consult with
g/wbetween the agency and the pharmaceutical industry. congressional committees, scientific and academic experts, health-care professionals,
s.orrepresentatives of patient and consumer advocacy groups, and the regulated industry
leakto develop recommendations for PDUFA V, including goals and plans for meeting the goals.
://wikiA public hearing and review of the Secretary’s recommendations must be held
httpfollowing its negotiations with the industry, and the Secretary must include with the
submission to Congress a summary of the public comments and changes made to the
recommendations in response to them.
Before presenting recommendations to Congress, the Secretary must make publicly
available on the FDA website the minutes of all agency negotiation meetings with the
regulated industry, including summaries of any substantive proposals made by any
negotiating party and any significant controversies or differences of opinions and their
resolution. [FDAAA 104; FFDCA 736B(d); 21 USC 379h-1]
The Secretary must submit annual fiscal and performance reports to Congress. Previous PDUFA legislation required the reports but did not direct that Annual Reports
the provision become part of USC Title 21. FDAAA codified this provision. [FDAAA 105; FFDCA 736B(a),(b); 21 USC 379h-2]
No provision. The Secretary must make publicly available on the FDA website the annual
performance and fiscal reports to congressional committees. [FDAAA 105; FFDCA
736B(c); 21 USC 379h-2]




Topic Previous Law FDAAA Title I
Sunset Dates The authority to assess, collect, and use drug fees ceased to be The authority to assess, collect, and use drug fees ceases to be effective October 1,
effective October 1, 2007, and the reporting requirements 2012. [FDAAA 106; not in FFDCA; 21 USC 379g note]
ceased to be effective 120 days later [January 29, 2008]. The reporting requirements cease to be effective January 31, 2013. [FDAAA 106; not
in FFDCA; 21 USC 379h-2]
Effective Date The provisions took effect on October 1, 2002. The provisions took effect on October 1, 2007. [FDAAA 107; not in FFDCA; 21 USC
379g note]


iki/CRS-RL34465
g/w
s.or
leak
://wiki
http





Title II of FDAAA, the Medical Device User Fee Amendments of 2007 (MDUFA 2007),
reauthorizes FDA’s authority to collect user fees from medical device manufacturers, and makes
certain other amendments to the regulation of devices. Congress initially gave the agency the
authority to collect such fees in 2002, with the Medical Device User Fee and Modernization Act 8
(MDUFMA; P.L. 107-250). MDUFMA established user fees for premarket applications (PMAs), 9
premarket notifications (510(k)s), and other types of requests to market medical devices. The
2002 law incorporated, by reference, performance goals for many types of premarket device
reviews. It also enabled third-parties to conduct establishment inspections, and added new
regulatory requirements for reprocessed single-use devices.
For further information, 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.


In FY2007, when FDAAA was enacted, medical device user fees generated $35,202,000. This
represents an increase of 144.7% over the amount first collected in FY2003. In FY2007, devices 10
user fees comprised 9.0% of the agency’s user fee revenue, and 1.8% of its total budget.
FDA’s authority to collect medical device user fees was due to expire on October 1, 2007.
Congress reauthorizes the authority in MDUFA 2007, Subtitle A. In Subtitle B, it amends some
aspects of the regulation of medical devices. The details of each of these are discussed below.
Subtitle A of MDUFA 2007 reauthorizes FDA’s expiring authority to collect user fees through
October 1, 2012, and makes certain other changes to MDUFMA. The primary change is that
MDUFA 2007 adds three new types of user fees (annual establishment fees, registration fees, and

30-day fees). The first two are to be paid regularly by establishments with devices on the market,


generating a predictable base of device user fee income for FDA. MDUFMA had only enabled
the collection of fees for applications related to FDA’s approval or clearance of a product, which
the agency had noted made the agency’s user fee income difficult to predict. This was because the
number of applications could vary from year to year. The agency asserted that, by contrast, fees
paid annually would result in a revenue stream that was more reliable. This move toward a more
predictable funding stream mirrors the approach taken by PDUFA for drugs and biological
products.
8
A PMA is generally required for new medical devices, and those that necessitate FDAs highest level of safety
controls.
9 A 510(k) is generally required for medical devices similar to ones already on the market.
10 CRS Report RL34334, The Food and Drug Administration: Budget and Statutory History, FY1980-FY2007,
coordinated by Judith A. Johnson.



MDUFA 2007 lowers the amounts of fees paid by device manufacturers for FY2008, and then
includes a subsequent annual increase in fee amounts through FY2012. Despite the FY2008
decrease in the amounts of individual fee amounts, the total fee revenue generated will increase
from FY2007 levels; revenue lost in reduced fee amounts will be offset by revenue generated by
new types of fees.
MDUFA 2007 changes some provisions relevant to specific types of fees. Both MDUFMA and
MDUFA 2007 generally establish fee amounts for various types of activities by setting them as a
proportion of the cost of submitting a PMA. The amount charged for a PMA is therefore also
called the base fee. MDUFA 2007 strikes a provision that had required the Secretary to adjust the
premarket notification fee amount annually in a unique way, instead it sets it, like other fees, as a
percentage of the base fee amount. For a different fee, the FDAAA-created establishment fee, the
law gives the Secretary the authority to increase the fee amount in FY2010 if too few
manufacturers have paid it.
MDUFA 2007 changes the law regarding reduced fees paid by small businesses in several ways.
Under MDUFMA, entities qualifying as small businesses had certain fees waived and paid others
at a reduced rate. MDUFA 2007 further reduces the fee amounts small businesses pay, removes a
provision that the assets of partners and parent firms be considered in small business
qualification, and enables foreign firms to qualify as small businesses.
Regarding modular applications, those submitted to FDA in separate pieces, MDUFA 2007 for
the first time also affords the possibility of refunds for applications withdrawn at different points.
MDUFA 2007 extends a trigger requirement beyond FY2007 indefinitely.11 The trigger, which is
designed to ensure that user fees supplement rather than supplant direct appropriations, requires
that there be a certain amount of medical device-related direct appropriations in order for the
Secretary to assess medical device user fees and be expected to meet performance goals.
MDUFA 2007 amends a provision regarding the collection of fees in excess of the amount
authorized. The previous law required that if fees collected for a fiscal year exceed the authorized
appropriation, the excess would be subtracted from the subsequent year’s authorization. By
contrast, MDUFA 2007 allows excess fees to be carried over to cover shortfalls over the course of
several years.
MDUFA 2007 amends a provision describing how FDA may use the device fees it collects. The
new provision in theory could have enabled fees to be expended on postmarket activites, but does
not appear, in practice, to have done so. It states that fees will be dedicated toward expediting the
process for the review of device applications and for assuring the safety and effectiveness of
devices, as set forth in a letter from the Secretary to relevant congressional committees 12
(“Commitment Letter”). It is conceivable that assuring the safety and effectiveness of devices
could be interpreted to encompass postmarket surveillance, however the Commitment Letter does
not list surveillance and enforcement activities. In addition, MDUFA 2007 maintains two separate
11
The FY2007 trigger was articulated in the Medical Device User Fee Stabilization Act of 2005 (P.L. 109-43).
12Commitment Letter” from Michael O. Leavitt to Edward M. Kennedy, September 27, 2007, at http://www.fda.gov/
cdrh/mdufma/commitmentletter.pdf.





MDUFMA provisions that articulate and generally limit the expenditure of user fee funds to 13
premarket activities.
MDUFA 2007 requires the Secretary to continue to file annual performance and fiscal reports
through FY2012, and writes these report requirements into the FFDCA. The law also requires that
the performance report include information on previous cohorts for which the Secretary had not
given a complete response.
In FDA’s development of its performance goal recommendations to the Congress, MDUFA 2007
maintains MDUFMA’s requirements that the agency consult with an array of groups, and take
specified steps to invite public input. Unlike the previous law, MDUFA 2007 specifies that the
recommendations be revised upon consideration of public comments, requires the
recommendations’ transmittal to Congress, and writes the performance goal-related requirements
into the FFDCA.
Separate from the user fee authorizations, MDUFA 2007 authorizes the appropriation of specific
sums from FY2008 through FY2012 for the review of postmarket safety information on medical
devices. MDUFMA made similar authorizations, though no funds were appropriated.
MDUFA 2007 became effective on October 1, 2007.
Subtitle B of MDUFA 2007 makes various changes to the regulation of medical devices. It
extends from FY2007 through FY2012 the authority to have third parties review premarket
notifications.
Producers of devices that are marketed in the United States are required to register annually with
FDA. MDUFA 2007 restricts the period within which device producers must register with the
Secretary. It also reduces from twice to once per year the requirement that those who register with
the Secretary provide a list of devices on which they perform specific functions (e.g., the
manufacture, preparation, propagation, compounding or processing of a device).
MDUFA 2007 amends electronic registration regulations to require electronic filing as a default,
and without necessitating rulemaking by the Secretary as would have previously been required.
MDUFA 2007 amends two portions of the FFDCA’s provisions regarding records and reports on
devices. First, it adds a requirement that the Secretary promulgate regulations establishing a
unique identification system for medical devices. Second, it modifies the reporting requirements
for devices linked to serious injuries or deaths.
MDUFA 2007 revises the requirements for inspections by accredited third parties in three ways.
First, it reduces administrative requirements associated with qualifying for the program. Second,
it expands participation in the program. Third, it permits device companies to voluntarily submit
13
21 USC 379j(h)(2)(A)(ii), 379i(5). The one partial exception to the premarket general rule was the ability to expend
user fee funds on the evaluation of postmarket studies that are required as a condition of approval.





to FDA reports by third parties assessing conformance with appropriate international quality
systems standards, such as those set by the International Standards Organization. FDA is to
consider the information in these reports in setting its inspection priorities.
MDUFA 2007 requires the Comptroller General to conduct two studies, and the FDA to conduct
one. The Comptroller General is required to conduct one study on the appropriate use of the
process under FFDCA 510(k) (premarket notification) to determine whether a device is safe and
effective. It is required to conduct a second study on nosocomial (hospital-acquired) infections
associated with medical devices. The FDA is required to conduct a study on whether the
relationship between indoor tanning device use and the development of skin damage warrants a
label change for the devices.




Table 3. Comparison of Medical Device User Fee Act 2007, Subtitle A (FDAAA Title II, Subtitle A) with Previous Law
Topic Previous Law FDAAA Title II, Subtitle A
Fees may be used only for purposes specified in FFDCA 737(8) (formerly 737(5)). (None is related to postmarket inspection and enforcement, except Use of Fees
evaluation of postmarket studies required as a condition of approval.)
The fees authorized by this title will be dedicated to meeting the Fees are dedicated toward expediting the review of applications and for assuring the
goals identified in the Commitment Letter. [MDUFMA 101]. safety and effectiveness of devices, as set forth in the Commitment Letter goals.
[FDAAA 201(c); 21 USC 379i note]
[Commitment letter goals do not include postmarket inspection and enforcement.]
Types of Fees All fee types were linked to device-related applications for FDA Previous fee types are maintained, and three are added. Two are for regularly
review. Fees included those for: premarket application (such as a occurring events: establishment registration and annual filing fees; one is for an
PMA); panel-track PMA supplement; BLA efficacy supplement; 180-application: 30-day notice fee. [FDAAA 211(3); FFDCA 737(5)-(7),(11),(13); 21 USC
day PMA supplement; real-time PMA supplement; 510(k) 379i]
premarket notification.
Fee Amounts Base fee was $281,600 for FY2007. Premarket notification fee was Base fee is reduced to $185,000 for FY2008, and it is to increase 8.5% per year.
iki/CRS-RL34465set annually, based on predicted aggregate income generated from all premarket notification fees collected. Premarket notification fees are set like all other fees, as a percentage of the base fee. [FDAAA 212(a)(2),(b); FFDCA 738(a)(2)(A), (b); 21 USC 379j(a)(2)(A), (b)]
g/w
s.orFee payment is due upon submission of application or of request for classification. [FDAAA 212(a)(3); FFDCA 373(a)(2)(C); 21 USC 379j(a)(2)(C)] Payment
leak Requirement is expanded to include new fee types. [FDAAA 212(a)(3); FFDCA
373(a)(2)(C); 21 USC 379j(a)(2)(C)]
://wikiRefunds for No provision. A 75% refund is specified for modular applications withdrawn before a second portion
httpModular is submitted and before first action. Applications withdrawn later may be refunded at
Applications the Secretary’s discretion. [FDAAA 212(a)(4); FFDCA 738(a)(2)(D)(iv)-(vi); 21 USC
379j(a)(2)(D)]
Annual No such fee. Secretary may increase the establishment registration fee amount in FY2010 up to an
Establishment additional 8.5% over the annual 8.5% increase if fewer than 12,250 establishments paid
Registration Fee the fee in FY2009. [FDAAA 212(c)(2); FFDCA 738(c); 21 USC 379j(c)]
State and federal governmental entities and Indian tribes are exempt from annual
establishment fees. [FDAAA 212(a)(5); FFDCA 738(a)(3); 21 USC 379j(a)]
Fees for Small In the small business qualification, the assets of partners and parent In the small business qualification, the assets of partners and parent firms are no longer
Businesses firms were considered. Qualification requirements depended on an considered. Qualification requirements may be satisfied by an alternative to an IRS tax
IRS tax filing. Small businesses paid at a rate of 38% of most user filing, so foreign businesses may qualify. Small businesses pay at a rate of 25% of most
fees, and 80% of the premarket notification fee. user fees, and 50% of premarket notification fees. [FDAAA 212(d),(e); FFDCA
378(d),(e); 21 USC 379j(d),(e)]




Topic Previous Law FDAAA Title II, Subtitle A
Applications and requests for classification for which fees apply will not be accepted if fees are not paid. [FDAAA 212(f); FFDCA 738(f); 21 USC 379j(f)] Effect of Failure
to Pay Fees Requirement is expanded to apply to new fee types. [FDAAA 212(f); FFDCA 738(f);
21 USC 379j(f)]
Direct appropriations must be more than one percent less than $205,720 multiplied by an adjustment factor, or else the Secretary may not collect user fees Conditions
and is not required to meet performance goals. [FDAAA 212(g); FFDCA 738(g); 21 USC 379j(g)] (Trigger)
Trigger specified through FY2007. Trigger extended indefinitely. [FDAAA 212(g); FFDCA 738(g); 21 USC 379j(g)]
Authorization of The following amounts of user fees were authorized to be The following amounts of user fees are authorized to be appropriated: $48,431,000
Appropriations appropriated: $25,125,000 for FY2003; $27,255,000 for FY2004; for FY2008; $52,547,000 for FY2009; $57,014,000 for FY2010; $61,860,000 for
$29,785,000 for FY2005; $32,615,000 for FY2006; and $35,000,000 FY2011; and $67,118,000 for FY2012. [FDAAA 212(h)(1); FFDCA 738(h)(3); 21 USC
for FY2007. 379j(h)(3)]
Offset User fees collected that exceeded the authorized appropriation for User fees collected between FY2008 and FY2011 are to be considered in aggregate. A
a fiscal year must have been subtracted from fees authorized to be reduction is to be made in fees in the final year (i.e., FY2012) only if the amount
collected for the subsequent year. collected in the four-year period exceeded the amount authorized for the same
period. [FDAAA 212(h)(2); FFDCA 738(h)(4); 21 USC 379j(h)(3)]
iki/CRS-RL34465Secretary is required to submit annually to relevant congressional committees a performance goal report and fiscal report. [MDUFMA 103; and FDAAA 213; Reporting
g/wFFDCA 738A; 21 USC 379j-1] Requirements
s.or The requirement is written into the FFDCA. The performance report is to include
leakinformation on all previous cohorts for which the Secretary has not given a complete
response. [FDAAA 213; FFDCA 738A; 21 USC 379j-1]
://wikiFDA is required to consult with an array of governmental, professional and consumer groups, publish its recommendations in the Federal Register, provide a Performance
httppublic comment period, and hold a public meeting. [MDUFMA 105; and FDAAA 213; FFDCA 738A; 21 USC 379j-1] Goal
Development Recommendations are to be revised upon consideration of public comments,
recommendations are to be transmitted to Congress, and performance goal-related
requirements are written into the FFDCA. [FDAAA 213; FFDCA 738A;
21 USC 379j-1]
Postmarket The following amounts were authorized for postmarket The following amounts are authorized to be appropriated for postmarket safety
Appropriations surveillance of medical devices (amounts are increases above the information on medical devices: $7,100,000 for FY2008, $7,455,000 for FY2009,
Authorization FY2002 appropriation): an increase of $3,000,000 for FY2003, an $7,827,750 for FY2010, $8,219,138 for FY2011, and $8,630,094 for FY2012. [FDAAA
increase of $6,000,000 for FY2004, an increase of such sums as 215]
may be necessary for FY2005 and each subsequent fiscal year.
Effective Date October 1, 2002. October 1, 2007; savings clause included. [FDAAA 214, 216; 21 USC 379i note]
Sunset October 1, 2007. October 1, 2012; for specified reports, January 31, 2013. [FDAAA 217; 21 USC 379i
note]




Table 4. Comparison of Medical Device User Fee Act 2007, Subtitle B (FDAAA Title II, Subtitle B) with Previous Law
Topic Previous Law Title II, Subtitle B
Authority for Authority was set to expire on October 1, 2007. Authority is set to expire on October 1, 2012. [FDAAA 221; FFDCA
Review of Third 523(c); 21 USC 360mm(c)]
Party Premarket
Notification
Registration Medical device producers were required to register with the Secretary Medical device producers must register with the Secretary between
prior to December 31 of each year. Device producers that registered with October 1 and December 31 of each year. [FDAAA 222; FFDCA 510(b);
the Secretary were required to provide a list of devices on which they 21 USC 360(b)] Device producers that register with the Secretary must
performed specific functions twice per year, in June and December. provide a list of devices on which they perform specific functions once per
year (between October 1 and December 31). [FDAAA 223; FFDCA 510(j);
21 USC 360(j)(2)]
Electronic Registrants would have had to file by electronic means upon a finding by Registrants must file electronically unless the Secretary grants a waiver.
Registration and the Secretary that the electronic receipt was feasible, unless the Secretary [FDAAA 224; FFDCA 510(p); 21 USC 360(p)]
Listing granted a request for waiver.
Unique Device No provision. The Secretary is required to promulgate regulations establishing a unique
iki/CRS-RL34465Identification System identification system for medical devices. [FDAAA 226; FFDCA 519(f); 21 USC 360i]
g/w
s.orFrequency of Device manufacturers and importers were generally required to report Adverse event reports must generally comply with 21 CFR 803 (regarding
leakReporting for serious injuries or deaths associated with their medical devices (adverse adverse event reporting for medical devices), unless the Secretary grants an
Certain Devices event reports). exemption or variance. Adverse event reports for devices granted
://wikiexemptions or variances, as well as for imported devices, are to submitted according to criteria established by the Secretary. [FDAAA 227; FFDCA
http519(a)(1); 21 USC 360(i)(a)(1)]




Topic Previous Law Title II, Subtitle B
Inspections by Program start-up language was included. A maximum of 15 parties could Program start-up language is deleted. Accredited party limit is deleted. An
Accredited Persons have been accredited. Certain time restrictions applied to device accredited person is required to notify the Secretary of any withdrawal,
establishment eligibility. One component of eligibility could have been met suspension, restriction, or expiration of his or her certificate of
by submitting a statement that the law of a country in which the device is conformance. Device establishment eligibility time restrictions are
marketed recognizes an inspection of the establishment by the Secretary. removed. A statement that the law of a country in which the device is
No time period was specified for an establishment or accredited person to marketed recognizes an inspection of the establishment by the Secretary is
respond to a Secretary’s request for information. An establishment’s use of no longer a component of an establishment’s eligibility. An establishment or
an accredited party inspection was restricted after a finding of “official accredited person is required to respond to a Secretary’s request for
action indicated.” information within 60 days. The Secretary may deny clearance if
information provided is untrue. The “official action indicated” restriction on
accredited party inspection is deleted. The Secretary is to take
harmonization with international standards into account when specifying
the required format for third party inspection reports. [FDAAA 228;
FFDCA 704(g); 21 USC 374(g)]
Reports The Secretary was required to request an IOM study on whether the The Comptroller General is required to conduct one study on the
medical device postmarket surveillance system provided adequate appropriate use of the process under FFDCA 510(k) (premarket
safeguards for pediatric populations. notification) to determine whether a device is safe and effective. [FDAAA
iki/CRS-RL34465225] Another required GAO study concerns nosocomial infections relating
g/wto medical devices. [FDAAA 229] The FDA is required to conduct a study
s.oron whether the relationship between indoor tanning device use and the development of skin damage warrants a label change. [FDAAA 230]
leak


://wiki
http





Title III of FDAAA is the Pediatric Medical Device Safety and Improvement Act of 2007
(PMDSIA). PMDSIA was enacted based upon reports of a critical need for pediatric medical
devices that help diagnose and treat diseases and conditions affecting children. Apparently,
developing medical devices for children is less profitable and more problematic than developing
them for adults. Fewer children need medical devices than adults, and children have physical
attributes (e.g., size, biochemistry, growth rates), activities, and environmental influences that are
different from those of adults.
For further information about medical device approval, see CRS Report RL32826, The Medical Device Approval
Process and Related Legislative Issues, by Erin D. Williams.


In order to encourage the development of the pediatric devices, PMDSIA creates some new
reporting requirements related to certain pediatric devices, offers several types of incentives to
manufacturers to create pediatric medical devices, and gives FDA the authority to require
postmarket studies of approved pediatric devices to ensure their continued efficacy and safety.
PMDSIA creates a set of reporting requirements for applications made under FFDCA 515 and 14
520(m). Section 515 governs PMAs to market class III devices (these require FDA’s highest
level of safety controls). Section 520(m) governs humanitarian device exemptions (HDEs). An
HDE 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. PMDSIA creates
requirements for both types of applications, inserting a new section, 515A, into the medical
device approval regulations.
Section 515A requires those requesting approval to market a device under 515 and 520(m) to
include, if readily available, a description of any pediatric subpopulation with the disease or
condition that the devices is intended to treat, and the number of affected pediatric patients.
Section 515A also allows the Secretary to conclude that adult data can be used to support a
reasonable assurance of effectiveness in pediatric subpopulations, as appropriate. The section also
requires the Secretary to report annually to relevant congressional committees, specified
information about pediatric devices approved in the preceding year.
PMDSIA creates one set of incentives for manufacturers to create pediatric medical devices by
making some modifications directly to the HDE. Primarily, PMDSIA exempts some specified
manufacturers of pediatric devices from the general HDE prohibition on selling a device for an
amount that exceeds its costs of research and development, fabrication, and distribution. The
exemption extends only to specified requests submitted on or before October 1, 2012. PMDSIA
14
The requirements do not attach to premarket notifications, called 510(k)s, which require a demonstration of
substantially equivalence to a device already on the market.



gives the Secretary specified pricing-exemption related enforcement and inspection authorities,
and creates reporting requirements for adverse events related to devices that qualify for the
pricing exemption. The law also requires the Comptroller General to submit a report to relevant
congressional committees on the impact of the pricing exemption.
Regarding funding for research on pediatric medical devices, the PMDSIA requires the Secretary
to establish a demonstration project to promote pediatric device development. The law authorizes
$6 million per year for FY2008 through FY2012 to support the demonstration grants and related
activities. The law also requires the National Institutes of Health (NIH) Director to designate a
contact point to help pediatric medical device developers locate funding. In addition, it requires
the Secretary to submit a plan for expanding pediatric medical device research and development
to relevant congressional committees.
Finally, the PMDSIA incorporates certain postmarket surveillance measures related to pediatric
medical devices. It expands the conditions under which the Secretary may require postmarket 15
studies as a condition of approval for class II or III devices to include devices expected to have
significant use in pediatric subpopulations. These studies may exceed the general 36-month
limitation in duration if necessary to assess the impact of the device on pediatric populations’
growth and development. The PMDSIA also includes a related 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.
15
Class II and III medical devices are those that require safety controls.




Table 5. Comparison of Pediatric Medical Device Safety and Improvement Act of 2007 (FDAAA Title III)
with Previous Law
Topic Previous Law FDAAA Title III
New Devices No provision. Applicants under FFDCA 515 or 520(m) are to include, if readily available, a
description of any pediatric subpopulations that suffer from the condition the
device is intended to treat, and the number of affected pediatric patients.
[FDAAA 302; FFDCA 515A(a)(1),(2); 21 USC 351 et seq.]
Annual Report No provision. The Secretary is to submit an annual report to the Committee on Health,
Education, Labor and Pensions (HELP), and the House Committee on Energy
and Commerce, that includes, for the preceding year: (1) the number of
devices approved for which a pediatric subpopulation suffers from the disease
or condition the device is intended to treat; (2) the number of devices labeled
for pediatric use; (3) the number of approved pediatric devices exempted
from a fee pursuant to pediatric conditions of use; and (4) the review times
for applications described above. [FDAAA 302; FFDCA 515A(a)(3); 21 USC
351 et seq.]
iki/CRS-RL34465Determination of No provision. The Secretary may conclude that adult data can be used to support a
g/wPediatric Effectiveness reasonable assurance of effectiveness in pediatric subpopulations, as
s.orand Subpopulation appropriate. A study for each pediatric subpopulation may not be necessary if
leakExtrapolation data from one could be extrapolated to another. [FDAAA 302; FFDCA
515A(b),(c); 21 USC 351 et seq.]
://wikiA person granted an HDE is not permitted to sell the device for an amount that exceeds the costs of research and development, fabrication, and Modification to
httpdistribution of the device. [FFDCA 520(m)(3)] Humanitarian Device
Exemption The general prohibition remains, but a person granted an HDE is permitted
to sell the device for an amount that exceeds the costs of research and
development, fabrication, and distribution of the device if the following
criteria are met: (1) the device is intended to treat and is labeled for use in a
pediatric subpopulation; (2) the device was not approved for pediatric use
prior to the act’s date of enactment; (3) the number of devices distributed
does not exceed a distribution number specified by the Secretary that may
not exceed the number specified by the Secretary for the HDE; (4) the
applicant immediately notifies the Secretary if the number of devices
distributed exceeds the allowable annual distribution number; and (5) the
request is submitted on or before October 1, 2012. [FDAAA 303(a); FFDCA
520(m)(3),(5),(6)(A); 21 USC 360j(m)]




Topic Previous Law FDAAA Title III
Pediatric HDE No provision. The Secretary may inspect the records relating to the number of devices
Inspection distributed during any calendar year for any person granted an HDE
exemption from effectiveness requirements under the new pediatric rule.
[FDAAA 303(a); FFDCA 520(m)(6)(B); 21 USC 360j(m)]
Pediatric HDE No provision. A person may petition the Secretary to change, and the Secretary may
Modification modify, up to 4,000, the number of devices sold under the new pediatric
HDE. [FDAAA 303(a); FFDCA 520(m)(6)(C); 21 USC 360j(m)]
HDE Enforcement No provision. If the Secretary discovers through notification or inspection that the number
of devices marketed exceeded the projected annual distribution number, the
HDE pricing restriction will apply from that point forward. [FDAAA 303(a);
FFDCA 520(m)(6)(D); 21 USC 360j(m)]
Definition of Pediatric No provision. For purposes of the HDE, pediatric patients means patients who are 21 years
Patients and Pediatric of age or younger at the time of diagnosis or treatment.
Subpopulation For purposes of the HDE and FFDCA 515A, pediatric subpopulation has the
same meaning as in FFDCA 520(m)(6)(E)(ii), i.e., neonates, infants, children,
iki/CRS-RL34465or adolescents. [FDAAA 302, 303(a); FFDCA 515,520(m)(6)(E); 21 USC
g/w351,360j(m)]
s.orDuring the one-year period beginning on the date on which a drug received a period of market exclusivity under FFDCA 505A, any report of an Adverse Event
leakadverse event regarding the drug that the Secretary receives is to be referred to the Office of Pediatric Therapeutics (OPT). [BPCA 17(b)] Reporting, Review of
Reports The drug adverse event requirements remain in effect, and the Secretary is
://wikirequired to report adverse events regarding devices exempt from the HDE
httpprice prohibition to the OPT. OPT Director is to provide a periodic review
of the reports by the Pediatric Advisory Committee, obtain the Committee’s
recommendations, and report back to the Secretary. OPT is also to provide
for an annual review by the Committee of all devices granted the pediatric
HDE, to ensure that the exemption remains appropriate. [FDAAA 303(a);
FFDCA 520(m)(7),(8); 21 USC 360j(m)]
Comptroller General No provision. By January 1, 2012, the Comptroller General is to submit a report to the
Report Senate HELP and House Energy and Commerce Committees on the impact of
the new pediatric HDE pricing exemption. [FDAAA 303(b)]
Guidance No provision. Within 180 days of enactment, the Commissioner must issue guidance for
institutional review committees on how to evaluate requests for approval for
devices for which an HDE has been granted. [FDAAA 303(c); 21 USC 360
note]




Topic Previous Law FDAAA Title III
Point of Contact for No provision. NIH Director is required to designate a point of contact or office to help
Available Funding innovators and physicians identify some sources of funding available for
pediatric medical device development. [FDAAA 304; PHSA 402(b)(23); 42
USC 282(b)]
Plan for Pediatric No provision. Not later than 180 days after enactment, the Secretary, acting through the
Medical Device Commissioner, in collaboration with the Directors of NIH and the Agency for
Research Healthcare Research and Quality, is required to submit to the Senate HELP
and House Energy and Commerce Committees a plan for expanding pediatric
medical device research and development. [FDAAA 304(b)]
Demonstration Grants No provision. The Secretary is required to establish a demonstration project to promote
for Improving Pediatric pediatric device development. Grants are to help connect innovators with
Device Availability manufacturers, manage the device development process, guide innovators to
federal resources, and provide business assistance. Consortia receiving grants
are required to coordinate with points of contact at NIH and FDA. Grantees
are also required to report their effectiveness, impact, and device
development status to the Secretary annually. For the demonstration grants,
iki/CRS-RL34465$6 million per year is authorized from FY2008 through FY2012. [FDAAA 305; 42 USC 282 note]
g/w
s.orOPT and Pediatric The duties of FDA’s OPT and Pediatric Advisory Committee were The duties of FDA’s OPT are expanded to include increasing pediatric access
leakAdvisory Committee restricted to drug-related activities. [P.L. 107-109, 17(b)] to medical devices. [FDAAA 306; 21 USC 393a(b); 42 USC 284m note]
The Secretary may require, by order, that a manufacturer conduct The Secretary may require, by order or as a condition of approval, that a Postmarket
://wikipostmarket surveillance as a condition of approval for any class II or manufacturer conduct postmarket surveillance for any class II or class III Surveillance
httpclass III device the failure of which would be reasonably likely to have device—(i) the failure of which would be reasonably likely to have serious
serious adverse health consequences or which is intended to be—(1) adverse health consequences; (ii) that is expected to have significant use in
implanted in the human body for more than one year, or (2) a life-pediatric subpopulations; or (iii) that is intended to be (I) implanted in the
sustaining or life-supporting device used outside a device user facility. human body for more than one year, or (II) a life-sustaining or life-supporting
device used outside a device user facility. [FDAAA 307; FFDCA 522(b); 21
USC 360l]
Postmarket surveillance studies required under the section may be a maximum of 36 months in duration. [FFDCA 522(b)]
The general 36-month limitation still applies; however the Secretary may
require, as a condition of approval, postmarket studies of longer than 36
months for devices that are expected to have a significant use in pediatric
populations, if the extended time is necessary to assess the safety of the
device. [FDAAA 307; FFDCA 522(b); 21 USC 360l]




Topic Previous Law FDAAA Title III
The Secretary is required to provide a procedure for a timely review by an appropriate scientific advisory panel or advisory committee, regarding any Dispute Resolution
obligation concerning drugs or devices under FFDCA or PHSA 351 over which there is a scientific controversy between the Secretary and a person
who was a sponsor, applicant, or manufacturer. [FFDCA 562; 21 USC 360bbb-1]
In addition to previous rights of review, a manufacturer may also request a
review under FFDCA 562 (dispute resolution) of any order or condition
requiring postmarket surveillance under this section, during which time the
device shall not be deemed adulterated, misbranded, or otherwise in violation
of approval or clearance unless necessary to protect public health. [FDAAA
307; FFDCA 522(c); 21 USC 360l]


iki/CRS-RL34465
g/w
s.or
leak
://wiki
http




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 products that do not work for them, or receiving too much or too little of a potentially
useful drug. Studies show that, depending on the maturation and development of a child’s organs
and other factors, some drugs vary in how long they stay in the body, affecting their usefulness.
Some side effects are unique to children or children of specific ages, including effects on growth 16
and development.
Recognizing the obstacles (which could be economic, ethical, legal, or mechanical) that make
manufacturers reluctant to conduct research to address these questions, FDA and Congress
developed two approaches to facilitate pediatric research. FDAAA continues both programs. The
first, the Pediatric Research Equity Act (FDAAA Title IV, discussed in this section) is a
mandatory program that requires pediatric assessments as part of every new application regarding
a new ingredient, indication, dosage form, dosing regimen, or route of administration. The
second, the Best Pharmaceuticals for Children Act (FDAAA Title V, discussed in the following
section of this report) is voluntary, offering a six-month marketing exclusivity for a product in
return for pediatric studies.
For further information, see CRS Report RL33986, FDA’s Authority to Ensure That Drugs Prescribed to Children Are Safe
and Effective, by Susan Thaul.


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 17


promulgate it. Congress gave FDA that authority with the enactment of the Pediatric Research
Equity Act of 2003 (PREA; P.L. 108-155). PREA requirements cover all drug and biological
product applications or supplements to applications concerning a new active ingredient, new
indication, new dosage form, new dosing regiment, or new route of administration. The Act
includes provisions for deferrals and waivers. PREA also authorizes the Secretary to require the
sponsor of an already approved and marketed drug or biological product to submit a pediatric
assessment based on criteria described in the law.
The Pediatric Research Equity Act of 2007, Title IV of FDAAA, reauthorizes PREA, amending it
to strengthen standards for required tests, explanation of deferrals, labeling, and publicly
accessible information. PREA now requires the Secretary to establish an internal committee,
composed of FDA employees with specified expertise, to participate in the review of pediatric
plans and assessments, deferrals, and waivers. The law requires the Secretary to track assessments
and labeling changes and to make that information publicly accessible; establishes a dispute
16
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.
17 See Association of Am. Physicians and Surgeons, Inc. v. United States Food and Drug Admin., 2002 U.S. Dist.
LEXIS 19689 (October 17, 2002).



resolution procedure, which allows the Commissioner, after specified steps, to deem a drug to be
misbranded if a manufacturer refuses to make a requested labeling change; and includes review
and reporting reporting requirements for adverse events.
PREA requires reports from both the Institute of Medicine (IOM) and the Government
Accountability Office (GAO). It also continues to link the program’s authorization to the five-
year authority FDAAA provides to the pediatric exclusivity program. (See discussion of FDAAA
Title V in the next section of this report.)




Table 6. Comparison of Pediatric Research Equity Act of 2007 (FDAAA Title IV) with Previous Law
Topic Previous Law FDAAA Title IV
A person submitting an application (or a supplement to an application) to market a drug or biologic with a new active ingredient, new indication, new Authority Regarding
dosage form, new dosing regimen, or new route of administration must submit with the application a pediatric assessment. [FDAAA 402(a); FFDCA New Drugs and
505B(a)(1); 21 USC 355c] Biological Products
The reauthorizing law specifies that this Act applies to applications
submitted on or after the date of FDAAA’s enactment. [FDAAA 402(a);
FFDCA 505B(a)(1); 21 USC 355c]
The assessments must contain data, gathered using appropriate formulations for each age group for which the assessment is required, that are adequate
to assess the safety and effectiveness of the drug or the biological product for the claimed indications in all relevant pediatric subpopulations, and to
support dosing and administration for each pediatric subpopulation for which the drug or the biological product is safe and effective. [FDAAA 402(a);
FFDCA 505B(a)(2); 21 USC 355c]
If the course of the disease and the effects of the drug are sufficiently similar in adults and pediatric patients, FDAAA authorizes the Secretary to judge
pediatric effectiveness based on extrapolation from adequate and well-controlled studies in adults, usually supplemented with other information obtained
in pediatric patients, such as pharmacokinetic studies. A study may not be needed in each pediatric age group if data from one age group can be
iki/CRS-RL34465extrapolated to another age group. [FDAAA 402(a); FFDCA 505B(a)(2)(B); 21 USC 355c]
g/w A review for an application must include a brief documentation of data that
s.orsupport the extrapolation conclusions. [FDAAA 402(a); FFDCA 505B(a)(2);
leak21 USC 355c]


://wiki
http


Topic Previous Law FDAAA Title IV
The Secretary may (by order in the form of a letter) require the holder of an approved drug application or biologics license to submit by a specified Authority Regarding
date the required assessments. [FDAAA 402(a); FFDCA 505B(b)(1); 21 USC 355c] Already Marketed
FDAAA specifies that the Secretary’s letter requiring assessments of an Drugs and Biological Products
approved drug must refer to a declined written request for pediatric
exclusivity related studies (under FFDCA 505A) for a labeled indication and
that the written request was not referred to the Foundation of the NIH for
pediatric studies. It also expands “holder” to “sponsor or holder.” [FDAAA
402(a); FFDCA 505B(b)(1); 21 USC 355c]
To do so, the Secretary must find that: [FDAAA 402(a); FFDCA 505B(b)(1); 21 USC 355c]
(A) the drug or biological product is used for a substantial number of (A) the drug or biological product is used for a substantial number of
pediatric patients for the labeled indications; pediatric patients for the labeled indications;
and the absence of adequate labeling could pose significant risks to and the presence of adequate pediatric labeling “could confer a benefit on
pediatric patients; pediatric patients;” [FDAAA 402(a); FFDCA 505B(b)(1)(A); 21 USC 355c]
or (B) there is reason to believe that the drug or biological product or (B) there is reason to believe that the drug or biological product would
iki/CRS-RL34465would represent a meaningful therapeutic benefit over existing therapies for pediatric patients for one or more of the claimed indications; represent a meaningful therapeutic benefit over existing therapies for pediatric patients for one or more of the claimed indications; [FDAAA
g/w402(a); FFDCA 505B(b)(1)(B); 21 USC 355c]
s.orand the absence of adequate labeling could pose significant risks to
leakpediatric patients.
://wiki[Clause did not appear independently of the other two findings.] or (C) the absence of adequate labeling could pose a risk to pediatric
httppatients. [FDAAA authorizes the Secretary to act based on this independently of the previous two types of finding.] [FDAAA 402(a);
FFDCA 505B(b)(1)(C); 21 USC 355c]




Topic Previous Law FDAAA Title IV
For a new drug or biological product, the Secretary may defer submission of some or all required assessments until a specified date after approval of Deferrals
the drug or issuance of the license for a biological product upon finding that the drug or biological product is ready for approval for use in adults before
pediatric studies are complete; pediatric studies should be delayed until additional safety or effectiveness data have been collected; or there is another
appropriate reason for deferral. The applicant must also submit to the Secretary certification of the grounds for deferring the assessments; a
description of the planned or ongoing studies; and evidence that the studies are being conducted or will be conducted with due diligence and at the
earliest possible time. [FDAAA 402(a); FFDCA 505B(a)(3); 21 USC 355c]
No provision. An applicant must include a timeline for the completion of such studies.
FDAAA requires an annual review of each approved deferral, for which the
applicant must submit to the Secretary detailed information on its progress
in conducting pediatric studies or, if no progress has been made, evidence of
documentation that such studies will be conducted with due diligence and at
the earliest possible time. It also requires that all information submitted as
part of this annual review be promptly made available to the public, including
through the FDA website. [FDAAA 402(a); FFDCA 505B(a)(3); 21 USC
355c]
Full waiver. At the request of an applicant (or, for a new drug or biological product, on the initiative of the Secretary), the Secretary shall grant a full Waivers
iki/CRS-RL34465waiver, as appropriate, of the requirement to submit assessments under this subsection if the applicant certifies and the Secretary finds that (1) necessary studies are impossible or highly impracticable (because, for example, the number of patients in that age group is so small or patients in that
g/wage group are geographically dispersed); or (2) there is evidence strongly suggesting that the drug or biological product would be ineffective or unsafe
s.orin all pediatric age groups. [FDAAA 402(a); FFDCA 505B(a)(4)(A) and 505B(b)(2)(A); 21 USC 355c]
leakPartial waiver. At the request of an applicant (or, for a new drug or biological product, on the initiative of the Secretary), the Secretary shall grant a
://wikipartial waiver, as appropriate, of the requirement to submit assessments under this subsection with respect to a specific pediatric age group if the applicant certifies and the Secretary finds that: (1) necessary studies are impossible or highly impracticable; (2) there is evidence strongly suggesting that
httpthe drug or biological product would be ineffective or unsafe in that age group; (3) the drug or biological product does not represent a meaningful
therapeutic benefit over existing therapies for pediatric patients in that age group, is not likely to be used in a substantial number of pediatric patients in
that age group, and (for a marketed drug or biological product) the absence of adequate labeling could not pose significant risks to pediatric patients; or
(4) the applicant can demonstrate that reasonable attempts to produce a pediatric formulation necessary for that age group have failed. [FDAAA
402(a); FFDCA 505B(a)(4)(B) and 505B(b)(2)(B); 21 USC 355c]
If a waiver is granted on the grounds that it is not possible to develop a pediatric formulation, the waiver shall cover only the pediatric groups requiring
that formulation. [FDAAA 402(a); 505B(b)(2)(C); 21 USC 355c]
An applicant seeking a full or partial waiver must submit to the Secretary
documentation detailing why a pediatric formulation cannot be developed. If
a waiver is granted, the applicant’s submission must promptly be made
public, including through posting on the FDA website. [FDAAA 402(a);
FFDCA 505B(a)(4)(C) and 505B(b)(2)(C); 21 USC 355c]
Labeling If the Secretary grants a full or partial waiver because there is evidence that a drug or biological product would be ineffective or unsafe in pediatric
populations, the information shall be included in the labeling for the drug or biological product. [FDAAA 402(a); FFDCA 505B(a)(4)(D) and
505B(b)(2)(D); 21 USC 355c]




Topic Previous Law FDAAA Title IV
Relationship to Other To require a sponsor to submit a pediatric assessment of an approved This paragraph regarding the Secretary’s requiring the holder of a approved
Pediatric Provisions drug or licensed biological product, the Secretary must have (1) issued a application for a drug or biological product to conduct pediatric studies no
written request for a study, (2) received no agreement to the study longer appears in FFDCA 505B. [FDAAA (Title V) places an altered version in
from the drug’s sponsor, and (3) certified that neither the program for FFDCA 505A. If the holder declines a written request for a pediatric study and the
pediatric studies of drugs (at NIH under PHSA 409I) or the Foundation Secretary continues to determine there is a need for such a study, the Secretary is
for the NIH (FNIH, under PHSA 499) had sufficient funds to conduct now required to determine whether FNIH has sufficient funds (no mention is
the study, or certified in the Federal Register that no contract or grant made of the NIH program for pediatric studies of drugs in this context). If funds
had been awarded under those programs although funds were available. are available, the Secretary must refer studies to FNIH and FNIH must fund them.
After determining that no holder will agree to the written request, the If FNIH does not have sufficient funds, the Secretary may require that the holder of the approved application conduct the studies under PREA (FFDCA 505B).
Secretary shall certify whether the Secretary has sufficient funds to [FDAAA 502(a); FFDCA 505A(n)(1)(A); 21 USC 355a]]
conduct the study, taking into account the prioritization under PHSA
409I.
Disclosure of Regarding requests for studies of approved products or the dissemination of
Confidential pediatric information following a completed pediatric assessment, FDAAA
Information states it does not alter or amend sections of U.S. Code titles regarding
Food and Drugs, Government Organization and Employees, or Crimes and
iki/CRS-RL34465Criminal Procedure regarding the disclosure of confidential information. [FDAAA 402(a); FFDCA 505B(b)(3) and 505B(h)(3); 21 USC 355c]
g/w
s.orThe law defined “meaningful therapeutic benefit over existing therapies” as when: (1) the drug or biological product would represent a significant Meaningful
leakimprovement in the treatment, diagnosis, or prevention of a disease, compared with marketed products adequately labeled for that use in the relevant pediatric population; or (2) the drug or biological product is in a class of products or for an indication for which there is a need for additional options. Therapeutic Benefit
://wiki[FDAAA 402(a); FFDCA 505B(c); 21 USC 355c]
httpThe law based the assessment on the Secretary’s estimation. FDAAA changes “the Secretary estimates” to “the Secretary determines.”
[FDAAA 402(a); FFDCA 505B(c); 21 USC 355c]
Misbranding A drug or biological product may be considered misbranded and subject to relevant enforcement action solely for the failure to submit a required
assessment or to request approval of a pediatric formulation in accordance with applicable provisions of this section.
However, the law does not allow enforcement action under the penalty (imprisonment or fines) authority of this title; and does not allow the failure to
submit the assessment or request to be the basis for a proceeding to withdraw approval for a drug or to revoke the license for a biological product.
[FDAAA 402(a); FFDCA 505B(d); 21 USC 355c]
Meeting with Sponsor Requires that the Secretary, before and during the investigational process for a new drug or biological product, meet with the sponsor of the new drug
or biological product to discuss information that the sponsor submits on plans and timelines for pediatric studies; or any planned request by the
sponsor for waiver or deferral of pediatric studies. [FDAAA 402(a); FFDCA 505B(e); 21 USC 355c]




Topic Previous Law FDAAA Title IV
Internal Committee No provision. The Secretary must establish an internal committee, composed of FDA
employees with specified expertise, to participate in the review of pediatric
plans, assessments, deferrals, and waivers. [FDAAA 403; FFDCA 505C; 21
USC 355d] (Note: This is the same internal committee to which FDAAA
502(a) [FFDCA 505A(f); 21 USC 355a] refers; see next section.)
The Secretary must document the internal committee’s activity, track
pending assessments, and place the information on the FDA website for
easy public access. The internal committee must conduct a retrospective
review and analysis of assessments, deferrals, and waivers to the Secretary,
who would be required to issue recommendations for improvements.
[FDAAA 402(a); FFDCA 505B(f); 21 USC 355c]
Review of Pediatric No provision. The review must include analysis of the quality and consistency of pediatric
Plans, Assessments, information in pediatric assessments and the appropriateness of waivers and
Deferrals, and deferrals granted. The Secretary must, based on such review, issue
Waivers recommendations to the review divisions for improvements and initiate
guidance to industry. The Secretary must, in consultation with the internal
iki/CRS-RL34465committee, track and make available to the public specified statistics on the numbers of assessments, study designs, deferral and waiver requested and
g/wgranted, pediatric formulations developed, labeling changes, etc. The report
s.ormust include the reasons for each of those events not happening. [FDAAA
leak402(a); FFDCA 505B(f); 21 USC 355c]
://wikiDispute Resolution No provision. FDAAA establishes a dispute resolution procedure for when a sponsor does not agree with the Commissioner’s request for a label change. In those
httpcases, it requires the Commissioner to refer the dispute to the Pediatric
Advisory Committee for review and recommendation. If the sponsor
continues to disagree with a requested labeling change, the Commissioner
may deem the drug to be misbranded. The Commissioner must refer the
dispute to the Pediatric Advisory Committee within 30 days of a sponsor’s
disagreeing to change the label. Nothing in this subsection shall preclude,
delay, or serve as the basis to stay other courses of action via the Pediatric
Advisory Committee process or an enforcement action under this Act.
[FDAAA 402(a); FFDCA 505B(g)(1); 21 USC 355c]
Labeling to Include No provision. Upon making a determination that a pediatric assessment does or does not
Secretary’s demonstrate that the subject drug is safe and effective in pediatric
Determination populations or subpopulations, including whether such assessment results
are inconclusive, the Secretary must order the label to include information
about those results and a statement of the Secretary’s determination.
[FDAAA 402(a); FFDCA 505B(g)(2); 21 USC 355c]




Topic Previous Law FDAAA Title IV
Dissemination of No provision. The Secretary must make available to the public in an easily accessible
Pediatric Information manner, including by posting on the FDA website, the medical, statistical,
and clinical pharmacology reviews of a submitted pediatric assessment. The
Secretary must require the sponsor of an assessment that results in certain
labeling changes to distribute such information to health care providers.
[FDAAA 402(a); FFDCA 505B(h); 21 USC 355c]
Adverse Event No provision. Following a labeling change, the Secretary must refer all adverse event
Reporting reports to the Office of Pediatric Therapeutics (OPT). For the first year
after the change, the OPT director must provide for their review by the
Pediatric Advisory Committee (PAC) and obtain its recommendations for
action by the Secretary. In subsequent years, the OPT director may refer
the adverse event reports to the PAC. FDAAA states that these
requirements “shall supplement, not supplant, other review of such adverse
event reports by the Secretary.” [FDAAA 402(a); FFDCA 505B(i); 21 USC
355c]
Orphan Drugs Unless the Secretary requires otherwise by regulation, this section does not apply to any drug for an indication for which orphan designation has been
iki/CRS-RL34465granted under this title. [FDAAA 402(a); FFDCA 505B(k); 21 USC 355c]
g/wInstitute of Medicine No provision. FDAAA requires that the Secretary contract with the IOM to conduct a
s.orStudy study and report to Congress regarding pediatric studies and resulting
leaklabeling changes. It directs that the IOM review and assess, using a representative sample of studies, the use of extrapolation, alternative
://wikiendpoints, neonatal assessment tools, number and type of pediatric adverse events, and ethical issues in pediatric clinical trials. [FDAAA 402(a); FFDCA
http505B(l); 21 USC 355c]
Government No codified provision. FDAAA requires a GAO report, in consultation with the Secretary, to
Accountability Office Congress by January 1, 2011, that addresses the effectiveness of FFDCA
Report 505A and 505B and PHSA 409I in ensuring that medicines used by children
are tested and properly labeled. It specifies required elements of that
report. FDAAA does not indicate that this provision be placed within the
U.S. Code. [FDAAA 404; not in FFDCA or USC]
Reference to Sunset The authority under this section shall remain in effect so long as an application subject to this section may be accepted for filing by the Secretary on or
before the date specified in the market exclusivity for pediatric studies of drugs section of this title. [FDAAA 402(a); FFDCA 505B(m); 21 USC 355c]







Title V of FDAAA reauthorizes and changes legislation first passed in 1997. As part of the FDA
Modernization Act of 1997 (P.L. 105-115), Congress provided drug manufacturers with a
financial incentive to conduct pediatric use studies on their patented products. The “Pediatric
Studies of Drugs” provision provided that 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 18
product. This tool is the second approach that FDA and Congress have taken to encouraging
pediatric drug research, the other, required pediatric assessments of new products, is discussed in
the preceding section of this report regarding FDAAA Title IV.
For further information, see CRS Report RL33986, FDA’s Authority to Ensure That Drugs Prescribed to Children Are Safe
and Effective, by Susan Thaul.


In 2002, the Best Pharmaceuticals for Children Act (BPCA 2002; P.L. 107-109) reauthorized the
exclusivity provisions for another five years. It also added provisions to encourage pediatric
research of products that were no longer covered by patent or other marketing exclusivity
agreements, to which pediatric exclusivity was not relevant. It required the Secretary to list those
off-patent products for which pediatric studies are needed to assess safety and effectiveness. It
also established an off-patent research fund at NIH (PHSA 409I) and authorized appropriations of
$200 million for FY2002 and such sums as are necessary for each of the five years until the
provisions were set to sunset on October 1, 2007.
For on-patent drugs whose manufacturers declined FDA’s written requests for studies (and,
therefore, exclusivity), BPCA 2002 amended FFDCA 505A to allow FDA to refer drugs needing
pediatric studies to the Foundation for the NIH (FNIH, PHSA 499), creating a second program of 19
FDA-NIH collaboration.
Other provisions in the 2002 BPCA included giving priority status to pediatric supplemental
applications; the establishment of an FDA Office of Pediatric Therapeutics (OPT); the definition
of pediatric age groups to include neonates; and a direction to the Secretary to contract with the
IOM for a review of regulations, federally prepared or supported reports, and federally supported
evidence-based research, all relating to clinical research involving children. The IOM report to
Congress was also to include recommendations on best practices relating to research involving 20
children.
Title V of FDAAA again reauthorizes the pediatric exclusivity program, amending FFDCA 505A
to sunset on October 1, 2012. It also encourages research on off-patent products, strengthens the
18
During that six-month period, FDA would not grant marketing approval to another identical product (usually a
generic).
19 The Foundation supports the research mission of NIH using public-private partnerships; see http://www.fnih.org/
aboutus/aboutus.shtml.
20 See IOM, Ethical Conduct of Clinical Research Involving Children, Committee on Clinical Research Involving
Children (Washington, DC: National Academies Press, 2004), done with funding from NIH and FDA.



requirements for labeling changes based on the results of pediatric use studies, and provides for
the reporting of adverse events.
FDAAA authorizes the Secretary to grant additional marketing exclusivity, for both new drugs
and drugs already on the market, only after a sponsor has completed and reported on the studies
that the Secretary has requested in writing, including appropriate formulations of the drug for
each age group of interest, and after any appropriate labeling changes are approved, all within the
agreed upon time frames. An applicant who turns down a request on the grounds that developing
appropriate pediatric formulations of the drug is not possible must provide evidence to support
that claim.
The new law requires that the sponsor propose pediatric labeling resulting from the studies. For a
product studied under this section, the labeling must include study results and the Secretary’s
determination whether those results demonstrate the drug’s safety and effectiveness (if the results
do or do not indicate safety and effectiveness, or if they are inconclusive). The product sponsor
must disseminate labeling change information to health care providers, and the Commissioner
must report to the Secretary on the review of all adverse event reports and recommendations on
actions in response. Other provisions of the law set time frames for the actions it requires.
Public notice requirements are expanded beyond the current notice of an exclusivity decision to
include copies of the written request. The Secretary must also publicly identify any drug with a
developed pediatric formulation that studies had demonstrated to be safe and effective for
children that an applicant has not introduced onto the market within one year.
A new dispute resolution process includes referral to the Pediatric Advisory Committee. The
internal review committee, which FDAAA Title IV requires the Secretary to establish, must
review all written requests. The Secretary, with that committee, must track all pediatric studies
and labeling changes according to specified questions.
Other provisions require applicants to submit, along with the report of requested studies, all
postmarket adverse event reports regarding that drug; refine study scope to allow the Secretary to
include preclinical studies; and except from exclusivity any drug with another exclusivity that is
to expire in less than nine months.
FDAAA amends PHSA Section 409I (as discussed earlier), which required that the Secretary,
through the NIH Director and in consultation with the Commissioner and pediatric research
experts, list approved drugs for which pediatric studies are needed to assess safety and
effectiveness. It changes the specifications from an annual list of approved drugs to a list, revised
every three years, of priority study needs in pediatric therapeutics, including drugs or indications.
If the Secretary determines there is a need for pediatric information for a drug for which pediatric
studies have not been completed, the Secretary must either issue a proposal to award a grant to
conduct such studies, if funds are available through FNIH, or refer the drug for inclusion on the
list established under PHSA Section 409I. FDAAA also requires reports from the IOM and the
GAO.
The provisions in Title V of FDAAA make up the following two tables: the first addressing
amendments to FFDCA, the second relating to PHSA.




Table 7. Comparison of Best Pharmaceuticals for Children Act of 2007
(FDAAA Title V, Section 502(a)) with Previous Law
Topic Previous Law FDAAA Title V, Section 502(a)
As used in this section, the term “pediatric studies” or “studies” means at least one clinical investigation (that, at the Secretary’s discretion, may include Definition of
pharmacokinetic studies) in pediatric age groups (including neonates in appropriate cases) in which a drug is anticipated to be used. [FDAAA 502(a); Studies
FFDCA 505A(a); 21 USC 355a]
Adds that, at the Secretary’s discretion, clinical investigation may include preclinical studies. [FDAAA 502(a);
FFDCA 505A(a); 21 USC 355a]
Six-month pediatric exclusivity is granted if, prior to approval of an application that is submitted under section 355(b)(1) of this title, the Secretary Market Exclusivity
determines that information relating to the use of a new drug in the pediatric population may produce health benefits in that population, the Secretary for New Drugs
makes a written request for pediatric studies (which shall include a timeframe for completing such studies), and such studies are completed within any such
timeframe and the reports thereof submitted in accordance with subsection (d)(2) of this section or accepted in accordance with subsection (d)(3) of this
section. [FDAAA 502(a); FFDCA 505A(b); 21 USC 355a]
Adds that the applicant agrees to the request and that such studies are completed using appropriate
formulations for each age group for which the study is requested. [FDAAA 502(a); FFDCA 505A(b)(1); 21
iki/CRS-RL34465USC 355a]
g/wSix-month pediatric exclusivity is granted if the Secretary determines that information relating to the use of an approved drug in the pediatric population Market Exclusivity
s.ormay produce health benefits in that population and makes a written request to the holder of an approved application under section 355(b)(1) of this title for Already
leakfor pediatric studies (which shall include a timeframe for completing such studies), the holder agrees to the request, the studies are completed within any Marketed Drugs
such timeframe, and the reports thereof are submitted in accordance with subsection (d)(2) of this section or accepted in accordance with subsection
://wiki(d)(3) of this section. [FDAAA 502(a); FFDCA 505A(c); 21 USC 355a]
http Adds that such studies are completed using appropriate formulations for each age group for which the study
is requested. [FDAAA 502(a); FFDCA 505A(c)(1); 21 USC 355a]
Extension of Extended by six months other exclusivities granted (such as for new drugs, certain generic drugs, drugs for rare diseases or conditions) under the FFDCA.
Exclusivity [FDAAA 502(a); FFDCA 505A(b)(1)(B) and 505A(c)(1)(B); 21 USC 355a]
Exception No provision. Adds that the Secretary shall not extend the exclusivity period if the determination is made less than 9
months before the expiration of exclusivity period. [FDAAA 502(a); FFDCA 505A(b)(2) and 505A(c)(2); 21
USC 355a]




Topic Previous Law FDAAA Title V, Section 502(a)
The Secretary may, pursuant to a written request and after consultation with the sponsor of an application for an investigational new drug or a new drug, Agreement for
or the holder of an approved application for a drug, agree with the sponsor or holder for the conduct of pediatric studies for such drug. Such agreement Studies
shall be in writing and shall include a timeframe for such studies. [FDAAA 502(a); FFDCA 505A(d)(1); 21 USC 355a]
Request for studies. Adds that a single written request may relate to more than one use of a drug; and may
include uses that are both approved and unapproved. [FDAAA 502(a); FFDCA 505A(d)(1); 21 USC 355a]
Combines language relating to new drugs and already approved drugs.
Requires the applicant or holder to respond to the Secretary’s written request within 180 days, indicating
either when studies will be initiated or the reasons for declining the request. [FDAAA 502(a); FFDCA
505A(d)(2); 21 USC 355a]
No provision. An applicant or holder who does not agree with the request on the grounds that it is not possible to
develop the appropriate pediatric formulation must submit to the Secretary the reasons such pediatric
formulations cannot be developed. [FDAAA 502(a); FFDCA 505A(d)(2)(ii); 21 USC 355a]
No provision. An applicant or holder who agrees to the request for such studies shall provide the Secretary, at the same
time as the submission of the reports of such studies, with all available postmarket adverse event reports
iki/CRS-RL34465regarding the subject drug. [FDAAA 502(a); FFDCA 505A(d)(2)(B); 21 USC 355a]
g/wThe law directs the Secretary to take into account adequate representation of children of ethnic and racial minorities. [FDAAA 502(a); FFDCA 505A(d); Representation of
s.or21 USC 355a] Minorities
leakThe Secretary is required to do this in The Secretary is required to do this “[i]n issuing such a request.” [FDAAA 502(a); FFDCA 505A(d)(1); 21
reaching an agreement regarding written USC 355a]


://wikiprotocols.
http


Topic Previous Law FDAAA Title V, Section 502(a)
The Secretary must determine if such studies were or were not conducted in accordance with the original written request and the written agreement and Determination by
reported in accordance with the requirements of the Secretary for filing, and so notify the sponsor or holder within a specified number of days after the Secretary
submission of the report of the studies. [FDAAA 502(a); FFDCA 505A(d)(3); 21 USC 355a]
If the sponsor or holder and the Secretary FDAAA requires that the Secretary make the determination within 180 days of the report’s submission.
agree upon written protocols for the [FDAAA 502(a); FFDCA 505A(d)(3); 21 USC 355a]
studies, the studies requirement is satisfied
upon the completion of the studies and
submission of the reports thereof in
accordance with the original written
request and the written agreement. For
agreed upon studies, the Secretary was
required to make the determination within
60 days of the report’s submission.
If the sponsor or holder and the Secretary
had not agreed in writing on the protocols
for the studies, the requirement for
iki/CRS-RL34465pediatric studies was satisfied when such studies had been completed and the
g/wreports accepted by the Secretary. The
s.orSecretary was required to accept or reject
leaksuch reports and so notify the sponsor or
holder not later than 90 days after the
://wikisubmission of the reports of the studies.
httpThe Secretary’s only responsibility in accepting or rejecting the reports shall be to determine whether the studies fairly respond to the written request,
have been conducted in accordance with commonly accepted scientific principles and protocols, and have been reported in accordance with the
requirements of the Secretary for filing. [FDAAA 502(a); FFDCA 505A(d)(3); 21 USC 355a]
Written Request If the Secretary makes a written request Addresses requests for studies of both new drugs and already approved drugs together; see above.


to Holders of for pediatric studies (including neonates, as
Approved appropriate) under subsection (c) of this
Applications for section to the holder of an approved new
Drugs that Have drug application, the holder, not later than
Market Exclusivity 180 days after receiving the written
request, shall respond to the Secretary as
to the intention of the holder to act on
the request by indicating when the
pediatric studies will be initiated, if the
holder agrees to the request; or indicating
that the holder does not agree to the
request.


Topic Previous Law FDAAA Title V, Section 502(a)
The Secretary is required to act if the manufacturer does not agree to a written request within the specified time period, and if the Secretary determines Referral if Pediatric
that there is a continuing need for information relating to the use of the drug in the pediatric population (including neonates, as appropriate). [Previous law Studies Not
addressed this in FFDCA 505A(d)(4)(B); and FDAAA 502(a) places it in FFDCA 505A(n); 21 USC 355a] Completed: No
The Secretary was to refer the drug to The Secretary must make the determination whether further study is needed through the internal Agreement to Request
FNIH, established under 42 USC 290b, for committee established under FFDCA 505C. Different procedures are specified for drugs with and without
the conduct of the pediatric studies current patents.
described in the written request.
For a drug with an unexpired patent, the Secretary must first certify whether FNIH has sufficient funding for
the studies in the written request.
-If funding is available, requires the Secretary to refer the written request to FNIH, and requires FNIH to
fund the studies.
-If funding is not available, the Secretary must consider whether to require pediatric assessments under
FFDCA 505B(b). [FDAAA 502(a); FFDCA 505A(n)(1)(A); 21 USC 355a]
For a drug with no current patent, requires that the Secretary refer the drug for inclusion on the list
iki/CRS-RL34465established under PHSA 409I. [FDAAA 502(a); FFDCA 505A(n)(1)(B); 21 USC 355a]
g/wPublic Notice The Secretary shall give public notice of FDAAA deletes this provision and adds: For a drug for which the Secretary decides not to require an
s.orthe name of the drug, the name of the manufacturer, and the indications to be assessment under FFDCA 505B, the Secretary must give public notice and the basis for that decision. [FDAAA 502(a); FFDCA 505A(n)(2); 21 USC 355a]
leakstudied made in a referral to the FNIH.
://wikiLack of Funds On referral of a drug under subparagraph The law was rewritten so that for a drug with an unexpired patent, the Secretary must certify whether the
http(B)(i), FNIH shall issue a proposal to award a grant to conduct the requested FNIH has sufficient funding to conduct the studies before referring a request to FNIH. [FDAAA 502(a); FFDCA 505A(n)(1)(A); 21 USC 355a]
studies unless FNIH certifies to the It requires the FNIH to fund a study that the Secretary does refer. [FDAAA 502(a); FFDCA 505A(n)(1)(A);
Secretary, within a timeframe that the 21 USC 355a].
Secretary determines is appropriate
through guidance, that FNIH does not
have funds available under PHSA 499 to
conduct the requested studies. If FNIH so
certifies, the Secretary shall refer the drug
for inclusion on the list established under
PHSA 409I for the conduct of the studies.
No Requirement Nothing in this subsection shall be No provision.


to Refer construed to require that every declined
written request shall be referred to FNIH.


Topic Previous Law FDAAA Title V, Section 502(a)
Written Requests For a drug for which a written request had FDAAA changes how the Secretary would handle a declined request for studies. If a written request is not
for New Drugs not been accepted before marketing accepted by the sponsor or holder of an application, and the Secretary does not refer the request to FNIH
approval, if the Secretary determines that (under FFDCA 505A(n)(1)(A)), the Secretary may require the holder to submit a pediatric assessment under
there is a continuing need for information FFDCA 505B(b)(1). [FDAAA 502(a); FFDCA 505A(n)(1)(A); 21 USC 355a]
relating to the use of the drug in the
pediatric population (including neonates, as
appropriate), the Secretary shall issue a
written request after the date of approval
of the drug. [FFDCA 505A(d)(4)(F)]
Delay of Effective The Secretary shall delay for up to 90 days No provision.
Date for Certain the approval of a generic or other product
Application whose application relies on safety and
effectiveness studies conducted by an
entity other than the applicant (such as for
a new formulation (under FFDCA
505(b)(2)) or a generic version (under
FFDCA 505(j)) until a determination is
iki/CRS-RL34465made regarding pediatric studies under
g/wthis section (FFDCA 505A). In the event
s.orthat requirements of this section are satisfied, the applicable six-month
leakmarketing exclusivity shall be deemed to
://wikihave been running during the period of delay.
httpThe Secretary shall publish a notice of any determination that the requirements for the conduct of pediatric studies have been met and that submissions Notice of
and approvals under FFDCA 505(b)(2) or (j) [generic] for a drug will be subject to the provisions of this section. [FDAAA 502(a); FFDCA 505A(e)(1); 21 Determinations on
USC 355a] Studies
Such notice must be published within 30 days of the Secretary’s determination regarding market exclusivity Requirement
and must include a copy of the written request under subsection (b) or (c). [FDAAA 502(a); FFDCA
505A(e)(1); 21 USC 355a]
No provision. The Secretary must publicly identify any drug with a developed pediatric formulation that studies have
demonstrated to be safe and effective for children if its sponsor has not introduced the pediatric formulation
onto the market within one year. [FDAAA 502(a); FFDCA 505A(e)(2); 21 USC 355a]
Internal Review of No provision. The internal review committee, which FDAAA 403 requires the Secretary to establish, must review all
Written Requests written requests. It may review studies submitted pursuant to this provision to make recommendations to
and Pediatric the Secretary on whether to accept or reject the studies. The Secretary must, in consultation with the
Studies internal committee, track pediatric studies and labeling changes; and make available to the public specified
information such as types of studies, and drugs and uses studied. [FDAAA 502(a); FFDCA 505A(f); 21
USC355a]




Topic Previous Law FDAAA Title V, Section 502(a)
Limitations A drug to which the six-month period under subsection (b) or (c) of this section has already been applied (1) may receive an additional six-month period
under subsection (c)(1)(A)(ii) of this section for a supplemental application if all other requirements under this section are satisfied, except that such a
drug may not receive any additional such period under subsection (c)(2) of this section; and (2) may not receive any additional such period under
subsection (c)(1)(B) of this section. [FDAAA 502(a); FFDCA 505A(g); 21 USC 355a]
Relationship to Notwithstanding any other provision of law, if any pediatric study is required by a provision of law (including a regulation) other than this section and such
Pediatric Research study meets the completeness, timeliness, and other requirements of this section, such study shall be deemed to satisfy the requirement for market
Requirements exclusivity pursuant to this section. [FDAAA 502(a); FFDCA 505A(h); 21 USC 355a]
Any supplement to an application under FFDCA 505 proposing a labeling change pursuant to a report on a pediatric study under this section shall be Priority Status for
considered to be a priority supplement; and shall be subject to the performance goals established by the Commissioner for priority drugs. [FDAAA 502(a); Labeling Changes
FFDCA 505A(i)(1); 21 USC 355a]
This provision now refers to pediatric applications and supplements. [FDAAA 502(a); FFDCA 505A(i)(1); 21
USC 355a]
If, not later than 180 days after the date of submission of the application, the Commissioner determines that there is a disagreement with the sponsor on Labeling Change
appropriate changes to the labeling for the drug that is the subject of the application, the Commissioner must request that the sponsor of the application Dispute Resolution
make any labeling change that the Commissioner determines to be appropriate; and if the sponsor of the application does not agree to make a labeling
iki/CRS-RL34465change requested by the Commissioner, the Commissioner shall refer the matter to the Pediatric Advisory Committee. [FDAAA 502(a); FFDCA
g/w505A(i)(2)(A); 21 USC 355a]
s.orThe law specified that the Commissioner FDAAA refers to the Commissioner’s determining that “the sponsor and the Commissioner have been
leakdetermined that the related application unable to reach agreement.” It also adds that the Commissioner must make the referral if the sponsor does
was approvable and that the only open not agree within 30 days of the request. [FDAAA 502(a); FFDCA 505A(i)(2)(A); 21 USC 355a]
://wikiissue is the labeling change.
httpNot later than 90 days after receiving a referral, the Pediatric Advisory Committee shall review the pediatric study reports, and make a recommendation
to the Commissioner concerning appropriate labeling changes, if any.
The Commissioner shall consider the recommendations of the Pediatric Advisory Committee and, if appropriate, not later than 30 days after receiving the
recommendation, make a request to the sponsor of the application to make any labeling change that the Commissioner determines to be appropriate.
If the sponsor of the application, within 30 days after receiving a request, does not agree to make a labeling change requested by the Commissioner, the
Commissioner may deem the drug that is the subject of the application to be misbranded.
Nothing in this subsection limits the authority of the United States to bring an enforcement action under this chapter when a drug lacks appropriate
pediatric labeling. Neither course of action (the Pediatric Advisory Committee process or an enforcement action referred to in the preceding sentence)
shall preclude, delay, or serve as the basis to stay the other course of action. [FDAAA 502(a); FFDCA 505A(i)(2)(E); 21 USC 355a]
Secretary’s No provision. The Secretary must, upon determining that a pediatric study conducted under this section does or does not
Determination demonstrate that the drug that is the subject of the study is safe and effective, including whether such study
Public results are inconclusive, in pediatric populations or subpopulations, order the labeling of such product to
include information about the results of the study and a statement of the Secretary’s determination.
[FDAAA 502(a); FFDCA 505A(j); 21 USC 355a]




Topic Previous Law FDAAA Title V, Section 502(a)
Not later than a specified number of days after the date of submission of a report on a pediatric study under this section, the Commissioner shall make Dissemination of
available to the public a summary of the medical and clinical pharmacology reviews of pediatric studies conducted for the supplement, including by Pediatric
publication in the Federal Register. [FDAAA 502(a); FFDCA 505A(k)(1); 21 USC 355a] Information
The law allowed up to 180 days. FDAAA allows up to 210 days. It also substitutes the Secretary for the Commissioner, adds statistical
reviews, and refers to studies conducted under subsection (b) or (c). [FDAAA 502(a); FFDCA 505A(k)(1);
21 USC 355a]
Requires, for studies that result in labeling changes reflected in the annual summary distribution, that their
sponsors distribute, at least annually, such information to health care providers. [FDAAA 502(a); FFDCA
505A(k)(2); 21 USC 355a]
Regarding dissemination of information of pediatric studies under this section, FDAAA states it does not alter or amend sections of U.S. Code titles
regarding Food and Drugs, Government Organization and Employees, or Crimes and Criminal Procedure regarding the disclosure of confidential
information. [FDAAA 502(a); FFDCA 505A was (j)(2), now (k)(3); 21 USC 355a]
Adverse Event No provision. The Secretary must, for the year following a labeling change, ensure referral of all adverse event reports to
Reporting the OPT, whose director must provide for their review by the Pediatric Advisory Committee and obtain its
recommendations for action by the Secretary.
iki/CRS-RL34465In subsequent years, the Secretary must, as appropriate, refer all pediatric adverse event reports for a drug
g/wfor which a pediatric study was conducted under this section to the OPT, whose director may refer them
s.orfor review and recommendation to the Pediatric Advisory Committee.
leakFDAAA states that these requirements “shall supplement, not supplant, other review of such adverse event
://wikireports by the Secretary.” [FDAAA 502(a); FFDCA 505A(l); 21 USC 355a]
httpInteraction of Exclusivities If the generic drug exclusivity period overlaps with the pediatric exclusivity period, the period will be extended by the number of days of the overlap. [FDAAA 502(a); FFDCA 505A(m); 21 USC 355a]
Prompt Approval A drug for which an application has been submitted or approved under an abbreviated new drug application (ANDA, for a generic drug) shall not be
of Generic Drugs considered ineligible for approval under that section or misbranded on the basis that the labeling of the drug omits a pediatric indication or any other
When Pediatric aspect of labeling pertaining to pediatric use when the omitted indication or other aspect is protected by patent or by certain exclusivities.
Information Is Labeling. The Secretary may require that the labeling of an approved generic drug (FFDCA 505(j)) that omits a pediatric indication or other required aspect
Added to Labeling of labeling include: a statement that the product is not labeled for all or specific pediatric uses because of marketing exclusivity held by another
manufacturer; and a statement of any appropriate pediatric contraindications, warnings, or precautions that the Secretary considers necessary.
FDAAA includes a clause to preserve pediatric exclusivity and other provisions under certain paragraphs of FFDCA 505, 505A, 505(j). [FDAAA 502(a);
FFDCA 505A(o); 21 USC 355a]




Topic Previous Law FDAAA Title V, Section 502(a)
Institute of No provision. The Secretary must contract, within 3 years of enactment, with the IOM to conduct a study and report to
Medicine Study Congress regarding the written requests and studies conducted pursuant to this section. The IOM must
review representative requests and studies since 1997 and labeling changes made as a result of such studies;
assess the use of extrapolation, alternative endpoints, neonatal assessment tools, and ethical issues in
pediatric clinical trials; and review and assess the pediatric studies of biological products; and make
recommendations regarding appropriate incentives for encouraging pediatric studies of biologics. [FDAAA
502(a); FFDCA 505A(p); 21 USC 355a]
Secretary’s Report The Secretary was required to conduct a No provision.
to Congress study of all relevant issues, as specified,
and report to Congress, by January 1,
2001, based on the experience under the
program established under this section.
The law provides a sunset date by which all written requests for pediatric studies must be made, applications accepted for filing, and all other requirements Sunset
met to receive a 6-month marketing exclusivity under this section. [FDAAA 502(a); FFDCA 505A; 21 USC 355a]
The sunset date was October 1, 2007. The sunset date is October 1, 2012. [FDAAA 502(a); FFDCA 505A(q); 21 USC 355a]


iki/CRS-RL34465
g/w
s.or
leak
://wiki
http


Table 8. Comparison of Best Pharmaceuticals for Children Act of 2007
(FDAAA Title V, Sections 502(b-f) and 503) with Previous Law
Topic Previous Law FDAAA Title V, Sections 502(b-f) and 503
The Secretary, acting through the NIH Director and in consultation The focus of the list is changed to “a priority list of needs in pediatric List of Priority Issues in
with the Commissioner and experts in pediatric research, shall develop, therapeutics, including drugs or indications that require study.” The Pediatric Therapeutics
prioritize, and publish an annual list of approved drugs needing Secretary must develop and publish the list not later than one year after
additional studies of safety and effectiveness in the pediatric population. enactment, and revise it every three years. [FDAAA 502(b); PHSA
409I(a)(1); 42 USC 284m]
The criteria for developing and prioritizing the list of drugs included The section refers to a list of needs, rather than a list of drugs. It also
available information, need for information, whether new pediatric replaces the existing criteria with others that give examples within the
studies concerning the drug may produce health benefits in the categories of therapeutic gaps in pediatrics; particular pediatric diseases,
pediatric population; and whether reformulation of the drug is disorders or conditions where more complete knowledge and testing of
necessary. therapeutics may be beneficial in pediatric populations; and the adequacy
of necessary infrastructure to conduct pediatric pharmacological
research. [FDAAA 502(b); PHSA 409I(a)(2); 42 USC 284m]
iki/CRS-RL34465The Secretary shall award contracts to entities that have the expertise to conduct pediatric clinical trials (including qualified universities, hospitals, laboratories, contract research organizations, federally funded programs such as pediatric pharmacology research units, other public or private Funding of Pediatric Studies and Research
g/winstitutions, or individuals) to enable the entities to conduct pediatric studies concerning one or more drugs identified in the list. [FDAAA 502(b);
s.orPHSA 409I(b); 42 USC 284m]
leak The Secretary must act through NIH. The description of entities is
://wikiexpanded to include expertise with clinical trials “or other research”; and practice groups. In addition to contracts, the Secretary may use
httpgrants or other appropriate funding mechanisms. [FDAAA 502(b); PHSA
409I(b); 42 USC 284m]
Process for Proposed No provision. The NIH Director must submit, as appropriate, proposed pediatric
Pediatric Study Requests study requests for consideration by the Commissioner for pediatric
and Labeling Changes studies of a specific pediatric indication on the list of priority issues in
pediatric therapeutics. The request must include the information
required by FFDCA 505A requests.
The NIH Director may submit a proposed pediatric study request for a
drug for which there is an approved or submitted application under
FFDCA Section 505(j); and there is no patent protection or market
exclusivity protection for at least one form of the drug under the
FFDCA; and additional studies are needed to assess the safety and
effectiveness of the use of the drug in the pediatric population. [FDAAA
502(b); PHSA 409I(c)(1); 42 USC 284m]




Topic Previous Law FDAAA Title V, Sections 502(b-f) and 503
The Commissioner, in consultation with the NIH Director, may issue a written request (which shall include a timeframe for negotiations for an Written Request to
agreement) for pediatric studies to all holders of an approved application for the drug under FFDCA 505 [21 USC 355]. Such a written request Holders of Approved
shall be made in a manner equivalent to the manner in which a written request is made under subsection (a) or (b) of FFDCA 505A [21 USC 355a], Applications for Drugs
including with respect to information provided on the pediatric studies to be conducted pursuant to the request. [FDAAA 502(b); PHSA 409I(c)(2); Lacking Exclusivity
42 USC 284m]
The written request referred to a study of a drug identified in the list of The written request refers to a study of an indication or indications
drugs for which pediatric studies are needed. submitted pursuant to the list of priority issues in pediatric therapeutics.
Studies must use appropriate formulations for each age group for which
the study is requested. [FDAAA 502(b); PHSA 409I(c)(2); 42 USC
284m]
If the Commissioner does not receive a response to a written request within 30 days of the date on which a request was issued, or if a referral is Requests for Contract
made, the Secretary, acting through the NIH Director and in consultation with the Commissioner, shall publish a request for contract proposals to Proposals
conduct the pediatric studies described in the written request. [FDAAA 502(b); PHSA 409I(c)(3); 42 USC 284m]
The Secretary must publish the request if the Commissioner has not
received a response to a written request within 30 days. [FDAAA
502(b); PHSA 409I(c)(3); 42 USC 284m]
iki/CRS-RL34465
g/wDisqualification A holder that receives a first right of refusal shall not be entitled to respond to a request for contract proposals. [FDAAA 502(b); PHSA 409I(c)(4); 42 USC 284m]
s.or
leakGuidance Not later than 270 days after January 4, 2002, the Commissioner shall No provision.
promulgate guidance to establish the process for the submission of
://wikiresponses to written requests.
httpA contract under this section may be awarded only if a proposal for the contract is submitted to the Secretary in such form and manner, and Funding
containing such agreements, assurances, and information as the Secretary determines to be necessary to carry out this section. [FDAAA 502(b);
PHSA 409I(c)(5); 42 USC 284m]
The Secretary may allow grants or other funding in addition to
contracts. [FDAAA 502(b); PHSA 409I(c)(5); 42 USC 284m]
On completion of a pediatric study in accordance with a contract awarded under this section, a report concerning the study shall be submitted to Reporting of Studies
the NIH Director and the Commissioner. The report shall include all data generated in connection with the study. [FDAAA 502(b); PHSA
409I(c)(6)(A); 42 USC 284m]
The section refers to “an award” rather than “a contract.” It also
requires that the report include the written request. [FDAAA 502(b);
PHSA 409I(c)(6)(A); 42 USC 284m]
Availability of Reports Each report submitted shall be considered to be in the public domain (subject to FFDCA 505A(d)(4)(D) [21 USC 355a (d)(4)(D)]) and shall be
assigned a docket number by the Commissioner. An interested person may submit written comments concerning such pediatric studies to the
Commissioner, and the written comments shall become part of the docket file with respect to each of the drugs.




Topic Previous Law FDAAA Title V, Sections 502(b-f) and 503
Action by Commissioner The Commissioner shall take appropriate action in response to the reports. [FDAAA 502(b); PHSA 409I(c)(6)(B,C); 42 USC 284m]
During the 180-day period after the date on which a report is submitted, the Commissioner must review the report and such other data as are Requests for Labeling
available concerning the safe and effective use in the pediatric population of the drug studied; and negotiate with the holders of approved Change
applications for the drug studied for any labeling changes that the Commissioner determines to be appropriate and requests the holders to make.
The Commissioner must place in the public docket file a copy of the report and of any requested labeling changes; and publish in the Federal
Register a summary of the report and a copy of any requested labeling changes. [FDAAA 502(b); PHSA 409I(c)(7)(A,B,C); 42 USC 284m]
The Commissioner must also post information on the FDA website.
[FDAAA 502(b); PHSA 409I(c)(7)(C); 42 USC 284m]
If, not later than the end of the 180-day period specified, the holder of an approved application for the drug involved does not agree to any labeling Dispute Resolution
change requested by the Commissioner under that paragraph, the Commissioner shall refer the request to the Pediatric Advisory Committee. Not
later than 90 days after receiving a referral, the Pediatric Advisory Committee shall review the available information on the safe and effective use of
the drug in the pediatric population, including study reports submitted under this section, and make a recommendation to the Commissioner as to
appropriate labeling changes, if any. Not later than 30 days after receiving a recommendation from the Pediatric Advisory Committee, the
Commissioner shall consider the recommendation and, if appropriate, make a request to the holders of approved applications for the drug to make
any labeling change that the Commissioner determines to be appropriate.
iki/CRS-RL34465If a holder of an approved application for a drug, within 30 days after receiving a request to make a labeling change, does not agree to make a
g/wrequested labeling change, the Commissioner may deem the drug to be misbranded under FFDCA. [FDAAA 502(b); PHSA 409I(c); 42 USC 284m]
s.orNothing in this subsection limits the authority of the United States to bring an enforcement action under the Federal Food, Drug, and Cosmetic
leakAct [21 USC 301 et seq.] when a drug lacks appropriate pediatric labeling. Neither course of action (the Pediatric Advisory Committee process or
an enforcement action referred to in the preceding sentence) shall preclude, delay, or serve as the basis to stay the other course of action.
://wiki[FDAAA 502(b); PHSA 409I(c)(11); 42 USC 284m]
httpRecommendation for If a pediatric study completed under public contract indicates that a The FDAAA-amended PHSA 409I(c) does not include this provision,
Formulation Changes formulation change is necessary and the Secretary agrees, the Secretary which had been PHSA 409I(c)(12).
shall send a nonbinding letter of recommendation regarding that change
to each holder of an approved application.
Dissemination of Pediatric No provision. Requires that the Secretary, acting through the NIH Director and within
Information one year of enactment, study and report to Congress on the feasibility
of establishing a compilation of information on pediatric drug use.
[FDAAA 502(b); PHSA 409I(d); 42 USC 284m]
There are authorized to be appropriated to carry out this section $200 million for the first year; and such sums as are necessary for each of the Authorization of
succeeding fiscal years. Any amount appropriated shall remain available to carry out this section until expended. [FDAAA 502(b); PHSA 409I(e)(1); Appropriations
42 USC 284m]
FY2002 was specified as the first year and reference was made to five FY2008 is specified as the first year and the section refers to four
succeeding years. succeeding years. [FDAAA 502(b); PHSA 409I(e)(1); 42 USC 284m]




Topic Previous Law FDAAA Title V, Sections 502(b-f) and 503
The law continues to require the Secretary, acting through the Director of NIH, to establish a nonprofit corporation to be known as the Foundation for the
Foundation for the NIH, which shall not be an agency or instrumentality of the U.S. Government. FNIH is to support the NIH in its mission National Institutes of
(including collection of funds for pediatric pharmacologic research), and to advance collaboration with biomedical researchers from universities, industry, Health (FNIH)
and nonprofit organizations. FNIH may solicit and accept gifts, grants, and other donations, establish accounts, and invest and expend funds in
support of various education and research programs, including a program to collect funds for certain pediatric pharmacologic research and studies.
The law includes requirements regarding a board of directors, corporate and financial organization and reporting, service of federal employees,
intellectual property rights, dissemination of scientific results by grantees and FNIH. FNIH may transfer funds to the NIH and any funds transferred
under this paragraph shall be subject to all federal limitations relating to federally-funded research. The law authorizes to be appropriated for FNIH
an aggregate $500,000 for each fiscal year. [PHSA 499(c)(1)(C); 42 USC 290b(c)(1)(C)]
The FNIH provision related to drugs that the Secretary had referred Regarding a drug with an unexpired patent for which the Secretary
for listing as needing pediatric studies. These included drugs with an requested pediatric pharmacologic research and studies that the sponsor
approved or submitted application under FFDCA 505(j) [generic drugs], declined, the Secretary must first determine whether FNIH has sufficient
drugs without patent protection or marketing exclusivity, or drugs with funds to initiate and fund in its entirety. If there are sufficient funds, the
patent protection whose sponsors declined the Secretary’s requests for Secretary must then refer the study to the FNIH. If there are insufficient
study. FNIH was to issue a proposal to award a grant to conduct such funds, the Secretary must consider whether to require the pediatric
studies unless FNIH certified to the Secretary that FNIH did not have assessments under FFDCA 505B(b) (PREA). [FDAAA 502(c); PHSA
available funds, in which case the Secretary was required to refer the 499(c)(1)(C); 42 USC 290b(c)(1)(C)]
iki/CRS-RL34465drug for inclusion on the list established under PHSA 409I. [PHSA
g/w499(c)(1)(C) referred to PHSA 409I(a)(1)(A) and FFDCA
s.or505A(d)(4)(C), each of which FDAAA has amended as well.]
leakThe law continues to require that the Secretary convene and consult an advisory committee on pediatric pharmacology. It specifies the committee Advisory Committee on
composition, and requires that the committee advise and make recommendations to the Secretary, through the Commissioner and in consultation Pediatric Pharmacology
://wikiwith the NIH Director, on matters relating to pediatric pharmacology. Specifies that the matters include pediatric research; identification of
httpresearch priorities related to pediatric pharmacology and the need for additional treatments of specific pediatric diseases or conditions; and the ethics, design, and analysis of clinical trials related to pediatric pharmacology. [Section 14 of the Best Pharmaceuticals for Children Act; 42 USC
284m note]
FDAAA extends the advisory committee for another five years.
[FDAAA 502(d); Section 14 of the Best Pharmaceuticals for Children
Act; 42 USC 284m note]




Topic Previous Law FDAAA Title V, Sections 502(b-f) and 503
The law continues the Pediatric Subcommittee of the Oncologic Drugs Advisory Committee. [Section 15 of the Best Pharmaceuticals for Children Pediatric Subcommittee of
Act; 42 USC 284m note] the Oncologic Drugs
Advisory Committee FDAAA requires that the Subcommittee provide recommendations to
the internal review committee created under FFDCA 505B(f) regarding
implementation of the Pediatric Research Equity Amendments and the
Best Pharmaceuticals for Children amendments to FFDCA sections
505A and 505B with respect to the treatment of pediatric cancers.
FDAAA also extends operations of the subcommittee for five years; and
updates, to January 31, 2009, the requirement for the Secretary’s report
to congressional committees on patient access to new therapeutic
agents for pediatric cancer, including access to single patient use of new
therapeutic agents. [FDAAA 502(e); Section 15 of the Best
Pharmaceuticals for Children Act; 42 USC 284m note]
Toll-Free Number for This provision is not in previous law; it refers to a proposed rule (69 FR Requires that the rule proposed by the Commissioner on April 22,
Consumer Reports of 21778, April 22, 2004). 2004, take effect on January 1, 2008, unless the Commissioner issues the
Adverse Events final rule before that date. Excluded from the rule’s application are a
iki/CRS-RL34465drug approved under FFDCA Section 505, a nonprescription drug, and a drug whose packaging includes a toll-free number with which to report
g/wadverse events to the manufacturer or distributor. [FDAAA 502(f)]
s.or
leakIn order to ensure the future supply of researchers dedicated to the care and research needs of children, the Director of the Institute, after consultation with the Administrator of the Health Resources and Services Administration, shall support activities to provide for: an increase in the Investment in Tomorrow’s Pediatric
://wikinumber and size of institutional training grants to institutions supporting pediatric training; and an increase in the number of career development awards for health professionals who intend to build careers in pediatric basic and clinical research. [PHSA 452G(2); 42 USC 285g-10(a)(2)] Researchers
http
FDAAA inserts “..., including pediatric pharmacological research.”
[FDAAA 503(a); PHSA 452G(2); 42 USC 285g-10(a)(2)]
The law authorized to be appropriated such sums as may be necessary FDAAA does not have an authorization of appropriations provision for
for each of FY2001 through FY2005. this subsection.
The law authorizes the Secretary, in consultation with the Director of NIH, to establish a pediatric research loan repayment program. Through Loan Repayment for
such program, the Secretary shall enter into contracts with qualified health professionals who agree to conduct pediatric research, in exchange for Pediatric Research
the Federal Government repayment of certain principal and interest of the educational loans of such professionals. The law also addresses
reimbursements for tax liability; and the application of other loan repayment provisions. [PHSA 487F(a)(1); 42 USC 288-6(a)(1)]
FDAAA inserts after “pediatric research”: “including pediatric
pharmacological research.” [FDAAA 503(b); PHSA 487F(a)(1); 42 USC
288-6(a)(1)]






Title VI of FDAAA adds new FFDCA Sections 770, 771, and 772 requiring the establishment of
the Reagan-Udall Foundation for the Food and Drug Administration (the Foundation), a nonprofit
corporation to advance FDA’s mission regarding product development, innovation, and safety.
The initial Board of Directors (the Commissioner, and the directors of NIH, CDC, and AHRQ) is
to select the appointed members from a National Academy of Sciences-provided candidate list
and then resign from the board. The ongoing board is to include representatives from industry,
academic research organizations, government agencies, patient or consumer advocacy
organizations, and health care providers.
FDAAA directs the Foundation to 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. Title VI directs the Commissioner to
transfer between $500,000 and $1,250,000 to the Foundation from FDA appropriations each year.
FDAAA added a new FFDCA Section 910 that requires 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.
A new FFDCA Section 566 authorizes the Secretary, through the Commissioner, to enter into
collaborative agreements (Critical Path Public-Private Partnerships) with eligible educational or
tax-exempt organizations to implement the FDA Critical Path Initiative. The agreements are to
develop 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.
The provision specifies the expertise and experience required of a partner entity. It requires the
Secretary to submit an annual report to the authorizing congressional committees, and authorizes
to be appropriated $5 million for FY2008 and such sums as may be necessary for each of FY2009
through FY2012.




Table 9. Law Created by Reagan-Udall Foundation (FDAAA Title VI)
Topic FDAAA Title VI
FDAAA establishes a nonprofit corporation to be known as the Reagan-Udall Foundation for the Food and Drug Administration (The Foundation), to Reagan-Udall
advance the mission of the FDA to modernize medical, veterinary, food, food ingredient, and cosmetic product development, accelerate innovation, and Foundation for the
enhance product safety. The law lists the duties of the Foundation, criteria for formation, conduct duties, terms and administrative powers of the Board FDA
of Directors, and the Executive Director. The duties of the Foundation are to include “taking into consideration the Critical Path reports and priorities
published by the Food and Drug Administration, identify unmet needs in the development, manufacture, and evaluation of the safety and effectiveness,
including postapproval, of devices, including diagnostics, biologics, and drugs, and the safety of food, food ingredients, and cosmetics, including the
incorporation of more sensitive and predictive tools and devices to measure safety.”
The law stipulates the roles of federal employees involved in the Foundation’s functions. The ex officio members of the Board shall serve as
incorporators and shall take whatever actions necessary to incorporate the Foundation. The Foundation shall be considered a corporation under
Section 501(c) of the Internal Revenue Code of 1986, and shall be subject to the provisions of such section. The Executive Director may solicit and
accept on behalf of the Foundation, any funds, gifts, grants, devises, or bequests of real or personal property, including from private entities, for the
purposes of carrying out the duties of the Foundation. The Executive Director shall ensure that the funds received from the U.S. Treasury are held in
separate accounts from funds received from other sources.
To carry out certain provisions in this subtitle, from amounts appropriated to the FDA for each fiscal year, the Commissioner shall transfer to the
iki/CRS-RL34465Foundation not less than $500,000 and not more than $1,250,000.
g/wRecipients of grants, contracts, fellowships, memoranda of understanding, or cooperative agreements from the Foundation shall report to the
s.orFoundation regarding their activities on an annual basis. Beginning with FY2009, the Executive Director shall submit to Congress and the Commissioner
leakan annual report on the Foundation’s activities. [FDAAA 601; FFDCA 770; 21 USC 379dd]
://wikiThe Foundation shall, if practicable, be located not more than 20 miles from the District of Columbia. [FDAAA 601; FFDCA 771; 21 USC 379dd-1]
httpThe Commissioner shall receive and assess the required annual reports concerning the Foundation; and, beginning with FY2009, submit to Congress an
annual report summarizing the information provided by the Foundation, and other required information. The provisions of this subchapter shall have no
effect on any grant, contract, memorandum of understanding, or cooperative agreement between the FDA and any other entity entered into before, on,
or after the date of enactment. 742(b) of the FFDCA (21 USC 379l(b)) is amended by adding at the end the following: “Any such fellowships and training
programs under this section or under Section 770(d)(2)(A)(ix) may include provision by such scientists and physicians of services on a voluntary and
uncompensated basis, as the Secretary determines appropriate. Such scientists and physicians shall be subject to all legal and ethical requirements
otherwise applicable to officers or employees of the Department of Health and Human Services.” [FDAAA 601; FFDCA 772; 21 USC 379dd-2]
Office of the Chief A new section in FFDCA requires the Secretary to create an Office of the Chief Scientist within FDA’s Office of the Commissioner. (Duties specified).
Scientist [FDAAA 602; FFDCA 910; 21 USC 399a]
Critical Path Public-FDAAA authorizes the Secretary, acting through the Commissioner, to enter into collaborative agreements (Critical Path Public-Private Partnerships)
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 FY2009
through FY2012. [FDAAA 603; FFDCA 566; 21 USC 360bbb-5]






Title VII of FDAAA, Conflicts of Interest, contains provisions that revise FDA’s approach to
advisory committee members’ 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 FDA must eliminate or reduce conflicts of interest in its committees. 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 reported that FDA advisory committees are biased in favor of drug approval, 21
and that many committee members have conflicts of interest.
For further information, see CRS Report RS22691, FDA Advisory Committee Conflict of Interest, by Erin D. Williams.


Prior to the passage of FDAAA, the law generally required that committee members be free from
conflicts of interest, but allowed for exceptions to that rule under specific circumstances. A
conflict of interest might have required a potential committee member to disclose the conflict,
refrain from voting, and/or not participate in a committee, depending on the nature of the conflict.
The law was articulated primarily in three locations: (1) the Federal Advisory Committee Act (5
USC Appendix; FACA); (2) the FDA advisory committee policy (21 USC 355(n)), which applied
only to trials of drugs and biologics—not devices; and (3) a law governing special government
employees—such as advisory committee members—Acts Affecting Personal Financial Interest
(18 USC 208).
FDAAA inserts a new provision into Chapter VII, Subchapter A, of the FFDCA, effective
October 1, 2007. The provision changes 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 repeal 21USC 355(n), but move much of its
substance to a new location; the effect is that the requirements previously only applicable to drug
and biologic advisory committees apply to committees providing advice on all types of products
that FDA regulates.
FDAAA defines an advisory committee as a FACA-covered entity that provides the Secretary
with advice and recommendations regarding activities of the FDA, and defines financial interest
as defined under 18 USC 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.
FDAAA requires advisory committee member recruitment mechanisms to be focused on reaching
experts from areas such as academia, medical research institutions, and public interest and
21
See, for example, Shankar Vedantam, “Group Says FDA, Advisory Panels Show Bias Toward Drug Approvals,
Washington Post, August 9, 2006, available online at http://www.washingtonpost.com/wp-dyn/content/article/2006/08/
28/AR2006082800984.html.



consumer groups. It also discourages the number of permissible exceptions to the financial
conflict rules, such as the use of waivers or written certifications.
FDAAA requires advisory committee members’ full financial disclosure prior to a meeting on a
related matter. It precludes participation by a member with a conflict of interest unless exempted
by the Office of Government Ethics. The Act also allows a waiver of the voting restriction if
necessary to provide the committee with essential expertise.
FDAAA restricts the percentage of committees’ membership that may consist of people who have
received one of three types of exceptions to the financial conflict prohibitions: (1) waivers
granted by the Secretary under newly created FDAAA provisions, (2) written determinations
under 18 USC 208(b)(1), and (3) written certifications under 208(b)(3). The Secretary is required
to determine the number and proportion of advisory members who received exceptions in
FY2007. For FY2008 through FY2012, the Secretary must reduce the proportion of excepted
members by an additional 5% per year from the FY2007 number. This limitation does not apply
to financial interest exemptions made under 18 USC 208(b)(2).
FDAAA requires public disclosures for conflict-of-interest determinations, certifications, and
waivers (but not 208(b)(2) exemptions), except for those exempted from disclosure under the
Freedom of Information Act of 1974 (5 USC 522). It requires the Secretary to submit annual
reports regarding advisory committee membership and conflict-of-interest waivers. It also
requires the Secretary to review and update FDA conflict-of-interest guidance not less than once
every five years.




Table 10. Comparison of Conflicts of Interest (FDAAA Title VII) with Previous Law
Topic Previous Law FDAAA Title VII
Advisory FDA advisory committee policy applied only to FDA policy applies to all Federal Advisory Committee Act (FACA) committees that provides advice or
Committee drug and biologic advisory committees. [21 USC recommendations to the Secretary regarding the FDA. [FDAAA 701(a); FFDCA 712(a)(1); 21 USC 371 et
355(n)] seq.]
Financial [A committee member who] participates personally and substantially as a government officer or employee, through decision, approval, disapproval,
Interest recommendation, the rendering of advice, investigation, or otherwise, in a judicial or other proceeding, application, request for a ruling or other
determination, contract, claim, controversy, charge, accusation, arrest, or other particular matter in which, to his knowledge, he, his spouse, minor child,
general partner, organization in which he is serving as officer, director, trustee, general partner or employee, or any person or organization with whom
he is negotiating or has any arrangement concerning prospective employment, has a financial interest. (Defined in 18 USC 208(a)) [Notes: The scope of
disqualifying financial interests under 18 USC 208(a) have been interpreted to include any potential for gain or loss to the employee, which would include
interests such as stock ownership according to 5 C.F.R. 2640.103(b). Exemptions and waivers in 18 USC 208(b) apply. Penalties in 18 USC 216 apply.]
[FDAAA 701(a); FFDCA 712(a)(2); 21 USC 371 et seq.]
The Commissioner is required to publish one or more notices in the Federal Register each year requesting nominations for voting members. [21 CFR 14.82] Recruitment
In addition to publications in the Federal Register, the Secretary is required to develop and implement
iki/CRS-RL34465strategies on effective outreach to potential members of advisory committees at universities, colleges,
g/wother academic research centers, professional and medical societies, and patient and consumer groups. The Secretary shall seek input from professional medical and scientific societies to determine the most
s.oreffective informational and recruitment activities. The Secretary shall also take into account the advisory
leakcommittees with the greatest number of vacancies. [FDAAA 701(a); FFDCA 712(b)(1); 21 USC 371 et
seq.]
://wiki
httpEvaluation and Criteria No provision. When considering a term appointment to an advisory committee, the Secretary shall review the expertise of the individual and the financial disclosure report filed by the individual pursuant to the Ethics in
Government Act of 1978 for each individual under consideration for the appointment, so as to reduce
the likelihood that an appointed individual will later require an exemption or waiver under 18 USC
208(b). [FDAAA 701(a); FFDCA 712(b)(2); 21 USC 371 et seq.]
Disclosure of Each member of a drug or biologic advisory Prior to a meeting of an advisory committee, each member of the committee shall disclose to the
Financial committee had to publicly disclose all conflicts of Secretary financial interests in accordance with subsection 18 USC 208(b). [FDAAA 701(a); FFDCA
Interests interest that he or she may have with the work 712(c)(1); 21 USC 371 et seq.]


to be undertaken by the panel. [21 U.S.C. 355(n)]


Topic Previous Law FDAAA Title VII
18 USC 208, which remains in effect, allows criminal penalties to be imposed on any person participating in an advisory committee who has conflicts based on Prohibitions In
certain financial interests, such as current or future employment, or on a directorship role in an organization. The scope of these disqualifying financial General
interests has been interpreted broadly in regulation to include any potential for gain or loss to the employee. [5 C.F.R. 2640.103(b)]
An advisory committee member may not participate with respect to any matter considered by the
advisory committee if such member (or an immediate family member of such member) has a financial
interest that could be affected by the advice given to the Secretary with respect to such matter, excluding
interests exempted in regulations issued by the Director of the Office of Government Ethics as too
remote or inconsequential to affect the integrity of the services of the government officers or employees
to which such regulations apply. [FDAAA 701(a); FFDCA 712(c)(2)(A); 21 USC 371 et seq.]
21 USC 208(b), which remains in effect, provides for four exceptions to the general prohibition on acts affecting a personal financial interest: (1) a written Waivers and
determination that the interest is not substantial, (2) an exemption because the interest is too remote, (3) a certification that the need for the individual’s Exemptions
services outweighs the potential for a conflict, and (4) certain exemptions if the conflict relates to one’s Indian or Native Alaskan status.
A committee may confer with any person who The Secretary may grant a waiver of the FDAAA-created prohibition to allow a non-voting or voting
may have information or views relevant to any member to participate if such waiver is necessary to afford the advisory committee essential expertise.
matter pending before the committee. [21 CFR [FDAAA 701(a); FFDCA 712(c)(2)(B); 21 USC 371 et seq.]
14.31(a)]
iki/CRS-RL34465
g/wWaiver Limitations No provision. Limitations are placed on three types of exceptions to the financial conflict prohibitions: (1) waivers granted by the Secretary under newly created FDAAA provisions, (2) written determinations under 18
s.orUSC 208(b), and (3) written certifications under 208(b)(3). For FY2007, the Secretary is required to
leakdetermine the number and proportion of advisory members who received exceptions, and limit the total
number of exceptions to the following proportions of the FY2007 number: 95% for FY2008, 90% for
://wikiFY2009, 85% for FY2010, 80% for FY2011, and 75% for FY2012. [FDAAA 701(a); FFDCA 712(c)(2)(C);
http21 USC 371 et seq.]
Disclosure of No provision. For waivers granted under the terms of FDAAA or under 18 USC 208(b)(1) or (3), the Secretary is to
Waiver disclose on the FDA website the type, nature, and magnitude of the pertinent financial interests and the
reasons for the Secretary’s action. The disclosure should not include information that is not subject to a
Freedom of Information Act request. The Secretary is required to make the disclosure not less than 15
days prior to an advisory committee meeting, or, in the event that the financial interests became known
to the Secretary less than 30 days prior to the meeting, no later than the date of the meeting. Disclosures
are to be included in the public record and transcript of each meeting. [FDAAA 701(a); FFDCA
712(c)(3),(d); 21 USC 371 et seq.]
Annual Report No provision. The Secretary is to submit annual reports to relevant congressional committees describing advisory
committee vacancies, nominees, and the number of nominees willing to serve; the number of conflict-
related disclosures per meeting and the percentage of members who did not require such disclosures; the
number of times required disclosures occurred less than 30 days in advance of meetings; and how the
Secretary plans to reduce the number of vacancies on advisory committees and increase the number of
nominations, including those of academicians or practitioners. [FDAAA 701(a); FFDCA 712(e); 21 USC
371 et seq.]




Topic Previous Law FDAAA Title VII
Guidance The Secretary is to review and update FDA conflict of interest guidance not less than once every five
Review years. [FDAAA 701(a); FFDCA 712(f); 21 USC 371 et seq.]
Conforming 21 USC 355(n) applied conflicts provisions only Provisions that were in 21 USC 355(n) are moved to FFDCA Title VII, subchapter A [21 USC 371], as
Amendment to committees focused on drugs and biologics. modified, so that they apply to all FDA FACA advisory committees. [FDAAA 701(b); FFDCA 505(n); 21
USC 355(n)]
Effective Date No provision. October 1, 2007. [FDAAA 701(a); 21 USC 355 note]


iki/CRS-RL34465
g/w
s.or
leak
://wiki
http




Title VIII of FDAAA, Clinical Trial Databases, expands requirements for the registration of
clinical trials, and adds requirements for the publication of their results. The text of the title was
arrived at after extensive discussions, which required an understanding of the nature of scientific
inquiry and medical product development.
Scientific inquiry is, at its best, an objective exercise in which results are not pre-ordained, and all
valid findings are published. Medical product development depends upon traditional scientific
methods, and product sponsors are typically business enterprises. Prior to marketing, product
sponsors are required to demonstrate the safety and effectiveness of their products, typically
through clinical trials. However, both sponsors and medical journals may be reluctant to publish
the results of trials that fail to show that products perform better than a placebo, or that raise too
many safety concerns. In 2004, Congress and others raised questions about the safety and
effectiveness of several FDA-approved products (e.g., antidepressants, anti-inflammatory drugs, 22
and cardiac stents) about which unfavorable trial results had not been publicly disclosed. The
issue of public access to all trial results, regardless of their findings, then gained significant
traction.
For further information, see CRS Report RL32832, Clinical Trials Reporting and Publication, by Erin D. Williams.


Prior to the enactment of FDAAA, clinical trial registration was required at the outset of certain
clinical trials testing drugs to treat life-threatening diseases or conditions. This requirement was
criticized because it did not mandate the registration of a broader range of trials, because it
contained no enforcement mechanism, and because it did not require the posting of trial results.
Title VIII of FDAAA contains provisions related to all three criticisms.
FDAAA’s provisions apply to trials involving not only drugs, but also devices and biologics. The
Act includes requirements pertaining to most clinical trials beyond Phase I. In general, FDAAA
requires that specified information be submitted by the trial’s responsible party (RP; usually the
trial sponsor), to the NIH Director. Following submission, the NIH Director is to make the
information publicly available via the Internet, with specified exceptions. Enforcement
mechanisms are provided for noncompliant RPs. For the purpose of carrying out the clinical trials
database provisions, FDAAA authorizes $10,000,000 for each fiscal year. Further details of the
way that FDAAA amends current law are discussed below, in subsections entitled Registry;
Results; Coordination, Compliance, and Enforcement; and Other Items.
FDAAA requires the expansion of the existing data bank (clinicaltrials.gov, which is hosted by
the National Library of Medicine) to include the registration of applicable drug, device, and
biologics trials as described above. Submissions for the registry are to include four types of
material: descriptive information about the trial, recruitment information for potential subjects,
22
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.



trial location and contact information, and administrative data, such as protocol identification
numbers. The information required by FDAAA includes and expands upon that required under
previous law, as well as elements of the World Health Organization’s International Clinical Trials 23
Registry Platform registration data set. The Secretary may modify these requirements by
regulation.
In making the information public, the NIH Director is to ensure that it is searchable in a number
of specified ways. The Director is also to ensure that the registry is easily used by the public, and
that entries may be easily compared.
FDAAA generally requires the RP to submit information to the NIH Director within 21 days after
the first patient is enrolled in the trial. This requirement is similar to the one that existed
previously. The NIH Director is required to post information about drug and biologics trials not
later than 30 days after the information is submitted by the RP. In contrast, for device trials,
information is to be posted not earlier than the date of FDA approval or clearance, and not later
than 30 days after approval or clearance.
The RP for an applicable clinical trial is required to submit updates to the NIH Director to reflect
changes to registry information. The Director is to make the update information publicly available
and generally ensure that previously submitted information remains accessible.
Previous law allowed for the inclusion of results information with the consent of the trial sponsor,
but did not require it. FDAAA requires the Secretary, acting through the NIH Director, to expand
the registry to include results of applicable clinical trials and to ensure that the results are made
publicly available via the Internet. Three categories of results information are to be added
according to the following timeframe. First, beginning 90 days after FDAAA enactment, the
Secretary is to ensure that the registry contains links to specified existing results. Second, within
one year after FDAAA enactment, the Secretary, acting through the NIH Director, is to expand
the registry to include specified basic results. Third, within three years after FDAAA enactment,
the Secretary is to add information to create an expanded registry and results data bank by
rulemaking.
The first type of results to be made available in the registry, existing results, consists of links to
existing FDA and NIH documentation. These results must be posted for clinical trials that form
the primary basis of an efficacy claim or are conducted after product approval or clearance. Links
to this information are to be posted not earlier than 30 days after the approval or clearance of the
product, or not later than 30 days after the information becomes publicly available.
The second type of results to be made available in the registry, basic results, consists of
demographic, outcome, and scientific point of contact information, as well as agreements that
restrict the principal investigator (PI) to publicly discuss or publish results. These results must be
submitted for products that FDA has approved, licensed, or cleared. The RP is to submit basic
23
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.





results information to the Secretary within one year following the earlier of the estimated or
actual completion date of the trial, with certain exceptions.
The third type of results information, expanded registry and results, is to be submitted to and
made available in the registry pursuant to rulemaking. Rulemaking is to occur within three years
of FDAAA enactment. Rulemaking is to require the submission of clinical trial information for
approved or cleared products, and is to determine whether results information for unapproved
products should be included as well. The expanded registry and results database is to include
basic results, as well as: (1) a non-technical summary of results; (2) a technical summary of
results; (3) protocol information; and (4) such other categories the Secretary determines are
appropriate.
FDAAA directs the Secretary to promulgate a second set of regulations regarding adverse event
reporting. Not later than 18 months after FDAAA enactment, the Secretary is to determine the
best method for including appropriate information on serious and frequent adverse events in the
registry and results database. If the Secretary fails to take action within 24 months after FDAAA
enactment, the Secretary must include specified adverse-event related elements in the registry and
results database. As amended by P.L. 110-316, FDAAA’s adverse event reporting requirements
apply to drugs, biologics, and medical devices. The House passed a measure that would expand it 24
to devices as well.
An RP may voluntarily submit information about trials that are not required for submission if the
RP has made submissions for all required trials. If necessary to protect public health, the
Secretary may require the submission of additional registry and results information.
The former registry law did not contain any specific compliance or enforcement measures. By
contrast, FDAAA contains four sets of enforcement and compliance requirements, and specifies
civil penalties for noncompliance. One set attaches to federal grant funding. A second set of
compliance requirements must be met when submitting a drug, biological product, or device
submission to the FDA. A third set of FDAAA requirements specifies that clinical trial
information submitted by the RP must be truthful and not misleading in any particular. Under a
fourth set of requirements, the NIH Director is to include a notification in the database if an RP
fails to submit required clinical trials registry or results information.
Previous law did not specify penalties or enforcement mechanisms related to registry
requirements. Previous law contained general mechanisms for enforcing compliance with FDA
requirements that may have been applicable, but which FDA never used for registry requirement
violations. FDAAA amends the prohibited acts section of the FFDCA, to clarify that the clinical
trial databases provisions are enforceable. FDAAA also amends the FFDCA’s civil monetary
penalty provisions, articulating those for noncompliance with the clinical trial database
requirements.
24
H.Con.Res. 217





FDAAA contains a few additional provisions pertaining to informed consent, state clinical trial
databases, and FFDCA violations. It requires the Secretary to update investigational new drug
regulations so that informed consent includes a statement that clinical trial information has been
or will be submitted for inclusion in the registry databank. Previous law contained informed
consent requirements, but none specific to the registry.
The Act prohibits any state or political subdivision from requiring the registration of clinical trials
or their results in a database. It also specifies that the fact of submission of off-label use clinical
trial information, if in compliance with revised registry and results database requirements, is not
to be construed as evidence of a new intended use. In addition, the availability of compliant
database submissions is not to be considered as labeling, adulteration, or misbranding under the
FFDCA.




Table 11. Comparison of Clinical Trial Databases (FDAAA Title VIII) with Previous Law
Topic Previous Law FDAAA Title VIII
Types of Trials Requirements applied to drug trials only. Requirements apply to applicable trials of drugs, devices, and biologics. [FDAAA
801(a)(2); PHSA 402(j)(1)(A)(i)-(iii); 42 USC 282(j)]
Applicable Drug and Applicable drug trials are: (1) investigational new drug Applicable drug and biologics trials are controlled clinical investigations, other than Phase
Biologic Trials (trials for trials (whether federally or privately funded) of I clinical investigations, of a drug subject to FFDCA 505 or PHSA 351. [FDAAA 801(a)(2);
which registration and, in experimental treatments for serious or life-threatening PHSA 402(j)(1)(A)(iii); 42 USC 282(j)]
some cases, results diseases and conditions under regulations promulgated [Clinical investigations is defined as in 21 CFR 312.3 or successor regulations: any
reporting is required) pursuant to section 21 USC 355(i) [re: investigational experiment in which a drug is administered or dispensed to, or used involving, one or
new drugs]; or (2) treatment use of investigational more human subjects. For the purposes of this part, an experiment is any use of a drug
new drugs: information pertaining to experimental except for the use of a marketed drug in the course of medical practice.
treatments for serious or life-threatening diseases and
conditions that may be available - (i) under a treatment Phase I is defined as in 21 CFR 312.21or any successor regulation: the initial introduction
investigational new drug application that has been of an investigational new drug into humans. Phase 1 studies are typically closely
submitted to the Secretary under 21 USC 360bbb(c); monitored and may be conducted in patients or normal volunteer subjects.]
or (ii) as a Group C cancer drug (as defined by the
iki/CRS-RL34465National Cancer Institute). Trials of biologics are not applicable.
g/w
s.orApplicable Device Trials None. Applicable device trials are prospective clinical studies of health outcomes comparing an
leak(trials for which intervention with a device subject to FFDCA 510(k) [re device clearance], 515 [re:
registration and, in some premarket approval of devices], or 520(m) [re: humanitarian devices] against a control in
://wikicases, results reporting is required) human subjects (other than a small clinical trial to determine the feasibility of a device, or a clinical trial to test prototype devices where the primary outcome measure relates to
httpfeasibility and not to health outcomes); and pediatric postmarket surveillance as required
under FFDCA 522 [as amended by the PMDSIA provisions of FDAAA]. [FDAAA
801(a)(2); PHSA 402(j)(1)(A)(ii); 42 USC 282(j)]
Responsible Party (RP; The sponsor is to submit required information. The RP is the sponsor, as defined by 21 CFR 50.3 [a person who initiates a clinical
the person required to investigation, but who does not actually conduct the investigation...]. The RP may be the
submit information) PI if designated by sponsor, grantee, contractor, or awardee, so long as the PI is
responsible for conducting the trial, has access to and control over data, has the right to
publish trial results, and has the authority to meet the RP responsibilities. [FDAAA
801(a)(2); PHSA 402(j)(1)(A)(ix); 42 USC 282(j)]
Who Receives the Required information is to be submitted to the NIH Director. [FDAAA 801(a)(2); PHSA 402(j)(2)(C),(D)(iv); 42 USC 282(j)]
Information
Public Access The Secretary is to disseminate via information The NIH Director shall ensure clinical trial information is made publicly available through
systems, which were to include toll-free telephone the Internet, and in a manner easily used by the public and with entries that are easily
communications compared. [FDAAA 801(a)(2); PHSA 402(j)(2)(A)(i),(3)(B)(ii),(G); 42 USC 282(j)]




Topic Previous Law FDAAA Title VIII
Content of Registry Submissions are to include the trial purpose, eligibility The registry submission is to include: (1) descriptive information (title, summary, purpose,
Submission criteria, location(s) of trial, enrollment point of outcome measures, etc.); (2) recruitment information (eligibility criteria, gender, age
contact, description of whether and how the limits, etc.); (3) location and contact information (sponsor name, RP, facility information,
manufacturer or sponsor will respond to requests for etc.); and (4) administrative data (protocol identification numbers, FDA IND/IDE protocol
protocol exception, with appropriate safeguards, for number, etc.). (Note: FDAAA submission requirements are worded differently than
single-patient and expanded protocol use of the new under previous law, but include all elements that were required under previous law.)
drug, particularly in children. With sponsor consent, [FDAAA 801(a)(2); PHSA 402(j)(2)(A)(ii); 42 USC 282(j)]
submissions may include the results of trials, potential The Secretary may modify these requirements by regulation, if the Secretary provides a
toxicities, or adverse effects. rationale as to why the modification improves and does not reduce the information.
[FDAAA 801(a)(2); PHSA 402(j)(2)(A)(iii); 42 USC 282(j)]
Note: the Secretary is not required to post information otherwise protected under 5
USC 552. [FDAAA 801(a)(2); PHSA 402(j)(6); 42 USC 282(j)]
Registry Searchable Not specified. The NIH Director is to ensure that it is searchable by keyword, the disease or condition
Categories being studied, the name of the intervention, the location of the trial, the age group being
studied, and the trial phase, sponsor, recruitment status, and identification number(s). An
additional category is to be added within 18 months of FDAAA enactment—safety issue
iki/CRS-RL34465being studied as a primary or secondary outcome. The Director is to make the registry
g/wsearchable by other elements that the Director deems necessary. [FDAAA 801(a)(2);
s.orPHSA 402(j)(2)(B)(i); 42 USC 282(j)]
leakTiming of Submission to Required information is to be submitted not later than For trials initiated or ongoing 90 days after FDAAA enactment, the RP is to submit
Registry 21 days after the approval of the protocol. required information not later than the later of: (1) 90 days after FDAAA enactment; (2)
://wiki21 days after the first patient is enrolled in the trial; or (3) for trials that are not for
httpserious or life-threatening diseases or conditions that are ongoing as of the date of
enactment, one year after the date of enactment. [FDAAA 801(a)(2); PHSA 402(j)(2)(C);
42 USC 282(j)]
Timing of Registry Posting No provision. The NIH Director is required to post information about drug and biologics trials not later
than 30 days after the information is submitted by the RP. For device trials, information is
to be posted not earlier than the date of clearance under FFDCA 510(k), or approval
under FFDCA 515 or 520(m), and not later than 30 days after approval or clearance.
Beginning one year after enactment, for devices previously cleared or approved, registry
information is to be posted not later than 30 days after the date that clinical trial results
information is required to be posted by the Secretary. [FDAAA 801(a)(2); PHSA
402(j)(2)(D); 42 USC 282(j)]
Glossary No provision. The Secretary, acting through the NIH Director, shall ensure that a glossary of technical
terms is publicly posted. [FDAAA 801(a)(2); PHSA 402(j)(3)(B)(iii); 42 USC 282(j)]




Topic Previous Law FDAAA Title VIII
Content of Results With sponsor consent, the registry may include There are three different categories of results information:
Postings information about the results of included trials, -Existing results include: (1) FDA Information (pertinent advisory committee
including potential toxicities or adverse effects. documentation, FDA results assessments, FDA public health advisories, etc.); and (2) NIH
Information (pertinent Medline citations and NLM product label entries). The Secretary
may also provide links to the above types of results information for trials submitted to
the data bank prior to FDAAA’s enactment. [FDAAA 801(a)(2); PHSA 402(j)(3)(A)(ii); 42
USC 282(j)]
-Basic results include: (1) demographic and baseline characteristics of the patient sample;
(2) primary and secondary outcomes (which the NIH Director is to link to outcome
measure information submitted with registration); (3) point of contact for scientific
information and results; and (4) any agreements between the sponsor and PI that restrict
the ability of the PI to publicly discuss or publish results in a scientific or academic journal.
[FDAAA 801(a)(2); PHSA 402(j)(3)(C); 42 USC 282(j)]
-Expanded registry and results include basic results, as well as: (1) a non-tecnhical summary
of results; (2) a technical summary of results; (3) protocol information; (4) such other
categories the Secretary determines are appropriate. [FDAAA 801(a)(2); PHSA
iki/CRS-RL34465402(j)(3)(D)(iii); 42 USC 282(j)]
g/w-The Secretary is not required to post information otherwise protected under 5 USC
s.or552. [FDAAA 801(a)(2); PHSA 402(j)(6); 42 USC 282(j)]
leak
Risk Communication No provision. The Secretary, acting through the NIH Director, shall ensure that information created in
://wikiconsultation with risk communication experts is to be provided to help ensure that the specified basic results in the database do not mislead patients or the public. [FDAAA
http801(a)(2); PHSA 402(j)(3)(B)(iii); 42 USC 282(j)]




Topic Previous Law FDAAA Title VIII
Trials For Which Results Trials that have sponsor consent for posting of results. -Existing results are to be posted for trials submitted after the enactment of FDAAA that
Are To Be Posted form the primary basis of an efficacy claim or are conducted after the drug or biologics is
approved or after the device is cleared or approved for which the specified information is
publicly available. [FDAAA 801(a)(2); PHSA 402(j)(3)(A)(i); 42 USC 282(j)]
-Basic results are to be posted for drugs that are approved under FFDCA 505, biologics
licenced under PHSA 351, and devices cleared under 510(k) or approved under 515 or
520(m). [FDAAA 801(a)(2); PHSA 402(j)(3)(C); 42 USC 282(j)]
-Expanded registry and results are to include information for each applicable clinical trial for
drugs that are approved under FFDCA 505, biologics licenced under PHSA 351, and
devices cleared under 510(k) or approved under 515 or 520(m). Rulemaking is to
establish whether information shall also be required for applicable clinical trials for drugs
not approved under FFDCA 505, biologics not licenced under PHSA 351, and devices not
cleared under 510(k) or not approved under 515 or 520(m) (whether approval, licensure,
or approval was sought). [FDAAA 801(a)(2); PHSA 402(j)(3)(D)(ii); 42 USC 282(j)]
-Additional submissions may be made voluntarily if an RP has made submissions for all
required trials. Additional submissions may also be required by the Secretary if necessary
iki/CRS-RL34465to protect the public health. [FDAAA 801(a)(2); PHSA 402(j)(4); 42 USC 282(j)]
g/wTiming of Results Not specified. -Existing results information is publicly available and does not require submission by the
s.orSubmission RP.
leak
-Basic results are to be submitted not later than one year following the earlier of the
://wikiestimated or actual completion date of the trial. This time period may be expanded to 18 months via expanded registry or results-related rulemaking. This time period may be
httpdelayed for up to two years with the submission of a certificate that approval of a new
use is being sought. If a manufacturer makes such a certification, it must make equal
certifications for all required trials for a given application. The Secretary may grant a
waiver to results submission if extraordinary circumstances justify it, as long as it is
consistent with public health or national security. The Secretary may grant an extension if
the RP makes a written request demonstrating good cause. If an extension is granted, the
Secretary must notify the NIH Director within 30 days.
-Expanded registry and results are to be submitted pursuant to rulemaking according to the
same timeline as basic results. [FDAAA 801(a)(2); PHSA 402(j)(3)(D)(iv); 42 USC 282(j)]
-If necessary to protect public health, the Secretary may require the submission of registry
and results for a specified clinical trial information within 30 days of notice to the RP.
[FDAAA 801(a)(2); PHSA 402(j)(4)(B); 42 USC 282(j)]




Topic Previous Law FDAAA Title VIII
Timing of Results Posting Not specified. -Existing results links are to be provided beginning not later than 90 days after FDAAA
enactment, and not earlier than 30 days after the approval or clearance of the product, or
not later than 30 days after the information becomes publicly available. [FDAAA
801(a)(2); PHSA 402(j)(3)(A)(i); 42 USC 282(j)]
-Basic results are to be posted beginning not later than one year after FDAAA enactment
and not later than 30 days after submission.
-Expanded registry and results are to be posted not later than 30 days following submission,
pursuant to rulemaking. [FDAAA 801(a)(2); PHSA 402(j)(3)(C),(D),(G); 42 USC 282(j)]
Expanded Registry and Not applicable. In addition to the points specified above, required rulemaking regarding the expanded
Results Rulemaking registry and results database is to: (1) determine whether the time period for submission
of results should be increased from one year to 18 months; (2) specify whether and by
when expanded information must be submitted regarding trials for which basic results
submissions were made prior to the rule’s enactment; (3) establish a standard submission
format, additional information that is nontechnical and understandable to patients, and
procedures for quality control; (4) specify the appropriate timing and requirements for
updates of clinical trial information; (5) specify requirements for a statement
iki/CRS-RL34465accompanying voluntary submissions; and (6) specify additions or modifications to the
g/wmanner of reporting the basic results information. In the rulemaking process the
s.orSecretary is to consider the World Health Organization data set, and is to hold a public
leakmeeting 18 months after FDAAA’s enactment to provide an opportunity for public input regarding the rulemaking requirements. [FDAAA 801(a)(2); PHSA 402(j)(3)(D); 42 USC
://wiki282(j)]
httpAdverse Events With sponsor consent, the registry may include Not later than 18 months after FDAAA enactment, the Secretary is to determine the
information about the results of included trials, best method for including appropriate information on serious and frequent adverse
including potential toxicities or adverse effects. events in the registry and results database. If the Secretary fails to take action within 24
months after FDAAA enactment, the Secretary must, in consultation with risk
communication experts, include the following elements in the registry and results
database: (1) a table of serious adverse events (both anticipated and unanticipated)
grouped by organ system, with number and frequency of such event in each arm of the
trial; and (2) a similar table of other adverse events that exceed a frequency of five
percent within any arm of the trial. Adverse event clinical trial information is deemed to
be included in the registry and results database pursuant to the basic results
requirements. (Note: FDAAA’s adverse event reporting requirements were limited to
drugs and biologics, but P.L. 110-316 expanded the requirements to medical devices as
well.) The House passed a measure that would expand it to devices as well (H.Cong.Res
217).) [FDAAA 801(a)(2); PHSA 402(j)(3)(I); 42 USC 282(j)]




Topic Previous Law FDAAA Title VIII
Registry Updates No provision. The RP for an applicable clinical trial shall submit updates to the NIH Director to reflect
changes to registry information. Updates shall: (1) be submitted not less than once every
12 months, unless there were no changes; (2) include the dates of any such changes; and
(3) be submitted regarding changes in recruitment status or trial completion not later
than 30 days after the change. The Director shall make update information publicly
available, and, except with regard to recruitment status, individual site status, location,
and contact information, ensure that previously submitted information remains accessible.
[FDAAA 801(a)(2); PHSA 402(j)(4)(C); 42 USC 282(j)]
Coordination and No provision. For trials supported by grants from HHS agencies, any required grant or progress report
Compliance: HHS Funded forms must include a certification that the RP has made all required submissions to the
Trials registry and results database. The heads of the HHS agencies must verify that such
information has been submitted before releasing funding. Grantees who have not made all
required submissions are to be given notice and an opportunity to remedy their
noncompliance. [FDAAA 801(a)(2); PHSA 402(j)(5)(A); 42 USC 282(j)]
Coordination and No provision. For research without HHS funding, but supported by grants from other federal agencies,
Compliance: Trials the Secretary must consult with other agencies conducting research in accordance with
iki/CRS-RL34465Funded by Federal Agencies Other Than any part of 45 CFR 46 (federal protections for human research subjects) and develop strategies comparable to the HHS protocol for ensuring required submissions are made.
g/wHHS [FDAAA 801(a)(2); PHSA 402(j)(5)(A)(iv); 42 USC 282(j)]
s.or
leakFDA Application Certifications No provision. Applications for approval or clearance of drugs, devices, and biologics are to include a certification that the RP has made all required submissions to the registry and results
://wikidatabase. Where available, such certification is to include the National Clinical Trial control numbers. FFDCA 505, 510, 515, and 520 (governing submissions for drug,
httpbiologic and device approval as well as device clearance and humanitarian device
exemptions) are each amended to include the statement that “such application shall
include the certification requirement under PHSA 402(j)(5)(B) (which shall not be
considered an element of such application).” [FDAAA 801(a)(2); PHSA 402(j)(5)(B); 42
USC 282(j)]
Truthfulness of Submitted No provision. Clinical trial information submitted by the RP must be truthful and not misleading in any
Information particular. [FDAAA 801(a)(2); PHSA 402(j)(5)(D); 42 USC 282(j)]
Quality Control Pilot No provision. The Secretary must conduct a pilot project to determine the best method of quality
Project control (QC) to ensure that submitted information is not false or misleading in any
particular and is non-promotional. The pilot project shall continue until the effective date
of the regulations for the expanded registry and results database. The regulations are to
incorporate recommendations from the project. If the Secretary determines that clinical
trial information was not submitted or did not meet QC standards as required, the
Secretary must notify and give the RP an opportunity to remedy the noncompliance.
[FDAAA 801(a)(2); PHSA 402(j)(5)(C); 42 USC 282(j)]




Topic Previous Law FDAAA Title VIII
Public Notice of No provision. The NIH Director is to include a notification in the database if an RP fails to submit
Noncompliance required clinical trials registry or results information. The notice is to state the nature of
the noncompliance, note any penalties imposed under the act, and state whether the RP
has corrected the information. If the RP failed to submit required information, the notice
is to contain the statement “The entry for this clinical trial was not complete at the time
of submission, as required by law. This may or may not have any bearing on the accuracy
of the information in the entry.” If the RP submitted false or misleading information, the
notice is to contain the statement “The entry for this clinical trial was found to be false or
misleading and therefore not in compliance with the law.” If the RP failed to submit
primary and secondary outcomes, the notice is to contain the statement “The entry for
this clinical trial did not contain information on the primary and secondary outcomes at
the time of submission, as required by law. This may or may not have any bearing on the
accuracy of the information in the entry.” The Director is to ensure that the public may
search the database for entries that include noncompliance notices. [FDAAA 801(a)(2);
PHSA 402(j)(5)(E); 42 USC 282(j)]
Authorization of Such sums as may have been necessary were The amount of $10,000,000 per fiscal year is authorized for carrying out the clinical trials
Appropriations authorized. database provisions. [FDAAA 801(a)(2); PHSA 402(j)(7); 42 USC 282(j)]
iki/CRS-RL34465Prohibited Acts The law did not specify penalties or enforcement The prohibited acts section of the FFDCA (21 USC 331) is amended, specifying that the
g/wmechanisms related to registry requirements. General following are illegal: (1) the failure to submit a certification or submitting a false
s.ormechanisms for enforcing compliance with FDA certification of compliance with FDAAA’s clinical trial database provisions; (2) the failure
leakrequirements may have been applicable, but were not to submit FDAAA-required clinical trial information; and (3) the submission of FDAAA-
applied by the FDA. required clinical trial information that is false or misleading in any particular. [FDAAA
://wiki801(b)(1); FFDCA 301(jj); 21 USC 331]
httpCivil Monetary Penalties The law provided general penalties for violations of Violators of FDAAA clinical trial database provisions may be subjected to not more than
prohibited acts, which FDA may have been able, but $10,000 for all violations adjudicated in a single proceeding, and not more than $10,000
did not, apply to database infractions. Violators could per day for each day of violation after FDAAA-required notification of noncompliance is
be imprisoned for not more than one year or fined issued until the violation is corrected. [FDAAA 801(b)(2); FFDCA 303(f); 21 USC 333]
not more than $1,000, or both. Violators could be
fined up to $10,000 if the violation occurred after a
conviction under the applicable section, or with the
intent to defraud or mislead.
Investigational New Drug Previous law contained informed consent FDAAA amends the FFDCA provisions pertaining to investigational new drugs (21 USC
Informed Consent requirements, but none specific to the registry. 355(i)), requiring the Secretary to update regulations to include in the informed consent
documents and process a statement that clinical trial information has been or will be
submitted for inclusion in the registry databank pursuant to FDAAA. [FDAAA 801(b)(3);
FFDCA 505(b)(1); 21 USC 355(b),(i)]
Pediatric Postmarket No provision. Within 12 months of enactment, the Secretary is to issue guidance on how the database
Surveillance Guidance requirements apply to a PMDSIA pediatric postmarket surveillance that is not a clinical
trial. [FDAAA 801(c); 42 USC 282 note]




Topic Previous Law FDAAA Title VIII
State Preemption No provision. No state or political subdivision of any state may establish or continue in effect any
requirement for the registration of clinical trials or for the inclusion of information
relating to the results of clinical trials in a database. [FDAAA 801(d)(1);42 USC 282 note]
Rule of Construction No provision. The fact of submission of off-label use clinical trial information, if in compliance with
PHSA 402(j) [revised registry and results database requirements], shall not be construed
by the Secretary or in any judicial proceeding as evidence of a new intended use. The
availability of compliant database submissions shall not be considered as labeling,
adulteration, or misbranding under the FFDCA (21 USC 301 et seq.). [FDAAA 801(d)(2);
42 USC 282 note]


iki/CRS-RL34465
g/w
s.or
leak
://wiki
http





Title IX of FDAAA gives the FDA new authorities to ensure drug safety and effectiveness. These
build on decades of incremental additions to FDA’s regulatory scope and its ability to identify
drug safety problems and to correct or minimize them.
For further information, see CRS Report RL32797, Drug Safety and Effectiveness: Issues and Action Options After FDA
Approval, by Susan Thaul.


Since the 1938 passage of the FFDCA, the manufacturer of a new drug has had to demonstrate to
FDA the product’s safety before the agency would approve it for marketing in the United States.
In 1962, the Harris-Kefauver Amendments to the FFDCA added product effectiveness to the
premarket requirements. FDA 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 because, 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.
Prior to FDAAA, the law allowed FDA to require a postmarket study as a condition of its initial
approval of a marketing application, but did not authorize FDA to add such requirements after
approval. The law did not allow FDA to require that manufacturers submit drug advertising
material for review or approval before dissemination. Neither did it provide for civil penalties,
authorizing only the revocation of approval or licensing (or the threat of revocation) to compel
manufacturers to change labeling or advertising.
Subtitle A includes various provisions regarding postmarket studies and surveillance of human
drugs. Its provisions do not apply to veterinary drugs.
FDAAA authorizes the Secretary, under specified conditions after a drug is on the market, to
require a study or a clinical trial. The Secretary may determine the need for such a study or trial
based on newly acquired information. To require a postapproval study or trial, the Secretary must
determine that (1) other reports or surveillance would not be adequate, and (2) the study or trial
would assess a known serious risk or signals of serious risk, or identify a serious risk. The law
directs the Secretary regarding dispute resolution procedures.
FDAAA authorizes the Secretary, upon learning of new relevant safety information, to require a
labeling change. It also creates procedures, including time limits, for notification, review, dispute
resolution, and violation, regarding labeling change requirements.



FDAAA authorizes the Secretary to require, under specified conditions, a risk evaluation and
mitigation strategy (REMS) at the time of a new application, after initial approval or licensing
when a new indication or other change is introduced, or when the Secretary becomes aware of
new information and determines a REMS is necessary. Any approved REMS must include a
timetable of assessments.
The Secretary may include requirements regarding instructions to patients and clinicians, and
restrictions on distribution or use (and a system to monitor their implementation). The law allows
a waiver from REMS restrictions on distribution or use for certain medical countermeasures in
the time of a declared public health emergency, and creates a mechanism to assure access to a
drug with a REMS for off-label use for a serious or life-threatening disease or condition.
FDA practice has long included most of the elements that a REMS may include. FDAAA gives
FDA, through the REMS process, the authority for structured follow-through, dispute resolution,
and enforcement. These include required reviews of approved REMS at specified times initially
and then as the Secretary determines; detailed procedures for the review of both proposed REMS
and required or voluntary assessments or modifications; establishment of a Drug Safety Oversight
Board; and evaluation of 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.
FDAAA expands the definition of misbranding to include the failure to comply with certain
requirements regarding REMS, postmarket studies and clinical trials, and labeling. It establishes
civil monetary penalties for violations of those requirements. The maximum for one violation is
$250,000, up to $1 million for all violations within one adjudication proceeding. The law
describes escalating penalties, based on continuing violations and efforts at correction, up to $10
million in a single proceeding.
FDAAA creates a new FFDCA Section 503B to authorize the Secretary to require submission of a
television advertisement to the Secretary for review before its dissemination. Based on this
review, during which the Secretary may consider the impact the drug might have on specific
population groups (such as older and younger individuals, or racial and ethnic minorities), the
Secretary may recommend, but not require, changes in the ad. The law authorizes the Secretary to
require that an ad include certain disclosures without which the Secretary determines that the ad
would be false or misleading. These disclosures concern information about a serious risk listed in
a drug’s labeling, and the date of a drug’s approval.
An amendment to the FFDCA requires that television and radio ads present the required
information on side effects and contraindications in a clear, conspicuous, and neutral manner
(Section 502(n)).
A new FFDCA Section 303(g) establishes civil penalties for the dissemination of a false or
misleading direct-to-consumer (DTC) advertisement. The amount is limited to $250,000 for the





first violation in any three-year period, and to $500,000 for each subsequent violation in that
period.
FDAAA requires a study by the FDA Advisory Committee on Risk Communication and a report
to Congress from the Secretary regarding DTC advertising and its communication of health
information and its effect on information access and health disparities among population subsets.
FDAAA directs the Secretary to collaborate with public, academic, and private entities to develop
a postmarket risk identification and analysis system using electronic databases. Detailed
provisions require the Secretary to protect individually identifiable health information; consult the
Drug Safety and Risk Management Advisory Committee; communicate with key stakeholders;
coordinate with other drug safety data sources; and report to Congress. FDAAA authorizes the
appropriation of $25 million for each of FY2008 through FY2012 in addition to funds available
under PDUFA for these activities.
Various sections of Title IX of FDAAA, in addition to those described above, address the
provision of health information. One required report to Congress must address how best to
communicate risks and benefits to the public, including the use of REMS and whether to use a 25
unique symbol in the labeling of a new drug or indication. Any published DTC prescription
drug advertisement must include a statement encouraging the reporting of negative side effects to
FDA, along with a 1-800 number and website address. The Secretary must submit a report to
Congress after studying whether the statement in printed advertisements is appropriate for
television advertisements.
FDAAA authorizes increased appropriations to support components of the drug safety provisions.
For the surveillance and assessment activities, the Secretary may use $25 million of PDUFA fees
each year to carry out those activities. For REMS and other drug safety activities in this title, the
new law increases the revenue authorized under PDUFA by an additional $225 million over the
period FY2008 through FY2012, and designates its use for drug safety activities.
The provisions in Subtitle B of FDAAA Title IX address topics related to drug safety. The first
section requires the Secretary to issue guidance for the conduct of clinical trials of antibiotic
drugs; and convene a public meeting regarding orphan antibiotic products. A few sections address
the physical security of drug products, such as requiring the Secretary to develop standards and
technology to protect the drug supply chain against counterfeit and damaged drugs.
25
FDAAA does not define the term “published.” In general, it appears to apply to printed, rather than broadcast,
advertisements.





Other sections address communication with the public, expert committees, and others, about
agency actions and plans. The Secretary must develop and maintain an Internet Web site with
extensive drug safety information, and publish a list of all authorized generic drugs. The 26
Secretary must provide public access to action packages for product approval or licensure,
including certain reviews; and establish an Advisory Committee on Risk Communication. The
Secretary must refer an application for a new active ingredient to an FDA advisory committee or
include in the action letter reasons for not doing so. FDAAA requires that the Secretary report on
FDA’s implementation of its plan to respond to recommendations in the IOM 2006 report The
Future of Drug Safety.
The Secretary must also screen weekly the Adverse Event Reporting System database and report
quarterly regarding new safety information or potential signals of a serious risk; report on
procedures for addressing ongoing postmarket safety issues identified by the Office of
Surveillance and Epidemiology; and annually review the backlog of postmarket safety
commitments, report to Congress, and set relevant dates.
Finally, FDAAA prohibits the use in food of certain drugs or biological products, and prohibits
the Secretary from delaying the review of generic drug applications on the basis of certain citizen
petitions. P.L. 110-316 amended the FDAAA provision, adding the requirement that consideration
of petitions be separate and apart from review and approval of any application.
26
An action package is the compilation of FDA-generated documents, from the submission to final action, related to
review of an NDA or efficacy supplement; documents pertaining to the format and content of the application generated
during drug development; and labeling submitted by the applicant (FDA, “Action Packages for NDAs and Efficacy
Supplements, at http://www.fda.gov/cder/mapp/6020.8.pdf).




Table 12. Law Created by Enhanced Authorities Regarding Postmarket Safety of Drugs, Subtitle A
(FDAAA Title IX, Subtitle A)
Topic FDAAA Title IX, Subtitle A
Postmarket Studies and Clinical Trials No one may introduce a drug or biological product [hereinafter “drug”] into interstate commerce if its sponsor is in violation of the
Secretary’s requirement for postapproval studies or clinical trials, or requests for labeling changes related to safety.
The Secretary may require a postapproval study or clinical trial on the basis of scientific data including information regarding a
chemically or pharmacologically related drug. The purpose of a required postapproval study or clinical trial must be to assess a
known serious risk or signals of serious risk, or to identify a serious risk. The Secretary may require a postapproval study or clinical
trial after learning of new safety information. In requiring a study or trial, the Secretary must require a timetable and periodic reports.
A sponsor that fails to comply with such requirements must demonstrate good cause.
To require a postapproval study, the Secretary must determine that other reports or surveillance would be inadequate to assess a
known serious risk, a signal of serious risk, or to identify unexpected serious risks. To require a postapproval clinical trial, the
Secretary must determine that a postapproval study would be inadequate for the purpose.
The sponsor may appeal a requirement to conduct a study or clinical trial by using dispute resolution procedures established by the
Secretary. [FDAAA 901(a); FFDCA 505(o); 21 USC 355]
iki/CRS-RL34465Labeling Changes The Secretary may, upon learning of new relevant safety information, require that the sponsor submit a supplement for a labeling
g/wchange. FDAAA creates procedures, including time limits, for notification, review, dispute resolution, and violation. It also authorizes
s.orthe Secretary to accelerate timelines if the Secretary concludes that the labeling change is necessary to protect the public health.
leak[FDAAA 901(a); FFDCA 505(o); 21 USC 355]
://wikiRisk Evaluation and Mitigation Strategies (REMS) The introduction of a drug or biological product into interstate commerce is prohibited if its sponsor is not in compliance with any risk evaluation and mitigation strategy (REMS) required by the Secretary or fails to conduct a postmarket study required of a drug
httpthat received accelerated approval because it addressed a serious or life-threatening illness. [FDAAA 901(a); FFDCA 505(p); 21 USC
355]
REMS The Secretary may require that the sponsor of a drug or biologic application or supplement to an application, including one for a new
indication for use, submit a proposed REMS. The Secretary may require a REMS with fewer elements for a product under an
abbreviated new drug application.
Pre-approval: If the Secretary (acting through the office responsible for reviewing the drug and the office responsible for postapproval
safety with respect to the drug) determines such a strategy is necessary to ensure that the benefits of the drug involved outweigh the
risks of the drug, the Secretary may require a REMS.
Postapproval: If the Secretary becomes aware of new safety information and determines a REMS necessary, the Secretary may require
one. [FDAAA 901(b); FFDCA 550-1; 21 USC 355-1]
REMS: Minimal Strategy An approved REMS must include a timetable of assessments of the approved REMS. This includes an assessment no less frequently
than at 18 months and again at 3 years after a drug is initially approved; in the seventh year; and, subsequently, at a frequency
(including none, after the 3-year period following REMS approval) as the Secretary determines. [FDAAA 901(b); FFDCA 505-1; 21
USC 355-1]




Topic FDAAA Title IX, Subtitle A
REMS: Optional Elements A REMS may include information to patients, to include Medication Guide and patient package insert, and a communication plan to health
care providers, such as letters, information about REMS, and explanations of safety protocols. [FDAAA 901(b); FFDCA 505-1; 21 USC
355-1]
REMS: Safe Access to Drugs with The Secretary may require restrictions on distribution or use, along with a system to monitor implementation, based on the Secretary’s
Known Serious Risks evaluation of the elements needed to assure safe use. The restrictions may include required training and experience of the prescribing
health care provider; special certification of providers or health care settings; dispensing limited to certain health care settings;
evidence of safe-use conditions (such as laboratory results); patient monitoring; and patient enrollment in registries.
The Secretary may waive any required restriction for use of certain medical countermeasures during a declared public health
emergency. The Secretary must minimize burdens on patient access (e.g., a patient with a serious or life-threatening disease or
condition, or one who lives in a rural or medically underserved area) to a drug and on the health care delivery system. FDAAA
authorizes expanded access for an off-label use for a serious or life-threatening disease or condition. It also prohibits a sponsor from
using a restriction on distribution to block or delay approval of a generic drug application. [FDAAA 901(b); FFDCA 505-1; 21 USC
355-1]
REMS: Assessments A sponsor may submit a voluntary assessment of an approved REMS at any time. Assessments are required at prearranged times, and
when the Secretary determines that new information indicates an existing element should be modified or included. The Secretary’s
determination must be based on new safety or effectiveness information. Required is an assessment of how well the elements to
iki/CRS-RL34465assure safe use are meeting the goal of increasing safe access to drugs with known serious risks and whether the goal or such
g/welements should be modified; and an assessment of the status of required postapproval studies and clinical trials. [FDAAA 901(b);
s.orFFDCA 505-1; 21 USC 355-1]
leakREMS: Modifications Modifications may be made that include the assessment timetable; or the addition, modification, or removal of a restriction on
distribution or use. [FDAAA 901(b); FFDCA 505-1; 21 USC 355-1]
://wikiREMS: Review and Dispute Resolution The Secretary must promptly review each proposed REMS and each assessment of an approved REMS. The review must follow
httpspecified procedures, including timeframes. These include: dispute resolution, including review by a Drug Safety Oversight Board
(made up of federal government scientists and health care practitioners), use of advisory committees, and administrative appeals;
addressing drug class effects; and coordinating assessment timetables with efforts of other countries.
A dispute resolution occurring before an initial approval must follow procedures set forth in the letters described in FDAAA 101(c).
FDAAA creates a Drug Safety Oversight Board to be composed of scientists and health care practitioners who are federal employees
and who the Secretary appoints.
The Secretary must describe any required REMS or modification as part of an action letter on an application or in an order following
an assessment. Such action letters and orders, and any deferrals, must be made publicly available. [FDAAA 901(b); FFDCA 505-1; 21
USC 355-1]
Regulation of Biological Products An applicant for a biological product license must be subject to FFDCA Sections 505(o), 505(p), and 505-1. [FDAAA 901(c); PHSA
351; 42 USC 262]




Topic FDAAA Title IX, Subtitle A
Advertisements: Prereview The Secretary may require a prereview (at least 45 days before dissemination) of any television advertisement for a drug. The
Secretary may recommend changes that are necessary to protect the consumer, or that are consistent with prescribing information
for the product under review; and, if appropriate, statements to include in advertisements to address the specific efficacy of the drug
as it relates to specific population groups, including elderly populations, children, and racial and ethnic minorities.
The Secretary is not authorized to make or direct changes in any material submitted pursuant to this subsection.
The Secretary may, in formulating recommendations, take into consideration the impact of the advertised drug on elderly
populations, children, and racially and ethnically diverse communities. [FDAAA 901(d)(2); FFDCA 503B; 21 USC 353b]
Advertisements: Required Disclosures The Secretary may require inclusion of a disclosure in an advertisement if the Secretary determines that the advertisement would be
false or misleading without a specific disclosure about a serious risk listed in the labeling of the drug involved.
The Secretary may require, for not more than two years from approval, the advertisement to include a specific disclosure of the
approval date if the Secretary determines that the advertisement would otherwise be false or misleading. [FDAAA 901(d)(2); FFDCA
503B; 21 USC 353b]
Advertisements: Statement of Side In a television or radio direct-to-consumer (DTC) advertisement of a drug that states the name of the drug and its conditions of use,
Effects and Contraindications the major statement relating to side effects and contraindications must be presented in a clear, conspicuous, and neutral manner. The
iki/CRS-RL34465Secretary must establish standards, by regulation, for determining whether a major statement meets those criteria. [FDAAA 901(d)(3); FFDCA 502(n); 21 USC 352(n)]
g/w
s.orAdvertisements: Civil Penalties FDAAA establishes civil penalties for the sponsor of a drug or biologic who disseminates a DTC advertisement that is false or misleading. It authorizes a civil monetary penalty not to exceed $250,000 for the first violation in any 3-year period, and not to
leakexceed $500,000 for each subsequent violation in any 3-year period. No other civil monetary penalties in this act shall apply to a
://wikiviolation regarding DTC advertising. Repeated dissemination of the same or similar advertisement prior to the receipt of a written notice shall be considered one violation. After such notification, all violations under this paragraph occurring in a single day shall be
httpconsidered one violation. The law directs how to consider publications published less frequently than daily, and specifies procedures,
after the provision of written notice and opportunity for a hearing, regarding reviews, subpoenas, modifications, and judicial review.
Civil penalties may not be assessed if the sponsor had submitted an advertisement for prereview and incorporated each comment
received from the Secretary. If an applicant fails to pay an assessed civil penalty, the Attorney General may recover that amount plus
interest. [FDAAA 901(d)(4); FFDCA 303(g); 21 USC 333]
Advertisements: Report The Secretary must, with the advice of the Advisory Committee on Risk Communication and within two years of enactment, report
to the Congress on DTC advertising and its ability to communicate to subsets of the general population. The Advisory Committee on
Risk Communication must study DTC advertising as it relates to increased access to health information and decreased health
disparities for these populations, and make recommendations in a report that the Secretary must submit to Congress. [FDAAA
901(d)(5)]
Effect on Pediatric Studies Rule of construction states that this section is not to be construed as affecting the Secretary’s authorities to request pediatric studies
under FFDCA 505A or to require such studies under FFDCA 505B. [FDAAA 901(e); 21 USC 355a note]
Enforcement: Misbranding FDAAA includes as misbranding the failure to comply with REMS requirements regarding assessments, additional elements included,
or a restriction on distribution or use; or failure to comply with requirements relating to postmarket studies and clinical trials or
labeling. [FDAAA 902(a); FFDCA 502(y,z); 21 USC 352]




Topic FDAAA Title IX, Subtitle A
Enforcement: Civil Penalties An applicant who violates a REMS requirement or a requirement regarding postmarket studies or clinical trials or labeling is subject
to a civil monetary penalty of not more than $250,000 per violation, and not to exceed $1 million for all such violations adjudicated in
a single proceeding. If a violation continues after the Secretary provides notice of such violation to the applicant, the Secretary may
impose a civil penalty of $250,000 for the first 30 days, doubling for every subsequent 30-day period, up to $1 million for one 30-day
period, and up to $10 million for all such violations adjudicated in a single proceeding. The Secretary must, in determining the amount
of civil penalty, consider whether the sponsor is making efforts toward correcting the violation. [FDAAA 902(b); FFDCA 303(f); 21
USC 333]
No Effect on Withdrawal or Suspension The Secretary may withdraw the approval of an application or suspend the approval of an application without first ordering the
of Approval applicant to submit an assessment of the approved REMS. [FDAAA 903; FFDCA 505(e); 21 USC 355(e)]
Benefit-Risk Assessments The Commissioner must submit to Congress, within a year of enactment, a report on how best to communicate to the public the risks
and benefits of new drugs and the role of the REMS in assessing such risks and benefits. As part of such study, the Commissioner shall
consider the possibility of including in the labeling and any DTC advertisements of a newly approved drug or indication a unique
symbol indicating the newly approved status of the drug or indication for a period after approval. [FDAAA 904]
Active Postmarket Risk Identification The Secretary must, in collaboration with public, academic, and private entities, develop methods to get access to data sources;
and Analysis (APRIA): Develop Methods develop validated methods set up a system to analyze safety data from multiple sources; and convene an expert committee to advise
and Establish System the Secretary on the development of tools and methods for the ethical and scientific uses for, and communication of, postmarketing
iki/CRS-RL34465data.
g/wUsing the methods developed (above), the Secretary must establish a Postmarket Risk Identification and Analysis System and establish
s.orand maintain procedures to: use electronic health data for risk identification and analysis; provide standardized reporting of adverse
leakevent data; and use federal, private, and other data sources to conduct active adverse event surveillance and identify trends and
patterns. In carrying out these activities, the Secretary must attend to timeliness of reporting, use of private sector resources, and
://wikidevelopment of other approaches to gathering drug safety data. [FDAAA 905(a); FFDCA 505(k)(3); 21 USC 355]
httpAPRIA: Advanced Analysis of Drug The Secretary must establish collaborations with public, academic, and private entities to provide for advanced analysis of drug safety
Safety Data data to improve postmarket drug safety risk-benefit analysis, provide routine access to expertise, and enhance the Secretary’s ability
to make timely assessments. These analyses must protect individually identifiable health information. The Secretary must seek
recommendations from the Drug Safety and Risk Management Advisory Committee and other FDA advisory committees regarding
priority drug safety questions and mechanisms for answering them. The Secretary must establish procedures for the development of
drug safety collaborations.
The Secretary must provide the analyses, including their methods and results, about a drug to the drug’s sponsor. Regarding
contracts from the Secretary, FDAAA defines criteria by which entities can qualify, contract requirements, and other procedures.
The Secretary must provide for appropriate communications with key public, scientific, public health, medical, and other key
stakeholders; and, to the extent practicable, coordinate with activities of other entities that have drug safety data sources.[FDAAA
905(a); FFDCA 505(k)(4); 21 USC 355]
Disclosure of Data Rule of construction states that this section is not to be construed to prohibit the lawful disclosure or use of data or information
(such as individually identifiable health information) by an entity other than to protect privacy. [FDAAA 905(b); 21 USC 355 note]
Report to Congress The Secretary must report to Congress on the use of the active postmarket risk identification and analysis system. [FDAAA 905(c)]




Topic FDAAA Title IX, Subtitle A
Authorization of Appropriations To carry out the FDAAA-required risk identification and analysis activities for which funds are available under the prescription drug
user fee program (FFDCA 736), FDAAA authorizes the appropriation of an additional $25 million for each of FY2008 through
FY2012. [FDAAA 905(d)]
GAO Report The Comptroller General must evaluate and report on data privacy, confidentiality, and security issues relating to the active
postmarket risk identification and analysis system, and recommend actions, if necessary, to the congressional authorizing committees.
[FDAAA 905(e)]
Any published DTC advertisement must include the following statement printed in conspicuous text: “You are encouraged to report Advertisements: Toll-Free Number
negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch, or call 1-800-FDA-1088.” [FDAAA 906(a);
FFDCA 502(n); 21 USC 352]
The Secretary must, in consultation with the Advisory Committee on Risk Communication, study whether the statement required in
published DTC advertisements is appropriate for television DTC advertisements; and report findings and determinations to Congress.
If the Secretary determines that including the statement is appropriate, the Secretary must issue regulations to implement such a
requirement. [FDAAA 906(b); 21 USC 352 note]
No Effect on Veterinary Medicine The provisions of this subtitle do not apply to a licensed veterinarian’s use of drugs within a veterinarian-client-patient relationship.
[FDAAA 907; 21 USC 355 note]
iki/CRS-RL34465Authorization of Appropriations FDAAA authorizes to be appropriated, for carrying out this subtitle and the amendments it made, $25 million for each of FY2008
g/wthrough FY2012. This authorization is in addition to any other funds (see above) available for carrying out these activities. [FDAAA
s.or908]
leakEffective Dates All provisions in Subtitle A of Title IX begin 180 days after enactment. [FDAAA 909; 21 USC 331 note]


://wiki
http


Table 13. Law Created by Enhanced Authorities Regarding Postmarket Safety of Drugs,
Subtitle B (FDAAA Title IX, Subtitle B)
Topic FDAAA Title IX, Subtitle B
Clinical Trial Guidance for Antibiotic The Secretary must, within one year of enactment, issue guidance for the conduct of clinical trials with respect to antibiotic drugs, and
Drugs review and update such guidance within five years of enactment. [FDAAA 911; FFDCA 511; 21 USC 360a]
Prohibition Against Food to Which It is a prohibited act (under FFDCA Section 301, and therefore subject to FFDCA penalties) to introduce into food drugs or biologics
Drugs or Biological Products Have that are either FDA approved/licensed or for which substantial clinical investigations have been instituted and made public, except in
Been Added specified circumstances. [FDAAA 912; FFDCA 301(ll); 21 USC 331]
Pharmaceutical Security The Secretary must develop standards and identify and validate effective technologies for the purpose of securing the drug supply
chain against counterfeit, diverted, subpotent, standard, adulterated, misbranded, or expired drugs. The Secretary (in consultation
with other federal agencies, including the Departments of Justice, Homeland Security, and Commerce, and manufacturers,
distributors, pharmacies, and other supply chain stakeholders) must develop and prioritize standards for the identification, validation,
authentication, and tracking and tracing of prescription drugs. The Secretary must develop a standardized numerical identifier to be
applied to a prescription drug at the point of manufacturing and repackaging; address promising technologies, such as radiofrequency
identification technology, nanotechnology, encryption technologies, and other track-and-trace technologies; undertake enhanced and
iki/CRS-RL34465joint enforcement activities with other federal and state agencies; and establish regional capabilities for validation and inspection. [FDAAA 913; FFDCA 505D; 21 USC 355e]
g/w
s.orCitizen Petitions and Petitions for Stay The Secretary may not delay the review or approval of generic or abbreviated new drug applications on the basis of a petition that
leakof Agency Action (Regarding the Approval of Generic Drugs) seeks to have the Secretary take, or refrain from taking, actions relating to the application’s approval. This prohibition is excepted when the Secretary determines that a delay is necessary to protect the public health. FDAAA provides detailed procedures involving
://wikidetermination by the Secretary; notification; format; public disclosure; denial based on intent to delay; final agency action; extension of petition period; certification and verification regarding the completeness of information submitted and whether and from whom
httppayment is received; exhaustion of administrative remedies; and annual reports. [FDAAA 914; FFDCA 505(q); 21 USC 355]
Postmarket Drug Safety Information The Secretary must develop and maintain an Internet website with an extensive range of easily searchable drug safety information to
for Patients and Providers allow patients and health care providers better access to information. The website must include links to other government sites;
professional and patient labeling; FDA alerts, warning letters, guidance documents, and regulations; summaries of aggregate
surveillance data; and the clinical trials registry and results data bank.
At the later of 18 months after a drug’s approval or after 10,000 individuals have used the drug, the Secretary must prepare a
summary analysis of adverse drug reaction reports, including identification of any previously unidentified risks, potential new risks, or
known risks reported in unusual number. The Secretary may contract with public and private entities to fulfill these requirements.
The Advisory Committee on Risk Communication must review and evaluate the types of information on the website, and recommend
ways to facilitate the dispensing of risk communication information to patients and providers. [FDAAA 915; FFDCA 505(r); 21 USC
355]




Topic FDAAA Title IX, Subtitle B
Public Access to Action Packages for Within 48 hours of an application’s approval, the Secretary must publish on the FDA website a summary review that documents
Approval conclusions from all reviewing disciplines, noting critical issues and disagreements with the applicant and how they were resolved,
recommendations for action and an explanation of any nonconcurrence with review conclusions.
Within 30 days of an application’s approval, the Secretary must publish on the FDA website (without disclosing trade secrets or
confidential information) the action package for approval of a drug or licensure of a biologic, which includes: FDA-generated
documents related to the review; documents pertaining to the application’s format and contact that were generated during drug
development; labeling submitted by the application; the summary review (described above); the Division Director and Office
Director’s decision document, which includes a brief statement of concurrence with the summary review, and a separate review of
addendum if disagreeing with summary review or to add further analysis; and identification (with consent) of FDA participants in the
decision.
FDAAA declares that a scientific review of an application is considered the work of the reviewer and shall not be altered by
management or the reviewer once final. [FDAAA 916; FFDCA 505(l); 21 USC 355(l)]
Risk Communication The Secretary must establish an Advisory Committee on Risk Communication to include experts on risk communication, experts on
specific risks, and representatives of patient, consumer, and health professional organizations. The Secretary must partner with
nongovernmental groups to develop robust and multifaceted systems for communication to health care providers about emerging
postmarket drug risks. [FDAAA 917; FFDCA 567; 21 USCbbb-6]
iki/CRS-RL34465Referral to Advisory Committee The Secretary must, before approving a drug that includes a new active ingredient, refer the drug to an FDA advisory committee. If
g/wreferral is not made, the action letter on the application must include a summary of the reasons why the Secretary did not do so.
s.or[FDAAA 918; FFDCA 505(s); 21 USC 355]
leak
Response to IOM 2006 Report The Secretary must submit, within one year, a report updating FDA’s implementation of its plan to respond to the recommendations
://wikiin the IOM 2006 report The Future of Drug Safety, to include an assessment of FDA’s implementation of REMS requirements. [FDAAA 919]
http
Authorized Generic Drugs The Commissioner must publish (within nine months of enactment) on the FDA website a list of all authorized generic drugs; update
the list quarterly; and notify relevant federal agencies of those updates. An authorized generic drug is defined, for this section, as one
that had previously been approved under FFDCA 505(c) and then “marketed, sold, or distributed directly or indirectly to retail class
of trade under a different labeling, packaging (other than repackaging as the listed drug in blister packs, unit doses, or similar packaging
for use in institutions), product code, labeler code, trade name, or trade mark than the listed drug.” [FDAAA 920; FFDCA 505(t); 21
USC 355]
Adverse Drug Reaction Reports The Secretary must conduct regular, biweekly screening of the Adverse Event Reporting System (AERS) database and post a quarterly
report of any new safety information or potential signal of a serious risk identified by AERS within the last quarter.
The Secretary must report within two years of enactment on FDA procedures and processes for addressing ongoing postmarket
safety issues identified by the Office of Surveillance and Epidemiology (OSE) and how OSE recommendations are handled within the
agency.
The Secretary must annually review the entire backlog of postmarket safety commitments to determine which require revision or
should be eliminated; report to Congress on these determinations; and assign start and estimated completion dates. [FDAAA 921;
FFDCA 505(k); 21 USC 355]






Title X of FDAAA, entitled Food Safety, contains provisions designed to enhance FDA’s
authority and responsibilities to ensure the safety of the food supply. These were added to
FDAAA after several widely reported outbreaks of food-borne illness that affected hundreds of
individuals. In response, many members of Congress expressed concern about both domestic and
imported food products and whether the current food safety system is adequate for handling the
current globalized food supply.
As enacted, FDAAA requires the Secretary to establish processing and ingredient standards,
update labeling requirements for pet food, and establish an early warning and surveillance system
to identify adulteration and outbreaks of illness associated with pet food. The Secretary is to work
with states to improve the safety of produce and strengthen state food safety programs. The Act
requires the creation of a registry for reportable information on foods (including human and
animal products) with safety problems that allows for the identification of the supply chain of the
reportable food. Alerts are to be issued for such foods, with records maintained and available for
inspection. Additional provisions require attention to aquaculture and seafood inspection,
environmental risks associated with genetically engineered seafood products, imported foods,
pesticide monitoring and ginseng dietary supplements.
This section was contributed by Donna V. Porter, Specialist in Nutrition and Food Safety, Domestic Social Policy
Division.
For further information, see CRS Report RS22779, Food Safety: Provisions in the Food and Drug Administration
Amendments Act of 2007, by Donna V. Porter.



Title XI of FDAAA, entitled Other Provisions, contains provisions relating to a number of topics.
It is divided into two subtitles. Subtitle A—In General covers a range of topics: FDA employee
publications, tropical disease treatments, genetic tests, NIH, and severability of FDAAA. Subtitle
B—Antibiotic Access and Innovation focuses solely on that issue. Both are discussed below.
The first topic addressed in Subtitle A is agency clearance of employee scientific publications.
The Secretary is required to establish and make publicly available clear written policies to
implement the publication provisions. For FDA officers or employees who are directed by policy
to obtain agency review or clearance prior to their work’s publication or presentation, FDAAA
provides a timeline for such review or clearance. Nothing in the policy is to be construed as
affecting any restrictions on publication or presentation provided by other law.
The second topic addressed in Subtitle A is the introduction of a priority review voucher as an
incentive to develop medical products that treat tropical diseases. Qualifying diseases are those



listed in the law, and any other infectious disease the Secretary designates by regulation. Diseases
designated by regulation must disproportionately affect poor and marginalized populations, and
must have treatments with no significant market in developed nations. The FDAAA provision
adds a new use to the older FDA priority review mechanism. Rather than (or in addition to)
providing the possible financial benefit of priority review to a sponsor for its tropical disease
product application, FDAAA directs FDA to reward that sponsor for developing that product by
giving it a priority review voucher that it can use for any one proposed subsequent product that
would not otherwise qualify for priority review. The new provision further alters FDA’s priority
review mechanism by allowing the tropical disease product sponsor to transfer the voucher,
including by sale, to another entity. The Secretary is to establish a user fee program and set the
fee amounts for sponsors of human drug applications that are the subject of a priority review
voucher.
The third topic addressed is the regulation of genetic testing. FDAAA requires that, if the
specified Secretary’s Advisory Committee does not complete and submit its report and
recommendations regarding regulation and oversight of genetic testing to the Secretary by July
2008, the Secretary is to enter into a contract with the IOM to conduct a study and issue a report
on the topic.
The fourth topic consists of technical amendments to sections of the PHSA (42 USC 201 et seq.),
making five changes. Though the section is titled “NIH Technical Amendments,” the first
provision does not apply to NIH, but is rather a correction to P.L. 109-417, the Pandemic and All-
Hazards Preparedness Act, and applies to the hospital preparedness program administered by the
HHS Assistant Secretary for Preparedness and Response. The provision amends PHSA Section

319C-2 to make appropriate reference to the applicable funding formula for hospital preparedness 27


and surge capacity grants. The second provision adds minority health disparities to the types of
data that the NIH Director is to assemble to assess research priorities. The third provision adds
postdoctoral training funded through research grants to the list of research activities that the NIH
Director is required to catalog in a biennial report to Congress. The fourth provision designates
PHSA 403C (relating to the drug diethylstilbestrol) as 403D. The fifth provision specifies that
each institution that receives an NIH award for training graduate students under its subchapter
(PHSA, Title IV, Part A) need only report to NIH information regarding postdoctoral training
funded through research grants, and not each degree-granting program at the institution. It further
indicates that leaves of absence are to be subtracted when calculating the average time between
graduate study and receipt of a doctoral degree.
The fifth topic addressed is severability. It directs that if any provision of FDAAA is found to be
unconstitutional, the remainder of the Act shall remain in effect.
FDAAA addresses antibiotic access and innovation by amending both the FFDCA and the PHSA.
It also requires a GAO report assessing the effect of these provisions.
Under separate sections of the FFDCA, FDA both regulates antibiotics and provides incentives
for the development of orphan drugs. FDAAA links those approaches by amending the Orphan
27
See CRS Report RL33589, The Pandemic and All-Hazards Preparedness Act (P.L. 109-417): Provisions and
Changes to Preexisting Law, by Sarah A. Lister and Frank Gottron.





Drug Act to require the Commissioner to consider (including convening a public meeting) which
serious and life-threatening infectious diseases might be designated as rare diseases. If
appropriate, the Secretary, by issuing new guidance, could designate product development
activities for those diseases as qualifying for grants and contracts under the Orphan Drug Act.
FDAAA also extends the Secretary’s authority to issue grants and contracts for orphan drug
development, and authorizes the appropriation of $30 million for each of FY2008 through
FY2012.
FDAAA also adds a new subsection to FFDCA that allows a sponsor to consider as the same
active ingredient a specific kind of chemical variant (a non-racemic drug) of an ingredient in an
approved (racemic) drug. In addition, a separate provision of the law amends the PHSA to require
the Secretary, through the Commissioner, to make publicly available clinically susceptible
concentrations of bacteria (amounts that characterize the level of bacterial susceptibility and
resistance to a drug).




Table 14. Comparison of Other Provisions, Subtitle A (FDAAA Title XI, Subtitle A) with Previous Law
Topic Previous Law FDAAA Title XI, Subtitle A
Policy on the Review No parallel provision in 21 USC 371. The Secretary is required to establish and make publicly available written policies to implement the
and Clearance of publication provisions and govern the timely submission, review, clearance, and disclaimer requirements
Scientific Articles for articles. Article means a paper, poster, abstract, book, book chapter, or other published writing.
Published by FDA An FDA employee or officer required by FDA policy to submit an article for review and clearance prior
Employees to publication or presentation must do so not less than 30 days in advance. Within 30 days, the
reviewer may provide written clearance, which may contain the condition of specified changes. If the
supervising official has not cleared or reviewed the article as of the 31st day after submission, the
employee may consider the article not to have been cleared, and may submit or present it with an
appropriate disclaimer. Nothing in the policy shall be construed as affecting any restrictions on
publication or presentation provided by other law. [FDAAA 1101; FFDCA 713; 21 USC 379d-2]
Tropical Disease No provision. The sponsor of an application for an eligible tropical disease product that is approved after FDAAA
Priority Review enactment shall receive a priority review voucher for use with a later application. Priority review is
defined by FFDCA 735(1) to mean review and action by the Secretary on such application not later
than 6 months after receipt by the Secretary of such application, as described in the FDA Manual of
iki/CRS-RL34465Policies and Procedures, and goals identified in the letters described in FDAAA 101(c). Qualifying
g/wdiseases include tuberculosis, malaria, blinding trachoma, Buruli ulcer, cholera, dengue/dengue
s.orhaemorrhagic fever, dracunculiasis (guinea-worm disease), fascioliasis, human African trypanosomiasis,
leakleishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, schistosomiasis, soil transmitted helmithiasis, and yaws. The Secretary may also include, by regulation, any other infectious disease that has no
://wikisignificant market in developed nations and that disproportionately affects poor and marginalized populations. The Secretary is to establish a user fee program and annually set the fee amount to be paid
httpwith the submission of the human drug application for which the voucher is used. [FDAAA 1102;
FFDCA 524; 21 USC 360n]
Improving Genetic No provision. If the Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS) does not complete
Test Safety and Quality and submit the Regulatory Oversight of Genetic/Genomic Testing Report and Action Recommendations to the
Secretary by July 2008, the Secretary shall enter into a contract with the IOM to conduct a study to
assess the overall safety and quality of genetic tests and prepare a report that includes
recommendations to improve federal oversight and regulations of genetic tests. The study is to take
into account relevant reports by SACGHS and other groups, and to be completed not later than one
year after the date the contract was entered. Nothing in the section is to be construed to require the
delay of related federal regulatory efforts. [FDAAA 1103]




Topic Previous Law FDAAA Title XI, Subtitle A
Under P.L. 109-417, the Pandemic and All-The amounts of appropriations awards to states and political subdivisions supporting partnerships for NIH Technical
Hazards Preparedness Act, regarding the state and regional hospital preparedness to improve surge capacity is to be determined based upon the Amendments
hospital preparedness program applicable funding formula for hospital preparedness and surge capacity grants (PHSA 319C-1(i)).
administered by the HHS Assistant [FDAAA 1104(1); PHSA 319C-2(j)(3)(B); 42 USC 247d-3b]
Secretary for Preparedness and Response,
the amounts of awards to states and
political subdivisions supporting
partnerships for state and regional hospital
preparedness to improve surge capacity
was to be determined based upon PHSA
319C-1(h) [grants for real time disease
detection improvement].
The NIH Director was to assemble The NIH Director is to assemble accurate data to be used to assess research priorities including
accurate data to be used to assess research information to better evaluate scientific opportunity, public health burdens, and progress in reducing
priorities, including information to better minority and other health disparities. [FDAAA 1104(2); PHSA 402(b)(4); 42 USC 282]
evaluate scientific opportunity, public health
burdens, and progress in reducing health
iki/CRS-RL34465disparities.
g/wThe NIH Director was required to submit The NIH Director is required to submit to Congress a biennial report consisting of, among other
s.orto Congress a biennial report consisting of, information, training activities, including investigator-initiated awards for postdoctoral training and
leakamong other information, training activities, postdoctoral training funded through research grants. [FDAAA 1104(3); PHSA 403(a)(4)(C)(iv)(III); 21 USC
including investigator-initiated awards for 283]
://wikipostdoctoral training.
httpThe PHSA section relating to the drug The PHSA section relating to the drug diethylstilbestrol is redesignated as 403D. [FDAAA 1104(4); PHSA
diethylstilbestrol was the second of two 403D; 21 USC 283a-3]
sections numbered 403C.
Each institution receiving an award under Each institution receiving an award under this title [PHSA, Title IV] for the training of graduate students
this title [PHSA, Title IV] for the training of for doctoral degrees shall annually report to the NIH Director, with respect to its NIH-supported
graduate students for doctoral degrees graduate students at such institution: (1) the percentage of such students admitted for study who
shall annually report to the NIH Director, successfully attain a doctoral degree; and (2) for students described in paragraph (1), the average time
with respect to each degree-granting (not including any leaves of absence) between the beginning of graduate study and the receipt of a
program at such institution: (1) the doctoral degree. (Emphasis added). [FDAAA 1104(5); PHSA 403C(a); 42 USC 283a-2]


percentage of students admitted for study
who successfully attain a doctoral degree;
and (2) for students described in paragraph
(1), the average time between the beginning
of graduate study and the receipt of a
doctoral degree. (PHSA 403C(a)).


Topic Previous Law FDAAA Title XI, Subtitle A
Severability Clause No provision. If any provision of FDAAA or the application of such provision or amendment is found to be
unconstitutional, the remainder of the Act and amendments made by it and the application of the
provisions of such to any person or circumstance shall not be affected thereby. [FDAAA 1105; 21 USC
301 note]
Table 15. Law Created by Antibiotic Access and Innovation (FDAAA Title XI, Subtitle B)
Topic FDAAA Title XI, Subtitle B
Clinically Susceptible The Secretary, through the Commissioner, must identify and make publicly available clinically susceptible concentrations that characterize the
Concentrations level of bacterial susceptibility and resistance to a drug. [FDAAA 1111; 42 USC 247d-5a]
The Commissioner must convene a public meeting and issue guidance, if appropriate, regarding which serious and life threatening infectious Orphan Drugs
diseases might be designated as rare diseases, making drug development for treating such diseases eligible for assistance pursuant to the
Orphan Drug Act (21 USC 360ee) or other incentives. [FDAAA 1112(a)]
iki/CRS-RL34465FDAAA reauthorizes grants and contracts for orphan drugs (21 USC 360ee), authorizing the appropriation of $30 million for each of FY2008
g/wthrough FY2012. [FDAAA 1112(b); amends Sec. 5(c) of the Orphan Drug Act; 21 USC 360ee(c)]
s.or
leakExclusivity of Certain Drugs Containing Single Enantiomers An applicant for a non-racemic drug containing, as an active ingredient, a single enantiomer that is contained in a racemic drug approved in another application, may elect to have the single enantiomer considered the same active ingredient as that contained in the approved racemic
://wikidrug, under certain circumstances. [FDAAA 1113; FFDCA 505(u); 21 USC 355]
httpGAO Report The Comptroller General, by January 1, 2012, must report to Congress regarding the effect of provisions in this subtitle in encouraging the
development of new antibiotics and other drugs; and in preventing or delaying timely generic drug entry into the market. [FDAAA 1114]






Table A-1. Appropriations Authorized in FDAAA, FY2008-FY2012
(Dollars in thousands)
Purpose FY2008 FY2009 FY2010 FY2011 FY2012
PDUFA Feesab $417,783 $427,783 $437,783 $447,783 $457,783
[FDAAA 103(b), (e)(1); 21 USC 379h(b),(e)(3)]
DTC Television Advertisement Review Feesab $6,250 $6,250 $6,250 $6,250 $6,250
[FDAAA 104; 21 USC 379h-1(b),(g)(3)]
MDUFA Feesa [FDAAA 212; 21 USC 379j(a)] $48,431 $52,547 $57,014 $61,860 $67,118
Device Postmarket Safety [FDAAA 215] $7,100 $7,455 $7,828 $8,219 $8,630
Grants for Improving Pediatric Device $6,000 $6,000 $6,000 $6,000 $6,000
Availability [FDAAA 305; 42 USC 282 note]
Program for Pediatric Studies of Drugs $200,000 such sums as may be necessary
[FDAAA 502(b); 42 USC 284m]
Critical Path Public-Private Partnerships $5,000 such sums as may be necessary
[FDAAA 603; 21 USC 360bbb-5(f)]
Clinical Trial Databasesc $10,000 $10,000 $10,000 $10,000 $10,000
[FDAAA 801(a); 42 USC 282(j)]
Active Postmarket Risk Identification and $25,000 $25,000 $25,000 $25,000 $25,000
Analysis [FDAAA 905(d); 21 USC 355 note]
Postmarket Studies and Surveillance $25,000 $25,000 $25,000 $25,000 $25,000
[FDAAA 908; 21 USC 355 note]
Development of Orphan Drugs $30,000 $30,000 $30,000 $30,000 $30,000
[FDAAA 1112(b); 21 USC 360ee(c)]
a. This authorization is for the collection of user fees from private entities.
b. FY2009 - FY2012 fee amounts are baseline numbers to be adjusted annually based upon inflation, workload,
rent, and other factors.
c. This authorization of $10 million per year continues indefinitely.







The following chart contains a listing of FDAAA action items with deadlines for government
officials. It is broken down by FDAAA title. Within each title, action items are listed by deadline.
More detailed information regarding each of the items in the chart is available in the section of
this report that corresponds to the title in which it is listed.
The following notes may be helpful to the reader. First, the chart includes federal agency
personnel deadlines with specific dates only. It does not list deadlines for action by non-
governmental personnel, though FDAAA includes many of these. Neither does it list required
actions for federal agency personnel that have no specific deadlines, though FDAAA contains
many of these as well. Second, for user ease, the title of the person required to take action is
bolded. Third, for items that require action at regular intervals (such as annual reports), only the
initial item is listed by date. The requirement for recurrence is specified in the text.




Table B-1. FDAAA Action Items with Deadlines for Government Officials, by Title and Date
Deadline Required Action
Title I: Prescription Drug User Fee Amendments of 2007
October 1, 2007 The Secretary assesses and collects DTC television advertisement review fees. [FDAAA 104; 21 USC 379h-1]
October 27, 2007 The Secretary publishes initial Federal Register notice requesting any person to notify the Secretary within 30 days of the number of DTC television
advertisements the person intends to submit for advisory review within FY2008. [FDAAA 104; 21 USC 379h-1]
December 26, 2007 The Secretary establishes DTC television advertisement
review fee amounts for FY2008. [FDAAA 104; 21 USC 379h-1]
June 1, 2008 The Secretary publishes, annually, subsequent Federal Register notices requesting any person to notify the Secretary within 30 days of the number of DTC
television advertisements the person intends to submit for advisory review within the next fiscal year. [FDAAA 104; 21 USC 379h-1]
August 1, 2008 The Secretary establishes, annually, DTC television advertisement review fee amounts for the next fiscal year. [FDAAA 104; 21 USC 379h-1]
January 28, 2009 The Secretary submits, annually through 2013, a PDUFA performance report and a PDUFA fiscal report to Congress. [FDAAA 105; 21 USC 379h-2]
iki/CRS-RL34465November 1, 2009 The Secretary terminates, annually, DTC television advertisement review fee collection program if the total of operating reserves and fee revenues falls below
g/wa required amount. [FDAAA 104; 21 USC 379h-1]
s.orJanuary 15, 2012 The Secretary transmits recommendations for PDUFA reauthorization to Congress. [FDAAA 105; 21 USC 379h-2]
leakJanuary 28, 2012 The Secretary refunds DTC television advertisement review fee amounts remaining in the operating reserve on a pro-rata basis. (Refunds occur earlier if DTC
://wikitelevision advertisement fee collection program is terminated early). [FDAAA 104; 21 USC 379h-1]
httpTitle II: Medical Device User Fee Amendments of 2007
September 27, 2008 The Comptroller General submits to Congress a report on the appropriate use of the 510(k) process to determine whether a new device is safe and
effective. [FDAAA 225]
September 27, 2008 The Comptroller General submits to Congress a report on nosocomial infections relating to medical devices. [FDAAA 229]
September 27, 2008 The Secretary submits to Congress a report on labeling information on the relationship between indoor tanning devices and the development of skin cancer
or other skin damage. [FFDCA 230]
January 28, 2009 The Secretary submits, annually through 2013, a MDUFA performance report and a MDUFA fiscal report to Congress. [FDAAA 213; 21 USC 738A]




Deadline Required Action
January 15, 2012 The Secretary transmits recommendations for MDUFA reauthorization to Congress. [FDAAA 213; 21 USC 738A]
Title III: Pediatric Medical Device Safety and Improvement Act of 2007
December 26, 2007 The Secretary issues a request for proposals for grants or contracts to nonprofit consortia for demonstration projects to promote pediatric device
development. [FDAAA 305; 42 USC 282 note]
September 27, 2008 The Secretary provides for annual review by the Pediatric Advisory Committee of pediatric devices exempted from HDE pricing restrictions. [FDAAA 303; 21
USC 260j(m)]
March 25, 2008 The Commissioner issues guidance for institutional review boards on how to evaluate requests to approve devices for which an exemption from HDE pricing
restrictions has been granted. [FDAAA 303; 21 USC 360j note]
March 25, 2008 The Secretary submits to relevant congressional committees a plan for expanding pediatric medical device research and development. [FDAA 304; 42 USC
282(b)]
June 23, 2008a The Secretary makes a determination on the grants or contracts to nonprofit consortia for demonstration projects to promote pediatric device development.
[FDAAA 305; 42 USC 282 note]
March 27, 2009 The Secretary submits to relevant congressional committees the first annual report regarding pediatric medical devices. [FDAAA 302; 21 USC 360e-1]
iki/CRS-RL34465January 1, 2012 The Comptroller General submits to relevant congressional committees a report on the impact of exempting qualifying devices from humanitarian device
g/wexemption pricing restrictions. [FDAAA 303; 21 USC 260j(m)]
s.or
leakTitle IV: Pediatric Research Equity Act of 2007
://wikiSeptember 27, 2007 The Secretary requires that sponsors of assessments that result in specified labeling changes made pursuant to PREA distribute such information to health care providers. [FDAAA 402; 21 USC 355c]
httpOctober 27, 2007 The Secretary utilizes newly established internal review committee to provide consultation to reviewing divisions on specified pediatric plans and assessments.
[FDAAA 402; 21 USC 355c]
September 27, 2008 Newly established internal committee conducts a retrospective review and analysis of PREA assessments submitted and deferrals and waivers granted since
2003. [FDAAA 402; 21 USC 355c]
September 27, 2010 The Secretary contracts with IOM to conduct a study and report to Congress regarding studies conducted pursuant to PREA or precursor regulations.
[FDAAA 402; 21 USC 355c]
January 1, 2011 The Comptroller General submits to Congress a report that addresses the effectiveness of specified provisions (PREA and BPCA) in ensuring that medicines
used by children are tested and properly labeled. [FDAAA 404]
Title V: Best Pharmaceuticals for Children Act of 2007
September 27, 2007 The Commissioner puts into effect specified dispute resolution processes to be used when the Commissioner and sponsor have been unable to reach an
agreement on appropriate labeling changes. [FDAAA 502(a)(1); 21 USC 355a]
September 27, 2007 The Secretary includes as a requirement of a written request that the sponsors of specified studies resulting in labeling changes reflected in the BPCA-specified
annual review distribute, at least annually, such information to health care providers. [FDAAA 502(a)(1); 21 USC 355a]




Deadline Required Action
September 27, 2007 The Secretary ensures that during the one-year period beginning on the date that a labeling change is approved pursuant to a specified provision of BPCA, all
adverse events reports that have been received for the drug are referred to the OPT. During the following years, the Secretary refers reports as appropriate.
[FDAAA 502(a)(1); 21 USC 355a]
September 27, 2007 The Secretary begins creating certain requirements for specified drugs for which pediatric studies have not been completed and for which there is a continuing
need for information relating to their use in pediatric populations. [FDAAA 502(a)(1); 21 USC 355a]
January 1, 2008 Unless the Commissioner issues a final rule by this date, the proposed rule entitled Toll-Free Number for Reporting Adverse Events on Labeling for Human Drug
Products takes effect. [FDAAA 502(f)]
September 27, 2008 The Secretary studies the feasibility of establishing a compilation of information on pediatric drug use and reports the finding to Congress. [FDAAA 502(b); 42
USC 284m]
September 27, 2008 The Secretary develops and publishes a priority list of needs in pediatric therapeutics. [FDAAA 502(b); 42 USC 284m]
September 27, 2010 The Secretary enters into a contract with the IOM to study and report to Congress regarding written requests made and the studies conducted pursuant to
BPCA. [FDAAA 502(a)(1); 21 USC 355a]
Title VI: Reagan-Udall Foundation
iki/CRS-RL34465October 27, 2007 The Secretary convenes a meeting of the ex officio members of the Foundation’s Board of Directors to accomplish specified purposes. [FDAAA 601; 21 USC 379dd]
g/w
s.orMarch 27, 2009 The Secretary submits, annually, a report to Congress regarding critical path public-private partnerships. [FDAAA 603; 21 USC 360bbb-5]
leakSeptember 1, 2009 The Commissioner submits, annually, to Congress a report summarizing the Foundation Director’s annual report and other information. [FDAAA 601; 21
://wikiUSC 379dd-2]
httpTitle VII: Conflicts of Interest
October 1, 2007 The Secretary determines the proportion of people who served as advisory committee members under specified conflict of interest exceptions in 2007.
[FDAAA 701; 21 USC 379d-1]
February 1, 2008 The Secretary submits, annually, to relevant congressional committees a report with specified information about conflict of interest execptions made for
advisory committee members. [FDAAA 701; 21 USC 379d-1]
September 27, 2012 The Secretary, not less than every 5 years, reviews guidance with respect to advisory committees. [FDAAA 701; 21 USC 379d-1]
Title VIII: Clinical Trial Databases
December 26, 2007 The Secretary ensures that the registry data bank contains links to existing results of those trials that form the primary basis of an efficacy claim or are
conducted after a product is approved or cleared, not later than 30 days after the results
information becomes publicly available. [FDAAA 801(a)(2); 42 USC 282(j)(3)(A)(i)]
January 25, 2008a The NIH Director ensures that clinical trial information is posted in the registry data bank for applicable trials initiated or ongoing as of December 26, 2007,
to test drugs that treat life threatening diseases or conditions. [FDAAA 801(a)(2); 42 USC 282(j)(2)(C)(i) and (D)(i)]




Deadline Required Action
September 27, 2008 The Secretary issues guidance on how the registry and data bank requirements apply to certain specified pediatric postmarket surveillance that is not a clinical
trial. [FDAAA 801(c); 42 USC 282 note]
September 27, 2008 The Secretary includes basic results in the registry and results data bank for approved drugs, licensed biologics, and approved or cleared devices. [FDAAA
801(a)(2); 42 USC 282(j)(3)(C)]
October 27, 2008 The NIH Director ensures that clinical trial information is posted in the registry data bank for applicable trials of devices cleared or approved as of September
27, 2007. [FDAAA 801(a)(2); 42 USC 282(j)(2)(D)(ii)]
March 27, 2009 The Secretary holds a public meeting regarding the inclusion of expanded results in the registry and results data bank. [FDAAA 801(a)(2); 42 USC
282(j)(3)(D)(vii)]
March 27, 2009 The NIH Director ensures that the public may search the registry data bank by safety issue being studied. [FDAAA 801(a)(2); 42 USC 282(j)(2)(C)]
March 27, 2009 The Secretary determines, by regulation, the best method for including information on serious adverse events and frequent adverse events in the registry and
results data bank. [FDAAA 801(a)(2); 42 USC 282(j)(3)(I)(i)]
September 27, 2009 If the Secretary fails to determine, by regulation, the best method for including information on serious adverse events and frequent adverse events in the
registry and results data bank, a clause in FDAAA creating a regulation on the topic takes effect. [FDAAA 801(a)(2); 42 USC 282(j)(3)(I)(ii)]
iki/CRS-RL34465October 27, 2009a The NIH Director ensures that clinical trial information is posted in the registry data bank for applicable trials initiated or ongoing as of December 26, 2007, that test drugs that treat non-life threatening diseases or conditions. [FDAAA 801(a)(2); 42 USC 282(j)(2)(C)(iii) and (D)(i)]
g/w
s.orSeptember 27, 2010 The Secretary includes, by regulation, expanded results in the registry and results data bank. [FDAAA 801(a)(2); 42 USC 282(j)(3)(D)(i)]
leakTitle IX: Enhanced Authorities Regarding Postmarket Safety of Drugs
://wikiOctober 11, 2007 The Secretary screens, bi-weekly, the existing Adverse Event Reporting System (AERS) database. [FDAAA 921; 21 USC 355]
httpDecember 27, 2007 The Secretary posts quarterly reports of new safety information or potential signals of a serious risk identified by AERS. [FDAAA 921; 21 USC 355]
March 27, 2008 The Secretary conducts a study to determine whether a statement FDAAA requires for inclusion in published direct-to-consumer advertisements is
appropriate for inclusion in television ads. [FDAAA 906(b); 21 USC 352 note]
June 27, 2008 The Commissioner publishes on FDA’s website a complete list of authorized generic drugs; updates the list quarterly; notifies relevant federal agencies about
the list and coming updates. [FDAAA 920; 21 USC 355]
September 27, 2008 The Commissioner submits to Congress a report on how best to communicate to the public the risks and benefits of new drugs and the role of risk
evaluation and mitigation strategies in assessing such risks and benefits. [FDAAA 904]
September 27, 2008 The Secretary issues guidance for the conduct of clinical trials with respect to antibiotic drugs. [FDAAA 911; 21 USC 360a]
September 27, 2008 The Secretary submits annually to Congress a report on delays in approvals per citizen petitions for stays of agency action. [FDAAA 914(a); 21 USC 355]
September 27, 2008 The Secretary submits a report to Congress on ways to encourage the early submission of citizen petitions for stays of agency action. [FDAAA 914(b)]
September 27, 2008 The Secretary develops and maintains a website providing postmarket safety information for patients and providers. [FDAAA 915; 21 USC 355]




Deadline Required Action
September 27, 2008 The Secretary issues a report responding to the 2006 IOM report: The Future of Drug Safety—Promoting and Protecting the Health of the Public. [FDAAA 919]
September 27, 2008 The Secretary annually reviews the entire backlog of postmarket safety commitments, determines which require revision or elimination, reports the
determinations to Congress, and assigns start dates and estimated completion dates for the commitments. [FDAAA 921; 21 USC 355]
March 27, 2009 The Comptroller General evaluates data privacy, confidentiality, and security issues relating to active postmarket risk identification and analysis (APRIA), and
makes recommendations to relevant congressional committees. [FDAAA 905(e)]
September 27, 2009 To prepare for the establishment of APRIA, the Secretary develops methods to access, link, and analyze safety data from disparate data sources, and convenes
a committee of experts to make recommendations to the Secretary on the development of tools and methods for the ethical and scientific uses for, and
communication of postmarketing data. [FDAAA 905(a); 21 USC 355]
September 27, 2009 The Secretary reports to Congress on FDA procedures and processes for addressing ongoing postmarket safety issues identified by the existing Office of
Surveillance and Epidemiology, and how FDA handles recommendations of the Office. [FDAAA 921; 21 USC 355]
March 27, 2010 The Secretary establishes, by regulation, standards for determining whether a major statement in a direct-to-consumer advertisement relating to side effects is
presented in the required manner. [FDAAA 901(d)(3); 21 USC 352 note]
March 27, 2010 The Secretary develops standard numerical identifiers to validate, authenticate, track and trace prescription drugs. [FDAAA 913; 21 USC 355e]
iki/CRS-RL34465September 27, 2010a The Secretary establishes and maintains the APRIA surveillance system as specified. [FDAAA 905(a); 21 USC 355]
g/wMarch 26, 2011a The Secretary establishes and implements procedures to contract with one or more qualified entities to classify or analyze aggregate APRIA data, allow for
s.orprompt investigation of priority drug safety questions, perform advanced research and analysis on identified drug safety risks, more effectively focus postapproval
leakstudies and clinical trials, and carry out other activities the Secretary deems necessary. [FDAAA 905(a); 21 USC 355]
://wikiSeptember 27, 2011 The Secretary reports to Congress on the ways the Secretary has used APRIA to identify specific drug safety signals and to better understand the outcomes associated with marketed drugs. [FDAAA 905(c)]
httpSeptember 27, 2012 The Secretary reviews and updates the guidance for the conduct of clinical trials with respect to antibiotic drugs. [FDAAA 911; 21 USC 360a]
Title X: Food Safety
March 25, 2008 The Secretary submits a report to Congress on enhanced aquaculture and seafood inspection. [FDAAA 1006; 21 USC 2105]
June 1, 2008 The Commissioner submits, annually, to Congress a report concerning the results of the Administration’s pesticide residue monitoring program. [FDAAA
1010; 21 USC 2109]
June 27, 2008 The Secretary issues a guidance to industry about submitting reports and providing notifications to other persons in the supply chain as required by
regulations related to the Reportable Food Registry. [FDAAA 1005(f); 21 USC 350f note]
September 27, 2008 The Secretary establishes an early warning and surveillance system for pet food. [FDAAA 1002(b); 21 USC 2102]
September 27, 2008 The Secretary establishes a Reportable Food Registry. [FDAAA 1005(b); 21 USC 350f]
September 27, 2008 The Secretary submits, annually, to relevant congressional committees, a report with specified information about food regulation, inspection and importation.
[FDAAA 1009; 21 USC 2108]




Deadline Required Action
September 27, 2009 The Secretary establishes for pet food, by regulation, ingredient standards, processing standards, and updated labeling standards. [FDAAA 1002(a); 21 USC
2102]
Title XI: Other Provisions
July 2008 If the Secretary’s Advisory Committee on Genetics, Health, and Society does not complete and submit a specified report on the regulation of genetic testing,
the Secretary enters into a contract with the IOM to conduct, by July 2009, a study of the safety and quality of genetic tests. [FDAAA 1103]
September 27, 2008 The Secretary may issue a priority review voucher to the sponsor of a tropical disease product. [FDAAA 1102; 21 USC 360n]
October 1, 2008 The Secretary establishes, annually, the amount of the priority review user fee. [FDAAA 1102; 21 USC 360n]
January 1, 2012 The Comptroller General submits to relevant congressional committees a report that examines specified effects of FDAAA’s Antibiotic Access and
Innovation provisions. [FDAAA 1114]
a. These dates are contingent on prior deadline(s). If an earlier task is completed prior or subsequent to the deadline specified in law, this date would be adjusted
accordingly.


iki/CRS-RL34465
g/w
s.or
leak
://wiki
http




Table C-1. FDAAA Authorities with Sunset Dates
Authority (FDAAA Title) Citation
Expiring October 1, 2012
PDUFA fee collection (I) FDAAA 106; 21 USC 379g note
DTC television advertisement fee collection (I) FDAAA 106; 21 USC 379g note
MDUFA fee collection (II) FDAAA 217; 21 USC 379i note
Third party review of premarket notification (II) FDAAA 221; 21 USC 360m(c)
Pediatric device pricing exemption in humanitarian device exemption (III) FDAAA 303; 21 USC 360j(m)
PREA pediatric study requirement (IV) FDAAA 402; 21 USC 355c
BPCA pediatric market exclusivity (V) FDAAA 502(a)(1); 21 USC 355a
Exclusivity of certain drugs containing enantiomers (XI) FDAAA 1113; 21 USC 355
Expiring January 31, 2013
PDUFA reporting requirements (I) FDAAA 106; 21 USC 379g note
MDUFA reporting requirements (II) FDAAA 217; 21 USC 379i note






APRIA active postmarket risk identification and analysis
BPCA Best Pharmaceuticals for Children Act
(P.L. 107-109, reauthorized in FDAAA Title V)
CFR Code of Federal Regulations
CRS Congressional Research Service
DTC direct-to-consumer (as in DTC advertising)
FDA Food and Drug Administration
FDAAA FDA Amendments Act of 2007 (P.L. 110-85)
FDAMA FDA Modernization Act of 1997 (P.L. 105-115)
FFDCA Federal Food, Drug, and Cosmetic Act (21 USC § 301 et seq.)
FNIH Foundation for the National Institutes of Health
GAO Government Accountability Office
HDE Humanitarian Device Exemption
HELP Senate Committee on Health, Education, Labor, and Pensions
HHS Department of Health and Human Services
IOM Institute of Medicine
MDUFA 2007 Medical Device User Fee Amendments of 2007 (FDAAA Title II)
MDUFMA Medical Device User Fee and Modernization Act of 2002
(P.L. 107-250)
NIH National Institutes of Health
OPT Office of Pediatric Therapeutics, FDA
OSE Office of Surveillance and Epidemiology, FDA
PDUFA I Prescription Drug User Fee Act of 1992 (P.L. 102-571)
PDUFA II the 1997 reauthorization of the Prescription Drug User Fee Act
(P.L. 105-115, Title I)
PDUFA III Prescription Drug User Fee Amendments of 2002
(P.L. 107-188, Title V)
PDUFA IV Prescription Drug User Fee Amendments of 2007 (FDAAA Title I)
PHSA Public Health Service Act (42 USC § 201 et seq.)
PI principal investigator
PMA Premarket Application (see MDUFMA and MDUFA 2007)
PMDSIA Pediatric Medical Device Safety and Improvement Act of 2007 (FDAAA Title III)
PREA Pediatric Research Equity Act of 2003 (P.L. 108-155, reauthorized in FDAAA
Title IV)
QC quality control
RP responsible party
USC United States Code






Erin D. Williams Susan Thaul
Specialist in Public Health and Bioethics Specialist in Drug Safety and Effectiveness
ewilliams@crs.loc.gov, 7-4897 sthaul@crs.loc.gov, 7-0562