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Prepared for Members and Committees of Congress
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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.
Introduction ..................................................................................................................................... 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
Registry ................................................................................................................................... 56
Results..................................................................................................................................... 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
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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
safety of most human foods,1 all animal feeds, and certain other products such as cosmetics.2 The
agency also regulates the safety and effectiveness of human drugs, biologics (e.g., vaccines),
medical devices, and animal drugs.3 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.
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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
is described briefly in this report, but addressed in more detail in a separate CRS report.4 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
drug and biological products and expands the authorized uses of fee revenue.5 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
budget.6
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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
1987 to 17 months in 1994.7 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 $11.25
million in fees by 120 days after enactment, the DTC advisory review user fee program shall not
commence and all collected fees shall be refunded.
Reauthorization and Report Requirements. FDAAA codifies certain core elements of the
prescription drug user fee program that, although included in PDUFA I, II, and III, were never
placed into the FFDCA. One is the requirement for annual performance and fiscal reports to
Congress. The others relate to the Secretary's interaction and communication with various
stakeholders. These include public hearings regarding the Secretary's negotiations with industry
regarding performance goals; and the requirement that the Secretary, in preparation for the next
PDUFA reauthorization, consult with congressional committees, scientific and academic experts,
health-care professionals, representatives of patient and consumer advocacy groups, and the
regulated industry to develop recommendations for PDUFA V, including goals and plans for
meeting the goals.
Effective Dates. The amendments in this title took effect on October 1, 2007. Authority to assess,
collect, and use drug fees ceases to be effective October 1, 2012. The reporting requirements
cease to be effective January 31, 2013.
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fi latot eunever eef eht )noillim 7.11$ ot pu( esaerced ot yraterceS eht stcerid wal ehT .noisivorp oN -tneR dna tneR
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AAADF[ .segnahc etairporppa yna ekam tsum ,detelpmoc neeb sah yduts eht
ecno ,dna ,detelpmoc neeb sah yduts eht sselnu segnahc ekam ton yam yraterceS ehT
.snoitadnemmocer detnarraw yna ekam dna seitivitca weiver ni segnahc rof tnemtsujda
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.noitalfni
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na naht erom ni tluser ton yam seitivitca weiver ni segnahc rof tnemtsujda ehT dehsilbatse esoht naht ssel erew taht raey lacsif a rof seunever
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.dettimbus stnemelppus gnirutcafunam dna ,stnemelppus
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.detsujda sa ,7002YF rof 000,003,952$ dna
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rof dereviled ro decudortni dna noitacilppa gurd namuh a rednu devorppa
neeb sah taht tcudorp gurd a evah ton od taht esoht ot sessenisub elbigile worran ot
dednapxe si ssenisub llams a fo noitinifed eht ,seef fo snoitcuder dna sreviaw gnidrageR
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]h973 CSU
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eht fo stessa dna secnatsmucric eht ylno redisnoc yam yraterceS eht ,noitcuder
ro reviaw a tnarg ot rehtehw gnidiced ni ,taht dna ,tnacilppa eht sa deman si ohw
nosrep a ot seef fo noitcuder ro reviaw a stnarg yraterceS eht taht seificeps AAADF
]h973 CSU 12 ;)d(637 ACDFF ;)d(301
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I eltiT AAADF waL suoiverP cipoT
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launna eht etisbew ADF eht no elbaliava ylcilbup ekam tsum yraterceS ehT .noisivorp oN
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taht tcerid ton did tub stroper eht deriuqer noitalsigel AFUDP suoiverP .ssergnoC ot stroper ecnamrofrep dna lacsif launna timbus tsum yraterceS ehT stropeR launnA
]1-h973 CSU 12 ;)d(B637 ACDFF ;401 AAADF[ .noituloser
rieht dna snoinipo fo secnereffid ro seisrevortnoc tnacifingis yna dna ytrap gnitaitogen
yna yb edam slasoporp evitnatsbus yna fo seirammus gnidulcni ,yrtsudni detaluger
eht htiw sgniteem noitaitogen ycnega lla fo setunim eht etisbew ADF eht no elbaliava
ylcilbup ekam tsum yraterceS eht ,ssergnoC ot snoitadnemmocer gnitneserp erofeB
.meht ot esnopser ni snoitadnemmocer
eht ot edam segnahc dna stnemmoc cilbup eht fo yrammus a ssergnoC ot noissimbus
eht htiw edulcni tsum yraterceS eht dna ,yrtsudni eht htiw snoitaitogen sti gniwollof
dleh eb tsum snoitadnemmocer s'yraterceS eht fo weiver dna gniraeh cilbup A
.slaog
eht gniteem rof snalp dna slaog gnidulcni ,V AFUDP rof snoitadnemmocer poleved ot
yrtsudni detaluger eht dna ,spuorg ycacovda remusnoc dna tneitap fo sevitatneserper
,slanoisseforp erac-htlaeh ,strepxe cimedaca dna cifitneics ,seettimmoc lanoissergnoc .yrtsudni lacituecamrahp eht dna ycnega eht neewteb
htiw tlusnoc ,noitazirohtuaer AFUDP txen eht rof noitaraperp ni ,tsum yraterceS ehT ,ACDFF yb deriuqer ,snoitaitogen morf tluser slasoporp ehT
]2-h973 CSU 12 ;)b(,)a(B637 ACDFF ;501 AAADF[ .noisivorp siht deifidoc AAADF
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llahs margorp eef resu weiver yrosivda tnemesitrevda noisivelet CTD eht ,denibmoc
seef evreser gnitarepo dna seef weiver yrosivda ni noillim 52.11$ tsael ta deviecer ton
sah yraterceS eht ,tnemtcane retfa syad 021 ro ,7002 ,1 rebmevoN fo retal eht yb ,fI
.dnuf gnitarepo na hsilbatse
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8002YF fo hcae rof eunever ni noillim 52.6$ sezirohtua wal ehT .eef evreser gnitarepo
na dna eef weiver yrosivda na edulcni dluow hcihw ,seef wen eht dessessa eb dluow
sweiver hcus tseuqer taht srerutcafunam ylnO .yrosivda eb dluow sesnopser ADF
dna ,yratnulov eb dluow stnemesitrevda gurd noisivelet )CTD( remusnoc-ot-tcerid stnemesitrevdA
fo weiver noitanimessid-erp rof stseuqer rerutcafunaM .stnemesitrevda gurd niatrec fo weiveR yrosivdA
fo weiver yrosivda ot gnitaler seef fo noitcelloc dna tnemssessa eht sezirohtua wal ehT .noisivorp oN eht rof seeF resU
I eltiT AAADF waL suoiverP cipoT
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ton ;601 AAADF[ .3102 ,13 yraunaJ evitceffe eb ot esaec stnemeriuqer gnitroper ehT
.]8002 ,92 yraunaJ[ retal syad 021 evitceffe eb ot desaec
]eton g973 CSU 12 ;ACDFF ni ton ;601 AAADF[ .2102 stnemeriuqer gnitroper eht dna ,7002 ,1 rebotcO evitceffe
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I eltiT AAADF waL suoiverP cipoT
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
(MDUFMA; P.L. 107-250). MDUFMA established user fees for premarket applications (PMAs),8
premarket notifications (510(k)s),9 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.
ees ,noitamrofni rehtruf roF
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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
user fees comprised 9.0% of the agency's user fee revenue, and 1.8% of its total budget.10
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 FDA's 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
("Commitment Letter").12 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).
12
"Commitment 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
premarket activities.13
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.
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eht gnirussa rof dna snoitacilppa fo weiver eht gnitidepxe drawot detacided era seeF eht gniteem ot detacided eb lliw eltit siht yb dezirohtua seef ehT
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.raey lacsif tneuqesbus hcae dna 5002YF rof yrassecen eb yam
]512 sa smus hcus fo esaercni na ,4002YF rof 000,000,6$ fo esaercni
AAADF[ .2102YF rof 490,036,8$ dna ,1102YF rof 831,912,8$ ,0102YF rof 057,728,7$ na ,3002YF rof 000,000,3$ fo esaercni na :)noitairporppa 2002YF noitazirohtuA
,9002YF rof 000,554,7$ ,8002YF rof 000,001,7$ :secived lacidem no noitamrofni eht evoba sesaercni era stnuoma( secived lacidem fo ecnallievrus snoitairporppA
ytefas tekramtsop rof detairporppa eb ot dezirohtua era stnuoma gniwollof ehT tekramtsop rof dezirohtua erew stnuoma gniwollof ehT tekramtsoP
]1-j973 CSU 12
;A837 ACDFF ;312 AAADF[ .ACDFF eht otni nettirw era stnemeriuqer
detaler-laog ecnamrofrep dna ,ssergnoC ot dettimsnart eb ot era snoitadnemmocer
,stnemmoc cilbup fo noitaredisnoc nopu desiver eb ot era snoitadnemmoceR
tnempoleveD
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a edivorp ,retsigeR laredeF eht ni snoitadnemmocer sti hsilbup ,spuorg remusnoc dna lanoisseforp ,latnemnrevog fo yarra na htiw tlusnoc ot deriuqer si ADF ecnamrofreP
]1-j973 CSU 12 ;A837 ACDFF ;312 AAADF[ .esnopser
etelpmoc a nevig ton sah yraterceS eht hcihw rof strohoc suoiverp lla no noitamrofni
edulcni ot si troper ecnamrofrep ehT .ACDFF eht otni nettirw si tnemeriuqer ehT
]1-j973 CSU 12 ;A837 ACDFF stnemeriuqeR
;312 AAADF dna ;301 AMFUDM[ .troper lacsif dna troper laog ecnamrofrep a seettimmoc lanoissergnoc tnaveler ot yllaunna timbus ot deriuqer si yraterceS gnitropeR
])3()h(j973 CSU 12 ;)4()h(837 ACDFF ;)2()h(212 AAADF[ .doirep
emas eht rof dezirohtua tnuoma eht dedeecxe doirep raey-ruof eht ni detcelloc .raey tneuqesbus eht rof detcelloc
tnuoma eht fi ylno )2102YF ,.e.i( raey lanif eht ni seef ni edam eb ot si noitcuder eb ot dezirohtua seef morf detcartbus neeb evah tsum raey lacsif a
A .etagergga ni deredisnoc eb ot era 1102YF dna 8002YF neewteb detcelloc seef resU rof noitairporppa dezirohtua eht dedeecxe taht detcelloc seef resU tesffO
])3()h(j973 .7002YF rof
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rof 000,068,16$ ;0102YF rof 000,410,75$ ;9002YF rof 000,745,25$ ;8002YF rof ;4002YF rof 000,552,72$ ;3002YF rof 000,521,52$ :detairporppa snoitairporppA
000,134,84$ :detairporppa eb ot dezirohtua era seef resu fo stnuoma gniwollof ehT eb ot dezirohtua erew seef resu fo stnuoma gniwollof ehT fo noitazirohtuA
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seef resu tcelloc ton yam yraterceS eht esle ro ,rotcaf tnemtsujda na yb deilpitlum 027,502$ naht ssel tnecrep eno naht erom eb tsum snoitairporppa tceriD snoitidnoC
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A eltitbuS ,II eltiT AAADF waL suoiverP cipoT
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dettimbus ot era ,secived detropmi rof sa llew sa ,secnairav ro snoitpmexe
detnarg secived rof stroper tneve esrevdA .ecnairav ro noitpmexe .)stroper tneve seciveD niatreC
na stnarg yraterceS eht sselnu ,)secived lacidem rof gnitroper tneve esrevda esrevda( secived lacidem rieht htiw detaicossa shtaed ro seirujni suoires rof gnitropeR
gnidrager( 308 RFC 12 htiw ylpmoc yllareneg tsum stroper tneve esrevdA troper ot deriuqer yllareneg erew sretropmi dna srerutcafunam eciveD fo ycneuqerF
]i063 CSU metsyS
12 ;)f(915 ACDFF ;622 AAADF[ .secived lacidem rof metsys noitacifitnedi noitacifitnedI
euqinu a gnihsilbatse snoitaluger etaglumorp ot deriuqer si yraterceS ehT .noisivorp oN eciveD euqinU
.reviaw rof tseuqer a detnarg gnitsiL
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.reviaw a stnarg yraterceS eht sselnu yllacinortcele elif tsum stnartsigeR yb gnidnif a nopu snaem cinortcele yb elif ot dah evah dluow stnartsigeR cinortcelE
])2()j(063 CSU 12
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rep ecno snoitcnuf cificeps mrofrep yeht hcihw no secived fo tsil a edivorp .rebmeceD dna enuJ ni ,raey rep eciwt snoitcnuf cificeps demrofrep
tsum yraterceS eht htiw retsiger taht srecudorp eciveD ])b(063 CSU 12 yeht hcihw no secived fo tsil a edivorp ot deriuqer erew yraterceS eht
;)b(015 ACDFF ;222 AAADF[ .raey hcae fo 13 rebmeceD dna 1 rebotcO htiw deretsiger taht srecudorp eciveD .raey hcae fo 13 rebmeceD ot roirp
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noitacifitoN
tekramerP ytraP
])c(mm063 CSU 12 ;)c(325 drihT fo weiveR
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B eltitbuS ,II eltiT waL suoiverP cipoT
waL suoiverP htiw )B eltitbuS ,II eltiT AAADF( B eltitbuS ,7002 tcA eeF resU eciveD lacideM fo nosirapmoC .4 elbaT
]032 AAADF[ .egnahc lebal a stnarraw egamad niks fo tnempoleved
eht dna esu ecived gninnat roodni neewteb pihsnoitaler eht rehtehw no
yduts a tcudnoc ot deriuqer si ADF ehT ]922 AAADF[ .secived lacidem ot
gnitaler snoitcefni laimocoson snrecnoc yduts OAG deriuqer rehtonA ]522
AAADF[ .evitceffe dna efas si ecived a rehtehw enimreted ot )noitacifiton .snoitalupop cirtaidep rof sdraugefas
tekramerp( )k(015 ACDFF rednu ssecorp eht fo esu etairporppa etauqeda dedivorp metsys ecnallievrus tekramtsop ecived lacidem
eht no yduts eno tcudnoc ot deriuqer si lareneG rellortpmoC ehT eht rehtehw no yduts MOI na tseuqer ot deriuqer saw yraterceS ehT stropeR
])g(473 CSU 12 ;)g(407 ACDFF
;822 AAADF[ .stroper noitcepsni ytrap driht rof tamrof deriuqer eht
gniyficeps nehw tnuocca otni sdradnats lanoitanretni htiw noitazinomrah
ekat ot si yraterceS ehT .deteled si noitcepsni ytrap detidercca
no noitcirtser "detacidni noitca laiciffo" ehT .eurtnu si dedivorp noitamrofni
fi ecnaraelc yned yam yraterceS ehT .syad 06 nihtiw noitamrofni ".detacidni noitca
rof tseuqer s'yraterceS a ot dnopser ot deriuqer si nosrep detidercca laiciffo" fo gnidnif a retfa detcirtser saw noitcepsni ytrap detidercca na
ro tnemhsilbatse nA .ytilibigile s'tnemhsilbatse na fo tnenopmoc a regnol on fo esu s'tnemhsilbatse nA .noitamrofni rof tseuqer s'yraterceS a ot dnopser
si yraterceS eht yb tnemhsilbatse eht fo noitcepsni na sezingocer detekram ot nosrep detidercca ro tnemhsilbatse na rof deificeps saw doirep emit oN
si ecived eht hcihw ni yrtnuoc a fo wal eht taht tnemetats A .devomer .yraterceS eht yb tnemhsilbatse eht fo noitcepsni na sezingocer detekram
era snoitcirtser emit ytilibigile tnemhsilbatse eciveD .ecnamrofnoc si ecived eht hcihw ni yrtnuoc a fo wal eht taht tnemetats a gnittimbus yb
fo etacifitrec reh ro sih fo noitaripxe ro ,noitcirtser ,noisnepsus tem neeb evah dluoc ytilibigile fo tnenopmoc enO .ytilibigile tnemhsilbatse
,lawardhtiw yna fo yraterceS eht yfiton ot deriuqer si nosrep detidercca ecived ot deilppa snoitcirtser emit niatreC .detidercca neeb evah snosreP detiderccA
nA .deteled si timil ytrap detiderccA .deteled si egaugnal pu-trats margorP dluoc seitrap 51 fo mumixam A .dedulcni saw egaugnal pu-trats margorP yb snoitcepsnI
B eltitbuS ,II eltiT waL suoiverP cipoT
¢
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.
lavorppA eciveD lacideM ehT ,62823LR tropeR SRC ees ,lavorppa ecived lacidem tuoba noitamrofni rehtruf roF
.smailliW .D nirE yb ,seussI evitalsigeL detaleR dna ssecorP
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
520(m).14 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
studies as a condition of approval for class II or III devices15 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.
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eht )5( dna ;rebmun noitubirtsid launna elbawolla eht sdeecxe detubirtsid
secived fo rebmun eht fi yraterceS eht seifiton yletaidemmi tnacilppa
eht )4( ;EDH eht rof yraterceS eht yb deificeps rebmun eht deecxe ton
yam taht yraterceS eht yb deificeps rebmun noitubirtsid a deecxe ton seod
detubirtsid secived fo rebmun eht )3( ;tnemtcane fo etad s'tca eht ot roirp
esu cirtaidep rof devorppa ton saw ecived eht )2( ;noitalupopbus cirtaidep
a ni esu rof delebal si dna taert ot dednetni si ecived eht )1( :tem era airetirc
gniwollof eht fi ecived eht fo noitubirtsid dna ,noitacirbaf ,tnempoleved
dna hcraeser fo stsoc eht sdeecxe taht tnuoma na rof ecived eht lles ot
dettimrep si EDH na detnarg nosrep a tub ,sniamer noitibihorp lareneg ehT
noitpmexE
])3()m(025 ACDFF[ .ecived eht fo noitubirtsid eciveD nairatinamuH
dna ,noitacirbaf ,tnempoleved dna hcraeser fo stsoc eht sdeecxe taht tnuoma na rof ecived eht lles ot dettimrep ton si EDH na detnarg nosrep A ot noitacifidoM
].qes te 153 CSU 12 ;)c(,)b(A515
ACDFF ;203 AAADF[ .rehtona ot detalopartxe eb dluoc eno morf atad noitalopartxE
fi yrassecen eb ton yam noitalupopbus cirtaidep hcae rof yduts A .etairporppa noitalupopbuS dna
sa ,snoitalupopbus cirtaidep ni ssenevitceffe fo ecnarussa elbanosaer ssenevitceffE cirtaideP
a troppus ot desu eb nac atad tluda taht edulcnoc yam yraterceS ehT .noisivorp oN fo noitanimreteD
].qes te 153
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semit weiver eht )4( dna ;esu fo snoitidnoc cirtaidep ot tnausrup eef a morf
detpmexe secived cirtaidep devorppa fo rebmun eht )3( ;esu cirtaidep rof
delebal secived fo rebmun eht )2( ;taert ot dednetni si ecived eht noitidnoc ro
esaesid eht morf sreffus noitalupopbus cirtaidep a hcihw rof devorppa secived
fo rebmun eht )1( :raey gnidecerp eht rof ,sedulcni taht ,ecremmoC dna
ygrenE no eettimmoC esuoH eht dna ,)PLEH( snoisneP dna robaL ,noitacudE
,htlaeH no eettimmoC eht ot troper launna na timbus ot si yraterceS ehT .noisivorp oN tropeR launnA
].qes te 153 CSU 12 ;)2(,)1()a(A515 ACDFF ;203 AAADF[
.stneitap cirtaidep detceffa fo rebmun eht dna ,taert ot dednetni si ecived
eht noitidnoc eht morf reffus taht snoitalupopbus cirtaidep yna fo noitpircsed
a ,elbaliava ylidaer fi ,edulcni ot era )m(025 ro 515 ACDFF rednu stnacilppA .noisivorp oN seciveD weN
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]eton
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rof lavorppa rof stseuqer etaulave ot woh no seettimmoc weiver lanoitutitsni
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])m(j063 CSU 12 ;)8(,)7()m(025 ACDFF
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cirtaidep eht detnarg secived lla fo eettimmoC eht yb weiver launna na rof
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weiver cidoirep a edivorp ot si rotceriD TPO .TPO eht ot noitibihorp ecirp
EDH eht morf tpmexe secived gnidrager stneve esrevda troper ot deriuqer
si yraterceS eht dna ,tceffe ni niamer stnemeriuqer tneve esrevda gurd ehT
stropeR
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na fo troper yna ,A505 ACDFF rednu ytivisulcxe tekram fo doirep a deviecer gurd a hcihw no etad eht no gninnigeb doirep raey-eno eht gniruD tnevE esrevdA
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eht sah noitalupopbus cirtaidep ,A515 ACDFF dna EDH eht fo sesoprup roF
noitalupopbuS
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eht ,rebmun noitubirtsid launna detcejorp eht dedeecxe detekram secived fo
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cirtaidep wen eht rednu dlos secived fo rebmun eht ,000,4 ot pu ,yfidom noitacifidoM
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.elur cirtaidep wen eht rednu stnemeriuqer ssenevitceffe morf noitpmexe
EDH na detnarg nosrep yna rof raey radnelac yna gnirud detubirtsid noitcepsnI
secived fo rebmun eht ot gnitaler sdrocer eht tcepsni yam yraterceS ehT .noisivorp oN EDH cirtaideP
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63 naht regnol fo seiduts tekramtsop ,lavorppa fo noitidnoc a sa ,eriuqer
yam yraterceS eht revewoh ;seilppa llits noitatimil htnom-63 lareneg ehT
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a taht ,lavorppa fo noitidnoc a sa ro redro yb ,eriuqer yam yraterceS ehT tcudnoc rerutcafunam a taht ,redro yb ,eriuqer yam yraterceS ehT tekramtsoP
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]eton 282 CSU 24
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,stnarg noitartsnomed eht roF .yllaunna yraterceS eht ot sutats tnempoleved
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stnarg gniviecer aitrosnoC .ecnatsissa ssenisub edivorp dna ,secruoser laredef
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htiw srotavonni tcennoc pleh ot era stnarG .tnempoleved ecived cirtaidep cirtaideP gnivorpmI rof
etomorp ot tcejorp noitartsnomed a hsilbatse ot deriuqer si yraterceS ehT .noisivorp oN stnarG noitartsnomeD
])b(403 AAADF[ .tnempoleved dna hcraeser ecived lacidem
cirtaidep gnidnapxe rof nalp a seettimmoC ecremmoC dna ygrenE esuoH dna
PLEH etaneS eht ot timbus ot deriuqer si ,ytilauQ dna hcraeseR erachtlaeH hcraeseR
rof ycnegA eht dna HIN fo srotceriD eht htiw noitaroballoc ni ,renoissimmoC eciveD lacideM
eht hguorht gnitca ,yraterceS eht ,tnemtcane retfa syad 081 naht retal toN .noisivorp oN cirtaideP rof nalP
])b(282 CSU
24 ;)32()b(204 ASHP ;403 AAADF[ .tnempoleved ecived lacidem cirtaidep
rof elbaliava gnidnuf fo secruos emos yfitnedi snaicisyhp dna srotavonni gnidnuF elbaliavA
pleh ot eciffo ro tcatnoc fo tniop a etangised ot deriuqer si rotceriD HIN .noisivorp oN rof tcatnoC fo tnioP
III eltiT AAADF waL suoiverP cipoT
]l063 CSU 12 ;)c(225 ACDFF ;703
AAADF[ .htlaeh cilbup tcetorp ot yrassecen sselnu ecnaraelc ro lavorppa fo
noitaloiv ni esiwrehto ro ,dednarbsim ,detaretluda demeed eb ton llahs ecived
eht emit hcihw gnirud ,noitces siht rednu ecnallievrus tekramtsop gniriuqer
noitidnoc ro redro yna fo )noituloser etupsid( 265 ACDFF rednu weiver
a tseuqer osla yam rerutcafunam a ,weiver fo sthgir suoiverp ot noitidda nI
]1-bbb063 CSU 12 ;265 ACDFF[ .rerutcafunam ro ,tnacilppa ,rosnops a saw ohw
nosrep a dna yraterceS eht neewteb ysrevortnoc cifitneics a si ereht hcihw revo 153 ASHP ro ACDFF rednu secived ro sgurd gninrecnoc noitagilbo
yna gnidrager ,eettimmoc yrosivda ro lenap yrosivda cifitneics etairporppa na yb weiver ylemit a rof erudecorp a edivorp ot deriuqer si yraterceS ehT noituloseR etupsiD
III eltiT AAADF waL suoiverP cipoT
¢
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
and development.16
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.
efaS erA nerdlihC ot debircserP sgurD tahT erusnE ot ytirohtuA s'ADF ,68933LR tropeR SRC ees ,noitamrofni rehtruf roF
.luahT nasuS yb ,evitceffE dna
In 1998, FDA published the Pediatric Rule, which mandated that manufacturers submit pediatric
testing data, referred to as a pediatric assessment, at the time of all new drug applications. In
2002, a federal court declared the rule invalid, holding that FDA lacked the statutory authority to
promulgate it.17 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.)
]c553 CSU 12
;)2()a(B505 ACDFF ;)a(204 AAADF[ .snoisulcnoc noitalopartxe eht troppus
taht atad fo noitatnemucod feirb a edulcni tsum noitacilppa na rof weiver A
]c553 CSU 12 ;)B()2()a(B505 ACDFF ;)a(204 AAADF[ .puorg ega rehtona ot detalopartxe
eb nac puorg ega eno morf atad fi puorg ega cirtaidep hcae ni dedeen eb ton yam yduts A .seiduts citenikocamrahp sa hcus ,stneitap cirtaidep ni
deniatbo noitamrofni rehto htiw detnemelppus yllausu ,stluda ni seiduts dellortnoc-llew dna etauqeda morf noitalopartxe no desab ssenevitceffe cirtaidep
egduj ot yraterceS eht sezirohtua AAADF ,stneitap cirtaidep dna stluda ni ralimis yltneiciffus era gurd eht fo stceffe eht dna esaesid eht fo esruoc eht fI
]c553 CSU 12 ;)2()a(B505 ACDFF
;)a(204 AAADF[ .evitceffe dna efas si tcudorp lacigoloib eht ro gurd eht hcihw rof noitalupopbus cirtaidep hcae rof noitartsinimda dna gnisod troppus
ot dna ,snoitalupopbus cirtaidep tnaveler lla ni snoitacidni demialc eht rof tcudorp lacigoloib eht ro gurd eht fo ssenevitceffe dna ytefas eht ssessa ot
etauqeda era taht ,deriuqer si tnemssessa eht hcihw rof puorg ega hcae rof snoitalumrof etairporppa gnisu derehtag ,atad niatnoc tsum stnemssessa ehT
]c553 CSU 12 ;)1()a(B505 ACDFF
;)a(204 AAADF[ .tnemtcane s'AAADF fo etad eht retfa ro no dettimbus
snoitacilppa ot seilppa tcA siht taht seificeps wal gnizirohtuaer ehT
]c553 CSU 12 ;)1()a(B505 stcudorP lacigoloiB
ACDFF ;)a(204 AAADF[ .tnemssessa cirtaidep a noitacilppa eht htiw timbus tsum noitartsinimda fo etuor wen ro ,nemiger gnisod wen ,mrof egasod dna sgurD weN
wen ,noitacidni wen ,tneidergni evitca wen a htiw cigoloib ro gurd a tekram ot )noitacilppa na ot tnemelppus a ro( noitacilppa na gnittimbus nosrep A gnidrageR ytirohtuA
VI eltiT AAADF waL suoiverP cipoT
waL suoiverP htiw )VI eltiT AAADF( 7002 fo tcA ytiuqE hcraeseR cirtaideP fo nosirapmoC .6 elbaT
]c553 CSU 12 ;)C()1()b(B505 ACDFF
;)a(204 AAADF[ ].gnidnif fo sepyt owt suoiverp eht fo yltnednepedni
siht no desab tca ot yraterceS eht sezirohtua AAADF[ .stneitap
cirtaidep ot ksir a esop dluoc gnilebal etauqeda fo ecnesba eht )C( ro ].sgnidnif owt rehto eht fo yltnednepedni raeppa ton did esualC[
.stneitap cirtaidep
ot sksir tnacifingis esop dluoc gnilebal etauqeda fo ecnesba eht dna
]c553 CSU 12 ;)B()1()b(B505 ACDFF ;)a(204
AAADF[ ;snoitacidni demialc eht fo erom ro eno rof stneitap cirtaidep ;snoitacidni demialc eht fo erom ro eno rof stneitap cirtaidep rof
rof seipareht gnitsixe revo tifeneb cituepareht lufgninaem a tneserper seipareht gnitsixe revo tifeneb cituepareht lufgninaem a tneserper dluow
dluow tcudorp lacigoloib ro gurd eht taht eveileb ot nosaer si ereht )B( ro tcudorp lacigoloib ro gurd eht taht eveileb ot nosaer si ereht )B( ro
]c553 CSU 12 ;)A()1()b(B505 ACDFF ;)a(204 AAADF[ ";stneitap cirtaidep ;stneitap cirtaidep
no tifeneb a refnoc dluoc" gnilebal cirtaidep etauqeda fo ecneserp eht dna ot sksir tnacifingis esop dluoc gnilebal etauqeda fo ecnesba eht dna
;snoitacidni delebal eht rof stneitap cirtaidep ;snoitacidni delebal eht rof stneitap cirtaidep
fo rebmun laitnatsbus a rof desu si tcudorp lacigoloib ro gurd eht )A( fo rebmun laitnatsbus a rof desu si tcudorp lacigoloib ro gurd eht )A(
]c553 CSU 12 ;)1()b(B505 ACDFF ;)a(204 AAADF[ :taht dnif tsum yraterceS eht ,os od oT
]c553 CSU 12 ;)1()b(B505 ACDFF ;)a(204
AAADF[ ".redloh ro rosnops" ot "redloh" sdnapxe osla tI .seiduts cirtaidep
rof HIN eht fo noitadnuoF eht ot derrefer ton saw tseuqer nettirw eht taht
dna noitacidni delebal a rof )A505 ACDFF rednu( seiduts detaler ytivisulcxe
cirtaidep rof tseuqer nettirw denilced a ot refer tsum gurd devorppa
na fo stnemssessa gniriuqer rettel s'yraterceS eht taht seificeps AAADF stcudorP
lacigoloiB dna sgurD
]c553 CSU 12 ;)1()b(B505 ACDFF ;)a(204 AAADF[ .stnemssessa deriuqer eht etad detekraM ydaerlA
deificeps a yb timbus ot esnecil scigoloib ro noitacilppa gurd devorppa na fo redloh eht eriuqer )rettel a fo mrof eht ni redro yb( yam yraterceS ehT gnidrageR ytirohtuA
VI eltiT AAADF waL suoiverP cipoT
]c553 CSU 12 ;)D()2()b(B505
dna )D()4()a(B505 ACDFF ;)a(204 AAADF[ .tcudorp lacigoloib ro gurd eht rof gnilebal eht ni dedulcni eb llahs noitamrofni eht ,snoitalupop
cirtaidep ni efasnu ro evitceffeni eb dluow tcudorp lacigoloib ro gurd a taht ecnedive si ereht esuaceb reviaw laitrap ro lluf a stnarg yraterceS eht fI gnilebaL
]c553 CSU 12 ;)C()2()b(B505 dna )C()4()a(B505 ACDFF
;)a(204 AAADF[ .etisbew ADF eht no gnitsop hguorht gnidulcni ,cilbup
edam eb yltpmorp tsum noissimbus s'tnacilppa eht ,detnarg si reviaw a
fI .depoleved eb tonnac noitalumrof cirtaidep a yhw gniliated noitatnemucod
yraterceS eht ot timbus tsum reviaw laitrap ro lluf a gnikees tnacilppa nA
]c553 CSU 12 ;)C()2()b(B505 ;)a(204 AAADF[ .noitalumrof taht
gniriuqer spuorg cirtaidep eht ylno revoc llahs reviaw eht ,noitalumrof cirtaidep a poleved ot elbissop ton si ti taht sdnuorg eht no detnarg si reviaw a fI
]c553 CSU 12 ;)B()2()b(B505 dna )B()4()a(B505 ACDFF ;)a(204
AAADF[ .deliaf evah puorg ega taht rof yrassecen noitalumrof cirtaidep a ecudorp ot stpmetta elbanosaer taht etartsnomed nac tnacilppa eht )4(
ro ;stneitap cirtaidep ot sksir tnacifingis esop ton dluoc gnilebal etauqeda fo ecnesba eht )tcudorp lacigoloib ro gurd detekram a rof( dna ,puorg ega taht
ni stneitap cirtaidep fo rebmun laitnatsbus a ni desu eb ot ylekil ton si ,puorg ega taht ni stneitap cirtaidep rof seipareht gnitsixe revo tifeneb cituepareht
lufgninaem a tneserper ton seod tcudorp lacigoloib ro gurd eht )3( ;puorg ega taht ni efasnu ro evitceffeni eb dluow tcudorp lacigoloib ro gurd eht
taht gnitseggus ylgnorts ecnedive si ereht )2( ;elbacitcarpmi ylhgih ro elbissopmi era seiduts yrassecen )1( :taht sdnif yraterceS eht dna seifitrec tnacilppa
eht fi puorg ega cirtaidep cificeps a ot tcepser htiw noitcesbus siht rednu stnemssessa timbus ot tnemeriuqer eht fo ,etairporppa sa ,reviaw laitrap
a tnarg llahs yraterceS eht ,)yraterceS eht fo evitaitini eht no ,tcudorp lacigoloib ro gurd wen a rof ,ro( tnacilppa na fo tseuqer eht tA .reviaw laitraP
]c553 CSU 12 ;)A()2()b(B505 dna )A()4()a(B505 ACDFF ;)a(204 AAADF[ .spuorg ega cirtaidep lla ni
efasnu ro evitceffeni eb dluow tcudorp lacigoloib ro gurd eht taht gnitseggus ylgnorts ecnedive si ereht )2( ro ;)desrepsid yllacihpargoeg era puorg ega
taht ni stneitap ro llams os si puorg ega taht ni stneitap fo rebmun eht ,elpmaxe rof ,esuaceb( elbacitcarpmi ylhgih ro elbissopmi era seiduts yrassecen
)1( taht sdnif yraterceS eht dna seifitrec tnacilppa eht fi noitcesbus siht rednu stnemssessa timbus ot tnemeriuqer eht fo ,etairporppa sa ,reviaw
lluf a tnarg llahs yraterceS eht ,)yraterceS eht fo evitaitini eht no ,tcudorp lacigoloib ro gurd wen a rof ,ro( tnacilppa na fo tseuqer eht tA .reviaw lluF sreviaW
]c553
CSU 12 ;)3()a(B505 ACDFF ;)a(204 AAADF[ .etisbew ADF eht hguorht
gnidulcni ,cilbup eht ot elbaliava edam yltpmorp eb weiver launna siht fo trap
sa dettimbus noitamrofni lla taht seriuqer osla tI .emit elbissop tseilrae eht
ta dna ecnegilid eud htiw detcudnoc eb lliw seiduts hcus taht noitatnemucod
fo ecnedive ,edam neeb sah ssergorp on fi ,ro seiduts cirtaidep gnitcudnoc ni
ssergorp sti no noitamrofni deliated yraterceS eht ot timbus tsum tnacilppa
eht hcihw rof ,larrefed devorppa hcae fo weiver launna na seriuqer AAADF
.seiduts hcus fo noitelpmoc eht rof enilemit a edulcni tsum tnacilppa nA .noisivorp oN
]c553 CSU 12 ;)3()a(B505 ACDFF ;)a(204 AAADF[ .emit elbissop tseilrae
eht ta dna ecnegilid eud htiw detcudnoc eb lliw ro detcudnoc gnieb era seiduts eht taht ecnedive dna ;seiduts gniogno ro dennalp eht fo noitpircsed
a ;stnemssessa eht gnirrefed rof sdnuorg eht fo noitacifitrec yraterceS eht ot timbus osla tsum tnacilppa ehT .larrefed rof nosaer etairporppa
rehtona si ereht ro ;detcelloc neeb evah atad ssenevitceffe ro ytefas lanoitidda litnu deyaled eb dluohs seiduts cirtaidep ;etelpmoc era seiduts cirtaidep
erofeb stluda ni esu rof lavorppa rof ydaer si tcudorp lacigoloib ro gurd eht taht gnidnif nopu tcudorp lacigoloib a rof esnecil eht fo ecnaussi ro gurd eht
fo lavorppa retfa etad deificeps a litnu stnemssessa deriuqer lla ro emos fo noissimbus refed yam yraterceS eht ,tcudorp lacigoloib ro gurd wen a roF slarrefeD
VI eltiT AAADF waL suoiverP cipoT
]c553 CSU 12 ;)e(B505 ACDFF ;)a(204 AAADF[ .seiduts cirtaidep fo larrefed ro reviaw rof rosnops
eht yb tseuqer dennalp yna ro ;seiduts cirtaidep rof senilemit dna snalp no stimbus rosnops eht taht noitamrofni ssucsid ot tcudorp lacigoloib ro
gurd wen eht fo rosnops eht htiw teem ,tcudorp lacigoloib ro gurd wen a rof ssecorp lanoitagitsevni eht gnirud dna erofeb ,yraterceS eht taht seriuqeR rosnopS htiw gniteeM
]c553 CSU 12 ;)d(B505 ACDFF ;)a(204 AAADF[
.tcudorp lacigoloib a rof esnecil eht ekover ot ro gurd a rof lavorppa wardhtiw ot gnideecorp a rof sisab eht eb ot tseuqer ro tnemssessa eht timbus
ot eruliaf eht wolla ton seod dna ;eltit siht fo ytirohtua )senif ro tnemnosirpmi( ytlanep eht rednu noitca tnemecrofne wolla ton seod wal eht ,revewoH
.noitces siht fo snoisivorp elbacilppa htiw ecnadrocca ni noitalumrof cirtaidep a fo lavorppa tseuqer ot ro tnemssessa
deriuqer a timbus ot eruliaf eht rof ylelos noitca tnemecrofne tnaveler ot tcejbus dna dednarbsim deredisnoc eb yam tcudorp lacigoloib ro gurd A gnidnarbsiM
]c553 CSU 12 ;)c(B505 ACDFF ;)a(204 AAADF[
".senimreted yraterceS eht" ot "setamitse yraterceS eht" segnahc AAADF .noitamitse s'yraterceS eht no tnemssessa eht desab wal ehT
]c553 CSU 12 ;)c(B505 ACDFF ;)a(204 AAADF[
.snoitpo lanoitidda rof deen a si ereht hcihw rof noitacidni na rof ro stcudorp fo ssalc a ni si tcudorp lacigoloib ro gurd eht )2( ro ;noitalupop cirtaidep
tnaveler eht ni esu taht rof delebal yletauqeda stcudorp detekram htiw derapmoc ,esaesid a fo noitneverp ro ,sisongaid ,tnemtaert eht ni tnemevorpmi tifeneB citueparehT
tnacifingis a tneserper dluow tcudorp lacigoloib ro gurd eht )1( :nehw sa "seipareht gnitsixe revo tifeneb cituepareht lufgninaem" denifed wal ehT lufgninaeM
]c553 CSU 12 ;)3()h(B505 dna )3()b(B505 ACDFF ;)a(204 AAADF[
.noitamrofni laitnedifnoc fo erusolcsid eht gnidrager erudecorP lanimirC
dna semirC ro ,seeyolpmE dna noitazinagrO tnemnrevoG ,sgurD dna dooF
gnidrager seltit edoC .S.U fo snoitces dnema ro retla ton seod ti setats noitamrofnI
AAADF ,tnemssessa cirtaidep detelpmoc a gniwollof noitamrofni cirtaidep laitnedifnoC
fo noitanimessid eht ro stcudorp devorppa fo seiduts rof stseuqer gnidrageR fo erusolcsiD
.I904
ASHP rednu noitazitiroirp eht tnuocca otni gnikat ,yduts eht tcudnoc
]]a553 CSU 12 ;)A()1()n(A505 ACDFF ;)a(205 AAADF[ ot sdnuf tneiciffus sah yraterceS eht rehtehw yfitrec llahs yraterceS
.)B505 ACDFF( AERP rednu seiduts eht tcudnoc noitacilppa devorppa eht fo eht ,tseuqer nettirw eht ot eerga lliw redloh on taht gninimreted retfA
redloh eht taht eriuqer yam yraterceS eht ,sdnuf tneiciffus evah ton seod HINF fI
.meht dnuf tsum HINF dna HINF ot seiduts refer tsum yraterceS eht ,elbaliava era .elbaliava erew sdnuf hguohtla smargorp esoht rednu dedrawa neeb dah
sdnuf fI .)txetnoc siht ni sgurd fo seiduts cirtaidep rof margorp HIN eht fo edam tnarg ro tcartnoc on taht retsigeR laredeF eht ni deifitrec ro ,yduts eht
si noitnem on( sdnuf tneiciffus sah HINF rehtehw enimreted ot deriuqer won tcudnoc ot sdnuf tneiciffus dah )994 ASHP rednu ,HINF( HIN eht rof
si yraterceS eht ,yduts a hcus rof deen a si ereht enimreted ot seunitnoc yraterceS noitadnuoF eht ro )I904 ASHP rednu HIN ta( sgurd fo seiduts cirtaidep
eht dna yduts cirtaidep a rof tseuqer nettirw a senilced redloh eht fI .A505 ACDFF rof margorp eht rehtien taht deifitrec )3( dna ,rosnops s'gurd eht morf
ni noisrev deretla na secalp )V eltiT( AAADF[ .B505 ACDFF ni sraeppa regnol yduts eht ot tnemeerga on deviecer )2( ,yduts a rof tseuqer nettirw
on seiduts cirtaidep tcudnoc ot tcudorp lacigoloib ro gurd a rof noitacilppa a deussi )1( evah tsum yraterceS eht ,tcudorp lacigoloib desnecil ro gurd snoisivorP cirtaideP
devorppa a fo redloh eht gniriuqer s'yraterceS eht gnidrager hpargarap sihT devorppa na fo tnemssessa cirtaidep a timbus ot rosnops a eriuqer oT rehtO ot pihsnoitaleR
VI eltiT AAADF waL suoiverP cipoT
]c553 CSU 12 ;)2()g(B505 ACDFF ;)a(204 AAADF[
.noitanimreted s'yraterceS eht fo tnemetats a dna stluser esoht tuoba
noitamrofni edulcni ot lebal eht redro tsum yraterceS eht ,evisulcnocni era
stluser tnemssessa hcus rehtehw gnidulcni ,snoitalupopbus ro snoitalupop noitanimreteD
cirtaidep ni evitceffe dna efas si gurd tcejbus eht taht etartsnomed s'yraterceS
ton seod ro seod tnemssessa cirtaidep a taht noitanimreted a gnikam nopU .noisivorp oN edulcnI ot gnilebaL
]c553 CSU 12 ;)1()g(B505 ACDFF ;)a(204 AAADF[
.tcA siht rednu noitca tnemecrofne na ro ssecorp eettimmoC yrosivdA
cirtaideP eht aiv noitca fo sesruoc rehto yats ot sisab eht sa evres ro ,yaled
,edulcerp llahs noitcesbus siht ni gnihtoN .lebal eht egnahc ot gnieergasid
s'rosnops a fo syad 03 nihtiw eettimmoC yrosivdA cirtaideP eht ot etupsid
eht refer tsum renoissimmoC ehT .dednarbsim eb ot gurd eht meed yam
renoissimmoC eht ,egnahc gnilebal detseuqer a htiw eergasid ot seunitnoc
rosnops eht fI .noitadnemmocer dna weiver rof eettimmoC yrosivdA
cirtaideP eht ot etupsid eht refer ot renoissimmoC eht seriuqer ti ,sesac
esoht nI .egnahc lebal a rof tseuqer s'renoissimmoC eht htiw eerga ton seod
rosnops a nehw rof erudecorp noituloser etupsid a sehsilbatse AAADF .noisivorp oN noituloseR etupsiD
]c553 CSU 12 ;)f(B505 ACDFF ;)a(204
AAADF[ .gnineppah ton stneve esoht fo hcae rof snosaer eht edulcni tsum
troper ehT .cte ,segnahc gnilebal ,depoleved snoitalumrof cirtaidep ,detnarg
dna detseuqer reviaw dna larrefed ,sngised yduts ,stnemssessa fo srebmun
eht no scitsitats deificeps cilbup eht ot elbaliava ekam dna kcart ,eettimmoc
lanretni eht htiw noitatlusnoc ni ,tsum yraterceS ehT .yrtsudni ot ecnadiug
etaitini dna stnemevorpmi rof snoisivid weiver eht ot snoitadnemmocer sreviaW
eussi ,weiver hcus no desab ,tsum yraterceS ehT .detnarg slarrefed dna ,slarrefeD
dna sreviaw fo ssenetairporppa eht dna stnemssessa cirtaidep ni noitamrofni ,stnemssessA ,snalP
cirtaidep fo ycnetsisnoc dna ytilauq eht fo sisylana edulcni tsum weiver ehT .noisivorp oN cirtaideP fo weiveR
]c553 CSU 12 ;)f(B505 ACDFF ;)a(204 AAADF[
.stnemevorpmi rof snoitadnemmocer eussi ot deriuqer eb dluow ohw
,yraterceS eht ot sreviaw dna ,slarrefed ,stnemssessa fo sisylana dna weiver
evitcepsorter a tcudnoc tsum eettimmoc lanretni ehT .ssecca cilbup ysae
rof etisbew ADF eht no noitamrofni eht ecalp dna ,stnemssessa gnidnep
kcart ,ytivitca s'eettimmoc lanretni eht tnemucod tsum yraterceS ehT
).noitces txen ees ;srefer ]a553 CSU 12 ;)f(A505 ACDFF[ )a(205
AAADF hcihw ot eettimmoc lanretni emas eht si sihT :etoN( ]d553 CSU
12 ;C505 ACDFF ;304 AAADF[ .sreviaw dna ,slarrefed ,stnemssessa ,snalp
cirtaidep fo weiver eht ni etapicitrap ot ,esitrepxe deificeps htiw seeyolpme
ADF fo desopmoc ,eettimmoc lanretni na hsilbatse tsum yraterceS ehT .noisivorp oN eettimmoC lanretnI
VI eltiT AAADF waL suoiverP cipoT
]c553 CSU 12 ;)m(B505 ACDFF ;)a(204 AAADF[ .eltit siht fo noitces sgurd fo seiduts cirtaidep rof ytivisulcxe tekram eht ni deificeps etad eht erofeb
ro no yraterceS eht yb gnilif rof detpecca eb yam noitces siht ot tcejbus noitacilppa na sa gnol os tceffe ni niamer llahs noitces siht rednu ytirohtua ehT tesnuS ot ecnerefeR
]CSU ro ACDFF ni ton ;404 AAADF[ .edoC .S.U
eht nihtiw decalp eb noisivorp siht taht etacidni ton seod AAADF .troper
taht fo stnemele deriuqer seificeps tI .delebal ylreporp dna detset era
nerdlihc yb desu senicidem taht gnirusne ni I904 ASHP dna B505 dna A505 tropeR
ACDFF fo ssenevitceffe eht sesserdda taht ,1102 ,1 yraunaJ yb ssergnoC eciffO ytilibatnuoccA
ot ,yraterceS eht htiw noitatlusnoc ni ,troper OAG a seriuqer AAADF .noisivorp deifidoc oN tnemnrevoG
]c553 CSU 12 ;)l(B505
ACDFF ;)a(204 AAADF[ .slairt lacinilc cirtaidep ni seussi lacihte dna ,stneve
esrevda cirtaidep fo epyt dna rebmun ,sloot tnemssessa latanoen ,stniopdne
evitanretla ,noitalopartxe fo esu eht ,seiduts fo elpmas evitatneserper
a gnisu ,ssessa dna weiver MOI eht taht stcerid tI .segnahc gnilebal
gnitluser dna seiduts cirtaidep gnidrager ssergnoC ot troper dna yduts ydutS
a tcudnoc ot MOI eht htiw tcartnoc yraterceS eht taht seriuqer AAADF .noisivorp oN enicideM fo etutitsnI
]c553 CSU 12 ;)k(B505 ACDFF ;)a(204 AAADF[ .eltit siht rednu detnarg
neeb sah noitangised nahpro hcihw rof noitacidni na rof gurd yna ot ylppa ton seod noitces siht ,noitaluger yb esiwrehto seriuqer yraterceS eht sselnU sgurD nahprO
]c553
CSU 12 ;)i(B505 ACDFF ;)a(204 AAADF[ ".yraterceS eht yb stroper tneve
esrevda hcus fo weiver rehto ,tnalppus ton ,tnemelppus llahs" stnemeriuqer
eseht taht setats AAADF .CAP eht ot stroper tneve esrevda eht
refer yam rotcerid TPO eht ,sraey tneuqesbus nI .yraterceS eht yb noitca
rof snoitadnemmocer sti niatbo dna )CAP( eettimmoC yrosivdA cirtaideP
eht yb weiver rieht rof edivorp tsum rotcerid TPO eht ,egnahc eht retfa
raey tsrif eht roF .)TPO( scitueparehT cirtaideP fo eciffO eht ot stroper gnitropeR
tneve esrevda lla refer tsum yraterceS eht ,egnahc gnilebal a gniwolloF .noisivorp oN tnevE esrevdA
]c553 CSU 12 ;)h(B505 ACDFF ;)a(204 AAADF[
.sredivorp erac htlaeh ot noitamrofni hcus etubirtsid ot segnahc gnilebal
niatrec ni stluser taht tnemssessa na fo rosnops eht eriuqer tsum yraterceS
ehT .tnemssessa cirtaidep dettimbus a fo sweiver ygolocamrahp lacinilc dna
,lacitsitats ,lacidem eht ,etisbew ADF eht no gnitsop yb gnidulcni ,rennam noitamrofnI cirtaideP
elbissecca ylisae na ni cilbup eht ot elbaliava ekam tsum yraterceS ehT .noisivorp oN fo noitanimessiD
VI eltiT AAADF waL suoiverP cipoT
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
product.18 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.
efaS erA nerdlihC ot debircserP sgurD tahT erusnE ot ytirohtuA s'ADF ,68933LR tropeR SRC ees ,noitamrofni rehtruf roF
.luahT nasuS yb ,evitceffE dna
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
FDA-NIH collaboration.19
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
children.20
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.
]a553 CSU
12 ;)2()c(A505 dna )2()b(A505 ACDFF ;)a(205 AAADF[ .doirep ytivisulcxe fo noitaripxe eht erofeb shtnom
9 naht ssel edam si noitanimreted eht fi doirep ytivisulcxe eht dnetxe ton llahs yraterceS eht taht sddA .noisivorp oN noitpecxE
]a553 CSU 12 ;)B()1()c(A505 dna )B()1()b(A505 ACDFF ;)a(205 AAADF[ ytivisulcxE
.ACDFF eht rednu )snoitidnoc ro sesaesid erar rof sgurd ,sgurd cireneg niatrec ,sgurd wen rof sa hcus( detnarg seitivisulcxe rehto shtnom xis yb dednetxE fo noisnetxE
]a553 CSU 12 ;)1()c(A505 ACDFF ;)a(205 AAADF[ .detseuqer si
yduts eht hcihw rof puorg ega hcae rof snoitalumrof etairporppa gnisu detelpmoc era seiduts hcus taht sddA
]a553 CSU 12 ;)c(A505 ACDFF ;)a(205 AAADF[ .noitces siht fo )3()d(
noitcesbus htiw ecnadrocca ni detpecca ro noitces siht fo )2()d( noitcesbus htiw ecnadrocca ni dettimbus era foereht stroper eht dna ,emarfemit hcus
yna nihtiw detelpmoc era seiduts eht ,tseuqer eht ot seerga redloh eht ,)seiduts hcus gnitelpmoc rof emarfemit a edulcni llahs hcihw( seiduts cirtaidep rof sgurD detekraM
eltit siht fo )1()b(553 noitces rednu noitacilppa devorppa na fo redloh eht ot tseuqer nettirw a sekam dna noitalupop taht ni stifeneb htlaeh ecudorp yam ydaerlA rof
noitalupop cirtaidep eht ni gurd devorppa na fo esu eht ot gnitaler noitamrofni taht senimreted yraterceS eht fi detnarg si ytivisulcxe cirtaidep htnom-xiS ytivisulcxE tekraM
]a553 CSU
12 ;)1()b(A505 ACDFF ;)a(205 AAADF[ .detseuqer si yduts eht hcihw rof puorg ega hcae rof snoitalumrof
etairporppa gnisu detelpmoc era seiduts hcus taht dna tseuqer eht ot seerga tnacilppa eht taht sddA
]a553 CSU 12 ;)b(A505 ACDFF ;)a(205 AAADF[ .noitces
siht fo )3()d( noitcesbus htiw ecnadrocca ni detpecca ro noitces siht fo )2()d( noitcesbus htiw ecnadrocca ni dettimbus foereht stroper eht dna emarfemit
hcus yna nihtiw detelpmoc era seiduts hcus dna ,)seiduts hcus gnitelpmoc rof emarfemit a edulcni llahs hcihw( seiduts cirtaidep rof tseuqer nettirw a sekam
yraterceS eht ,noitalupop taht ni stifeneb htlaeh ecudorp yam noitalupop cirtaidep eht ni gurd wen a fo esu eht ot gnitaler noitamrofni taht senimreted sgurD weN rof
yraterceS eht ,eltit siht fo )1()b(553 noitces rednu dettimbus si taht noitacilppa na fo lavorppa ot roirp ,fi detnarg si ytivisulcxe cirtaidep htnom-xiS ytivisulcxE tekraM
]a553 CSU 12 ;)a(A505 ACDFF
;)a(205 AAADF[ .seiduts lacinilcerp edulcni yam noitagitsevni lacinilc ,noitercsid s'yraterceS eht ta ,taht sddA
]a553 CSU 12 ;)a(A505 ACDFF
;)a(205 AAADF[ .desu eb ot detapicitna si gurd a hcihw ni )sesac etairporppa ni setanoen gnidulcni( spuorg ega cirtaidep ni )seiduts citenikocamrahp seidutS
edulcni yam ,noitercsid s'yraterceS eht ta ,taht( noitagitsevni lacinilc eno tsael ta snaem "seiduts" ro "seiduts cirtaidep" mret eht ,noitces siht ni desu sA fo noitinifeD
)a(205 noitceS ,V eltiT AAADF waL suoiverP cipoT
waL suoiverP htiw ))a(205 noitceS ,V eltiT AAADF(
7002 fo tcA nerdlihC rof slacituecamrahP tseB fo nosirapmoC .7 elbaT
.slocotorp
]a553 CSU nettirw gnidrager tnemeerga na gnihcaer
12 ;)1()d(A505 ACDFF ;)a(205 AAADF[ ".tseuqer a hcus gniussi n]i[" siht od ot deriuqer si yraterceS ehT ni siht od ot deriuqer si yraterceS ehT
]a553 CSU 12 seitironiM
;)d(A505 ACDFF ;)a(205 AAADF[ .seitironim laicar dna cinhte fo nerdlihc fo noitatneserper etauqeda tnuocca otni ekat ot yraterceS eht stcerid wal ehT fo noitatneserpeR
]a553 CSU 12 ;)B()2()d(A505 ACDFF ;)a(205 AAADF[ .gurd tcejbus eht gnidrager
stroper tneve esrevda tekramtsop elbaliava lla htiw ,seiduts hcus fo stroper eht fo noissimbus eht sa emit
emas eht ta ,yraterceS eht edivorp llahs seiduts hcus rof tseuqer eht ot seerga ohw redloh ro tnacilppa nA .noisivorp oN
]a553 CSU 12 ;)ii()2()d(A505 ACDFF ;)a(205 AAADF[ .depoleved eb tonnac snoitalumrof
cirtaidep hcus snosaer eht yraterceS eht ot timbus tsum noitalumrof cirtaidep etairporppa eht poleved
ot elbissop ton si ti taht sdnuorg eht no tseuqer eht htiw eerga ton seod ohw redloh ro tnacilppa nA .noisivorp oN
]a553 CSU 12 ;)2()d(A505
ACDFF ;)a(205 AAADF[ .tseuqer eht gninilced rof snosaer eht ro detaitini eb lliw seiduts nehw rehtie
gnitacidni ,syad 081 nihtiw tseuqer nettirw s'yraterceS eht ot dnopser ot redloh ro tnacilppa eht seriuqeR
.sgurd devorppa ydaerla dna sgurd wen ot gnitaler egaugnal senibmoC
]a553 CSU 12 ;)1()d(A505 ACDFF ;)a(205 AAADF[ .devorppanu dna devorppa htob era taht sesu edulcni
yam dna ;gurd a fo esu eno naht erom ot etaler yam tseuqer nettirw elgnis a taht sddA .seiduts rof tseuqeR
]a553 CSU 12 ;)1()d(A505 ACDFF ;)a(205 AAADF[ .seiduts hcus rof emarfemit a edulcni llahs dna gnitirw ni eb llahs
tnemeerga hcuS .gurd hcus rof seiduts cirtaidep fo tcudnoc eht rof redloh ro rosnops eht htiw eerga ,gurd a rof noitacilppa devorppa na fo redloh eht ro seidutS
,gurd wen a ro gurd wen lanoitagitsevni na rof noitacilppa na fo rosnops eht htiw noitatlusnoc retfa dna tseuqer nettirw a ot tnausrup ,yam yraterceS ehT rof tnemeergA
)a(205 noitceS ,V eltiT AAADF waL suoiverP cipoT
.tseuqer
eht ot eerga ton seod redloh eht taht
gnitacidni ro ;tseuqer eht ot seerga redloh
eht fi ,detaitini eb lliw seiduts cirtaidep
eht nehw gnitacidni yb tseuqer eht
no tca ot redloh eht fo noitnetni eht ot
sa yraterceS eht ot dnopser llahs ,tseuqer
nettirw eht gniviecer retfa syad 081 ytivisulcxE tekraM
naht retal ton ,redloh eht ,noitacilppa gurd evaH taht sgurD
wen devorppa na fo redloh eht ot noitces rof snoitacilppA
siht fo )c( noitcesbus rednu )etairporppa devorppA
sa ,setanoen gnidulcni( seiduts cirtaidep rof fo sredloH ot
.evoba ees ;rehtegot sgurd devorppa ydaerla dna sgurd wen htob fo seiduts rof stseuqer sesserddA tseuqer nettirw a sekam yraterceS eht fI tseuqeR nettirW
]a553 CSU 12 ;)3()d(A505 ACDFF ;)a(205 AAADF[ .gnilif rof yraterceS eht fo stnemeriuqer
eht htiw ecnadrocca ni detroper neeb evah dna ,slocotorp dna selpicnirp cifitneics detpecca ylnommoc htiw ecnadrocca ni detcudnoc neeb evah
,tseuqer nettirw eht ot dnopser ylriaf seiduts eht rehtehw enimreted ot eb llahs stroper eht gnitcejer ro gnitpecca ni ytilibisnopser ylno s'yraterceS ehT
.seiduts eht fo stroper eht fo noissimbus
eht retfa syad 09 naht retal ton redloh
ro rosnops eht yfiton os dna stroper hcus
tcejer ro tpecca ot deriuqer saw yraterceS
ehT .yraterceS eht yb detpecca stroper
eht dna detelpmoc neeb dah seiduts
hcus nehw deifsitas saw seiduts cirtaidep
rof tnemeriuqer eht ,seiduts eht rof
slocotorp eht no gnitirw ni deerga ton dah
yraterceS eht dna redloh ro rosnops eht fI
.noissimbus s'troper eht fo syad 06
nihtiw noitanimreted eht ekam ot deriuqer
saw yraterceS eht ,seiduts nopu deerga
roF .tnemeerga nettirw eht dna tseuqer
nettirw lanigiro eht htiw ecnadrocca
ni foereht stroper eht fo noissimbus
dna seiduts eht fo noitelpmoc eht nopu
deifsitas si tnemeriuqer seiduts eht ,seiduts
]a553 CSU 12 ;)3()d(A505 ACDFF ;)a(205 AAADF[ eht rof slocotorp nettirw nopu eerga
.noissimbus s'troper eht fo syad 081 nihtiw noitanimreted eht ekam yraterceS eht taht seriuqer AAADF yraterceS eht dna redloh ro rosnops eht fI
]a553 CSU 12 ;)3()d(A505 ACDFF ;)a(205 AAADF[ .seiduts eht fo troper eht fo noissimbus
eht retfa syad fo rebmun deificeps a nihtiw redloh ro rosnops eht yfiton os dna ,gnilif rof yraterceS eht fo stnemeriuqer eht htiw ecnadrocca ni detroper yraterceS
dna tnemeerga nettirw eht dna tseuqer nettirw lanigiro eht htiw ecnadrocca ni detcudnoc ton erew ro erew seiduts hcus fi enimreted tsum yraterceS ehT yb noitanimreteD
)a(205 noitceS ,V eltiT AAADF waL suoiverP cipoT
.HINF ot derrefer eb llahs tseuqer nettirw
denilced yreve taht eriuqer ot deurtsnoc refeR ot
.noisivorp oN eb llahs noitcesbus siht ni gnihtoN tnemeriuqeR oN
.seiduts eht fo tcudnoc eht rof I904 ASHP
rednu dehsilbatse tsil eht no noisulcni rof
gurd eht refer llahs yraterceS eht ,seifitrec
os HINF fI .seiduts detseuqer eht tcudnoc
ot 994 ASHP rednu elbaliava sdnuf evah
ton seod HINF taht ,ecnadiug hguorht
.]a553 CSU 12 etairporppa si senimreted yraterceS
;)A()1()n(A505 ACDFF ;)a(205 AAADF[ .refer seod yraterceS eht taht yduts a dnuf ot HINF eht seriuqer tI eht taht emarfemit a nihtiw ,yraterceS
eht ot seifitrec HINF sselnu seiduts
]a553 CSU 12 ;)A()1()n(A505 ACDFF detseuqer eht tcudnoc ot tnarg a drawa
;)a(205 AAADF[ .HINF ot tseuqer a gnirrefer erofeb seiduts eht tcudnoc ot gnidnuf tneiciffus sah HINF ot lasoporp a eussi llahs HINF ,)i()B(
eht rehtehw yfitrec tsum yraterceS eht ,tnetap deripxenu na htiw gurd a rof taht os nettirwer saw wal ehT hpargarapbus rednu gurd a fo larrefer nO sdnuF fo kcaL
.HINF eht ot larrefer a ni edam deiduts
]a553 CSU 12 ;)2()n(A505 ACDFF ;)a(205 AAADF[ eb ot snoitacidni eht dna ,rerutcafunam
.noisiced taht rof sisab eht dna eciton cilbup evig tsum yraterceS eht ,B505 ACDFF rednu tnemssessa eht fo eman eht ,gurd eht fo eman eht
na eriuqer ot ton sediced yraterceS eht hcihw rof gurd a roF :sdda dna noisivorp siht seteled AAADF fo eciton cilbup evig llahs yraterceS ehT ecitoN cilbuP
]a553 CSU 12 ;)B()1()n(A505 ACDFF ;)a(205 AAADF[ .I904 ASHP rednu dehsilbatse
tsil eht no noisulcni rof gurd eht refer yraterceS eht taht seriuqer ,tnetap tnerruc on htiw gurd a roF
]a553 CSU 12 ;)A()1()n(A505 ACDFF ;)a(205 AAADF[ .)b(B505 ACDFF
rednu stnemssessa cirtaidep eriuqer ot rehtehw redisnoc tsum yraterceS eht ,elbaliava ton si gnidnuf fI-
.seiduts eht dnuf
ot HINF seriuqer dna ,HINF ot tseuqer nettirw eht refer ot yraterceS eht seriuqer ,elbaliava si gnidnuf fI-
.tseuqer nettirw eht ni seiduts eht
rof gnidnuf tneiciffus sah HINF rehtehw yfitrec tsrif tsum yraterceS eht ,tnetap deripxenu na htiw gurd a roF
.tseuqer nettirw eht ni debircsed
.stnetap tnerruc seiduts cirtaidep eht fo tcudnoc eht
tuohtiw dna htiw sgurd rof deificeps era serudecorp tnereffiD .C505 ACDFF rednu dehsilbatse eettimmoc rof ,b092 CSU 24 rednu dehsilbatse ,HINF
lanretni eht hguorht dedeen si yduts rehtruf rehtehw noitanimreted eht ekam tsum yraterceS ehT ot gurd eht refer ot saw yraterceS ehT tseuqeR
ot tnemeergA
]a553 CSU 12 ;)n(A505 ACDFF ni ti secalp )a(205 AAADF dna ;)B()4()d(A505 ACDFF ni siht desserdda oN :detelpmoC
wal suoiverP[ .)etairporppa sa ,setanoen gnidulcni( noitalupop cirtaidep eht ni gurd eht fo esu eht ot gnitaler noitamrofni rof deen gniunitnoc a si ereht taht toN seidutS
senimreted yraterceS eht fi dna ,doirep emit deificeps eht nihtiw tseuqer nettirw a ot eerga ton seod rerutcafunam eht fi tca ot deriuqer si yraterceS ehT cirtaideP fi larrefeR
)a(205 noitceS ,V eltiT AAADF waL suoiverP cipoT
]a553CSU
12 ;)f(A505 ACDFF ;)a(205 AAADF[ .deiduts sesu dna sgurd dna ,seiduts fo sepyt sa hcus noitamrofni
deificeps cilbup eht ot elbaliava ekam dna ;segnahc gnilebal dna seiduts cirtaidep kcart ,eettimmoc lanretni seidutS
eht htiw noitatlusnoc ni ,tsum yraterceS ehT .seiduts eht tcejer ro tpecca ot rehtehw no yraterceS eht cirtaideP dna
ot snoitadnemmocer ekam ot noisivorp siht ot tnausrup dettimbus seiduts weiver yam tI .stseuqer nettirw stseuqeR nettirW
lla weiver tsum ,hsilbatse ot yraterceS eht seriuqer 304 AAADF hcihw ,eettimmoc weiver lanretni ehT .noisivorp oN fo weiveR lanretnI
]a553 CSU 12 ;)2()e(A505 ACDFF ;)a(205 AAADF[ .raey eno nihtiw tekram eht otno
noitalumrof cirtaidep eht decudortni ton sah rosnops sti fi nerdlihc rof evitceffe dna efas eb ot detartsnomed
evah seiduts taht noitalumrof cirtaidep depoleved a htiw gurd yna yfitnedi ylcilbup tsum yraterceS ehT .noisivorp oN
]a553 CSU 12 ;)1()e(A505
ACDFF ;)a(205 AAADF[ .)c( ro )b( noitcesbus rednu tseuqer nettirw eht fo ypoc a edulcni tsum dna
ytivisulcxe tekram gnidrager noitanimreted s'yraterceS eht fo syad 03 nihtiw dehsilbup eb tsum eciton hcuS
tnemeriuqeR
]a553 CSU seidutS
12 ;)1()e(A505 ACDFF ;)a(205 AAADF[ .noitces siht fo snoisivorp eht ot tcejbus eb lliw gurd a rof ]cireneg[ )j( ro )2()b(505 ACDFF rednu slavorppa dna no snoitanimreteD
snoissimbus taht dna tem neeb evah seiduts cirtaidep fo tcudnoc eht rof stnemeriuqer eht taht noitanimreted yna fo eciton a hsilbup llahs yraterceS ehT fo ecitoN
.yaled
fo doirep eht gnirud gninnur neeb evah
ot demeed eb llahs ytivisulcxe gnitekram
htnom-xis elbacilppa eht ,deifsitas
era noitces siht fo stnemeriuqer taht
tneve eht nI .)A505 ACDFF( noitces siht
rednu seiduts cirtaidep gnidrager edam
si noitanimreted a litnu ))j(505 ACDFF
rednu( noisrev cireneg a ro ))2()b(505
ACDFF rednu( noitalumrof wen a
rof sa hcus( tnacilppa eht naht rehto ytitne
na yb detcudnoc seiduts ssenevitceffe
dna ytefas no seiler noitacilppa esohw noitacilppA
tcudorp rehto ro cireneg a fo lavorppa eht niatreC rof etaD
.noisivorp oN syad 09 ot pu rof yaled llahs yraterceS ehT evitceffE fo yaleD
])F()4()d(A505 ACDFF[ .gurd eht fo
lavorppa fo etad eht retfa tseuqer nettirw
a eussi llahs yraterceS eht ,)etairporppa
sa ,setanoen gnidulcni( noitalupop cirtaidep
eht ni gurd eht fo esu eht ot gnitaler
]a553 CSU 12 ;)A()1()n(A505 ACDFF ;)a(205 AAADF[ .)1()b(B505 ACDFF noitamrofni rof deen gniunitnoc a si ereht
rednu tnemssessa cirtaidep a timbus ot redloh eht eriuqer yam yraterceS eht ,))A()1()n(A505 ACDFF rednu( taht senimreted yraterceS eht fi ,lavorppa
HINF ot tseuqer eht refer ton seod yraterceS eht dna ,noitacilppa na fo redloh ro rosnops eht yb detpecca gnitekram erofeb detpecca neeb ton sgurD weN rof
ton si tseuqer nettirw a fI .seiduts rof tseuqer denilced a eldnah dluow yraterceS eht woh segnahc AAADF dah tseuqer nettirw a hcihw rof gurd a roF stseuqeR nettirW
)a(205 noitceS ,V eltiT AAADF waL suoiverP cipoT
]a553 CSU 12 ;)j(A505 ACDFF ;)a(205 AAADF[
.noitanimreted s'yraterceS eht fo tnemetats a dna yduts eht fo stluser eht tuoba noitamrofni edulcni
ot tcudorp hcus fo gnilebal eht redro ,snoitalupopbus ro snoitalupop cirtaidep ni ,evisulcnocni era stluser cilbuP
yduts hcus rehtehw gnidulcni ,evitceffe dna efas si yduts eht fo tcejbus eht si taht gurd eht taht etartsnomed noitanimreteD
ton seod ro seod noitces siht rednu detcudnoc yduts cirtaidep a taht gninimreted nopu ,tsum yraterceS ehT .noisivorp oN s'yraterceS
]a553 CSU 12 ;)E()2()i(A505 ACDFF ;)a(205 AAADF[ .noitca fo esruoc rehto eht yats ot sisab eht sa evres ro ,yaled ,edulcerp llahs
)ecnetnes gnidecerp eht ni ot derrefer noitca tnemecrofne na ro ssecorp eettimmoC yrosivdA cirtaideP eht( noitca fo esruoc rehtieN .gnilebal cirtaidep
etairporppa skcal gurd a nehw retpahc siht rednu noitca tnemecrofne na gnirb ot setatS detinU eht fo ytirohtua eht stimil noitcesbus siht ni gnihtoN
.dednarbsim eb ot noitacilppa eht fo tcejbus eht si taht gurd eht meed yam renoissimmoC
eht ,renoissimmoC eht yb detseuqer egnahc gnilebal a ekam ot eerga ton seod ,tseuqer a gniviecer retfa syad 03 nihtiw ,noitacilppa eht fo rosnops eht fI
.etairporppa eb ot senimreted renoissimmoC eht taht egnahc gnilebal yna ekam ot noitacilppa eht fo rosnops eht ot tseuqer a ekam ,noitadnemmocer
eht gniviecer retfa syad 03 naht retal ton ,etairporppa fi ,dna eettimmoC yrosivdA cirtaideP eht fo snoitadnemmocer eht redisnoc llahs renoissimmoC ehT
.yna fi ,segnahc gnilebal etairporppa gninrecnoc renoissimmoC eht ot
noitadnemmocer a ekam dna ,stroper yduts cirtaidep eht weiver llahs eettimmoC yrosivdA cirtaideP eht ,larrefer a gniviecer retfa syad 09 naht retal toN
.egnahc gnilebal eht si eussi
]a553 CSU 12 ;)A()2()i(A505 ACDFF ;)a(205 AAADF[ .tseuqer eht fo syad 03 nihtiw eerga ton nepo ylno eht taht dna elbavorppa saw
seod rosnops eht fi larrefer eht ekam tsum renoissimmoC eht taht sdda osla tI ".tnemeerga hcaer ot elbanu noitacilppa detaler eht taht denimreted
neeb evah renoissimmoC eht dna rosnops eht" taht gninimreted s'renoissimmoC eht ot srefer AAADF renoissimmoC eht taht deificeps wal ehT
]a553 CSU 12 ;)A()2()i(A505
ACDFF ;)a(205 AAADF[ .eettimmoC yrosivdA cirtaideP eht ot rettam eht refer llahs renoissimmoC eht ,renoissimmoC eht yb detseuqer egnahc
gnilebal a ekam ot eerga ton seod noitacilppa eht fo rosnops eht fi dna ;etairporppa eb ot senimreted renoissimmoC eht taht egnahc gnilebal yna ekam
noitacilppa eht fo rosnops eht taht tseuqer tsum renoissimmoC eht ,noitacilppa eht fo tcejbus eht si taht gurd eht rof gnilebal eht ot segnahc etairporppa noituloseR etupsiD
no rosnops eht htiw tnemeergasid a si ereht taht senimreted renoissimmoC eht ,noitacilppa eht fo noissimbus fo etad eht retfa syad 081 naht retal ton ,fI egnahC gnilebaL
]a553 CSU
12 ;)1()i(A505 ACDFF ;)a(205 AAADF[ .stnemelppus dna snoitacilppa cirtaidep ot srefer won noisivorp sihT
]a553 CSU 12 ;)1()i(A505 ACDFF
;)a(205 AAADF[ .sgurd ytiroirp rof renoissimmoC eht yb dehsilbatse slaog ecnamrofrep eht ot tcejbus eb llahs dna ;tnemelppus ytiroirp a eb ot deredisnoc segnahC gnilebaL
eb llahs noitces siht rednu yduts cirtaidep a no troper a ot tnausrup egnahc gnilebal a gnisoporp 505 ACDFF rednu noitacilppa na ot tnemelppus ynA rof sutatS ytiroirP
]a553 CSU 12 ;)h(A505 ACDFF ;)a(205 AAADF[ .noitces siht ot tnausrup ytivisulcxe stnemeriuqeR
tekram rof tnemeriuqer eht yfsitas ot demeed eb llahs yduts hcus ,noitces siht fo stnemeriuqer rehto dna ,ssenilemit ,ssenetelpmoc eht steem yduts hcraeseR cirtaideP
hcus dna noitces siht naht rehto )noitaluger a gnidulcni( wal fo noisivorp a yb deriuqer si yduts cirtaidep yna fi ,wal fo noisivorp rehto yna gnidnatshtiwtoN ot pihsnoitaleR
]a553 CSU 12 ;)g(A505 ACDFF ;)a(205 AAADF[ .noitces siht fo )B()1()c( noitcesbus
rednu doirep hcus lanoitidda yna eviecer ton yam )2( dna ;noitces siht fo )2()c( noitcesbus rednu doirep hcus lanoitidda yna eviecer ton yam gurd
a hcus taht tpecxe ,deifsitas era noitces siht rednu stnemeriuqer rehto lla fi noitacilppa latnemelppus a rof noitces siht fo )ii()A()1()c( noitcesbus rednu
doirep htnom-xis lanoitidda na eviecer yam )1( deilppa neeb ydaerla sah noitces siht fo )c( ro )b( noitcesbus rednu doirep htnom-xis eht hcihw ot gurd A snoitatimiL
)a(205 noitceS ,V eltiT AAADF waL suoiverP cipoT
]a553 CSU 12 ;)o(A505 ACDFF
;)a(205 AAADF[ .)j(505 ,A505 ,505 ACDFF fo shpargarap niatrec rednu snoisivorp rehto dna ytivisulcxe cirtaidep evreserp ot esualc a sedulcni AAADF
.yrassecen sredisnoc yraterceS eht taht snoituacerp ro ,sgninraw ,snoitacidniartnoc cirtaidep etairporppa yna fo tnemetats a dna ;rerutcafunam
rehtona yb dleh ytivisulcxe gnitekram fo esuaceb sesu cirtaidep cificeps ro lla rof delebal ton si tcudorp eht taht tnemetats a :edulcni gnilebal fo
tcepsa deriuqer rehto ro noitacidni cirtaidep a stimo taht ))j(505 ACDFF( gurd cireneg devorppa na fo gnilebal eht taht eriuqer yam yraterceS ehT .gnilebaL
gnilebaL ot deddA
sI noitamrofnI
.seitivisulcxe niatrec yb ro tnetap yb detcetorp si tcepsa rehto ro noitacidni dettimo eht nehw esu cirtaidep ot gniniatrep gnilebal fo tcepsa cirtaideP nehW
rehto yna ro noitacidni cirtaidep a stimo gurd eht fo gnilebal eht taht sisab eht no dednarbsim ro noitces taht rednu lavorppa rof elbigileni deredisnoc sgurD cireneG fo
eb ton llahs )gurd cireneg a rof ,ADNA( noitacilppa gurd wen detaiverbba na rednu devorppa ro dettimbus neeb sah noitacilppa na hcihw rof gurd A lavorppA tpmorP
]a553 CSU 12 ;)m(A505 ACDFF ;)a(205 AAADF[ seitivisulcxE
.palrevo eht fo syad fo rebmun eht yb dednetxe eb lliw doirep eht ,doirep ytivisulcxe cirtaidep eht htiw spalrevo doirep ytivisulcxe gurd cireneg eht fI fo noitcaretnI
]a553 CSU 12 ;)l(A505 ACDFF ;)a(205 AAADF[ ".yraterceS eht yb stroper
tneve esrevda hcus fo weiver rehto ,tnalppus ton ,tnemelppus llahs" stnemeriuqer eseht taht setats AAADF
.eettimmoC yrosivdA cirtaideP eht ot noitadnemmocer dna weiver rof
meht refer yam rotcerid esohw ,TPO eht ot noitces siht rednu detcudnoc saw yduts cirtaidep a hcihw rof
gurd a rof stroper tneve esrevda cirtaidep lla refer ,etairporppa sa ,tsum yraterceS eht ,sraey tneuqesbus nI
.yraterceS eht yb noitca rof snoitadnemmocer
sti niatbo dna eettimmoC yrosivdA cirtaideP eht yb weiver rieht rof edivorp tsum rotcerid esohw ,TPO eht gnitropeR
ot stroper tneve esrevda lla fo larrefer erusne ,egnahc gnilebal a gniwollof raey eht rof ,tsum yraterceS ehT .noisivorp oN tnevE esrevdA
]a553 CSU 12 ;)3()k( won ,)2()j( saw A505 ACDFF ;)a(205 AAADF[ .noitamrofni
laitnedifnoc fo erusolcsid eht gnidrager erudecorP lanimirC dna semirC ro ,seeyolpmE dna noitazinagrO tnemnrevoG ,sgurD dna dooF gnidrager
seltit edoC .S.U fo snoitces dnema ro retla ton seod ti setats AAADF ,noitces siht rednu seiduts cirtaidep fo noitamrofni fo noitanimessid gnidrageR
]a553 CSU 12 ;)2()k(A505
ACDFF ;)a(205 AAADF[ .sredivorp erac htlaeh ot noitamrofni hcus ,yllaunna tsael ta ,etubirtsid srosnops
rieht taht ,noitubirtsid yrammus launna eht ni detcelfer segnahc gnilebal ni tluser taht seiduts rof ,seriuqeR
]a553 CSU 12
;)1()k(A505 ACDFF ;)a(205 AAADF[ .)c( ro )b( noitcesbus rednu detcudnoc seiduts ot srefer dna ,sweiver
lacitsitats sdda ,renoissimmoC eht rof yraterceS eht setutitsbus osla tI .syad 012 ot pu swolla AAADF .syad 081 ot pu dewolla wal ehT
]a553 CSU 12 ;)1()k(A505 ACDFF ;)a(205 AAADF[ .retsigeR laredeF eht ni noitacilbup noitamrofnI
yb gnidulcni ,tnemelppus eht rof detcudnoc seiduts cirtaidep fo sweiver ygolocamrahp lacinilc dna lacidem eht fo yrammus a cilbup eht ot elbaliava cirtaideP
ekam llahs renoissimmoC eht ,noitces siht rednu yduts cirtaidep a no troper a fo noissimbus fo etad eht retfa syad fo rebmun deificeps a naht retal toN fo noitanimessiD
)a(205 noitceS ,V eltiT AAADF waL suoiverP cipoT
]a553 CSU 12 ;)q(A505 ACDFF ;)a(205 AAADF[ .2102 ,1 rebotcO si etad tesnus ehT .7002 ,1 rebotcO saw etad tesnus ehT
]a553 CSU 12 ;A505 ACDFF ;)a(205 AAADF[ .noitces siht rednu ytivisulcxe gnitekram htnom-6 a eviecer ot tem
stnemeriuqer rehto lla dna ,gnilif rof detpecca snoitacilppa ,edam eb tsum seiduts cirtaidep rof stseuqer nettirw lla hcihw yb etad tesnus a sedivorp wal ehT tesnuS
.noitces siht rednu dehsilbatse margorp
eht rednu ecneirepxe eht no desab ,1002
,1 yraunaJ yb ,ssergnoC ot troper dna
,deificeps sa ,seussi tnaveler lla fo yduts ssergnoC ot
.noisivorp oN a tcudnoc ot deriuqer saw yraterceS ehT tropeR s'yraterceS
]a553 CSU 12 ;)p(A505 ACDFF ;)a(205
AAADF[ .scigoloib fo seiduts cirtaidep gnigaruocne rof sevitnecni etairporppa gnidrager snoitadnemmocer
ekam dna ;stcudorp lacigoloib fo seiduts cirtaidep eht ssessa dna weiver dna ;slairt lacinilc cirtaidep
ni seussi lacihte dna ,sloot tnemssessa latanoen ,stniopdne evitanretla ,noitalopartxe fo esu eht ssessa
;seiduts hcus fo tluser a sa edam segnahc gnilebal dna 7991 ecnis seiduts dna stseuqer evitatneserper weiver
tsum MOI ehT .noitces siht ot tnausrup detcudnoc seiduts dna stseuqer nettirw eht gnidrager ssergnoC ydutS enicideM
ot troper dna yduts a tcudnoc ot MOI eht htiw ,tnemtcane fo sraey 3 nihtiw ,tcartnoc tsum yraterceS ehT .noisivorp oN fo etutitsnI
)a(205 noitceS ,V eltiT AAADF waL suoiverP cipoT
]m482 CSU 24 ;)1()c(I904 ASHP ;)b(205
AAADF[ .noitalupop cirtaidep eht ni gurd eht fo esu eht fo ssenevitceffe
dna ytefas eht ssessa ot dedeen era seiduts lanoitidda dna ;ACDFF
eht rednu gurd eht fo mrof eno tsael ta rof noitcetorp ytivisulcxe
tekram ro noitcetorp tnetap on si ereht dna ;)j(505 noitceS ACDFF
rednu noitacilppa dettimbus ro devorppa na si ereht hcihw rof gurd
a rof tseuqer yduts cirtaidep desoporp a timbus yam rotceriD HIN ehT
.stseuqer A505 ACDFF yb deriuqer
noitamrofni eht edulcni tsum tseuqer ehT .scituepareht cirtaidep
ni seussi ytiroirp fo tsil eht no noitacidni cirtaidep cificeps a fo seiduts segnahC gnilebaL dna
cirtaidep rof renoissimmoC eht yb noitaredisnoc rof stseuqer yduts stseuqeR ydutS cirtaideP
cirtaidep desoporp ,etairporppa sa ,timbus tsum rotceriD HIN ehT .noisivorp oN desoporP rof ssecorP
]m482 CSU 24 ;)b(I904
ASHP ;)b(205 AAADF[ .smsinahcem gnidnuf etairporppa rehto ro stnarg
esu yam yraterceS eht ,stcartnoc ot noitidda nI .spuorg ecitcarp dna
;"hcraeser rehto ro" slairt lacinilc htiw esitrepxe edulcni ot dednapxe
si seititne fo noitpircsed ehT .HIN hguorht tca tsum yraterceS ehT
]m482 CSU 24 ;)b(I904 ASHP
;)b(205 AAADF[ .tsil eht ni deifitnedi sgurd erom ro eno gninrecnoc seiduts cirtaidep tcudnoc ot seititne eht elbane ot )slaudividni ro ,snoitutitsni
etavirp ro cilbup rehto ,stinu hcraeser ygolocamrahp cirtaidep sa hcus smargorp dednuf yllaredef ,snoitazinagro hcraeser tcartnoc ,seirotarobal hcraeseR dna seidutS
,slatipsoh ,seitisrevinu deifilauq gnidulcni( slairt lacinilc cirtaidep tcudnoc ot esitrepxe eht evah taht seititne ot stcartnoc drawa llahs yraterceS ehT cirtaideP fo gnidnuF
]m482 CSU 24 ;)2()a(I904 ASHP ;)b(205 AAADF[ .hcraeser
lacigolocamrahp cirtaidep tcudnoc ot erutcurtsarfni yrassecen fo
ycauqeda eht dna ;snoitalupop cirtaidep ni laicifeneb eb yam scituepareht .yrassecen
fo gnitset dna egdelwonk etelpmoc erom erehw snoitidnoc ro sredrosid si gurd eht fo noitalumrofer rehtehw dna ;noitalupop cirtaidep
,sesaesid cirtaidep ralucitrap ;scirtaidep ni spag cituepareht fo seirogetac eht ni stifeneb htlaeh ecudorp yam gurd eht gninrecnoc seiduts
eht nihtiw selpmaxe evig taht srehto htiw airetirc gnitsixe eht secalper cirtaidep wen rehtehw ,noitamrofni rof deen ,noitamrofni elbaliava
osla tI .sgurd fo tsil a naht rehtar ,sdeen fo tsil a ot srefer noitces ehT dedulcni sgurd fo tsil eht gnizitiroirp dna gnipoleved rof airetirc ehT
]m482 CSU 24 ;)1()a(I904
ASHP ;)b(205 AAADF[ .sraey eerht yreve ti esiver dna ,tnemtcane .noitalupop cirtaidep eht ni ssenevitceffe dna ytefas fo seiduts lanoitidda
retfa raey eno naht retal ton tsil eht hsilbup dna poleved tsum yraterceS gnideen sgurd devorppa fo tsil launna na hsilbup dna ,ezitiroirp
ehT ".yduts eriuqer taht snoitacidni ro sgurd gnidulcni ,scituepareht ,poleved llahs ,hcraeser cirtaidep ni strepxe dna renoissimmoC eht htiw scitueparehT cirtaideP
cirtaidep ni sdeen fo tsil ytiroirp a" ot degnahc si tsil eht fo sucof ehT noitatlusnoc ni dna rotceriD HIN eht hguorht gnitca ,yraterceS ehT ni seussI ytiroirP fo tsiL
305 dna )f-b(205 snoitceS ,V eltiT AAADF waL suoiverP cipoT
waL suoiverP htiw )305 dna )f-b(205 snoitceS ,V eltiT AAADF(
7002 fo tcA nerdlihC rof slacituecamrahP tseB fo nosirapmoC .8 elbaT
.sgurd eht fo hcae ot tcepser htiw elif tekcod eht fo trap emoceb llahs stnemmoc nettirw eht dna ,renoissimmoC
eht ot seiduts cirtaidep hcus gninrecnoc stnemmoc nettirw timbus yam nosrep detseretni nA .renoissimmoC eht yb rebmun tekcod a dengissa
eb llahs dna )])D()4()d( a553 CSU 12[ )D()4()d(A505 ACDFF ot tcejbus( niamod cilbup eht ni eb ot deredisnoc eb llahs dettimbus troper hcaE stropeR fo ytilibaliavA
]m482 CSU 24 ;)A()6()c(I904 ASHP
;)b(205 AAADF[ .tseuqer nettirw eht edulcni troper eht taht seriuqer
osla tI ".tcartnoc a" naht rehtar "drawa na" ot srefer noitces ehT
]m482 CSU 24 ;)A()6()c(I904
ASHP ;)b(205 AAADF[ .yduts eht htiw noitcennoc ni detareneg atad lla edulcni llahs troper ehT .renoissimmoC eht dna rotceriD HIN eht
ot dettimbus eb llahs yduts eht gninrecnoc troper a ,noitces siht rednu dedrawa tcartnoc a htiw ecnadrocca ni yduts cirtaidep a fo noitelpmoc nO seidutS fo gnitropeR
]m482 CSU 24 ;)5()c(I904 ASHP ;)b(205 AAADF[ .stcartnoc
ot noitidda ni gnidnuf rehto ro stnarg wolla yam yraterceS ehT
]m482 CSU 24 ;)5()c(I904 ASHP
;)b(205 AAADF[ .noitces siht tuo yrrac ot yrassecen eb ot senimreted yraterceS eht sa noitamrofni dna ,secnarussa ,stnemeerga hcus gniniatnoc
dna ,rennam dna mrof hcus ni yraterceS eht ot dettimbus si tcartnoc eht rof lasoporp a fi ylno dedrawa eb yam noitces siht rednu tcartnoc A gnidnuF
.stseuqer nettirw ot sesnopser
fo noissimbus eht rof ssecorp eht hsilbatse ot ecnadiug etaglumorp
.noisivorp oN llahs renoissimmoC eht ,2002 ,4 yraunaJ retfa syad 072 naht retal toN ecnadiuG
]m482 CSU 24
;)4()c(I904 ASHP ;)b(205 AAADF[ .slasoporp tcartnoc rof tseuqer a ot dnopser ot deltitne eb ton llahs lasufer fo thgir tsrif a seviecer taht redloh A noitacifilauqsiD
]m482 CSU 24 ;)3()c(I904 ASHP ;)b(205
AAADF[ .syad 03 nihtiw tseuqer nettirw a ot esnopser a deviecer
ton sah renoissimmoC eht fi tseuqer eht hsilbup tsum yraterceS ehT
]m482 CSU 24 ;)3()c(I904 ASHP ;)b(205 AAADF[ .tseuqer nettirw eht ni debircsed seiduts cirtaidep eht tcudnoc
ot slasoporp tcartnoc rof tseuqer a hsilbup llahs ,renoissimmoC eht htiw noitatlusnoc ni dna rotceriD HIN eht hguorht gnitca ,yraterceS eht ,edam slasoporP
si larrefer a fi ro ,deussi saw tseuqer a hcihw no etad eht fo syad 03 nihtiw tseuqer nettirw a ot esnopser a eviecer ton seod renoissimmoC eht fI tcartnoC rof stseuqeR
]m482
CSU 24 ;)2()c(I904 ASHP ;)b(205 AAADF[ .detseuqer si yduts eht
hcihw rof puorg ega hcae rof snoitalumrof etairporppa esu tsum seidutS
.scituepareht cirtaidep ni seussi ytiroirp fo tsil eht ot tnausrup dettimbus .dedeen era seiduts cirtaidep hcihw rof sgurd
snoitacidni ro noitacidni na fo yduts a ot srefer tseuqer nettirw ehT fo tsil eht ni deifitnedi gurd a fo yduts a ot derrefer tseuqer nettirw ehT
]m482 CSU 24
;)2()c(I904 ASHP ;)b(205 AAADF[ .tseuqer eht ot tnausrup detcudnoc eb ot seiduts cirtaidep eht no dedivorp noitamrofni ot tcepser htiw gnidulcni ytivisulcxE gnikcaL
,]a553 CSU 12[ A505 ACDFF fo )b( ro )a( noitcesbus rednu edam si tseuqer nettirw a hcihw ni rennam eht ot tnelaviuqe rennam a ni edam eb llahs sgurD rof snoitacilppA
tseuqer nettirw a hcuS .]553 CSU 12[ 505 ACDFF rednu gurd eht rof noitacilppa devorppa na fo sredloh lla ot seiduts cirtaidep rof )tnemeerga devorppA fo sredloH
na rof snoitaitogen rof emarfemit a edulcni llahs hcihw( tseuqer nettirw a eussi yam ,rotceriD HIN eht htiw noitatlusnoc ni ,renoissimmoC ehT ot tseuqeR nettirW
305 dna )f-b(205 snoitceS ,V eltiT AAADF waL suoiverP cipoT
]m482 CSU 24 ;)1()e(I904 ASHP ;)b(205 AAADF[ .sraey gnideeccus .sraey gnideeccus
ruof ot srefer noitces eht dna raey tsrif eht sa deificeps si 8002YF evif ot edam saw ecnerefer dna raey tsrif eht sa deificeps saw 2002YF
]m482 CSU 24
;)1()e(I904 ASHP ;)b(205 AAADF[ .dednepxe litnu noitces siht tuo yrrac ot elbaliava niamer llahs detairporppa tnuoma ynA .sraey lacsif gnideeccus snoitairporppA
eht fo hcae rof yrassecen era sa smus hcus dna ;raey tsrif eht rof noillim 002$ noitces siht tuo yrrac ot detairporppa eb ot dezirohtua era erehT fo noitazirohtuA
]m482 CSU 24 ;)d(I904 ASHP ;)b(205 AAADF[
.esu gurd cirtaidep no noitamrofni fo noitalipmoc a gnihsilbatse fo
ytilibisaef eht no ssergnoC ot troper dna yduts ,tnemtcane fo raey eno noitamrofnI
nihtiw dna rotceriD HIN eht hguorht gnitca ,yraterceS eht taht seriuqeR .noisivorp oN cirtaideP fo noitanimessiD
.noitacilppa devorppa na fo redloh hcae ot
egnahc taht gnidrager noitadnemmocer fo rettel gnidnibnon a dnes llahs
.)21()c(I904 ASHP neeb dah hcihw yraterceS eht ,seerga yraterceS eht dna yrassecen si egnahc noitalumrof segnahC noitalumroF
,noisivorp siht edulcni ton seod )c(I904 ASHP dednema-AAADF ehT a taht setacidni tcartnoc cilbup rednu detelpmoc yduts cirtaidep a fI rof noitadnemmoceR
]m482 CSU 24 ;)11()c(I904 ASHP ;)b(205 AAADF[
.noitca fo esruoc rehto eht yats ot sisab eht sa evres ro ,yaled ,edulcerp llahs )ecnetnes gnidecerp eht ni ot derrefer noitca tnemecrofne na
ro ssecorp eettimmoC yrosivdA cirtaideP eht( noitca fo esruoc rehtieN .gnilebal cirtaidep etairporppa skcal gurd a nehw ].qes te 103 CSU 12[ tcA
citemsoC dna ,gurD ,dooF laredeF eht rednu noitca tnemecrofne na gnirb ot setatS detinU eht fo ytirohtua eht stimil noitcesbus siht ni gnihtoN
]m482 CSU 24 ;)c(I904 ASHP ;)b(205 AAADF[ .ACDFF rednu dednarbsim eb ot gurd eht meed yam renoissimmoC eht ,egnahc gnilebal detseuqer
a ekam ot eerga ton seod ,egnahc gnilebal a ekam ot tseuqer a gniviecer retfa syad 03 nihtiw ,gurd a rof noitacilppa devorppa na fo redloh a fI
.etairporppa eb ot senimreted renoissimmoC eht taht egnahc gnilebal yna
ekam ot gurd eht rof snoitacilppa devorppa fo sredloh eht ot tseuqer a ekam ,etairporppa fi ,dna noitadnemmocer eht redisnoc llahs renoissimmoC
eht ,eettimmoC yrosivdA cirtaideP eht morf noitadnemmocer a gniviecer retfa syad 03 naht retal toN .yna fi ,segnahc gnilebal etairporppa
ot sa renoissimmoC eht ot noitadnemmocer a ekam dna ,noitces siht rednu dettimbus stroper yduts gnidulcni ,noitalupop cirtaidep eht ni gurd eht
fo esu evitceffe dna efas eht no noitamrofni elbaliava eht weiver llahs eettimmoC yrosivdA cirtaideP eht ,larrefer a gniviecer retfa syad 09 naht retal
toN .eettimmoC yrosivdA cirtaideP eht ot tseuqer eht refer llahs renoissimmoC eht ,hpargarap taht rednu renoissimmoC eht yb detseuqer egnahc
gnilebal yna ot eerga ton seod devlovni gurd eht rof noitacilppa devorppa na fo redloh eht ,deificeps doirep yad-081 eht fo dne eht naht retal ton ,fI noituloseR etupsiD
]m482 CSU 24 ;)C()7()c(I904 ASHP ;)b(205 AAADF[
.etisbew ADF eht no noitamrofni tsop osla tsum renoissimmoC ehT
]m482 CSU 24 ;)C,B,A()7()c(I904 ASHP ;)b(205 AAADF[ .segnahc gnilebal detseuqer yna fo ypoc a dna troper eht fo yrammus a retsigeR
laredeF eht ni hsilbup dna ;segnahc gnilebal detseuqer yna fo dna troper eht fo ypoc a elif tekcod cilbup eht ni ecalp tsum renoissimmoC ehT
.ekam ot sredloh eht stseuqer dna etairporppa eb ot senimreted renoissimmoC eht taht segnahc gnilebal yna rof deiduts gurd eht rof snoitacilppa
devorppa fo sredloh eht htiw etaitogen dna ;deiduts gurd eht fo noitalupop cirtaidep eht ni esu evitceffe dna efas eht gninrecnoc elbaliava egnahC
era sa atad rehto hcus dna troper eht weiver tsum renoissimmoC eht ,dettimbus si troper a hcihw no etad eht retfa doirep yad-081 eht gniruD gnilebaL rof stseuqeR
]m482 CSU 24 ;)C,B()6()c(I904 ASHP ;)b(205 AAADF[ .stroper eht ot esnopser ni noitca etairporppa ekat llahs renoissimmoC ehT renoissimmoC yb noitcA
305 dna )f-b(205 snoitceS ,V eltiT AAADF waL suoiverP cipoT
]eton m482 CSU 24 ;tcA
nerdlihC rof slacituecamrahP tseB eht fo 41 noitceS ;)d(205 AAADF[
.sraey evif rehtona rof eettimmoc yrosivda eht sdnetxe AAADF
]eton m482
CSU 24 ;tcA nerdlihC rof slacituecamrahP tseB eht fo 41 noitceS[ .ygolocamrahp cirtaidep ot detaler slairt lacinilc fo sisylana dna ,ngised ,scihte
eht dna ;snoitidnoc ro sesaesid cirtaidep cificeps fo stnemtaert lanoitidda rof deen eht dna ygolocamrahp cirtaidep ot detaler seitiroirp hcraeser
fo noitacifitnedi ;hcraeser cirtaidep edulcni srettam eht taht seificepS .ygolocamrahp cirtaidep ot gnitaler srettam no ,rotceriD HIN eht htiw
noitatlusnoc ni dna renoissimmoC eht hguorht ,yraterceS eht ot snoitadnemmocer ekam dna esivda eettimmoc eht taht seriuqer dna ,noitisopmoc ygolocamrahP cirtaideP
eettimmoc eht seificeps tI .ygolocamrahp cirtaidep no eettimmoc yrosivda na tlusnoc dna enevnoc yraterceS eht taht eriuqer ot seunitnoc wal ehT no eettimmoC yrosivdA
].llew sa dednema sah AAADF hcihw fo hcae ,)C()4()d(A505
ACDFF dna )A()1()a(I904 ASHP ot derrefer )C()1()c(994
ASHP[ .I904 ASHP rednu dehsilbatse tsil eht no noisulcni rof gurd
])C()1()c(b092 CSU 24 ;)C()1()c(994 eht refer ot deriuqer saw yraterceS eht esac hcihw ni ,sdnuf elbaliava
ASHP ;)c(205 AAADF[ .)AERP( )b(B505 ACDFF rednu stnemssessa evah ton did HINF taht yraterceS eht ot deifitrec HINF sselnu seiduts
cirtaidep eht eriuqer ot rehtehw redisnoc tsum yraterceS eht ,sdnuf hcus tcudnoc ot tnarg a drawa ot lasoporp a eussi ot saw HINF .yduts
tneiciffusni era ereht fI .HINF eht ot yduts eht refer neht tsum yraterceS rof stseuqer s'yraterceS eht denilced srosnops esohw noitcetorp tnetap
eht ,sdnuf tneiciffus era ereht fI .yteritne sti ni dnuf dna etaitini ot sdnuf htiw sgurd ro ,ytivisulcxe gnitekram ro noitcetorp tnetap tuohtiw sgurd
tneiciffus sah HINF rehtehw enimreted tsrif tsum yraterceS eht ,denilced ,]sgurd cireneg[ )j(505 ACDFF rednu noitacilppa dettimbus ro devorppa
rosnops eht taht seiduts dna hcraeser cigolocamrahp cirtaidep detseuqer na htiw sgurd dedulcni esehT .seiduts cirtaidep gnideen sa gnitsil rof
yraterceS eht hcihw rof tnetap deripxenu na htiw gurd a gnidrageR derrefer dah yraterceS eht taht sgurd ot detaler noisivorp HINF ehT
])C()1()c(b092 CSU 24 ;)C()1()c(994 ASHP[ .raey lacsif hcae rof 000,005$ etagergga na
HINF rof detairporppa eb ot sezirohtua wal ehT .hcraeser dednuf-yllaredef ot gnitaler snoitatimil laredef lla ot tcejbus eb llahs hpargarap siht rednu
derrefsnart sdnuf yna dna HIN eht ot sdnuf refsnart yam HINF .HINF dna seetnarg yb stluser cifitneics fo noitanimessid ,sthgir ytreporp lautcelletni
,seeyolpme laredef fo ecivres ,gnitroper dna noitazinagro laicnanif dna etaroproc ,srotcerid fo draob a gnidrager stnemeriuqer sedulcni wal ehT
.seiduts dna hcraeser cigolocamrahp cirtaidep niatrec rof sdnuf tcelloc ot margorp a gnidulcni ,smargorp hcraeser dna noitacude suoirav fo troppus
ni sdnuf dnepxe dna tsevni dna ,stnuocca hsilbatse ,snoitanod rehto dna ,stnarg ,stfig tpecca dna ticilos yam HINF .snoitazinagro tiforpnon dna
,yrtsudni ,seitisrevinu morf srehcraeser lacidemoib htiw noitaroballoc ecnavda ot dna ,)hcraeser cigolocamrahp cirtaidep rof sdnuf fo noitcelloc gnidulcni( )HINF( htlaeH
noissim sti ni HIN eht troppus ot si HINF .tnemnrevoG .S.U eht fo ytilatnemurtsni ro ycnega na eb ton llahs hcihw ,HIN eht rof noitadnuoF fo setutitsnI lanoitaN
eht sa nwonk eb ot noitaroproc tiforpnon a hsilbatse ot ,HIN fo rotceriD eht hguorht gnitca ,yraterceS eht eriuqer ot seunitnoc wal ehT eht rof noitadnuoF
305 dna )f-b(205 snoitceS ,V eltiT AAADF waL suoiverP cipoT
])1()a(6-882
CSU 24 ;)1()a(F784 ASHP ;)b(305 AAADF[ ".hcraeser lacigolocamrahp
cirtaidep gnidulcni" :"hcraeser cirtaidep" retfa stresni AAADF
])1()a(6-882 CSU 24 ;)1()a(F784 ASHP[ .snoisivorp tnemyaper naol rehto fo noitacilppa eht dna ;ytilibail xat rof stnemesrubmier
sesserdda osla wal ehT .slanoisseforp hcus fo snaol lanoitacude eht fo tseretni dna lapicnirp niatrec fo tnemyaper tnemnrevoG laredeF eht
rof egnahcxe ni ,hcraeser cirtaidep tcudnoc ot eerga ohw slanoisseforp htlaeh deifilauq htiw stcartnoc otni retne llahs yraterceS eht ,margorp hcus hcraeseR cirtaideP
hguorhT .margorp tnemyaper naol hcraeser cirtaidep a hsilbatse ot ,HIN fo rotceriD eht htiw noitatlusnoc ni ,yraterceS eht sezirohtua wal ehT rof tnemyapeR naoL
.noitcesbus siht .5002YF hguorht 1002YF fo hcae rof
rof noisivorp snoitairporppa fo noitazirohtua na evah ton seod AAADF yrassecen eb yam sa smus hcus detairporppa eb ot dezirohtua wal ehT
])2()a(01-g582 CSU 24 ;)2(G254 ASHP ;)a(305 AAADF[
".hcraeser lacigolocamrahp cirtaidep gnidulcni ,..." stresni AAADF
])2()a(01-g582 CSU 24 ;)2(G254 ASHP[ .hcraeser lacinilc dna cisab cirtaidep ni sreerac dliub ot dnetni ohw slanoisseforp htlaeh rof sdrawa
tnempoleved reerac fo rebmun eht ni esaercni na dna ;gniniart cirtaidep gnitroppus snoitutitsni ot stnarg gniniart lanoitutitsni fo ezis dna rebmun srehcraeseR
eht ni esaercni na :rof edivorp ot seitivitca troppus llahs ,noitartsinimdA secivreS dna secruoseR htlaeH eht fo rotartsinimdA eht htiw noitatlusnoc cirtaideP s'worromoT
retfa ,etutitsnI eht fo rotceriD eht ,nerdlihc fo sdeen hcraeser dna erac eht ot detacided srehcraeser fo ylppus erutuf eht erusne ot redro nI ni tnemtsevnI
])f(205 AAADF[ .rotubirtsid ro rerutcafunam eht ot stneve esrevda
troper ot hcihw htiw rebmun eerf-llot a sedulcni gnigakcap esohw gurd
a dna ,gurd noitpircserpnon a ,505 noitceS ACDFF rednu devorppa gurd
a era noitacilppa s'elur eht morf dedulcxE .etad taht erofeb elur lanif stnevE esrevdA
eht seussi renoissimmoC eht sselnu ,8002 ,1 yraunaJ no tceffe ekat ,4002 .)4002 ,22 lirpA ,87712 fo stropeR remusnoC
,22 lirpA no renoissimmoC eht yb desoporp elur eht taht seriuqeR RF 96( elur desoporp a ot srefer ti ;wal suoiverp ni ton si noisivorp sihT rof rebmuN eerF-lloT
]eton m482 CSU 24 ;tcA nerdlihC rof slacituecamrahP
tseB eht fo 51 noitceS ;)e(205 AAADF[ .stnega cituepareht
wen fo esu tneitap elgnis ot ssecca gnidulcni ,recnac cirtaidep rof stnega
cituepareht wen ot ssecca tneitap no seettimmoc lanoissergnoc ot
troper s'yraterceS eht rof tnemeriuqer eht ,9002 ,13 yraunaJ ot ,setadpu
dna ;sraey evif rof eettimmocbus eht fo snoitarepo sdnetxe osla AAADF
.srecnac cirtaidep fo tnemtaert eht ot tcepser htiw B505 dna A505
snoitces ACDFF ot stnemdnema nerdlihC rof slacituecamrahP tseB
eht dna stnemdnemA ytiuqE hcraeseR cirtaideP eht fo noitatnemelpmi
gnidrager )f(B505 ACDFF rednu detaerc eettimmoc weiver lanretni eht
ot snoitadnemmocer edivorp eettimmocbuS eht taht seriuqer AAADF
eettimmoC yrosivdA
]eton m482 CSU 24 ;tcA sgurD cigolocnO eht
nerdlihC rof slacituecamrahP tseB eht fo 51 noitceS[ .eettimmoC yrosivdA sgurD cigolocnO eht fo eettimmocbuS cirtaideP eht seunitnoc wal ehT fo eettimmocbuS cirtaideP
305 dna )f-b(205 snoitceS ,V eltiT AAADF waL suoiverP cipoT
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 $5 million for FY2008 and such sums as may be necessary for each of FY2009
through FY2012.
]5-bbb063 CSU 12 ;665 ACDFF ;306 AAADF[ .2102YF hguorht
9002YF fo hcae rof yrassecen eb yam sa smus hcus dna 8002YF rof noillim 5$ detairporppa eb ot sezirohtua dna ;ytefas tcudorp lacidem gnicnahne
dna ,tnempoleved tcudorp lacidem fo noitarelecca eht gnilbane ,noitavonni tcudorp lacidem gniretsof fo esoprup eht rof hcaertuo dna ,noitacude
,hcraeser ni stcejorp evitaroballoc ,evitavonni gnipoleved yb evitaitinI htaP lacitirC ADF eht tnemelpmi ot snoitazinagro tpmexe-xat ro lanoitacude htiw spihsrentraP etavirP
)spihsrentraP etavirP-cilbuP htaP lacitirC( stnemeerga evitaroballoc otni retne ot ,renoissimmoC eht hguorht gnitca ,yraterceS eht sezirohtua AAADF -cilbuP htaP lacitirC
]a993 CSU 12 ;019 ACDFF ;206 AAADF[ tsitneicS
.)deificeps seituD( .renoissimmoC eht fo eciffO s'ADF nihtiw tsitneicS feihC eht fo eciffO na etaerc ot yraterceS eht seriuqer ACDFF ni noitces wen A feihC eht fo eciffO
]2-dd973 CSU 12 ;277 ACDFF ;106 AAADF[ ".secivreS namuH dna htlaeH fo tnemtrapeD eht fo seeyolpme ro sreciffo ot elbacilppa esiwrehto
stnemeriuqer lacihte dna lagel lla ot tcejbus eb llahs snaicisyhp dna stsitneics hcuS .etairporppa senimreted yraterceS eht sa ,sisab detasnepmocnu
dna yratnulov a no secivres fo snaicisyhp dna stsitneics hcus yb noisivorp edulcni yam )xi()A()2()d(077 noitceS rednu ro noitces siht rednu smargorp
gniniart dna spihswollef hcus ynA" :gniwollof eht dne eht ta gnidda yb dednema si ))b(l973 CSU 12( ACDFF eht fo )b(247 .tnemtcane fo etad eht retfa ro
,no ,erofeb otni deretne ytitne rehto yna dna ADF eht neewteb tnemeerga evitarepooc ro ,gnidnatsrednu fo mudnaromem ,tcartnoc ,tnarg yna no tceffe
on evah llahs retpahcbus siht fo snoisivorp ehT .noitamrofni deriuqer rehto dna ,noitadnuoF eht yb dedivorp noitamrofni eht gnizirammus troper launna
na ssergnoC ot timbus ,9002YF htiw gninnigeb ,dna ;noitadnuoF eht gninrecnoc stroper launna deriuqer eht ssessa dna eviecer llahs renoissimmoC ehT
]1-dd973 CSU 12 ;177 ACDFF ;106 AAADF[ .aibmuloC fo tcirtsiD eht morf selim 02 naht erom ton detacol eb ,elbacitcarp fi ,llahs noitadnuoF ehT
]dd973 CSU 12 ;077 ACDFF ;106 AAADF[ .seitivitca s'noitadnuoF eht no troper launna na
renoissimmoC eht dna ssergnoC ot timbus llahs rotceriD evitucexE eht ,9002YF htiw gninnigeB .sisab launna na no seitivitca rieht gnidrager noitadnuoF
eht ot troper llahs noitadnuoF eht morf stnemeerga evitarepooc ro ,gnidnatsrednu fo adnaromem ,spihswollef ,stcartnoc ,stnarg fo stneipiceR
.000,052,1$ naht erom ton dna 000,005$ naht ssel ton noitadnuoF
eht ot refsnart llahs renoissimmoC eht ,raey lacsif hcae rof ADF eht ot detairporppa stnuoma morf ,eltitbus siht ni snoisivorp niatrec tuo yrrac oT
.secruos rehto morf deviecer sdnuf morf stnuocca etarapes
ni dleh era yrusaerT .S.U eht morf deviecer sdnuf eht taht erusne llahs rotceriD evitucexE ehT .noitadnuoF eht fo seitud eht tuo gniyrrac fo sesoprup
eht rof ,seititne etavirp morf gnidulcni ,ytreporp lanosrep ro laer fo stseuqeb ro ,sesived ,stnarg ,stfig ,sdnuf yna ,noitadnuoF eht fo flaheb no tpecca
dna ticilos yam rotceriD evitucexE ehT .noitces hcus fo snoisivorp eht ot tcejbus eb llahs dna ,6891 fo edoC euneveR lanretnI eht fo )c(105 noitceS
rednu noitaroproc a deredisnoc eb llahs noitadnuoF ehT .noitadnuoF eht etaroprocni ot yrassecen snoitca revetahw ekat llahs dna srotaroprocni
sa evres llahs draoB eht fo srebmem oiciffo xe ehT .snoitcnuf s'noitadnuoF eht ni devlovni seeyolpme laredef fo selor eht setalupits wal ehT
".ytefas erusaem ot secived dna sloot evitciderp dna evitisnes erom fo noitaroprocni
eht gnidulcni ,scitemsoc dna ,stneidergni doof ,doof fo ytefas eht dna ,sgurd dna ,scigoloib ,scitsongaid gnidulcni ,secived fo ,lavorppatsop gnidulcni
,ssenevitceffe dna ytefas eht fo noitaulave dna ,erutcafunam ,tnempoleved eht ni sdeen temnu yfitnedi ,noitartsinimdA gurD dna dooF eht yb dehsilbup
seitiroirp dna stroper htaP lacitirC eht noitaredisnoc otni gnikat" edulcni ot era noitadnuoF eht fo seitud ehT .rotceriD evitucexE eht dna ,srotceriD fo
draoB eht fo srewop evitartsinimda dna smret ,seitud tcudnoc ,noitamrof rof airetirc ,noitadnuoF eht fo seitud eht stsil wal ehT .ytefas tcudorp ecnahne ADF
dna ,noitavonni etarelecca ,tnempoleved tcudorp citemsoc dna ,tneidergni doof ,doof ,yraniretev ,lacidem ezinredom ot ADF eht fo noissim eht ecnavda eht rof noitadnuoF
ot ,)noitadnuoF ehT( noitartsinimdA gurD dna dooF eht rof noitadnuoF lladU-nagaeR eht sa nwonk eb ot noitaroproc tiforpnon a sehsilbatse AAADF lladU-nagaeR
IV eltiT AAADF cipoT
)IV eltiT AAADF( noitadnuoF lladU-nagaeR yb detaerC waL .9 elbaT
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,
and that many committee members have conflicts of interest.21
.smailliW .D nirE yb ,tseretnI fo tcilfnoC eettimmoC yrosivdA ADF ,19622SR tropeR SRC ees ,noitamrofni rehtruf roF
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.
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].qes te 173 CSU 12 ;)2()b(217 ACDFF ;)a(107 AAADF[ .)b(802
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ni scihtE eht ot tnausrup laudividni eht yb delif troper erusolcsid laicnanif eht dna laudividni eht fo airetirC
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].qes
te 173 CSU 12 ;)1()b(217 ACDFF ;)a(107 AAADF[ .seicnacav fo rebmun tsetaerg eht htiw seettimmoc
yrosivda eht tnuocca otni ekat osla llahs yraterceS ehT .seitivitca tnemtiurcer dna lanoitamrofni evitceffe
tsom eht enimreted ot seiteicos cifitneics dna lacidem lanoisseforp morf tupni kees llahs yraterceS ehT
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]28.41 RFC 12[ .srebmem gnitov rof snoitanimon gnitseuqer raey hcae retsigeR laredeF eht ni seciton erom ro eno hsilbup ot deriuqer si renoissimmoC ehT tnemtiurceR
].qes te 173 CSU 12 ;)2()a(217 ACDFF ;)a(107 AAADF[
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fo epocs ehT :setoN[ ))a(802 CSU 81 ni denifeD( .tseretni laicnanif a sah ,tnemyolpme evitcepsorp gninrecnoc tnemegnarra yna sah ro gnitaitogen si eh
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].qes ])n(553
te 173 CSU 12 ;)1()a(217 ACDFF ;)a(107 AAADF[ .ADF eht gnidrager yraterceS eht ot snoitadnemmocer CSU 12[ .seettimmoc yrosivda cigoloib dna gurd eettimmoC
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IIV eltiT AAADF waL suoiverP cipoT
waL suoiverP htiw )IIV eltiT AAADF( tseretnI fo stcilfnoC fo nosirapmoC .01 elbaT
].qes te 173
CSU 12 ;)e(217 ACDFF ;)a(107 AAADF[ .srenoititcarp ro snaicimedaca fo esoht gnidulcni ,snoitanimon
fo rebmun eht esaercni dna seettimmoc yrosivda no seicnacav fo rebmun eht ecuder ot snalp yraterceS
eht woh dna ;sgniteem fo ecnavda ni syad 03 naht ssel derrucco serusolcsid deriuqer semit fo rebmun
eht ;serusolcsid hcus eriuqer ton did ohw srebmem fo egatnecrep eht dna gniteem rep serusolcsid detaler
-tcilfnoc fo rebmun eht ;evres ot gnilliw seenimon fo rebmun eht dna ,seenimon ,seicnacav eettimmoc
yrosivda gnibircsed seettimmoc lanoissergnoc tnaveler ot stroper launna timbus ot si yraterceS ehT .noisivorp oN tropeR launnA
].qes te 173 CSU 12 ;)d(,)3()c(217
ACDFF ;)a(107 AAADF[ .gniteem hcae fo tpircsnart dna drocer cilbup eht ni dedulcni eb ot era
serusolcsiD .gniteem eht fo etad eht naht retal on ,gniteem eht ot roirp syad 03 naht ssel yraterceS eht ot
nwonk emaceb stseretni laicnanif eht taht tneve eht ni ,ro ,gniteem eettimmoc yrosivda na ot roirp syad
51 naht ssel ton erusolcsid eht ekam ot deriuqer si yraterceS ehT .tseuqer tcA noitamrofnI fo modeerF
a ot tcejbus ton si taht noitamrofni edulcni ton dluohs erusolcsid ehT .noitca s'yraterceS eht rof snosaer
eht dna stseretni laicnanif tnenitrep eht fo edutingam dna ,erutan ,epyt eht etisbew ADF eht no esolcsid reviaW
ot si yraterceS eht ,)3( ro )1()b(802 CSU 81 rednu ro AAADF fo smret eht rednu detnarg sreviaw roF .noisivorp oN fo erusolcsiD
].qes te 173 CSU 12
;)C()2()c(217 ACDFF ;)a(107 AAADF[ .2102YF rof %57 dna ,1102YF rof %08 ,0102YF rof %58 ,9002YF
rof %09 ,8002YF rof %59 :rebmun 7002YF eht fo snoitroporp gniwollof eht ot snoitpecxe fo rebmun
latot eht timil dna ,snoitpecxe deviecer ohw srebmem yrosivda fo noitroporp dna rebmun eht enimreted
ot deriuqer si yraterceS eht ,7002YF roF .)3()b(802 rednu snoitacifitrec nettirw )3( dna ,)b(802 CSU
81 rednu snoitanimreted nettirw )2( ,snoisivorp AAADF detaerc ylwen rednu yraterceS eht yb detnarg snoitatimiL
sreviaw )1( :snoitibihorp tcilfnoc laicnanif eht ot snoitpecxe fo sepyt eerht no decalp era snoitatimiL .noisivorp oN reviaW
])a(13.41
].qes te 173 CSU 12 ;)B()2()c(217 ACDFF ;)a(107 AAADF[ RFC 12[ .eettimmoc eht erofeb gnidnep rettam
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gnitov ro gnitov-non a wolla ot noitibihorp detaerc-AAADF eht fo reviaw a tnarg yam yraterceS ehT ohw nosrep yna htiw refnoc yam eettimmoc A
.sutats naksalA evitaN ro naidnI s'eno ot setaler tcilfnoc eht fi snoitpmexe niatrec )4( dna ,tcilfnoc a rof laitnetop eht shgiewtuo secivres
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].qes te 173 CSU 12 ;)A()2()c(217 ACDFF ;)a(107 AAADF[ .ylppa snoitaluger hcus hcihw ot
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oot sa scihtE tnemnrevoG fo eciffO eht fo rotceriD eht yb deussi snoitaluger ni detpmexe stseretni
gnidulcxe ,rettam hcus ot tcepser htiw yraterceS eht ot nevig ecivda eht yb detceffa eb dluoc taht tseretni
laicnanif a sah )rebmem hcus fo rebmem ylimaf etaidemmi na ro( rebmem hcus fi eettimmoc yrosivda
eht yb deredisnoc rettam yna ot tcepser htiw etapicitrap ton yam rebmem eettimmoc yrosivda nA
])b(301.0462 .R.F.C 5[ .eeyolpme eht ot ssol ro niag rof laitnetop yna edulcni ot noitaluger ni yldaorb deterpretni neeb sah stseretni
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IIV eltiT AAADF waL suoiverP cipoT
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sa ,]173 CSU 12[ A retpahcbus ,IIV eltiT ACDFF ot devom era )n(553 CSU 12 ni erew taht snoisivorP ylno snoisivorp stcilfnoc deilppa )n(553 CSU 12 gnimrofnoC
].qes te 173 CSU 12 ;)f(217 ACDFF ;)a(107 AAADF[ .sraey weiveR
evif yreve ecno naht ssel ton ecnadiug tseretni fo tcilfnoc ADF etadpu dna weiver ot si yraterceS ehT ecnadiuG
IIV eltiT AAADF waL suoiverP cipoT
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,
and cardiac stents) about which unfavorable trial results had not been publicly disclosed.22 The
issue of public access to all trial results, regardless of their findings, then gained significant
traction.
.smailliW .D nirE yb ,noitacilbuP dna gnitropeR slairT lacinilC ,23823LR tropeR SRC ees ,noitamrofni rehtruf roF
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
Registry Platform registration data set.23 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
to devices as well.24
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.
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ylisae era taht seirtne htiw dna cilbup eht yb desu ylisae rennam a ni dna ,tenretnI eht enohpelet eerf-llot edulcni ot erew hcihw ,smetsys
hguorht elbaliava ylcilbup edam si noitamrofni lairt lacinilc erusne llahs rotceriD HIN ehT noitamrofni aiv etanimessid ot si yraterceS ehT sseccA cilbuP
noitamrofnI
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AAADF[ .seitilibisnopser PR eht teem ot ytirohtua eht sah dna ,stluser lairt hsilbup
ot thgir eht sah ,atad revo lortnoc dna ot ssecca sah ,lairt eht gnitcudnoc rof elbisnopser
si IP eht sa gnol os ,eedrawa ro ,rotcartnoc ,eetnarg ,rosnops yb detangised fi IP )noitamrofni timbus
eht eb yam PR ehT .]...noitagitsevni eht tcudnoc yllautca ton seod ohw tub ,noitagitsevni ot deriuqer nosrep eht
lacinilc a setaitini ohw nosrep a[ 3.05 RFC 12 yb denifed sa ,rosnops eht si PR ehT .noitamrofni deriuqer timbus ot si rosnops ehT ;PR( ytraP elbisnopseR
])j(282 CSU 24 ;)ii()A()1()j(204 ASHP ;)2()a(108
AAADF[ .]AAADF fo snoisivorp AISDMP eht yb dednema sa[ 225 ACDFF rednu
deriuqer sa ecnallievrus tekramtsop cirtaidep dna ;)semoctuo htlaeh ot ton dna ytilibisaef
ot setaler erusaem emoctuo yramirp eht erehw secived epytotorp tset ot lairt lacinilc a )deriuqer
ro ,ecived a fo ytilibisaef eht enimreted ot lairt lacinilc llams a naht rehto( stcejbus namuh si gnitroper stluser ,sesac
ni lortnoc a tsniaga ]secived nairatinamuh :er[ )m(025 ro ,]secived fo lavorppa tekramerp emos ni ,dna noitartsiger
:er[ 515 ,]ecnaraelc ecived er[ )k(015 ACDFF ot tcejbus ecived a htiw noitnevretni hcihw rof slairt(
na gnirapmoc semoctuo htlaeh fo seiduts lacinilc evitcepsorp era slairt ecived elbacilppA .enoN slairT eciveD elbacilppA
.elbacilppa
ton era scigoloib fo slairT .)etutitsnI recnaC lanoitaN
eht yb denifed sa( gurd recnac C puorG a sa )ii( ro
].stcejbus reetnulov lamron ro stneitap ni detcudnoc eb yam dna derotinom ;)c(bbb063 CSU 12 rednu yraterceS eht ot dettimbus
ylesolc yllacipyt era seiduts 1 esahP .snamuh otni gurd wen lanoitagitsevni na fo neeb sah taht noitacilppa gurd wen lanoitagitsevni
noitcudortni laitini eht :noitaluger rosseccus yna ro12.213 RFC 12 ni sa denifed si I esahP tnemtaert a rednu )i( - elbaliava eb yam taht snoitidnoc
.ecitcarp lacidem fo esruoc eht ni gurd detekram a fo esu eht rof tpecxe dna sesaesid gninetaerht-efil ro suoires rof stnemtaert
gurd a fo esu yna si tnemirepxe na ,trap siht fo sesoprup eht roF .stcejbus namuh erom latnemirepxe ot gniniatrep noitamrofni :sgurd wen
ro eno ,gnivlovni desu ro ,ot desnepsid ro deretsinimda si gurd a hcihw ni tnemirepxe lanoitagitsevni fo esu tnemtaert )2( ro ;]sgurd wen
yna :snoitaluger rosseccus ro 3.213 RFC 12 ni sa denifed si snoitagitsevni lacinilC[ lanoitagitsevni :er[ )i(553 CSU 12 noitces ot tnausrup )deriuqer si gnitroper
detaglumorp snoitaluger rednu snoitidnoc dna sesaesid stluser ,sesac emos
])j(282 CSU 24 ;)iii()A()1()j(204 ASHP gninetaerht-efil ro suoires rof stnemtaert latnemirepxe ni ,dna noitartsiger hcihw
;)2()a(108 AAADF[ .153 ASHP ro 505 ACDFF ot tcejbus gurd a fo ,snoitagitsevni lacinilc I fo )dednuf yletavirp ro yllaredef rehtehw( slairt rof slairt( slairT cigoloiB
esahP naht rehto ,snoitagitsevni lacinilc dellortnoc era slairt scigoloib dna gurd elbacilppA gurd wen lanoitagitsevni )1( :era slairt gurd elbacilppA dna gurD elbacilppA
])j(282 CSU 24 ;)iii(-)i()A()1()j(204 ASHP ;)2()a(108
AAADF[ .scigoloib dna ,secived ,sgurd fo slairt elbacilppa ot ylppa stnemeriuqeR .ylno slairt gurd ot deilppa stnemeriuqeR slairT fo sepyT
IIIV eltiT AAADF waL suoiverP cipoT
waL suoiverP htiw )IIIV eltiT AAADF( sesabataD lairT lacinilC fo nosirapmoC .11 elbaT
])j(282 CSU 24 ;)iii()B()3()j(204 ASHP ;)2()a(108 AAADF[ .detsop ylcilbup si smret
lacinhcet fo yrassolg a taht erusne llahs ,rotceriD HIN eht hguorht gnitca ,yraterceS ehT .noisivorp oN yrassolG
])j(282 CSU 24 ;)D()2()j(204
ASHP ;)2()a(108 AAADF[ .yraterceS eht yb detsop eb ot deriuqer si noitamrofni
stluser lairt lacinilc taht etad eht retfa syad 03 naht retal ton detsop eb ot si noitamrofni
yrtsiger ,devorppa ro deraelc ylsuoiverp secived rof ,tnemtcane retfa raey eno gninnigeB
.ecnaraelc ro lavorppa retfa syad 03 naht retal ton dna ,)m(025 ro 515 ACDFF rednu
lavorppa ro ,)k(015 ACDFF rednu ecnaraelc fo etad eht naht reilrae ton detsop eb ot
si noitamrofni ,slairt ecived roF .PR eht yb dettimbus si noitamrofni eht retfa syad 03 naht
retal ton slairt scigoloib dna gurd tuoba noitamrofni tsop ot deriuqer si rotceriD HIN ehT .noisivorp oN gnitsoP yrtsigeR fo gnimiT
])j(282 CSU 24
;)C()2()j(204 ASHP ;)2()a(108 AAADF[ .tnemtcane fo etad eht retfa raey eno ,tnemtcane
fo etad eht fo sa gniogno era taht snoitidnoc ro sesaesid gninetaerht-efil ro suoires
rof ton era taht slairt rof )3( ro ;lairt eht ni dellorne si tneitap tsrif eht retfa syad 12
)2( ;tnemtcane AAADF retfa syad 09 )1( :fo retal eht naht retal ton noitamrofni deriuqer .locotorp eht fo lavorppa eht retfa syad 12 yrtsigeR
timbus ot si PR eht ,tnemtcane AAADF retfa syad 09 gniogno ro detaitini slairt roF naht retal ton dettimbus eb ot si noitamrofni deriuqeR ot noissimbuS fo gnimiT
])j(282 CSU 24 ;)i()B()2()j(204 ASHP
;)2()a(108 AAADF[ .yrassecen smeed rotceriD eht taht stnemele rehto yb elbahcraes
yrtsiger eht ekam ot si rotceriD ehT .emoctuo yradnoces ro yramirp a sa deiduts gnieb
eussi ytefas--tnemtcane AAADF fo shtnom 81 nihtiw dedda eb ot si yrogetac lanoitidda
nA .)s(rebmun noitacifitnedi dna ,sutats tnemtiurcer ,rosnops ,esahp lairt eht dna ,deiduts
gnieb puorg ega eht ,lairt eht fo noitacol eht ,noitnevretni eht fo eman eht ,deiduts gnieb seirogetaC
noitidnoc ro esaesid eht ,drowyek yb elbahcraes si ti taht erusne ot si rotceriD HIN ehT .deificeps toN elbahcraeS yrtsigeR
])j(282 CSU 24 ;)6()j(204 ASHP ;)2()a(108 AAADF[ .255 CSU
5 rednu detcetorp esiwrehto noitamrofni tsop ot deriuqer ton si yraterceS eht :etoN
])j(282 CSU 24 ;)iii()A()2()j(204 ASHP ;)2()a(108 AAADF[
.noitamrofni eht ecuder ton seod dna sevorpmi noitacifidom eht yhw ot sa elanoitar
a sedivorp yraterceS eht fi ,noitaluger yb stnemeriuqer eseht yfidom yam yraterceS ehT .stceffe esrevda ro ,seiticixot
laitnetop ,slairt fo stluser eht edulcni yam snoissimbus
])j(282 CSU 24 ;)ii()A()2()j(204 ASHP ;)2()a(108 AAADF[ ,tnesnoc rosnops htiW .nerdlihc ni ylralucitrap ,gurd
).wal suoiverp rednu deriuqer erew taht stnemele lla edulcni tub ,wal suoiverp rednu wen eht fo esu locotorp dednapxe dna tneitap-elgnis
naht yltnereffid dedrow era stnemeriuqer noissimbus AAADF :etoN( .).cte ,rebmun rof ,sdraugefas etairporppa htiw ,noitpecxe locotorp
locotorp EDI/DNI ADF ,srebmun noitacifitnedi locotorp( atad evitartsinimda )4( dna ;).cte rof stseuqer ot dnopser lliw rosnops ro rerutcafunam
,noitamrofni ytilicaf ,PR ,eman rosnops( noitamrofni tcatnoc dna noitacol )3( ;).cte ,stimil eht woh dna rehtehw fo noitpircsed ,tcatnoc
ega ,redneg ,airetirc ytilibigile( noitamrofni tnemtiurcer )2( ;).cte ,serusaem emoctuo fo tniop tnemllorne ,lairt fo )s(noitacol ,airetirc noissimbuS
,esoprup ,yrammus ,eltit( noitamrofni evitpircsed )1( :edulcni ot si noissimbus yrtsiger ehT ytilibigile ,esoprup lairt eht edulcni ot era snoissimbuS yrtsigeR fo tnetnoC
IIIV eltiT AAADF waL suoiverP cipoT
])j(282 CSU 24 ;)iii()B()3()j(204 ASHP ;)2()a(108
AAADF[ .cilbup eht ro stneitap daelsim ton od esabatad eht ni stluser cisab deificeps
eht taht erusne pleh ot dedivorp eb ot si strepxe noitacinummoc ksir htiw noitatlusnoc
ni detaerc noitamrofni taht erusne llahs ,rotceriD HIN eht hguorht gnitca ,yraterceS ehT .noisivorp oN noitacinummoC ksiR
])j(282 CSU 24 ;)6()j(204 ASHP ;)2()a(108 AAADF[ .255
CSU 5 rednu detcetorp esiwrehto noitamrofni tsop ot deriuqer ton si yraterceS ehT-
])j(282 CSU 24 ;)iii()D()3()j(204
ASHP ;)2()a(108 AAADF[ .etairporppa era senimreted yraterceS eht seirogetac
rehto hcus )4( ;noitamrofni locotorp )3( ;stluser fo yrammus lacinhcet a )2( ;stluser fo
yrammus lacihncet-non a )1( :sa llew sa ,stluser cisab edulcni stluser dna yrtsiger dednapxE-
])j(282 CSU 24 ;)C()3()j(204 ASHP ;)2()a(108 AAADF[
.lanruoj cimedaca ro cifitneics a ni stluser hsilbup ro ssucsid ylcilbup ot IP eht fo ytiliba eht
tcirtser taht IP dna rosnops eht neewteb stnemeerga yna )4( dna ;stluser dna noitamrofni
cifitneics rof tcatnoc fo tniop )3( ;)noitartsiger htiw dettimbus noitamrofni erusaem
emoctuo ot knil ot si rotceriD HIN eht hcihw( semoctuo yradnoces dna yramirp )2(
;elpmas tneitap eht fo scitsiretcarahc enilesab dna cihpargomed )1( :edulcni stluser cisaB-
])j(282 CSU
24 ;)ii()A()3()j(204 ASHP ;)2()a(108 AAADF[ .tnemtcane s'AAADF ot roirp knab atad eht
ot dettimbus slairt rof noitamrofni stluser fo sepyt evoba eht ot sknil edivorp osla yam
yraterceS ehT .)seirtne lebal tcudorp MLN dna snoitatic enildeM tnenitrep( noitamrofnI
HIN )2( dna ;).cte ,seirosivda htlaeh cilbup ADF ,stnemssessa stluser ADF ,noitatnemucod
eettimmoc yrosivda tnenitrep( noitamrofnI ADF )1( :edulcni stluser gnitsixE- .stceffe esrevda ro seiticixot laitnetop gnidulcni
,slairt dedulcni fo stluser eht tuoba noitamrofni sgnitsoP
:noitamrofni stluser fo seirogetac tnereffid eerht era erehT edulcni yam yrtsiger eht ,tnesnoc rosnops htiW stluseR fo tnetnoC
IIIV eltiT AAADF waL suoiverP cipoT
])j(282 CSU 24 ;)B()4()j(204 ASHP ;)2()a(108 AAADF[
.PR eht ot eciton fo syad 03 nihtiw noitamrofni lairt lacinilc deificeps a rof stluser dna
yrtsiger fo noissimbus eht eriuqer yam yraterceS eht ,htlaeh cilbup tcetorp ot yrassecen fI-
])j(282 CSU 24 ;)vi()D()3()j(204 ASHP ;)2()a(108 AAADF[ .stluser cisab sa enilemit emas
eht ot gnidrocca gnikamelur ot tnausrup dettimbus eb ot era stluser dna yrtsiger dednapxE-
.syad 03 nihtiw rotceriD HIN eht yfiton tsum yraterceS
eht ,detnarg si noisnetxe na fI .esuac doog gnitartsnomed tseuqer nettirw a sekam PR eht
fi noisnetxe na tnarg yam yraterceS ehT .ytiruces lanoitan ro htlaeh cilbup htiw tnetsisnoc
si ti sa gnol sa ,ti yfitsuj secnatsmucric yranidroartxe fi noissimbus stluser ot reviaw
a tnarg yam yraterceS ehT .noitacilppa nevig a rof slairt deriuqer lla rof snoitacifitrec
lauqe ekam tsum ti ,noitacifitrec a hcus sekam rerutcafunam a fI .thguos gnieb si esu
wen a fo lavorppa taht etacifitrec a fo noissimbus eht htiw sraey owt ot pu rof deyaled
eb yam doirep emit sihT .gnikamelur detaler-stluser ro yrtsiger dednapxe aiv shtnom
81 ot dednapxe eb yam doirep emit sihT .lairt eht fo etad noitelpmoc lautca ro detamitse
eht fo reilrae eht gniwollof raey eno naht retal ton dettimbus eb ot era stluser cisaB-
.PR noissimbuS
eht yb noissimbus eriuqer ton seod dna elbaliava ylcilbup si noitamrofni stluser gnitsixE- .deificeps toN stluseR fo gnimiT
])j(282 CSU 24 ;)4()j(204 ASHP ;)2()a(108 AAADF[ .htlaeh cilbup eht tcetorp ot
yrassecen fi yraterceS eht yb deriuqer eb osla yam snoissimbus lanoitiddA .slairt deriuqer
lla rof snoissimbus edam sah PR na fi yliratnulov edam eb yam snoissimbus lanoitiddA-
])j(282 CSU 24 ;)ii()D()3()j(204 ASHP ;)2()a(108 AAADF[ .)thguos saw lavorppa ro
,erusnecil ,lavorppa rehtehw( )m(025 ro 515 rednu devorppa ton ro )k(015 rednu deraelc
ton secived dna ,153 ASHP rednu decnecil ton scigoloib ,505 ACDFF rednu devorppa ton
sgurd rof slairt lacinilc elbacilppa rof deriuqer eb osla llahs noitamrofni rehtehw hsilbatse
ot si gnikameluR .)m(025 ro 515 rednu devorppa ro )k(015 rednu deraelc secived
dna ,153 ASHP rednu decnecil scigoloib ,505 ACDFF rednu devorppa era taht sgurd
rof lairt lacinilc elbacilppa hcae rof noitamrofni edulcni ot era stluser dna yrtsiger dednapxE-
])j(282 CSU 24 ;)C()3()j(204 ASHP ;)2()a(108 AAADF[ .)m(025
ro 515 rednu devorppa ro )k(015 rednu deraelc secived dna ,153 ASHP rednu decnecil
scigoloib ,505 ACDFF rednu devorppa era taht sgurd rof detsop eb ot era stluser cisaB-
])j(282 CSU 24 ;)i()A()3()j(204 ASHP ;)2()a(108 AAADF[ .elbaliava ylcilbup
si noitamrofni deificeps eht hcihw rof devorppa ro deraelc si ecived eht retfa ro devorppa
si scigoloib ro gurd eht retfa detcudnoc era ro mialc ycaciffe na fo sisab yramirp eht mrof detsoP eB oT erA
taht AAADF fo tnemtcane eht retfa dettimbus slairt rof detsop eb ot era stluser gnitsixE- .stluser fo gnitsop rof tnesnoc rosnops evah taht slairT stluseR hcihW roF slairT
IIIV eltiT AAADF waL suoiverP cipoT
])j(282 CSU 24 ;)I()3()j(204 ASHP ;)2()a(108 AAADF[ ).)712
seR.gnoC.H( llew sa secived ot ti dnapxe dluow taht erusaem a dessap esuoH ehT ).llew
sa secived lacidem ot stnemeriuqer eht dednapxe 613-011 .L.P tub ,scigoloib dna sgurd
ot detimil erew stnemeriuqer gnitroper tneve esrevda s'AAADF :etoN( .stnemeriuqer
stluser cisab eht ot tnausrup esabatad stluser dna yrtsiger eht ni dedulcni eb
ot demeed si noitamrofni lairt lacinilc tneve esrevdA .lairt eht fo mra yna nihtiw tnecrep
evif fo ycneuqerf a deecxe taht stneve esrevda rehto fo elbat ralimis a )2( dna ;lairt
eht fo mra hcae ni tneve hcus fo ycneuqerf dna rebmun htiw ,metsys nagro yb depuorg
)detapicitnanu dna detapicitna htob( stneve esrevda suoires fo elbat a )1( :esabatad
stluser dna yrtsiger eht ni stnemele gniwollof eht edulcni ,strepxe noitacinummoc
ksir htiw noitatlusnoc ni ,tsum yraterceS eht ,tnemtcane AAADF retfa shtnom
42 nihtiw noitca ekat ot sliaf yraterceS eht fI .esabatad stluser dna yrtsiger eht ni stneve .stceffe esrevda ro seiticixot laitnetop gnidulcni
esrevda tneuqerf dna suoires no noitamrofni etairporppa gnidulcni rof dohtem tseb ,slairt dedulcni fo stluser eht tuoba noitamrofni
eht enimreted ot si yraterceS eht ,tnemtcane AAADF retfa shtnom 81 naht retal toN edulcni yam yrtsiger eht ,tnesnoc rosnops htiW stnevE esrevdA
])j(282
CSU 24 ;)D()3()j(204 ASHP ;)2()a(108 AAADF[ .stnemeriuqer gnikamelur eht gnidrager
tupni cilbup rof ytinutroppo na edivorp ot tnemtcane s'AAADF retfa shtnom 81 gniteem
cilbup a dloh ot si dna ,tes atad noitazinagrO htlaeH dlroW eht redisnoc ot si yraterceS
eht ssecorp gnikamelur eht nI .noitamrofni stluser cisab eht gnitroper fo rennam
eht ot snoitacifidom ro snoitidda yficeps )6( dna ;snoissimbus yratnulov gniynapmocca
tnemetats a rof stnemeriuqer yficeps )5( ;noitamrofni lairt lacinilc fo setadpu
rof stnemeriuqer dna gnimit etairporppa eht yficeps )4( ;lortnoc ytilauq rof serudecorp
dna ,stneitap ot elbadnatsrednu dna lacinhcetnon si taht noitamrofni lanoitidda ,tamrof
noissimbus dradnats a hsilbatse )3( ;tnemtcane s'elur eht ot roirp edam erew snoissimbus
stluser cisab hcihw rof slairt gnidrager dettimbus eb tsum noitamrofni dednapxe nehw
yb dna rehtehw yficeps )2( ;shtnom 81 ot raey eno morf desaercni eb dluohs stluser fo
noissimbus rof doirep emit eht rehtehw enimreted )1( :ot si esabatad stluser dna yrtsiger gnikameluR stluseR
dednapxe eht gnidrager gnikamelur deriuqer ,evoba deificeps stniop eht ot noitidda nI .elbacilppa toN dna yrtsigeR dednapxE
])j(282 CSU 24 ;)G(,)D(,)C()3()j(204 ASHP ;)2()a(108 AAADF[ .gnikamelur ot tnausrup
,noissimbus gniwollof syad 03 naht retal ton detsop eb ot era stluser dna yrtsiger dednapxE-
.noissimbus retfa syad 03 naht retal ton dna
tnemtcane AAADF retfa raey eno naht retal ton gninnigeb detsop eb ot era stluser cisaB-
])j(282 CSU 24 ;)i()A()3()j(204 ASHP ;)2()a(108
AAADF[ .elbaliava ylcilbup semoceb noitamrofni eht retfa syad 03 naht retal ton
ro ,tcudorp eht fo ecnaraelc ro lavorppa eht retfa syad 03 naht reilrae ton dna ,tnemtcane
AAADF retfa syad 09 naht retal ton gninnigeb dedivorp eb ot era sknil stluser gnitsixE- .deificeps toN gnitsoP stluseR fo gnimiT
IIIV eltiT AAADF waL suoiverP cipoT
])j(282 CSU 24 ;)C()5()j(204 ASHP ;)2()a(108 AAADF[
.ecnailpmocnon eht ydemer ot ytinutroppo na PR eht evig dna yfiton tsum yraterceS
eht ,deriuqer sa sdradnats CQ teem ton did ro dettimbus ton saw noitamrofni lairt
lacinilc taht senimreted yraterceS eht fI .tcejorp eht morf snoitadnemmocer etaroprocni
ot era snoitaluger ehT .esabatad stluser dna yrtsiger dednapxe eht rof snoitaluger eht fo
etad evitceffe eht litnu eunitnoc llahs tcejorp tolip ehT .lanoitomorp-non si dna ralucitrap
yna ni gnidaelsim ro eslaf ton si noitamrofni dettimbus taht erusne ot )CQ( lortnoc tcejorP
ytilauq fo dohtem tseb eht enimreted ot tcejorp tolip a tcudnoc tsum yraterceS ehT .noisivorp oN toliP lortnoC ytilauQ
])j(282 CSU 24 ;)D()5()j(204 ASHP ;)2()a(108 AAADF[ .ralucitrap noitamrofnI
yna ni gnidaelsim ton dna lufhturt eb tsum PR eht yb dettimbus noitamrofni lairt lacinilC .noisivorp oN dettimbuS fo ssenlufhturT
])j(282 CSU
24 ;)B()5()j(204 ASHP ;)2()a(108 AAADF[ ".)noitacilppa hcus fo tnemele na deredisnoc
eb ton llahs hcihw( )B()5()j(204 ASHP rednu tnemeriuqer noitacifitrec eht edulcni
llahs noitacilppa hcus" taht tnemetats eht edulcni ot dednema hcae era )snoitpmexe
ecived nairatinamuh dna ecnaraelc ecived sa llew sa lavorppa ecived dna cigoloib
,gurd rof snoissimbus gninrevog( 025 dna ,515 ,015 ,505 ACDFF .srebmun lortnoc
lairT lacinilC lanoitaN eht edulcni ot si noitacifitrec hcus ,elbaliava erehW .esabatad
stluser dna yrtsiger eht ot snoissimbus deriuqer lla edam sah PR eht taht noitacifitrec snoitacifitreC
a edulcni ot era scigoloib dna ,secived ,sgurd fo ecnaraelc ro lavorppa rof snoitacilppA .noisivorp oN noitacilppA ADF
])j(282 CSU 24 ;)vi()A()5()j(204 ASHP ;)2()a(108 AAADF[ SHH
.edam era snoissimbus deriuqer gnirusne rof locotorp SHH eht ot elbarapmoc seigetarts nahT rehtO seicnegA
poleved dna )stcejbus hcraeser namuh rof snoitcetorp laredef( 64 RFC 54 fo trap yna laredeF yb dednuF
htiw ecnadrocca ni hcraeser gnitcudnoc seicnega rehto htiw tlusnoc tsum yraterceS eht slairT :ecnailpmoC
,seicnega laredef rehto morf stnarg yb detroppus tub ,gnidnuf SHH tuohtiw hcraeser roF .noisivorp oN dna noitanidrooC
])j(282 CSU 24 ;)A()5()j(204 ASHP ;)2()a(108 AAADF[ .ecnailpmocnon
rieht ydemer ot ytinutroppo na dna eciton nevig eb ot era snoissimbus deriuqer
lla edam ton evah ohw seetnarG .gnidnuf gnisaeler erofeb dettimbus neeb sah noitamrofni
hcus taht yfirev tsum seicnega SHH eht fo sdaeh ehT .esabatad stluser dna yrtsiger slairT
eht ot snoissimbus deriuqer lla edam sah PR eht taht noitacifitrec a edulcni tsum smrof dednuF SHH :ecnailpmoC
troper ssergorp ro tnarg deriuqer yna ,seicnega SHH morf stnarg yb detroppus slairt roF .noisivorp oN dna noitanidrooC
])j(282 CSU 24 ;)C()4()j(204 ASHP ;)2()a(108 AAADF[
.elbissecca sniamer noitamrofni dettimbus ylsuoiverp taht erusne ,noitamrofni tcatnoc dna
,noitacol ,sutats etis laudividni ,sutats tnemtiurcer ot drager htiw tpecxe ,dna ,elbaliava
ylcilbup noitamrofni etadpu ekam llahs rotceriD ehT .egnahc eht retfa syad 03 naht
retal ton noitelpmoc lairt ro sutats tnemtiurcer ni segnahc gnidrager dettimbus eb )3(
dna ;segnahc hcus yna fo setad eht edulcni )2( ;segnahc on erew ereht sselnu ,shtnom 21
yreve ecno naht ssel ton dettimbus eb )1( :llahs setadpU .noitamrofni yrtsiger ot segnahc
tcelfer ot rotceriD HIN eht ot setadpu timbus llahs lairt lacinilc elbacilppa na rof PR ehT .noisivorp oN setadpU yrtsigeR
IIIV eltiT AAADF waL suoiverP cipoT
]eton 282 CSU 24 ;)c(108 AAADF[ .lairt
lacinilc a ton si taht ecnallievrus tekramtsop cirtaidep AISDMP a ot ylppa stnemeriuqer ecnadiuG ecnallievruS
esabatad eht woh no ecnadiug eussi ot si yraterceS eht ,tnemtcane fo shtnom 21 nihtiW .noisivorp oN tekramtsoP cirtaideP
])i(,)b(553 CSU 12 ;)1()b(505 ACDFF
;)3()b(108 AAADF[ .AAADF ot tnausrup knabatad yrtsiger eht ni noisulcni rof dettimbus
eb lliw ro neeb sah noitamrofni lairt lacinilc taht tnemetats a ssecorp dna stnemucod
tnesnoc demrofni eht ni edulcni ot snoitaluger etadpu ot yraterceS eht gniriuqer ,))i(553 .yrtsiger eht ot cificeps enon tub ,stnemeriuqer tnesnoC demrofnI
CSU 12( sgurd wen lanoitagitsevni ot gniniatrep snoisivorp ACDFF eht sdnema AAADF tnesnoc demrofni deniatnoc wal suoiverP gurD weN lanoitagitsevnI
.daelsim ro duarfed ot tnetni
eht htiw ro ,noitces elbacilppa eht rednu noitcivnoc
a retfa derrucco noitaloiv eht fi 000,01$ ot pu denif
eb dluoc srotaloiV .htob ro ,000,1$ naht erom ton
]333 CSU 12 ;)f(303 ACDFF ;)2()b(108 AAADF[ .detcerroc si noitaloiv eht litnu deussi denif ro raey eno naht erom ton rof denosirpmi eb
si ecnailpmocnon fo noitacifiton deriuqer-AAADF retfa noitaloiv fo yad hcae rof yad rep dluoc srotaloiV .snoitcarfni esabatad ot ylppa ,ton did
000,01$ naht erom ton dna ,gnideecorp elgnis a ni detacidujda snoitaloiv lla rof 000,01$ tub ,elba neeb evah yam ADF hcihw ,stca detibihorp
naht erom ton ot detcejbus eb yam snoisivorp esabatad lairt lacinilc AAADF fo srotaloiV fo snoitaloiv rof seitlanep lareneg dedivorp wal ehT seitlaneP yratenoM liviC
]133 CSU 12 ;)jj(103 ACDFF ;)1()b(108
AAADF[ .ralucitrap yna ni gnidaelsim ro eslaf si taht noitamrofni lairt lacinilc deriuqer .ADF eht yb deilppa
-AAADF fo noissimbus eht )3( dna ;noitamrofni lairt lacinilc deriuqer-AAADF timbus ot ton erew tub ,elbacilppa neeb evah yam stnemeriuqer
eruliaf eht )2( ;snoisivorp esabatad lairt lacinilc s'AAADF htiw ecnailpmoc fo noitacifitrec ADF htiw ecnailpmoc gnicrofne rof smsinahcem
eslaf a gnittimbus ro noitacifitrec a timbus ot eruliaf eht )1( :lagelli era gniwollof lareneG .stnemeriuqer yrtsiger ot detaler smsinahcem
eht taht gniyficeps ,dednema si )133 CSU 12( ACDFF eht fo noitces stca detibihorp ehT tnemecrofne ro seitlanep yficeps ton did wal ehT stcA detibihorP
])j(282 CSU 24 ;)7()j(204 ASHP ;)2()a(108 AAADF[ .snoisivorp esabatad .dezirohtua snoitairporppA
slairt lacinilc eht tuo gniyrrac rof dezirohtua si raey lacsif rep 000,000,01$ fo tnuoma ehT erew yrassecen neeb evah yam sa smus hcuS fo noitazirohtuA
])j(282 CSU 24 ;)E()5()j(204 ASHP
;)2()a(108 AAADF[ .seciton ecnailpmocnon edulcni taht seirtne rof esabatad eht hcraes
yam cilbup eht taht erusne ot si rotceriD ehT ".yrtne eht ni noitamrofni eht fo ycarucca
eht no gniraeb yna evah ton yam ro yam sihT .wal yb deriuqer sa ,noissimbus fo emit eht
ta semoctuo yradnoces dna yramirp eht no noitamrofni niatnoc ton did lairt lacinilc siht
rof yrtne ehT" tnemetats eht niatnoc ot si eciton eht ,semoctuo yradnoces dna yramirp
timbus ot deliaf PR eht fI ".wal eht htiw ecnailpmoc ni ton erofereht dna gnidaelsim
ro eslaf eb ot dnuof saw lairt lacinilc siht rof yrtne ehT" tnemetats eht niatnoc ot si eciton
eht ,noitamrofni gnidaelsim ro eslaf dettimbus PR eht fI ".yrtne eht ni noitamrofni eht fo
ycarucca eht no gniraeb yna evah ton yam ro yam sihT .wal yb deriuqer sa ,noissimbus fo
emit eht ta etelpmoc ton saw lairt lacinilc siht rof yrtne ehT" tnemetats eht niatnoc ot si
eciton eht ,noitamrofni deriuqer timbus ot deliaf PR eht fI .noitamrofni eht detcerroc sah
PR eht rehtehw etats dna ,tca eht rednu desopmi seitlanep yna eton ,ecnailpmocnon eht
fo erutan eht etats ot si eciton ehT .noitamrofni stluser ro yrtsiger slairt lacinilc deriuqer ecnailpmocnoN
timbus ot sliaf PR na fi esabatad eht ni noitacifiton a edulcni ot si rotceriD HIN ehT .noisivorp oN fo ecitoN cilbuP
IIIV eltiT AAADF waL suoiverP cipoT
]eton 282 CSU 24
;)2()d(108 AAADF[ .).qes te 103 CSU 12( ACDFF eht rednu gnidnarbsim ro ,noitaretluda
,gnilebal sa deredisnoc eb ton llahs snoissimbus esabatad tnailpmoc fo ytilibaliava
ehT .esu dednetni wen a fo ecnedive sa gnideecorp laiciduj yna ni ro yraterceS eht yb
deurtsnoc eb ton llahs ,]stnemeriuqer esabatad stluser dna yrtsiger desiver[ )j(204 ASHP
htiw ecnailpmoc ni fi ,noitamrofni lairt lacinilc esu lebal-ffo fo noissimbus fo tcaf ehT .noisivorp oN noitcurtsnoC fo eluR
]eton 282 CSU 24;)1()d(108 AAADF[ .esabatad a ni slairt lacinilc fo stluser eht ot gnitaler
noitamrofni fo noisulcni eht rof ro slairt lacinilc fo noitartsiger eht rof tnemeriuqer
yna tceffe ni eunitnoc ro hsilbatse yam etats yna fo noisividbus lacitilop ro etats oN .noisivorp oN noitpmeerP etatS
IIIV eltiT AAADF waL suoiverP cipoT
¢
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.
ADF retfA snoitpO noitcA dna seussI :ssenevitceffE dna ytefaS gurD ,79723LR tropeR SRC ees ,noitamrofni rehtruf roF
.luahT nasuS yb ,lavorppA
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
unique symbol in the labeling of a new drug or indication. Any published25 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
Secretary must provide public access to action packages for product approval or licensure,26
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).
]1-553 CSU
12 ;1-505 ACDFF ;)b(109 AAADF[ .senimreted yraterceS eht sa )lavorppa SMER gniwollof doirep raey-3 eht retfa ,enon gnidulcni(
ycneuqerf a ta ,yltneuqesbus ,dna ;raey htneves eht ni ;devorppa yllaitini si gurd a retfa sraey 3 ta niaga dna shtnom 81 ta naht
yltneuqerf ssel on tnemssessa na sedulcni sihT .SMER devorppa eht fo stnemssessa fo elbatemit a edulcni tsum SMER devorppa nA ygetartS laminiM :SMER
]1-553 CSU 12 ;1-055 ACDFF ;)b(109 AAADF[ .eno
eriuqer yam yraterceS eht ,yrassecen SMER a senimreted dna noitamrofni ytefas wen fo erawa semoceb yraterceS eht fI :lavorppatsoP
.SMER a eriuqer yam yraterceS eht ,gurd eht fo sksir
eht hgiewtuo devlovni gurd eht fo stifeneb eht taht erusne ot yrassecen si ygetarts a hcus senimreted )gurd eht ot tcepser htiw ytefas
lavorppatsop rof elbisnopser eciffo eht dna gurd eht gniweiver rof elbisnopser eciffo eht hguorht gnitca( yraterceS eht fI :lavorppa-erP
.noitacilppa gurd wen detaiverbba
na rednu tcudorp a rof stnemele rewef htiw SMER a eriuqer yam yraterceS ehT .SMER desoporp a timbus ,esu rof noitacidni
wen a rof eno gnidulcni ,noitacilppa na ot tnemelppus ro noitacilppa cigoloib ro gurd a fo rosnops eht taht eriuqer yam yraterceS ehT SMER
]553
CSU 12 ;)p(505 ACDFF ;)a(109 AAADF[ .ssenlli gninetaerht-efil ro suoires a desserdda ti esuaceb lavorppa detarelecca deviecer taht
gurd a fo deriuqer yduts tekramtsop a tcudnoc ot sliaf ro yraterceS eht yb deriuqer )SMER( ygetarts noitagitim dna noitaulave ksir )SMER(
yna htiw ecnailpmoc ni ton si rosnops sti fi detibihorp si ecremmoc etatsretni otni tcudorp lacigoloib ro gurd a fo noitcudortni ehT seigetartS noitagitiM dna noitaulavE ksiR
]553 CSU 12 ;)o(505 ACDFF ;)a(109 AAADF[
.htlaeh cilbup eht tcetorp ot yrassecen si egnahc gnilebal eht taht sedulcnoc yraterceS eht fi senilemit etarelecca ot yraterceS eht
sezirohtua osla tI .noitaloiv dna ,noituloser etupsid ,weiver ,noitacifiton rof ,stimil emit gnidulcni ,serudecorp setaerc AAADF .egnahc
gnilebal a rof tnemelppus a timbus rosnops eht taht eriuqer ,noitamrofni ytefas tnaveler wen fo gninrael nopu ,yam yraterceS ehT segnahC gnilebaL
]553 CSU 12 ;)o(505 ACDFF ;)a(109 AAADF[ .yraterceS
eht yb dehsilbatse serudecorp noituloser etupsid gnisu yb lairt lacinilc ro yduts a tcudnoc ot tnemeriuqer a laeppa yam rosnops ehT
.esoprup eht rof etauqedani eb dluow yduts lavorppatsop a taht enimreted tsum yraterceS
eht ,lairt lacinilc lavorppatsop a eriuqer oT .sksir suoires detcepxenu yfitnedi ot ro ,ksir suoires fo langis a ,ksir suoires nwonk
a ssessa ot etauqedani eb dluow ecnallievrus ro stroper rehto taht enimreted tsum yraterceS eht ,yduts lavorppatsop a eriuqer oT
.esuac doog etartsnomed tsum stnemeriuqer hcus htiw ylpmoc ot sliaf taht rosnops A
.stroper cidoirep dna elbatemit a eriuqer tsum yraterceS eht ,lairt ro yduts a gniriuqer nI .noitamrofni ytefas wen fo gninrael retfa lairt
lacinilc ro yduts lavorppatsop a eriuqer yam yraterceS ehT .ksir suoires a yfitnedi ot ro ,ksir suoires fo slangis ro ksir suoires nwonk
a ssessa ot eb tsum lairt lacinilc ro yduts lavorppatsop deriuqer a fo esoprup ehT .gurd detaler yllacigolocamrahp ro yllacimehc
a gnidrager noitamrofni gnidulcni atad cifitneics fo sisab eht no lairt lacinilc ro yduts lavorppatsop a eriuqer yam yraterceS ehT
.ytefas ot detaler segnahc gnilebal rof stseuqer ro ,slairt lacinilc ro seiduts lavorppatsop rof tnemeriuqer s'yraterceS
eht fo noitaloiv ni si rosnops sti fi ecremmoc etatsretni otni ]"gurd" retfaniereh[ tcudorp lacigoloib ro gurd a ecudortni yam eno oN slairT lacinilC dna seidutS tekramtsoP
A eltitbuS ,XI eltiT AAADF cipoT
)A eltitbuS ,XI eltiT AAADF(
A eltitbuS ,sgurD fo ytefaS tekramtsoP gnidrageR seitirohtuA decnahnE yb detaerC waL .21 elbaT
]262 CSU 24 ;153
ASHP ;)c(109 AAADF[ .1-505 dna ,)p(505 ,)o(505 snoitceS ACDFF ot tcejbus eb tsum esnecil tcudorp lacigoloib a rof tnacilppa nA stcudorP lacigoloiB fo noitalugeR
]1-553 CSU
12 ;1-505 ACDFF ;)b(109 AAADF[ .elbaliava ylcilbup edam eb tsum ,slarrefed yna dna ,sredro dna srettel noitca hcuS .tnemssessa na
gniwollof redro na ni ro noitacilppa na no rettel noitca na fo trap sa noitacifidom ro SMER deriuqer yna ebircsed tsum yraterceS ehT
.stnioppa yraterceS eht ohw dna
seeyolpme laredef era ohw srenoititcarp erac htlaeh dna stsitneics fo desopmoc eb ot draoB thgisrevO ytefaS gurD a setaerc AAADF
.)c(101 AAADF ni debircsed srettel eht ni htrof tes serudecorp wollof tsum lavorppa laitini na erofeb gnirrucco noituloser etupsid A
.seirtnuoc rehto fo stroffe htiw selbatemit tnemssessa gnitanidrooc dna ;stceffe ssalc gurd gnisserdda
;slaeppa evitartsinimda dna ,seettimmoc yrosivda fo esu ,)srenoititcarp erac htlaeh dna stsitneics tnemnrevog laredef fo pu edam(
draoB thgisrevO ytefaS gurD a yb weiver gnidulcni ,noituloser etupsid :edulcni esehT .semarfemit gnidulcni ,serudecorp deificeps
wollof tsum weiver ehT .SMER devorppa na fo tnemssessa hcae dna SMER desoporp hcae weiver yltpmorp tsum yraterceS ehT noituloseR etupsiD dna weiveR :SMER
]1-553 CSU 12 ;1-505 ACDFF ;)b(109 AAADF[ .esu ro noitubirtsid
no noitcirtser a fo lavomer ro ,noitacifidom ,noitidda eht ro ;elbatemit tnemssessa eht edulcni taht edam eb yam snoitacifidoM snoitacifidoM :SMER
]1-553 CSU 12 ;1-505 ACDFF
;)b(109 AAADF[ .slairt lacinilc dna seiduts lavorppatsop deriuqer fo sutats eht fo tnemssessa na dna ;deifidom eb dluohs stnemele
hcus ro laog eht rehtehw dna sksir suoires nwonk htiw sgurd ot ssecca efas gnisaercni fo laog eht gniteem era esu efas erussa
ot stnemele eht llew woh fo tnemssessa na si deriuqeR .noitamrofni ssenevitceffe ro ytefas wen no desab eb tsum noitanimreted
s'yraterceS ehT .dedulcni ro deifidom eb dluohs tnemele gnitsixe na setacidni noitamrofni wen taht senimreted yraterceS eht nehw
dna ,semit degnarraerp ta deriuqer era stnemssessA .emit yna ta SMER devorppa na fo tnemssessa yratnulov a timbus yam rosnops A stnemssessA :SMER
]1-553
CSU 12 ;1-505 ACDFF ;)b(109 AAADF[ .noitacilppa gurd cireneg a fo lavorppa yaled ro kcolb ot noitubirtsid no noitcirtser a gnisu
morf rosnops a stibihorp osla tI .noitidnoc ro esaesid gninetaerht-efil ro suoires a rof esu lebal-ffo na rof ssecca dednapxe sezirohtua
AAADF .metsys yreviled erac htlaeh eht no dna gurd a ot )aera devresrednu yllacidem ro larur a ni sevil ohw eno ro ,noitidnoc
ro esaesid gninetaerht-efil ro suoires a htiw tneitap a ,.g.e( ssecca tneitap no snedrub eziminim tsum yraterceS ehT .ycnegreme
htlaeh cilbup deralced a gnirud serusaemretnuoc lacidem niatrec fo esu rof noitcirtser deriuqer yna eviaw yam yraterceS ehT
.seirtsiger ni tnemllorne tneitap dna ;gnirotinom tneitap ;)stluser yrotarobal sa hcus( snoitidnoc esu-efas fo ecnedive
;sgnittes erac htlaeh niatrec ot detimil gnisnepsid ;sgnittes erac htlaeh ro sredivorp fo noitacifitrec laiceps ;redivorp erac htlaeh
gnibircserp eht fo ecneirepxe dna gniniart deriuqer edulcni yam snoitcirtser ehT .esu efas erussa ot dedeen stnemele eht fo noitaulave sksiR suoireS nwonK
s'yraterceS eht no desab ,noitatnemelpmi rotinom ot metsys a htiw gnola ,esu ro noitubirtsid no snoitcirtser eriuqer yam yraterceS ehT htiw sgurD ot sseccA efaS :SMER
]1-553
CSU 12 ;1-505 ACDFF ;)b(109 AAADF[ .slocotorp ytefas fo snoitanalpxe dna ,SMER tuoba noitamrofni ,srettel sa hcus ,sredivorp erac
htlaeh ot nalp noitacinummoc a dna ,tresni egakcap tneitap dna ediuG noitacideM edulcni ot ,stneitap ot noitamrofni edulcni yam SMER A stnemelE lanoitpO :SMER
A eltitbuS ,XI eltiT AAADF cipoT
]253 CSU 12 ;)z,y(205 ACDFF ;)a(209 AAADF[ .gnilebal
ro slairt lacinilc dna seiduts tekramtsop ot gnitaler stnemeriuqer htiw ylpmoc ot eruliaf ro ;esu ro noitubirtsid no noitcirtser a ro
,dedulcni stnemele lanoitidda ,stnemssessa gnidrager stnemeriuqer SMER htiw ylpmoc ot eruliaf eht gnidnarbsim sa sedulcni AAADF gnidnarbsiM :tnemecrofnE
]eton a553 CSU 12 ;)e(109 AAADF[ .B505 ACDFF rednu seiduts hcus eriuqer ot ro A505 ACDFF rednu
seiduts cirtaidep tseuqer ot seitirohtua s'yraterceS eht gnitceffa sa deurtsnoc eb ot ton si noitces siht taht setats noitcurtsnoc fo eluR seidutS cirtaideP no tceffE
])5()d(109
AAADF[ .ssergnoC ot timbus tsum yraterceS eht taht troper a ni snoitadnemmocer ekam dna ,snoitalupop eseht rof seitirapsid
htlaeh desaerced dna noitamrofni htlaeh ot ssecca desaercni ot setaler ti sa gnisitrevda CTD yduts tsum noitacinummoC ksiR
no eettimmoC yrosivdA ehT .noitalupop lareneg eht fo stesbus ot etacinummoc ot ytiliba sti dna gnisitrevda CTD no ssergnoC eht ot
troper ,tnemtcane fo sraey owt nihtiw dna noitacinummoC ksiR no eettimmoC yrosivdA eht fo ecivda eht htiw ,tsum yraterceS ehT tropeR :stnemesitrevdA
]333 CSU 12 ;)g(303 ACDFF ;)4()d(109 AAADF[ .tseretni
sulp tnuoma taht revocer yam lareneG yenrottA eht ,ytlanep livic dessessa na yap ot sliaf tnacilppa na fI .yraterceS eht morf deviecer
tnemmoc hcae detaroprocni dna weivererp rof tnemesitrevda na dettimbus dah rosnops eht fi dessessa eb ton yam seitlanep liviC
.weiver laiciduj dna ,snoitacifidom ,saneopbus ,sweiver gnidrager ,gniraeh a rof ytinutroppo dna eciton nettirw fo noisivorp eht retfa
,serudecorp seificeps dna ,yliad naht yltneuqerf ssel dehsilbup snoitacilbup redisnoc ot woh stcerid wal ehT .noitaloiv eno deredisnoc
eb llahs yad elgnis a ni gnirrucco hpargarap siht rednu snoitaloiv lla ,noitacifiton hcus retfA .noitaloiv eno deredisnoc eb llahs eciton
nettirw a fo tpiecer eht ot roirp tnemesitrevda ralimis ro emas eht fo noitanimessid detaepeR .gnisitrevda CTD gnidrager noitaloiv
a ot ylppa llahs tca siht ni seitlanep yratenom livic rehto oN .doirep raey-3 yna ni noitaloiv tneuqesbus hcae rof 000,005$ deecxe
ot ton dna ,doirep raey-3 yna ni noitaloiv tsrif eht rof 000,052$ deecxe ot ton ytlanep yratenom livic a sezirohtua tI .gnidaelsim
ro eslaf si taht tnemesitrevda CTD a setanimessid ohw cigoloib ro gurd a fo rosnops eht rof seitlanep livic sehsilbatse AAADF seitlaneP liviC :stnemesitrevdA
])n(253 CSU 12 ;)n(205 ACDFF ;)3()d(109
AAADF[ .airetirc esoht steem tnemetats rojam a rehtehw gninimreted rof ,noitaluger yb ,sdradnats hsilbatse tsum yraterceS
ehT .rennam lartuen dna ,suoucipsnoc ,raelc a ni detneserp eb tsum snoitacidniartnoc dna stceffe edis ot gnitaler tnemetats rojam eht snoitacidniartnoC dna stceffE
,esu fo snoitidnoc sti dna gurd eht fo eman eht setats taht gurd a fo tnemesitrevda )CTD( remusnoc-ot-tcerid oidar ro noisivelet a nI ediS fo tnemetatS :stnemesitrevdA
]b353 CSU 12 ;B305
ACDFF ;)2()d(109 AAADF[ .gnidaelsim ro eslaf eb esiwrehto dluow tnemesitrevda eht taht senimreted yraterceS eht fi etad lavorppa
eht fo erusolcsid cificeps a edulcni ot tnemesitrevda eht ,lavorppa morf sraey owt naht erom ton rof ,eriuqer yam yraterceS ehT
.devlovni gurd eht fo gnilebal eht ni detsil ksir suoires a tuoba erusolcsid cificeps a tuohtiw gnidaelsim ro eslaf
eb dluow tnemesitrevda eht taht senimreted yraterceS eht fi tnemesitrevda na ni erusolcsid a fo noisulcni eriuqer yam yraterceS ehT serusolcsiD deriuqeR :stnemesitrevdA
]b353 CSU 12 ;B305 ACDFF ;)2()d(109 AAADF[ .seitinummoc esrevid yllacinhte dna yllaicar dna ,nerdlihc ,snoitalupop
ylredle no gurd desitrevda eht fo tcapmi eht noitaredisnoc otni ekat ,snoitadnemmocer gnitalumrof ni ,yam yraterceS ehT
.noitcesbus siht ot tnausrup dettimbus lairetam yna ni segnahc tcerid ro ekam ot dezirohtua ton si yraterceS ehT
.seitironim cinhte dna laicar dna ,nerdlihc ,snoitalupop ylredle gnidulcni ,spuorg noitalupop cificeps ot setaler ti sa
gurd eht fo ycaciffe cificeps eht sserdda ot stnemesitrevda ni edulcni ot stnemetats ,etairporppa fi ,dna ;weiver rednu tcudorp eht rof
noitamrofni gnibircserp htiw tnetsisnoc era taht ro ,remusnoc eht tcetorp ot yrassecen era taht segnahc dnemmocer yam yraterceS
ehT .gurd a rof tnemesitrevda noisivelet yna fo )noitanimessid erofeb syad 54 tsael ta( weivererp a eriuqer yam yraterceS ehT weivererP :stnemesitrevdA
A eltitbuS ,XI eltiT AAADF cipoT
])c(509 AAADF[ .metsys sisylana dna noitacifitnedi ksir tekramtsop evitca eht fo esu eht no ssergnoC ot troper tsum yraterceS ehT ssergnoC ot tropeR
]eton 553 CSU 12 ;)b(509 AAADF[ .ycavirp tcetorp ot naht rehto ytitne na yb )noitamrofni htlaeh elbaifitnedi yllaudividni sa hcus(
noitamrofni ro atad fo esu ro erusolcsid lufwal eht tibihorp ot deurtsnoc eb ot ton si noitces siht taht setats noitcurtsnoc fo eluR ataD fo erusolcsiD
]553 CSU 12 ;)4()k(505 ACDFF ;)a(509
AAADF[.secruos atad ytefas gurd evah taht seititne rehto fo seitivitca htiw etanidrooc ,elbacitcarp tnetxe eht ot ,dna ;sredlohekats
yek rehto dna ,lacidem ,htlaeh cilbup ,cifitneics ,cilbup yek htiw snoitacinummoc etairporppa rof edivorp tsum yraterceS ehT
.serudecorp rehto dna ,stnemeriuqer tcartnoc ,yfilauq nac seititne hcihw yb airetirc senifed AAADF ,yraterceS eht morf stcartnoc
gnidrageR .rosnops s'gurd eht ot gurd a tuoba ,stluser dna sdohtem rieht gnidulcni ,sesylana eht edivorp tsum yraterceS ehT
.snoitaroballoc ytefas gurd
fo tnempoleved eht rof serudecorp hsilbatse tsum yraterceS ehT .meht gnirewsna rof smsinahcem dna snoitseuq ytefas gurd ytiroirp
gnidrager seettimmoc yrosivda ADF rehto dna eettimmoC yrosivdA tnemeganaM ksiR dna ytefaS gurD eht morf snoitadnemmocer
kees tsum yraterceS ehT .noitamrofni htlaeh elbaifitnedi yllaudividni tcetorp tsum sesylana esehT .stnemssessa ylemit ekam ot
ytiliba s'yraterceS eht ecnahne dna ,esitrepxe ot ssecca enituor edivorp ,sisylana tifeneb-ksir ytefas gurd tekramtsop evorpmi ot atad ataD ytefaS
ytefas gurd fo sisylana decnavda rof edivorp ot seititne etavirp dna ,cimedaca ,cilbup htiw snoitaroballoc hsilbatse tsum yraterceS ehT gurD fo sisylanA decnavdA :AIRPA
]553 CSU 12 ;)3()k(505 ACDFF ;)a(509 AAADF[ .atad ytefas gurd gnirehtag ot sehcaorppa rehto fo tnempoleved
dna ,secruoser rotces etavirp fo esu ,gnitroper fo ssenilemit ot dnetta tsum yraterceS eht ,seitivitca eseht tuo gniyrrac nI .snrettap
dna sdnert yfitnedi dna ecnallievrus tneve esrevda evitca tcudnoc ot secruos atad rehto dna ,etavirp ,laredef esu dna ;atad tneve
esrevda fo gnitroper dezidradnats edivorp ;sisylana dna noitacifitnedi ksir rof atad htlaeh cinortcele esu :ot serudecorp niatniam dna
hsilbatse dna metsyS sisylanA dna noitacifitnedI ksiR tekramtsoP a hsilbatse tsum yraterceS eht ,)evoba( depoleved sdohtem eht gnisU
.atad
gnitekramtsop ,fo noitacinummoc dna ,rof sesu cifitneics dna lacihte eht rof sdohtem dna sloot fo tnempoleved eht no yraterceS eht metsyS hsilbatsE dna
esivda ot eettimmoc trepxe na enevnoc dna ;secruos elpitlum morf atad ytefas ezylana ot metsys a pu tes sdohtem detadilav poleved sdohteM poleveD :)AIRPA( sisylanA dna
;secruos atad ot ssecca teg ot sdohtem poleved ,seititne etavirp dna ,cimedaca ,cilbup htiw noitaroballoc ni ,tsum yraterceS ehT noitacifitnedI ksiR tekramtsoP evitcA
]409 AAADF[ .lavorppa retfa doirep a rof noitacidni ro gurd eht fo sutats devorppa ylwen eht gnitacidni lobmys
euqinu a noitacidni ro gurd devorppa ylwen a fo stnemesitrevda CTD yna dna gnilebal eht ni gnidulcni fo ytilibissop eht redisnoc
llahs renoissimmoC eht ,yduts hcus fo trap sA .stifeneb dna sksir hcus gnissessa ni SMER eht fo elor eht dna sgurd wen fo stifeneb dna
sksir eht cilbup eht ot etacinummoc ot tseb woh no troper a ,tnemtcane fo raey a nihtiw ,ssergnoC ot timbus tsum renoissimmoC ehT stnemssessA ksiR-tifeneB
])e(553 CSU 12 ;)e(505 ACDFF ;309 AAADF[ .SMER devorppa eht fo tnemssessa na timbus ot tnacilppa lavorppA fo
eht gniredro tsrif tuohtiw noitacilppa na fo lavorppa eht dnepsus ro noitacilppa na fo lavorppa eht wardhtiw yam yraterceS ehT noisnepsuS ro lawardhtiW no tceffE oN
]333 CSU
12 ;)f(303 ACDFF ;)b(209 AAADF[ .noitaloiv eht gnitcerroc drawot stroffe gnikam si rosnops eht rehtehw redisnoc ,ytlanep livic fo
tnuoma eht gninimreted ni ,tsum yraterceS ehT .gnideecorp elgnis a ni detacidujda snoitaloiv hcus lla rof noillim 01$ ot pu dna ,doirep
yad-03 eno rof noillim 1$ ot pu ,doirep yad-03 tneuqesbus yreve rof gnilbuod ,syad 03 tsrif eht rof 000,052$ fo ytlanep livic a esopmi
yam yraterceS eht ,tnacilppa eht ot noitaloiv hcus fo eciton sedivorp yraterceS eht retfa seunitnoc noitaloiv a fI .gnideecorp elgnis a
ni detacidujda snoitaloiv hcus lla rof noillim 1$ deecxe ot ton dna ,noitaloiv rep 000,052$ naht erom ton fo ytlanep yratenom livic a ot
tcejbus si gnilebal ro slairt lacinilc ro seiduts tekramtsop gnidrager tnemeriuqer a ro tnemeriuqer SMER a setaloiv ohw tnacilppa nA seitlaneP liviC :tnemecrofnE
A eltitbuS ,XI eltiT AAADF cipoT
]eton 133 CSU 12 ;909 AAADF[ .tnemtcane retfa syad 081 nigeb XI eltiT fo A eltitbuS ni snoisivorp llA setaD evitceffE
]809
AAADF[ .seitivitca eseht tuo gniyrrac rof elbaliava )evoba ees( sdnuf rehto yna ot noitidda ni si noitazirohtua sihT .2102YF hguorht
8002YF fo hcae rof noillim 52$ ,edam ti stnemdnema eht dna eltitbus siht tuo gniyrrac rof ,detairporppa eb ot sezirohtua AAADF snoitairporppA fo noitazirohtuA
]eton 553 CSU 12 ;709 AAADF[
.pihsnoitaler tneitap-tneilc-nairaniretev a nihtiw sgurd fo esu s'nairaniretev desnecil a ot ylppa ton od eltitbus siht fo snoisivorp ehT enicideM yranireteV no tceffE oN
]eton 253 CSU 12 ;)b(609 AAADF[ .tnemeriuqer
a hcus tnemelpmi ot snoitaluger eussi tsum yraterceS eht ,etairporppa si tnemetats eht gnidulcni taht senimreted yraterceS eht fI
.ssergnoC ot snoitanimreted dna sgnidnif troper dna ;stnemesitrevda CTD noisivelet rof etairporppa si stnemesitrevda CTD dehsilbup
ni deriuqer tnemetats eht rehtehw yduts ,noitacinummoC ksiR no eettimmoC yrosivdA eht htiw noitatlusnoc ni ,tsum yraterceS ehT
]253 CSU 12 ;)n(205 ACDFF
;)a(609 AAADF[ ".8801-ADF-008-1 llac ro ,hctawdem/vog.adf.www//:ptth tisiV .ADF eht ot sgurd noitpircserp fo stceffe edis evitagen
troper ot degaruocne era uoY" :txet suoucipsnoc ni detnirp tnemetats gniwollof eht edulcni tsum tnemesitrevda CTD dehsilbup ynA rebmuN eerF-lloT :stnemesitrevdA
])e(509 AAADF[
.seettimmoc gnizirohtua lanoissergnoc eht ot ,yrassecen fi ,snoitca dnemmocer dna ,metsys sisylana dna noitacifitnedi ksir tekramtsop
evitca eht ot gnitaler seussi ytiruces dna ,ytilaitnedifnoc ,ycavirp atad no troper dna etaulave tsum lareneG rellortpmoC ehT tropeR OAG
])d(509 AAADF[ .2102YF
hguorht 8002YF fo hcae rof noillim 52$ lanoitidda na fo noitairporppa eht sezirohtua AAADF ,)637 ACDFF( margorp eef resu
gurd noitpircserp eht rednu elbaliava era sdnuf hcihw rof seitivitca sisylana dna noitacifitnedi ksir deriuqer-AAADF eht tuo yrrac oT snoitairporppA fo noitazirohtuA
A eltitbuS ,XI eltiT AAADF cipoT
]553
CSU 12 ;)r(505 ACDFF ;519 AAADF[ .sredivorp dna stneitap ot noitamrofni noitacinummoc ksir fo gnisnepsid eht etatilicaf ot syaw
dnemmocer dna ,etisbew eht no noitamrofni fo sepyt eht etaulave dna weiver tsum noitacinummoC ksiR no eettimmoC yrosivdA ehT
.stnemeriuqer eseht llifluf ot seititne etavirp dna cilbup htiw tcartnoc yam yraterceS ehT .rebmun lausunu ni detroper sksir nwonk
ro ,sksir wen laitnetop ,sksir deifitnedinu ylsuoiverp yna fo noitacifitnedi gnidulcni ,stroper noitcaer gurd esrevda fo sisylana yrammus
a eraperp tsum yraterceS eht ,gurd eht desu evah slaudividni 000,01 retfa ro lavorppa s'gurd a retfa shtnom 81 fo retal eht tA
.knab atad stluser dna yrtsiger slairt lacinilc eht dna ;atad ecnallievrus
etagergga fo seirammus ;snoitaluger dna ,stnemucod ecnadiug ,srettel gninraw ,strela ADF ;gnilebal tneitap dna lanoisseforp
;setis tnemnrevog rehto ot sknil edulcni tsum etisbew ehT .noitamrofni ot ssecca retteb sredivorp erac htlaeh dna stneitap wolla sredivorP dna stneitaP rof
ot noitamrofni ytefas gurd elbahcraes ylisae fo egnar evisnetxe na htiw etisbew tenretnI na niatniam dna poleved tsum yraterceS ehT noitamrofnI ytefaS gurD tekramtsoP
]553 CSU 12 ;)q(505 ACDFF ;419 AAADF[ .stroper launna dna ;seidemer evitartsinimda fo noitsuahxe ;deviecer si tnemyap
mohw morf dna rehtehw dna dettimbus noitamrofni fo ssenetelpmoc eht gnidrager noitacifirev dna noitacifitrec ;doirep noititep
fo noisnetxe ;noitca ycnega lanif ;yaled ot tnetni no desab lained ;erusolcsid cilbup ;tamrof ;noitacifiton ;yraterceS eht yb noitanimreted
gnivlovni serudecorp deliated sedivorp AAADF .htlaeh cilbup eht tcetorp ot yrassecen si yaled a taht senimreted yraterceS eht nehw )sgurD cireneG fo lavorppA
detpecxe si noitibihorp sihT .lavorppa s'noitacilppa eht ot gnitaler snoitca ,gnikat morf niarfer ro ,ekat yraterceS eht evah ot skees eht gnidrageR( noitcA ycnegA fo
taht noititep a fo sisab eht no snoitacilppa gurd wen detaiverbba ro cireneg fo lavorppa ro weiver eht yaled ton yam yraterceS ehT yatS rof snoititeP dna snoititeP nezitiC
]e553 CSU 12 ;D505 ACDFF ;319 AAADF[
.noitcepsni dna noitadilav rof seitilibapac lanoiger hsilbatse dna ;seicnega etats dna laredef rehto htiw seitivitca tnemecrofne tnioj
dna decnahne ekatrednu ;seigolonhcet ecart-dna-kcart rehto dna ,seigolonhcet noitpyrcne ,ygolonhcetonan ,ygolonhcet noitacifitnedi
ycneuqerfoidar sa hcus ,seigolonhcet gnisimorp sserdda ;gnigakcaper dna gnirutcafunam fo tniop eht ta gurd noitpircserp a ot deilppa
eb ot reifitnedi laciremun dezidradnats a poleved tsum yraterceS ehT .sgurd noitpircserp fo gnicart dna gnikcart dna ,noitacitnehtua
,noitadilav ,noitacifitnedi eht rof sdradnats ezitiroirp dna poleved tsum )sredlohekats niahc ylppus rehto dna ,seicamrahp ,srotubirtsid
,srerutcafunam dna ,ecremmoC dna ,ytiruceS dnalemoH ,ecitsuJ fo stnemtrapeD eht gnidulcni ,seicnega laredef rehto htiw
noitatlusnoc ni( yraterceS ehT .sgurd deripxe ro ,dednarbsim ,detaretluda ,dradnats ,tnetopbus ,detrevid ,tiefretnuoc tsniaga niahc
ylppus gurd eht gniruces fo esoprup eht rof seigolonhcet evitceffe etadilav dna yfitnedi dna sdradnats poleved tsum yraterceS ehT ytiruceS lacituecamrahP
]133 CSU 12 ;)ll(103 ACDFF ;219 AAADF[ .secnatsmucric deificeps deddA neeB
ni tpecxe ,cilbup edam dna detutitsni neeb evah snoitagitsevni lacinilc laitnatsbus hcihw rof ro desnecil/devorppa ADF rehtie era taht evaH stcudorP lacigoloiB ro sgurD
scigoloib ro sgurd doof otni ecudortni ot )seitlanep ACDFF ot tcejbus erofereht dna ,103 noitceS ACDFF rednu( tca detibihorp a si tI hcihW ot dooF tsniagA noitibihorP
]a063 CSU 12 ;115 ACDFF ;119 AAADF[ .tnemtcane fo sraey evif nihtiw ecnadiug hcus etadpu dna weiver sgurD
dna ,sgurd citoibitna ot tcepser htiw slairt lacinilc fo tcudnoc eht rof ecnadiug eussi ,tnemtcane fo raey eno nihtiw ,tsum yraterceS ehT citoibitnA rof ecnadiuG lairT lacinilC
B eltitbuS ,XI eltiT AAADF cipoT
)B eltitbuS ,XI eltiT AAADF( B eltitbuS
,sgurD fo ytefaS tekramtsoP gnidrageR seitirohtuA decnahnE yb detaerC waL .31 elbaT
]553 CSU 12 ;)k(505 ACDFF
;129 AAADF[ .setad noitelpmoc detamitse dna trats ngissa dna ;snoitanimreted eseht no ssergnoC ot troper ;detanimile eb dluohs
ro noisiver eriuqer hcihw enimreted ot stnemtimmoc ytefas tekramtsop fo golkcab eritne eht weiver yllaunna tsum yraterceS ehT
.ycnega
eht nihtiw deldnah era snoitadnemmocer ESO woh dna )ESO( ygoloimedipE dna ecnallievruS fo eciffO eht yb deifitnedi seussi ytefas
tekramtsop gniogno gnisserdda rof sessecorp dna serudecorp ADF no tnemtcane fo sraey owt nihtiw troper tsum yraterceS ehT
.retrauq tsal eht nihtiw SREA yb deifitnedi ksir suoires a fo langis laitnetop ro noitamrofni ytefas wen yna fo troper
ylretrauq a tsop dna esabatad )SREA( metsyS gnitropeR tnevE esrevdA eht fo gnineercs ylkeewib ,raluger tcudnoc tsum yraterceS ehT stropeR noitcaeR gurD esrevdA
]553 CSU
12 ;)t(505 ACDFF ;029 AAADF[ ".gurd detsil eht naht kram edart ro ,eman edart ,edoc relebal ,edoc tcudorp ,)snoitutitsni ni esu rof
gnigakcap ralimis ro ,sesod tinu ,skcap retsilb ni gurd detsil eht sa gnigakcaper naht rehto( gnigakcap ,gnilebal tnereffid a rednu edart fo
ssalc liater ot yltceridni ro yltcerid detubirtsid ro ,dlos ,detekram" neht dna )c(505 ACDFF rednu devorppa neeb ylsuoiverp dah taht
eno sa ,noitces siht rof ,denifed si gurd cireneg dezirohtua nA .setadpu esoht fo seicnega laredef tnaveler yfiton dna ;ylretrauq tsil eht
etadpu ;sgurd cireneg dezirohtua lla fo tsil a etisbew ADF eht no )tnemtcane fo shtnom enin nihtiw( hsilbup tsum renoissimmoC ehT sgurD cireneG dezirohtuA
]919
AAADF[ .stnemeriuqer SMER fo noitatnemelpmi s'ADF fo tnemssessa na edulcni ot ,ytefaS gurD fo erutuF ehT troper 6002 MOI eht ni
snoitadnemmocer eht ot dnopser ot nalp sti fo noitatnemelpmi s'ADF gnitadpu troper a ,raey eno nihtiw ,timbus tsum yraterceS ehT tropeR 6002 MOI ot esnopseR
]553 CSU 12 ;)s(505 ACDFF ;819 AAADF[
.os od ton did yraterceS eht yhw snosaer eht fo yrammus a edulcni tsum noitacilppa eht no rettel noitca eht ,edam ton si larrefer
fI .eettimmoc yrosivda ADF na ot gurd eht refer ,tneidergni evitca wen a sedulcni taht gurd a gnivorppa erofeb ,tsum yraterceS ehT eettimmoC yrosivdA ot larrefeR
]6-bbbCSU 12 ;765 ACDFF ;719 AAADF[ .sksir gurd tekramtsop
gnigreme tuoba sredivorp erac htlaeh ot noitacinummoc rof smetsys detecafitlum dna tsubor poleved ot spuorg latnemnrevognon
htiw rentrap tsum yraterceS ehT .snoitazinagro lanoisseforp htlaeh dna ,remusnoc ,tneitap fo sevitatneserper dna ,sksir cificeps
no strepxe ,noitacinummoc ksir no strepxe edulcni ot noitacinummoC ksiR no eettimmoC yrosivdA na hsilbatse tsum yraterceS ehT noitacinummoC ksiR
])l(553 CSU 12 ;)l(505 ACDFF ;619 AAADF[ .lanif ecno reweiver eht ro tnemeganam
yb deretla eb ton llahs dna reweiver eht fo krow eht deredisnoc si noitacilppa na fo weiver cifitneics a taht seralced AAADF
.noisiced
eht ni stnapicitrap ADF fo )tnesnoc htiw( noitacifitnedi dna ;sisylana rehtruf dda ot ro weiver yrammus htiw gnieergasid fi mudnedda
fo weiver etarapes a dna ,weiver yrammus eht htiw ecnerrucnoc fo tnemetats feirb a sedulcni hcihw ,tnemucod noisiced s'rotceriD
eciffO dna rotceriD noisiviD eht ;)evoba debircsed( weiver yrammus eht ;noitacilppa eht yb dettimbus gnilebal ;tnempoleved
gurd gnirud detareneg erew taht tcatnoc dna tamrof s'noitacilppa eht ot gniniatrep stnemucod ;weiver eht ot detaler stnemucod
detareneg-ADF :sedulcni hcihw ,cigoloib a fo erusnecil ro gurd a fo lavorppa rof egakcap noitca eht )noitamrofni laitnedifnoc
ro sterces edart gnisolcsid tuohtiw( etisbew ADF eht no hsilbup tsum yraterceS eht ,lavorppa s'noitacilppa na fo syad 03 nihtiW
.snoisulcnoc weiver htiw ecnerrucnocnon yna fo noitanalpxe na dna noitca rof snoitadnemmocer
,devloser erew yeht woh dna tnacilppa eht htiw stnemeergasid dna seussi lacitirc gniton ,senilpicsid gniweiver lla morf snoisulcnoc lavorppA
stnemucod taht weiver yrammus a etisbew ADF eht no hsilbup tsum yraterceS eht ,lavorppa s'noitacilppa na fo sruoh 84 nihtiW rof segakcaP noitcA ot sseccA cilbuP
B eltitbuS ,XI eltiT AAADF cipoT
¢
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.
yciloP laicoS citsemoD ,ytefaS dooF dna noitirtuN ni tsilaicepS ,retroP .V annoD yb detubirtnoc saw noitces sihT
.noisiviD
noitartsinimdA gurD dna dooF eht ni snoisivorP :ytefaS dooF ,97722SR tropeR SRC ees ,noitamrofni rehtruf roF
.retroP .V annoD yb ,7002 fo tcA stnemdnemA
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
and surge capacity grants.27 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).
]3011 AAADF[ .stroffe yrotaluger laredef detaler fo yaled
eht eriuqer ot deurtsnoc eb ot si noitces eht ni gnihtoN .deretne saw tcartnoc eht etad eht retfa raey
eno naht retal ton detelpmoc eb ot dna ,spuorg rehto dna SHGCAS yb stroper tnaveler tnuocca otni
ekat ot si yduts ehT .stset citeneg fo snoitaluger dna thgisrevo laredef evorpmi ot snoitadnemmocer
sedulcni taht troper a eraperp dna stset citeneg fo ytilauq dna ytefas llarevo eht ssessa
ot yduts a tcudnoc ot MOI eht htiw tcartnoc a otni retne llahs yraterceS eht ,8002 yluJ yb yraterceS
eht ot snoitadnemmoceR noitcA dna tropeR gnitseT cimoneG/citeneG fo thgisrevO yrotalugeR eht timbus dna ytilauQ dna ytefaS tseT
etelpmoc ton seod )SHGCAS( yteicoS dna ,htlaeH ,sciteneG no eettimmoC yrosivdA s'yraterceS eht fI .noisivorp oN citeneG gnivorpmI
]n063 CSU 12 ;425 ACDFF
;2011 AAADF[ .desu si rehcuov eht hcihw rof noitacilppa gurd namuh eht fo noissimbus eht htiw
diap eb ot tnuoma eef eht tes yllaunna dna margorp eef resu a hsilbatse ot si yraterceS ehT .snoitalupop
dezilanigram dna roop stceffa yletanoitroporpsid taht dna snoitan depoleved ni tekram tnacifingis
on sah taht esaesid suoitcefni rehto yna ,noitaluger yb ,edulcni osla yam yraterceS ehT .sway dna
,sisaihtimleh dettimsnart lios ,sisaimosotsihcs ,sisaicrecohcno ,sisairalif citahpmyl ,ysorpel ,sisainamhsiel
,sisaimosonapyrt nacirfA namuh ,sisailoicsaf ,)esaesid mrow-aeniug( sisailucnucard ,revef cigahrromeah
eugned/eugned ,arelohc ,reclu iluruB ,amohcart gnidnilb ,airalam ,sisolucrebut edulcni sesaesid
gniyfilauQ .)c(101 AAADF ni debircsed srettel eht ni deifitnedi slaog dna ,serudecorP dna seiciloP
fo launaM ADF eht ni debircsed sa ,noitacilppa hcus fo yraterceS eht yb tpiecer retfa shtnom 6 naht
retal ton noitacilppa hcus no yraterceS eht yb noitca dna weiver naem ot )1(537 ACDFF yb denifed
si weiver ytiroirP .noitacilppa retal a htiw esu rof rehcuov weiver ytiroirp a eviecer llahs tnemtcane weiveR ytiroirP
AAADF retfa devorppa si taht tcudorp esaesid laciport elbigile na rof noitacilppa na fo rosnops ehT .noisivorp oN esaesiD laciporT
]2-d973 CSU 12 ;317 ACDFF ;1011 AAADF[ .wal rehto yb dedivorp noitatneserp ro noitacilbup
no snoitcirtser yna gnitceffa sa deurtsnoc eb llahs ycilop eht ni gnihtoN .remialcsid etairporppa
na htiw ti tneserp ro timbus yam dna ,deraelc neeb evah ot ton elcitra eht redisnoc yam eeyolpme
ts
eht ,noissimbus retfa yad 13 eht fo sa elcitra eht deweiver ro deraelc ton sah laiciffo gnisivrepus
eht fI .segnahc deificeps fo noitidnoc eht niatnoc yam hcihw ,ecnaraelc nettirw edivorp yam reweiver
eht ,syad 03 nihtiW .ecnavda ni syad 03 naht ssel ton os od tsum noitatneserp ro noitacilbup ot
roirp ecnaraelc dna weiver rof elcitra na timbus ot ycilop ADF yb deriuqer reciffo ro eeyolpme ADF nA seeyolpmE
ADF yb dehsilbuP
.gnitirw dehsilbup rehto ro ,retpahc koob ,koob ,tcartsba ,retsop ,repap a snaem elcitrA .selcitra rof selcitrA cifitneicS
stnemeriuqer remialcsid dna ,ecnaraelc ,weiver ,noissimbus ylemit eht nrevog dna snoisivorp noitacilbup fo ecnaraelC dna
eht tnemelpmi ot seicilop nettirw elbaliava ylcilbup ekam dna hsilbatse ot deriuqer si yraterceS ehT .173 CSU 12 ni noisivorp lellarap oN weiveR eht no yciloP
A eltitbuS ,IX eltiT AAADF waL suoiverP cipoT
waL suoiverP htiw )A eltitbuS ,IX eltiT AAADF( A eltitbuS ,snoisivorP rehtO fo nosirapmoC .41 elbaT
.))a(C304 ASHP( .eerged larotcod
a fo tpiecer eht dna yduts etaudarg fo
gninnigeb eht neewteb emit egareva eht ,)1(
hpargarap ni debircsed stneduts rof )2( dna
;eerged larotcod a niatta yllufsseccus ohw
yduts rof dettimda stneduts fo egatnecrep
]2-a382 CSU 24 ;)a(C304 ASHP ;)5(4011 AAADF[ .)dedda sisahpmE( .eerged larotcod eht )1( :noitutitsni hcus ta margorp
a fo tpiecer eht dna yduts etaudarg fo gninnigeb eht neewteb )ecnesba fo sevael yna gnidulcni ton( gnitnarg-eerged hcae ot tcepser htiw
emit egareva eht ,)1( hpargarap ni debircsed stneduts rof )2( dna ;eerged larotcod a niatta yllufsseccus ,rotceriD HIN eht ot troper yllaunna llahs
ohw yduts rof dettimda stneduts hcus fo egatnecrep eht )1( :noitutitsni hcus ta stneduts etaudarg seerged larotcod rof stneduts etaudarg
detroppus-HIN sti ot tcepser htiw ,rotceriD HIN eht ot troper yllaunna llahs seerged larotcod rof fo gniniart eht rof ]VI eltiT ,ASHP[ eltit siht
stneduts etaudarg fo gniniart eht rof ]VI eltiT ,ASHP[ eltit siht rednu drawa na gniviecer noitutitsni hcaE rednu drawa na gniviecer noitutitsni hcaE
.C304 derebmun snoitces
]3-a382 CSU 12 ;D304 owt fo dnoces eht saw lortseblitslyhteid
ASHP ;)4(4011 AAADF[ .D304 sa detangiseder si lortseblitslyhteid gurd eht ot gnitaler noitces ASHP ehT gurd eht ot gnitaler noitces ASHP ehT
.gniniart larotcodtsop
]382 rof sdrawa detaitini-rotagitsevni gnidulcni
CSU 12 ;)III()vi()C()4()a(304 ASHP ;)3(4011 AAADF[ .stnarg hcraeser hguorht dednuf gniniart larotcodtsop ,seitivitca gniniart ,noitamrofni rehto gnoma
dna
gniniart larotcodtsop rof sdrawa detaitini-rotagitsevni gnidulcni ,seitivitca gniniart ,noitamrofni ,fo gnitsisnoc troper lainneib a ssergnoC ot
rehto gnoma ,fo gnitsisnoc troper lainneib a ssergnoC ot timbus ot deriuqer si rotceriD HIN ehT timbus ot deriuqer saw rotceriD HIN ehT
.seitirapsid
htlaeh gnicuder ni ssergorp dna ,snedrub
htlaeh cilbup ,ytinutroppo cifitneics etaulave
]282 CSU 24 ;)4()b(204 ASHP ;)2(4011 AAADF[ .seitirapsid htlaeh rehto dna ytironim retteb ot noitamrofni gnidulcni ,seitiroirp
gnicuder ni ssergorp dna ,snedrub htlaeh cilbup ,ytinutroppo cifitneics etaulave retteb ot noitamrofni hcraeser ssessa ot desu eb ot atad etarucca
gnidulcni seitiroirp hcraeser ssessa ot desu eb ot atad etarucca elbmessa ot si rotceriD HIN ehT elbmessa ot saw rotceriD HIN ehT
.]tnemevorpmi noitceted
esaesid emit laer rof stnarg[ )h(1-C913
ASHP nopu desab denimreted eb ot saw
yticapac egrus evorpmi ot ssenderaperp
latipsoh lanoiger dna etats rof spihsrentrap
gnitroppus snoisividbus lacitilop
dna setats ot sdrawa fo stnuoma eht
,esnopseR dna ssenderaperP rof yraterceS
]b3-d742 CSU 24 ;)B()3()j(2-C913 ASHP ;)1(4011 AAADF[ tnatsissA SHH eht yb deretsinimda
.))i(1-C913 ASHP( stnarg yticapac egrus dna ssenderaperp latipsoh rof alumrof gnidnuf elbacilppa margorp ssenderaperp latipsoh
eht nopu desab denimreted eb ot si yticapac egrus evorpmi ot ssenderaperp latipsoh lanoiger dna etats eht gnidrager ,tcA ssenderaperP sdrazaH stnemdnemA
rof spihsrentrap gnitroppus snoisividbus lacitilop dna setats ot sdrawa snoitairporppa fo stnuoma ehT -llA dna cimednaP eht ,714-901 .L.P rednU lacinhceT HIN
A eltitbuS ,IX eltiT AAADF waL suoiverP cipoT
]4111 AAADF[ .tekram eht otni yrtne gurd cireneg ylemit gniyaled ro gnitneverp ni dna ;sgurd rehto dna scitoibitna wen fo tnempoleved
eht gnigaruocne ni eltitbus siht ni snoisivorp fo tceffe eht gnidrager ssergnoC ot troper tsum ,2102 ,1 yraunaJ yb ,lareneG rellortpmoC ehT tropeR OAG
]553 CSU 12 ;)u(505 ACDFF ;3111 AAADF[ .secnatsmucric niatrec rednu ,gurd
cimecar devorppa eht ni deniatnoc taht sa tneidergni evitca emas eht deredisnoc remoitnane elgnis eht evah ot tcele yam ,noitacilppa rehtona sremoitnanE elgniS gniniatnoC
ni devorppa gurd cimecar a ni deniatnoc si taht remoitnane elgnis a ,tneidergni evitca na sa ,gniniatnoc gurd cimecar-non a rof tnacilppa nA sgurD niatreC fo ytivisulcxE
])c(ee063 CSU 12 ;tcA gurD nahprO eht fo )c(5 .ceS sdnema ;)b(2111 AAADF[ .2102YF hguorht
8002YF fo hcae rof noillim 03$ fo noitairporppa eht gnizirohtua ,)ee063 CSU 12( sgurd nahpro rof stcartnoc dna stnarg sezirohtuaer AAADF
])a(2111 AAADF[ .sevitnecni rehto ro )ee063 CSU 12( tcA gurD nahprO
eht ot tnausrup ecnatsissa rof elbigile sesaesid hcus gnitaert rof tnempoleved gurd gnikam ,sesaesid erar sa detangised eb thgim sesaesid
suoitcefni gninetaerht efil dna suoires hcihw gnidrager ,etairporppa fi ,ecnadiug eussi dna gniteem cilbup a enevnoc tsum renoissimmoC ehT sgurD nahprO
]a5-d742 CSU 24 ;1111 AAADF[ .gurd a ot ecnatsiser dna ytilibitpecsus lairetcab fo level snoitartnecnoC
eht eziretcarahc taht snoitartnecnoc elbitpecsus yllacinilc elbaliava ylcilbup ekam dna yfitnedi tsum ,renoissimmoC eht hguorht ,yraterceS ehT elbitpecsuS yllacinilC
B eltitbuS ,IX eltiT AAADF cipoT
)B eltitbuS ,IX eltiT AAADF( noitavonnI dna sseccA citoibitnA yb detaerC waL .51 elbaT
]eton 103
CSU 12 ;5011 AAADF[ .ybereht detceffa eb ton llahs ecnatsmucric ro nosrep yna ot hcus fo snoisivorp
eht fo noitacilppa eht dna ti yb edam stnemdnema dna tcA eht fo redniamer eht ,lanoitutitsnocnu
eb ot dnuof si tnemdnema ro noisivorp hcus fo noitacilppa eht ro AAADF fo noisivorp yna fI .noisivorp oN esualC ytilibareveS
A eltitbuS ,IX eltiT AAADF waL suoiverP cipoT
.yletinifedni seunitnoc raey rep noillim 01$ fo noitazirohtua sihT .c
.srotcaf rehto dna ,tner
,daolkrow ,noitalfni nopu desab yllaunna detsujda eb ot srebmun enilesab era stnuoma eef 2102YF - 9002YF .b
.seititne etavirp morf seef resu fo noitcelloc eht rof si noitazirohtua sihT .a
])c(ee063 CSU 12 ;)b(2111 AAADF[
000,03$ 000,03$ 000,03$ 000,03$ 000,03$ sgurD nahprO fo tnempoleveD
]eton 553 CSU 12 ;809 AAADF[
000,52$ 000,52$ 000,52$ 000,52$ 000,52$ ecnallievruS dna seidutS tekramtsoP
]eton 553 CSU 12 ;)d(509 AAADF[ sisylanA
000,52$ 000,52$ 000,52$ 000,52$ 000,52$ dna noitacifitnedI ksiR tekramtsoP evitcA
])j(282 CSU 24 ;)a(108 AAADF[
000,01$ 000,01$ 000,01$ 000,01$ 000,01$ csesabataD lairT lacinilC
])f(5-bbb063 CSU 12 ;306 AAADF[
yrassecen eb yam sa smus hcus 000,5$ spihsrentraP etavirP-cilbuP htaP lacitirC
]m482 CSU 24 ;)b(205 AAADF[
yrassecen eb yam sa smus hcus 000,002$ sgurD fo seidutS cirtaideP rof margorP
]eton 282 CSU 24 ;503 AAADF[ ytilibaliavA
000,6$ 000,6$ 000,6$ 000,6$ 000,6$ eciveD cirtaideP gnivorpmI rof stnarG
036,8$ 912,8$ 828,7$ 554,7$ 001,7$ ]512 AAADF[ ytefaS tekramtsoP eciveD
811,76$ 068,16$ 410,75$ 745,25$ 134,84$ ])a(j973 CSU 12 ;212 AAADF[ aseeF AFUDM
])3()g(,)b(1-h973 CSU 12 ;401 AAADF[
052,6$ 052,6$ 052,6$ 052,6$ 052,6$ ba seeF weiveR tnemesitrevdA noisiveleT CTD
])3()e(,)b(h973 CSU 12 ;)1()e( ,)b(301 AAADF[
387,754$ 387,744$ 387,734$ 387,724$ 387,714$ ba seeF AFUDP
2102YF 1102YF 0102YF 9002YF 8002YF esopruP
)sdnasuoht ni sra lloD(
2102YF-8002YF ,AAADF ni dezirohtuA snoitairporppA .1-A elbaT
£ ¡
¡
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.
]A837 CSU 12 ;312 AAADF[ .ssergnoC ot troper lacsif AFUDM a dna troper ecnamrofrep AFUDM a ,3102 hguorht yllaunna ,stimbus yraterceS ehT 9002 ,82 yraunaJ
]032 ACDFF[ .egamad niks rehto ro
recnac niks fo tnempoleved eht dna secived gninnat roodni neewteb pihsnoitaler eht no noitamrofni gnilebal no troper a ssergnoC ot stimbus yraterceS ehT 8002 ,72 rebmetpeS
]922 AAADF[ .secived lacidem ot gnitaler snoitcefni laimocoson no troper a ssergnoC ot stimbus lareneG rellortpmoC ehT 8002 ,72 rebmetpeS
]522 AAADF[ .evitceffe
dna efas si ecived wen a rehtehw enimreted ot ssecorp )k(015 eht fo esu etairporppa eht no troper a ssergnoC ot stimbus lareneG rellortpmoC ehT 8002 ,72 rebmetpeS
7002 fo stnemdnemA eeF resU eciveD lacideM :II eltiT
]1-h973 CSU 12 ;401 AAADF[ .)ylrae detanimret si margorp noitcelloc eef tnemesitrevda noisivelet
CTD fi reilrae rucco sdnufeR( .sisab atar-orp a no evreser gnitarepo eht ni gniniamer stnuoma eef weiver tnemesitrevda noisivelet CTD sdnufer yraterceS ehT 2102 ,82 yraunaJ
]2-h973 CSU 12 ;501 AAADF[ .ssergnoC ot noitazirohtuaer AFUDP rof snoitadnemmocer stimsnart yraterceS ehT 2102 ,51 yraunaJ
]1-h973 CSU 12 ;401 AAADF[ .tnuoma deriuqer a
woleb sllaf seunever eef dna sevreser gnitarepo fo latot eht fi margorp noitcelloc eef weiver tnemesitrevda noisivelet CTD ,yllaunna ,setanimret yraterceS ehT 9002 ,1 rebmevoN
]2-h973 CSU 12 ;501 AAADF[ .ssergnoC ot troper lacsif AFUDP a dna troper ecnamrofrep AFUDP a ,3102 hguorht yllaunna ,stimbus yraterceS ehT 9002 ,82 yraunaJ
]1-h973 CSU 12 ;401 AAADF[ .raey lacsif txen eht rof stnuoma eef weiver tnemesitrevda noisivelet CTD ,yllaunna ,sehsilbatse yraterceS ehT 8002 ,1 tsuguA
]1-h973 CSU 12 ;401 AAADF[ .raey lacsif txen eht nihtiw weiver yrosivda rof timbus ot sdnetni nosrep eht stnemesitrevda noisivelet
CTD fo rebmun eht fo syad 03 nihtiw yraterceS eht yfiton ot nosrep yna gnitseuqer seciton retsigeR laredeF tneuqesbus ,yllaunna ,sehsilbup yraterceS ehT 8002 ,1 enuJ
]1-h973 CSU 12 ;401 AAADF[ .8002YF rof stnuoma eef weiver
tnemesitrevda noisivelet CTD sehsilbatse yraterceS ehT 7002 ,62 rebmeceD
]1-h973 CSU 12 ;401 AAADF[ .8002YF nihtiw weiver yrosivda rof timbus ot sdnetni nosrep eht stnemesitrevda
noisivelet CTD fo rebmun eht fo syad 03 nihtiw yraterceS eht yfiton ot nosrep yna gnitseuqer eciton retsigeR laredeF laitini sehsilbup yraterceS ehT 7002 ,72 rebotcO
]1-h973 CSU 12 ;401 AAADF[ .seef weiver tnemesitrevda noisivelet CTD stcelloc dna sessessa yraterceS ehT 7002 ,1 rebotcO
7002 fo stnemdnemA eeF resU gurD noitpircserP :I eltiT
noitcA deriuqeR enildaeD
etaD dna eltiT yb ,slaiciffO tnemnrevoG rof senildaeD htiw smetI noitcA AAADF . 1-B elbaT
]a553 CSU 12 ;)1()a(205 AAADF[ .sredivorp erac htlaeh ot noitamrofni hcus ,yllaunna tsael ta ,etubirtsid weiver launna
deificeps-ACPB eht ni detcelfer segnahc gnilebal ni gnitluser seiduts deificeps fo srosnops eht taht tseuqer nettirw a fo tnemeriuqer a sa sedulcni yraterceS ehT 7002 ,72 rebmetpeS
]a553 CSU 12 ;)1()a(205 AAADF[ .segnahc gnilebal etairporppa no tnemeerga
na hcaer ot elbanu neeb evah rosnops dna renoissimmoC eht nehw desu eb ot sessecorp noituloser etupsid deificeps tceffe otni stup renoissimmoC ehT 7002 ,72 rebmetpeS
7002 fo tcA nerdlihC rof slacituecamrahP tseB :V eltiT
]404 AAADF[ .delebal ylreporp dna detset era nerdlihc yb desu
senicidem taht gnirusne ni )ACPB dna AERP( snoisivorp deificeps fo ssenevitceffe eht sesserdda taht troper a ssergnoC ot stimbus lareneG rellortpmoC ehT 1102 ,1 yraunaJ
]c553 CSU 12 ;204 AAADF[
.snoitaluger rosrucerp ro AERP ot tnausrup detcudnoc seiduts gnidrager ssergnoC ot troper dna yduts a tcudnoc ot MOI htiw stcartnoc yraterceS ehT 0102 ,72 rebmetpeS
]c553 CSU 12 ;204 AAADF[ .3002
ecnis detnarg sreviaw dna slarrefed dna dettimbus stnemssessa AERP fo sisylana dna weiver evitcepsorter a stcudnoc eettimmoc lanretni dehsilbatse ylweN 8002 ,72 rebmetpeS
]c553 CSU 12 ;204 AAADF[
.stnemssessa dna snalp cirtaidep deificeps no snoisivid gniweiver ot noitatlusnoc edivorp ot eettimmoc weiver lanretni dehsilbatse ylwen sezilitu yraterceS ehT 7002 ,72 rebotcO
]c553 CSU 12 ;204 AAADF[ .sredivorp
erac htlaeh ot noitamrofni hcus etubirtsid AERP ot tnausrup edam segnahc gnilebal deificeps ni tluser taht stnemssessa fo srosnops taht seriuqer yraterceS ehT 7002 ,72 rebmetpeS
7002 fo tcA ytiuqE hcraeseR cirtaideP :VI eltiT
])m(j062 CSU 12 ;303 AAADF[ .snoitcirtser gnicirp noitpmexe
ecived nairatinamuh morf secived gniyfilauq gnitpmexe fo tcapmi eht no troper a seettimmoc lanoissergnoc tnaveler ot stimbus lareneG rellortpmoC ehT 2102 ,1 yraunaJ
]1-e063 CSU 12 ;203 AAADF[ .secived lacidem cirtaidep gnidrager troper launna tsrif eht seettimmoc lanoissergnoc tnaveler ot stimbus yraterceS ehT 9002 ,72 hcraM
]eton 282 CSU 24 ;503 AAADF[
.tnempoleved ecived cirtaidep etomorp ot stcejorp noitartsnomed rof aitrosnoc tiforpnon ot stcartnoc ro stnarg eht no noitanimreted a sekam yraterceS ehT a 8002 ,32 enuJ
])b(282
CSU 24 ;403 AADF[ .tnempoleved dna hcraeser ecived lacidem cirtaidep gnidnapxe rof nalp a seettimmoc lanoissergnoc tnaveler ot stimbus yraterceS ehT 8002 ,52 hcraM
]eton j063 CSU 12 ;303 AAADF[ .detnarg neeb sah snoitcirtser
gnicirp EDH morf noitpmexe na hcihw rof secived evorppa ot stseuqer etaulave ot woh no sdraob weiver lanoitutitsni rof ecnadiug seussi renoissimmoC ehT 8002 ,52 hcraM
])m(j062 CSU
12 ;303 AAADF[ .snoitcirtser gnicirp EDH morf detpmexe secived cirtaidep fo eettimmoC yrosivdA cirtaideP eht yb weiver launna rof sedivorp yraterceS ehT 8002 ,72 rebmetpeS
]eton 282 CSU 24 ;503 AAADF[ .tnempoleved
ecived cirtaidep etomorp ot stcejorp noitartsnomed rof aitrosnoc tiforpnon ot stcartnoc ro stnarg rof slasoporp rof tseuqer a seussi yraterceS ehT 7002 ,62 rebmeceD
7002 fo tcA tnemevorpmI dna ytefaS eciveD lacideM cirtaideP :III eltiT
]A837 CSU 12 ;312 AAADF[ .ssergnoC ot noitazirohtuaer AFUDM rof snoitadnemmocer stimsnart yraterceS ehT 2102 ,51 yraunaJ
noitcA deriuqeR enildaeD
])i()D( dna )i()C()2()j(282 CSU 24 ;)2()a(108 AAADF[ .snoitidnoc ro sesaesid gninetaerht efil taert taht sgurd tset ot
,7002 ,62 rebmeceD fo sa gniogno ro detaitini slairt elbacilppa rof knab atad yrtsiger eht ni detsop si noitamrofni lairt lacinilc taht serusne rotceriD HIN ehT a 8002 ,52 yraunaJ
])i()A()3()j(282 CSU 24 ;)2()a(108 AAADF[ .elbaliava ylcilbup semoceb noitamrofni
stluser eht retfa syad 03 naht retal ton ,deraelc ro devorppa si tcudorp a retfa detcudnoc
era ro mialc ycaciffe na fo sisab yramirp eht mrof taht slairt esoht fo stluser gnitsixe ot sknil sniatnoc knab atad yrtsiger eht taht serusne yraterceS ehT 7002 ,62 rebmeceD
sesabataD lairT lacinilC :IIIV eltiT
]1-d973 CSU 12 ;107 AAADF[ .seettimmoc yrosivda ot tcepser htiw ecnadiug sweiver ,sraey 5 yreve naht ssel ton ,yraterceS ehT 2102 ,72 rebmetpeS
]1-d973 CSU 12 ;107 AAADF[ .srebmem eettimmoc yrosivda
rof edam snoitpcexe tseretni fo tcilfnoc tuoba noitamrofni deificeps htiw troper a seettimmoc lanoissergnoc tnaveler ot ,yllaunna ,stimbus yraterceS ehT 8002 ,1 yraurbeF
]1-d973 CSU 12 ;107 AAADF[
.7002 ni snoitpecxe tseretni fo tcilfnoc deificeps rednu srebmem eettimmoc yrosivda sa devres ohw elpoep fo noitroporp eht senimreted yraterceS ehT 7002 ,1 rebotcO
tseretnI fo stcilfnoC :IIV eltiT
]2-dd973 CSU
12 ;106 AAADF[ .noitamrofni rehto dna troper launna s'rotceriD noitadnuoF eht gnizirammus troper a ssergnoC ot ,yllaunna ,stimbus renoissimmoC ehT 9002 ,1 rebmetpeS
]5-bbb063 CSU 12 ;306 AAADF[ .spihsrentrap etavirp-cilbup htap lacitirc gnidrager ssergnoC ot troper a ,yllaunna ,stimbus yraterceS ehT 9002 ,72 hcraM
]dd973
CSU 12 ;106 AAADF[ .sesoprup deificeps hsilpmocca ot srotceriD fo draoB s'noitadnuoF eht fo srebmem oiciffo xe eht fo gniteem a senevnoc yraterceS ehT 7002 ,72 rebotcO
noitadnuoF lladU-nagaeR :IV eltiT
]a553 CSU 12 ;)1()a(205 AAADF[ .ACPB
ot tnausrup detcudnoc seiduts eht dna edam stseuqer nettirw gnidrager ssergnoC ot troper dna yduts ot MOI eht htiw tcartnoc a otni sretne yraterceS ehT 0102 ,72 rebmetpeS
]m482 CSU 24 ;)b(205 AAADF[ .scituepareht cirtaidep ni sdeen fo tsil ytiroirp a sehsilbup dna spoleved yraterceS ehT 8002 ,72 rebmetpeS
]m482 CSU
24 ;)b(205 AAADF[ .ssergnoC ot gnidnif eht stroper dna esu gurd cirtaidep no noitamrofni fo noitalipmoc a gnihsilbatse fo ytilibisaef eht seiduts yraterceS ehT 8002 ,72 rebmetpeS
])f(205 AAADF[ .tceffe sekat stcudorP
gurD namuH rof gnilebaL no stnevE esrevdA gnitropeR rof rebmuN eerF-lloT deltitne elur desoporp eht ,etad siht yb elur lanif a seussi renoissimmoC eht sselnU 8002 ,1 yraunaJ
]a553 CSU 12 ;)1()a(205 AAADF[ .snoitalupop cirtaidep ni esu rieht ot gnitaler noitamrofni rof deen
gniunitnoc a si ereht hcihw rof dna detelpmoc neeb ton evah seiduts cirtaidep hcihw rof sgurd deificeps rof stnemeriuqer niatrec gnitaerc snigeb yraterceS ehT 7002 ,72 rebmetpeS
]a553 CSU 12 ;)1()a(205 AAADF[
.etairporppa sa stroper srefer yraterceS eht ,sraey gniwollof eht gniruD .TPO eht ot derrefer era gurd eht rof deviecer neeb evah taht stroper stneve esrevda
lla ,ACPB fo noisivorp deificeps a ot tnausrup devorppa si egnahc gnilebal a taht etad eht no gninnigeb doirep raey-eno eht gnirud taht serusne yraterceS ehT 7002 ,72 rebmetpeS
noitcA deriuqeR enildaeD
]553 CSU 12 ;519 AAADF[ .sredivorp dna stneitap rof noitamrofni ytefas tekramtsop gnidivorp etisbew a sniatniam dna spoleved yraterceS ehT 8002 ,72 rebmetpeS
])b(419 AAADF[ .noitca ycnega fo syats rof snoititep nezitic fo noissimbus ylrae eht egaruocne ot syaw no ssergnoC ot troper a stimbus yraterceS ehT 8002 ,72 rebmetpeS
]553 CSU 12 ;)a(419 AAADF[ .noitca ycnega fo syats rof snoititep nezitic rep slavorppa ni syaled no troper a ssergnoC ot yllaunna stimbus yraterceS ehT 8002 ,72 rebmetpeS
]a063 CSU 12 ;119 AAADF[ .sgurd citoibitna ot tcepser htiw slairt lacinilc fo tcudnoc eht rof ecnadiug seussi yraterceS ehT 8002 ,72 rebmetpeS
]409 AAADF[ .stifeneb dna sksir hcus gnissessa ni seigetarts noitagitim dna noitaulave
ksir fo elor eht dna sgurd wen fo stifeneb dna sksir eht cilbup eht ot etacinummoc ot tseb woh no troper a ssergnoC ot stimbus renoissimmoC ehT 8002 ,72 rebmetpeS
]553 CSU 12 ;029 AAADF[ .setadpu gnimoc dna tsil eht
tuoba seicnega laredef tnaveler seifiton ;ylretrauq tsil eht setadpu ;sgurd cireneg dezirohtua fo tsil etelpmoc a etisbew s'ADF no sehsilbup renoissimmoC ehT 8002 ,72 enuJ
]eton 253 CSU 12 ;)b(609 AAADF[ .sda noisivelet ni noisulcni rof etairporppa
si stnemesitrevda remusnoc-ot-tcerid dehsilbup ni noisulcni rof seriuqer AAADF tnemetats a rehtehw enimreted ot yduts a stcudnoc yraterceS ehT 8002 ,72 hcraM
]553 CSU 12 ;129 AAADF[ .SREA yb deifitnedi ksir suoires a fo slangis laitnetop ro noitamrofni ytefas wen fo stroper ylretrauq stsop yraterceS ehT 7002 ,72 rebmeceD
]553 CSU 12 ;129 AAADF[ .esabatad )SREA( metsyS gnitropeR tnevE esrevdA gnitsixe eht ,ylkeew-ib ,sneercs yraterceS ehT 7002 ,11 rebotcO
sgurD fo ytefaS tekramtsoP gnidrageR seitirohtuA decnahnE :XI eltiT
])i()D()3()j(282 CSU 24 ;)2()a(108 AAADF[ .knab atad stluser dna yrtsiger eht ni stluser dednapxe ,noitaluger yb ,sedulcni yraterceS ehT 0102 ,72 rebmetpeS
])i()D( dna )iii()C()2()j(282 CSU 24 ;)2()a(108 AAADF[ .snoitidnoc ro sesaesid gninetaerht efil-non taert taht sgurd tset taht
,7002 ,62 rebmeceD fo sa gniogno ro detaitini slairt elbacilppa rof knab atad yrtsiger eht ni detsop si noitamrofni lairt lacinilc taht serusne rotceriD HIN ehT a 9002 ,72 rebotcO
])ii()I()3()j(282 CSU 24 ;)2()a(108 AAADF[ .tceffe sekat cipot eht no noitaluger a gnitaerc AAADF ni esualc a ,knab atad stluser dna yrtsiger
eht ni stneve esrevda tneuqerf dna stneve esrevda suoires no noitamrofni gnidulcni rof dohtem tseb eht ,noitaluger yb ,enimreted ot sliaf yraterceS eht fI 9002 ,72 rebmetpeS
])i()I()3()j(282 CSU 24 ;)2()a(108 AAADF[ .knab atad stluser
dna yrtsiger eht ni stneve esrevda tneuqerf dna stneve esrevda suoires no noitamrofni gnidulcni rof dohtem tseb eht ,noitaluger yb ,senimreted yraterceS ehT 9002 ,72 hcraM
])C()2()j(282 CSU 24 ;)2()a(108 AAADF[ .deiduts gnieb eussi ytefas yb knab atad yrtsiger eht hcraes yam cilbup eht taht serusne rotceriD HIN ehT 9002 ,72 hcraM
])iiv()D()3()j(282
CSU 24 ;)2()a(108 AAADF[ .knab atad stluser dna yrtsiger eht ni stluser dednapxe fo noisulcni eht gnidrager gniteem cilbup a sdloh yraterceS ehT 9002 ,72 hcraM
])ii()D()2()j(282 CSU 24 ;)2()a(108 AAADF[ .7002 ,72
rebmetpeS fo sa devorppa ro deraelc secived fo slairt elbacilppa rof knab atad yrtsiger eht ni detsop si noitamrofni lairt lacinilc taht serusne rotceriD HIN ehT 8002 ,72 rebotcO
])C()3()j(282 CSU 24 ;)2()a(108
AAADF[ .secived deraelc ro devorppa dna ,scigoloib desnecil ,sgurd devorppa rof knab atad stluser dna yrtsiger eht ni stluser cisab sedulcni yraterceS ehT 8002 ,72 rebmetpeS
]eton 282 CSU 24 ;)c(108 AAADF[ .lairt
lacinilc a ton si taht ecnallievrus tekramtsop cirtaidep deificeps niatrec ot ylppa stnemeriuqer knab atad dna yrtsiger eht woh no ecnadiug seussi yraterceS ehT 8002 ,72 rebmetpeS
noitcA deriuqeR enildaeD
]8012 CSU 12 ;9001 AAADF[
.noitatropmi dna noitcepsni ,noitaluger doof tuoba noitamrofni deificeps htiw troper a ,seettimmoc lanoissergnoc tnaveler ot ,yllaunna ,stimbus yraterceS ehT 8002 ,72 rebmetpeS
]f053 CSU 12 ;)b(5001 AAADF[ .yrtsigeR dooF elbatropeR a sehsilbatse yraterceS ehT 8002 ,72 rebmetpeS
]2012 CSU 12 ;)b(2001 AAADF[ .doof tep rof metsys ecnallievrus dna gninraw ylrae na sehsilbatse yraterceS ehT 8002 ,72 rebmetpeS
]eton f053 CSU 12 ;)f(5001 AAADF[ .yrtsigeR dooF elbatropeR eht ot detaler snoitaluger
yb deriuqer sa niahc ylppus eht ni snosrep rehto ot snoitacifiton gnidivorp dna stroper gnittimbus tuoba yrtsudni ot ecnadiug a seussi yraterceS ehT 8002 ,72 enuJ
]9012 CSU 12 ;0101
AAADF[ .margorp gnirotinom eudiser edicitsep s'noitartsinimdA eht fo stluser eht gninrecnoc troper a ssergnoC ot ,yllaunna ,stimbus renoissimmoC ehT 8002 ,1 enuJ
]5012 CSU 12 ;6001 AAADF[ .noitcepsni doofaes dna erutlucauqa decnahne no ssergnoC ot troper a stimbus yraterceS ehT 8002 ,52 hcraM
ytefaS dooF :X eltiT
]a063 CSU 12 ;119 AAADF[ .sgurd citoibitna ot tcepser htiw slairt lacinilc fo tcudnoc eht rof ecnadiug eht setadpu dna sweiver yraterceS ehT 2102 ,72 rebmetpeS
])c(509 AAADF[ .sgurd detekram htiw detaicossa
semoctuo eht dnatsrednu retteb ot dna slangis ytefas gurd cificeps yfitnedi ot AIRPA desu sah yraterceS eht syaw eht no ssergnoC ot stroper yraterceS ehT 1102 ,72 rebmetpeS
]553 CSU 12 ;)a(509 AAADF[ .yrassecen smeed yraterceS eht seitivitca rehto tuo yrrac dna ,slairt lacinilc dna seiduts
lavorppatsop sucof ylevitceffe erom ,sksir ytefas gurd deifitnedi no sisylana dna hcraeser decnavda mrofrep ,snoitseuq ytefas gurd ytiroirp fo noitagitsevni tpmorp
rof wolla ,atad AIRPA etagergga ezylana ro yfissalc ot seititne deifilauq erom ro eno htiw tcartnoc ot serudecorp stnemelpmi dna sehsilbatse yraterceS ehT a1102 ,62 hcraM
]553 CSU 12 ;)a(509 AAADF[ .deificeps sa metsys ecnallievrus AIRPA eht sniatniam dna sehsilbatse yraterceS ehT a0102 ,72 rebmetpeS
]e553 CSU 12 ;319 AAADF[ .sgurd noitpircserp ecart dna kcart ,etacitnehtua ,etadilav ot sreifitnedi laciremun dradnats spoleved yraterceS ehT 0102 ,72 hcraM
]eton 253 CSU 12 ;)3()d(109 AAADF[ .rennam deriuqer eht ni detneserp
si stceffe edis ot gnitaler tnemesitrevda remusnoc-ot-tcerid a ni tnemetats rojam a rehtehw gninimreted rof sdradnats ,noitaluger yb ,sehsilbatse yraterceS ehT 0102 ,72 hcraM
]553 CSU 12 ;129 AAADF[ .eciffO eht fo snoitadnemmocer seldnah ADF woh dna ,ygoloimedipE dna ecnallievruS
fo eciffO gnitsixe eht yb deifitnedi seussi ytefas tekramtsop gniogno gnisserdda rof sessecorp dna serudecorp ADF no ssergnoC ot stroper yraterceS ehT 9002 ,72 rebmetpeS
]553 CSU 12 ;)a(509 AAADF[ .atad gnitekramtsop fo noitacinummoc
dna ,rof sesu cifitneics dna lacihte eht rof sdohtem dna sloot fo tnempoleved eht no yraterceS eht ot snoitadnemmocer ekam ot strepxe fo eettimmoc a
senevnoc dna ,secruos atad etarapsid morf atad ytefas ezylana dna ,knil ,ssecca ot sdohtem spoleved yraterceS eht ,AIRPA fo tnemhsilbatse eht rof eraperp oT 9002 ,72 rebmetpeS
])e(509 AAADF[ .seettimmoc lanoissergnoc tnaveler ot snoitadnemmocer sekam
dna ,)AIRPA( sisylana dna noitacifitnedi ksir tekramtsop evitca ot gnitaler seussi ytiruces dna ,ytilaitnedifnoc ,ycavirp atad setaulave lareneG rellortpmoC ehT 9002 ,72 hcraM
]553 CSU 12 ;129 AAADF[ .stnemtimmoc eht rof setad noitelpmoc detamitse dna setad trats sngissa dna ,ssergnoC ot snoitanimreted
eht stroper ,noitanimile ro noisiver eriuqer hcihw senimreted ,stnemtimmoc ytefas tekramtsop fo golkcab eritne eht sweiver yllaunna yraterceS ehT 8002 ,72 rebmetpeS
]919 AAADF[ .cilbuP eht fo htlaeH eht gnitcetorP dna gnitomorP--ytefaS gurD fo erutuF ehT :troper MOI 6002 eht ot gnidnopser troper a seussi yraterceS ehT 8002 ,72 rebmetpeS
noitcA deriuqeR enildaeD
.ylgnidrocca
detsujda eb dluow etad siht ,wal ni deificeps enildaed eht ot tneuqesbus ro roirp detelpmoc si ksat reilrae na fI .)s(enildaed roirp no tnegnitnoc era setad esehT .a
]4111 AAADF[ .snoisivorp noitavonnI
dna sseccA citoibitnA s'AAADF fo stceffe deificeps senimaxe taht troper a seettimmoc lanoissergnoc tnaveler ot stimbus lareneG rellortpmoC ehT 2102 ,1 yraunaJ
]n063 CSU 12 ;2011 AAADF[ .eef resu weiver ytiroirp eht fo tnuoma eht ,yllaunna ,sehsilbatse yraterceS ehT 8002 ,1 rebotcO
]n063 CSU 12 ;2011 AAADF[ .tcudorp esaesid laciport a fo rosnops eht ot rehcuov weiver ytiroirp a eussi yam yraterceS ehT 8002 ,72 rebmetpeS
]3011 AAADF[ .stset citeneg fo ytilauq dna ytefas eht fo yduts a ,9002 yluJ yb ,tcudnoc ot MOI eht htiw tcartnoc a otni sretne yraterceS eht
,gnitset citeneg fo noitaluger eht no troper deificeps a timbus dna etelpmoc ton seod yteicoS dna ,htlaeH ,sciteneG no eettimmoC yrosivdA s'yraterceS eht fI 8002 yluJ
snoisivorP rehtO :IX eltiT
]2012
CSU 12 ;)a(2001 AAADF[ .sdradnats gnilebal detadpu dna ,sdradnats gnissecorp ,sdradnats tneidergni ,noitaluger yb ,doof tep rof sehsilbatse yraterceS ehT 9002 ,72 rebmetpeS
noitcA deriuqeR enildaeD
eton i973 CSU 12 ;712 AAADF )II( stnemeriuqer gnitroper AFUDM
eton g973 CSU 12 ;601 AAADF )I( stnemeriuqer gnitroper AFUDP
3102 ,13 yraunaJ gniripxE
553 CSU 12 ;3111 AAADF )IX( sremoitnane gniniatnoc sgurd niatrec fo ytivisulcxE
a553 CSU 12 ;)1()a(205 AAADF )V( ytivisulcxe tekram cirtaidep ACPB
c553 CSU 12 ;204 AAADF )VI( tnemeriuqer yduts cirtaidep AERP
)m(j063 CSU 12 ;303 AAADF )III( noitpmexe ecived nairatinamuh ni noitpmexe gnicirp ecived cirtaideP
)c(m063 CSU 12 ;122 AAADF )II( noitacifiton tekramerp fo weiver ytrap drihT
eton i973 CSU 12 ;712 AAADF )II( noitcelloc eef AFUDM
eton g973 CSU 12 ;601 AAADF )I( noitcelloc eef tnemesitrevda noisivelet CTD
eton g973 CSU 12 ;601 AAADF )I( noitcelloc eef AFUDP
2102 ,1 rebotcO gniripxE
noitatiC )eltiT AAADF( ytirohtuA
setaD tesnuS htiw seitirohtuA AAADF .1-C elbaT
¡
edoC setatS detinU CSU
ytrap elbisnopser PR
lortnoc ytilauq CQ
)VI eltiT
AAADF ni dezirohtuaer ,551-801 .L.P( 3002 fo tcA ytiuqE hcraeseR cirtaideP AERP
)III eltiT AAADF( 7002 fo tcA tnemevorpmI dna ytefaS eciveD lacideM cirtaideP AISDMP
)7002 AFUDM dna AMFUDM ees( noitacilppA tekramerP AMP
rotagitsevni lapicnirp IP
).qes te 102 § CSU 24( tcA ecivreS htlaeH cilbuP ASHP
)I eltiT AAADF( 7002 fo stnemdnemA eeF resU gurD noitpircserP VI AFUDP
)V eltiT ,881-701 .L.P(
2002 fo stnemdnemA eeF resU gurD noitpircserP III AFUDP
)I eltiT ,511-501 .L.P(
tcA eeF resU gurD noitpircserP eht fo noitazirohtuaer 7991 eht II AFUDP
)175-201 .L.P( 2991 fo tcA eeF resU gurD noitpircserP I AFUDP
ADF ,ygoloimedipE dna ecnallievruS fo eciffO ESO
ADF ,scitueparehT cirtaideP fo eciffO TPO
htlaeH fo setutitsnI lanoitaN HIN
)052-701 .L.P(
2002 fo tcA noitazinredoM dna eeF resU eciveD lacideM AMFUDM
)II eltiT AAADF( 7002 fo stnemdnemA eeF resU eciveD lacideM 7002 AFUDM
enicideM fo etutitsnI MOI
secivreS namuH dna htlaeH fo tnemtrapeD SHH
snoisneP dna ,robaL ,noitacudE ,htlaeH no eettimmoC etaneS PLEH
noitpmexE eciveD nairatinamuH EDH
eciffO ytilibatnuoccA tnemnrevoG OAG
htlaeH fo setutitsnI lanoitaN eht rof noitadnuoF HINF
).qes te 103 § CSU 12( tcA citemsoC dna ,gurD ,dooF laredeF ACDFF
)511-501 .L.P( 7991 fo tcA noitazinredoM ADF AMADF
)58-011 .L.P( 7002 fo tcA stnemdnemA ADF AAADF
noitartsinimdA gurD dna dooF ADF
)gnisitrevda CTD ni sa( remusnoc-ot-tcerid CTD
ecivreS hcraeseR lanoissergnoC SRC
snoitalugeR laredeF fo edoC RFC
)V eltiT AAADF ni dezirohtuaer ,901-701 .L.P(
tcA nerdlihC rof slacituecamrahP tseB ACPB
sisylana dna noitacifitnedi ksir tekramtsop evitca AIRPA
¢ ¡
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
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For other versions of this document, see http://wikileaks.org/wiki/CRS-RL34465