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pediatric use under the Best Pharmaceuticals for children Act' which 
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Testimony: 

Before the Subcommittee on Health, Committee on Energy and Commerce, 
House of Representatives: 

United States Government Accountability Office: 

GAO: 

For Release on Delivery Expected at 10:00 a.m. EDT: 

Tuesday, May 22, 2007: 

Pediatric Drug Research: 

The Study and Labeling of Drugs for Pediatric Use under the Best 
Pharmaceuticals for Children Act: 

Statement of Marcia Crosse: 
Director, Health Care: 

GAO-07-898T: 

GAO Highlights: 

Highlights of GAO-07-898T, a testimony before the Subcommittee on 
Health, Committee on Energy and Commerce, House of Representatives 

Why GAO Did This Study: 

About two-thirds of drugs that are prescribed for children have not 
been studied and labeled for pediatric use, placing children at risk of 
being exposed to ineffective treatment or incorrect dosing. The Best 
Pharmaceuticals for Children Act (BPCA), enacted in 2002, encourages 
the manufacturers, or sponsors, of drugs that still have marketing 
exclusivity—that is, are on-patent—to conduct pediatric drug studies, 
as requested by the Food and Drug Administration (FDA). If they do so, 
FDA may extend for 6 months the period during which no equivalent 
generic drugs can be marketed. This is referred to as pediatric 
exclusivity. BPCA also provides for the study of off-patent drugs. 

GAO was asked to testify on the study and labeling of drugs for 
pediatric use under BPCA. This testimony is based on Pediatric Drug 
Research: Studies Conducted under Best Pharmaceuticals for Children 
Act, GAO-07-557 (Mar. 22, 2007). GAO assessed (1) the extent to which 
pediatric drug studies were being conducted under BPCA for on-patent 
drugs, (2) the extent to which pediatric drug studies were being 
conducted under BPCA for off-patent drugs, and (3) the impact of BPCA 
on the labeling of drugs for pediatric use and the process by which the 
labeling was changed. GAO examined data about the drugs for which FDA 
requested studies under BPCA from 2002 through 2005 and interviewed 
relevant federal officials. 

What GAO Found: 

Drug sponsors have initiated pediatric drug studies for most of the on-
patent drugs for which FDA has requested such studies under BPCA, but 
no drugs were studied when sponsors declined these requests. Sponsors 
agreed to 173 of the 214 written requests for pediatric studies of on-
patent drugs. In cases where drug sponsors decline to study the drugs, 
BPCA provides for FDA to refer the study of these drugs to the 
Foundation for the National Institutes of Health (FNIH), a nonprofit 
corporation. FNIH had not funded studies for any of the nine drugs that 
FDA referred as of December 2005. 

Figure: Written Requests Issued under BPCA for the Study of On-Patent 
drugs (2002-2005): 

[See PDF for Image] 

Source: GAO. 

[End of figure] 

Few off-patent drugs identified by the National Institutes of Health 
(NIH) that need to be studied for pediatric use have been studied. BPCA 
provides for NIH to fund studies when drug sponsors decline written 
requests for off-patent drugs. While 40 such off-patent drugs were 
identified by 2005, FDA had issued written requests for 16. One written 
request was accepted by the drug sponsor. Of the remaining 15, NIH 
funded studies for 7 through December 2005. 

Most drugs granted pediatric exclusivity under BPCA (about 87 percent) 
had labeling changes—often because the pediatric drug studies found 
that children may have been exposed to ineffective drugs, ineffective 
dosing, overdosing, or previously unknown side effects. However, the 
process for approving labeling changes was often lengthy. For 18 drugs 
that required labeling changes (about 40 percent), it took from 238 to 
1,055 days for information to be reviewed and labeling changes to be 
approved. 

[Hyperlink, http://www.gao.gov/cgi-bin/getrpt?GAO-07-898T. 

To view the full product, including the scope and methodology, click on 
the link above. For more information, contact Marcia Crosse at (202) 
512-7119 or crossem@gao.gov. 

[End of section] 

Mr. Chairman and Members of the Subcommittee: 

Although children suffer from many of the same diseases as adults and 
are often treated with the same drugs, only about one-third of the 
drugs that are prescribed for children have been studied and labeled 
for pediatric use.[Footnote 1] This has placed children taking drugs 
for which there have not been adequate pediatric drug studies at risk 
of being exposed to ineffective treatment or receiving incorrect 
dosing. In order to encourage the study of more drugs for pediatric 
use,[Footnote 2] Congress passed the Best Pharmaceuticals for Children 
Act (BPCA) in 2002 to provide marketing incentives to drug sponsors for 
conducting pediatric drug studies.[Footnote 3] Drug sponsors (typically 
drug manufacturers) may obtain 6 months of additional market 
exclusivity for drugs on which they have conducted pediatric studies in 
accordance with pertinent law and regulations.[Footnote 4] This market 
exclusivity is known as pediatric exclusivity. When a drug has market 
exclusivity, it is protected from competition for a limited period; for 
example, the Food and Drug Administration (FDA) is prohibited from 
approving a generic copy for marketing.[Footnote 5] Generally, 
pediatric exclusivity can only be granted to those drugs that are on- 
patent--that is, those that still have market exclusivity[Footnote 6]-
-and for which FDA has issued a written request for pediatric drug 
studies.[Footnote 7] However, FDA can also request pediatric drug 
studies for off-patent drugs--drugs for which the patent or market 
exclusivity has expired. BPCA also included provisions designed to 
provide for the study of both on-patent and off-patent drugs that drug 
sponsors have declined to study. 

When FDA determines that a drug may provide health benefits to 
children, it may issue a written request to the drug sponsor to conduct 
pediatric drug studies on that drug. When a drug sponsor accepts a 
written request and conducts studies, FDA reviews the report from the 
pediatric drug studies to determine whether to grant pediatric 
exclusivity to the drug. If FDA is satisfied that the studies have been 
conducted and reported properly, the drug in question may receive 
additional market exclusivity. FDA also reviews these pediatric drug 
study reports to see if the drug requires labeling changes. 

BPCA provides for pediatric drug studies when the drug sponsor declines 
the written request. First, if a drug sponsor declines a written 
request from FDA to study an on-patent drug, BPCA provides for FDA to 
refer the drug to the Foundation for the National Institutes of Health 
(FNIH), which can fund the study if funds are available.[Footnote 8] 
Sponsors cannot receive pediatric exclusivity for on-patent drugs that 
drug sponsors decline to study. Second, BPCA provides for the funding 
of the study of off-patent drugs by the National Institutes of Health 
(NIH), which, in consultation with FDA and experts in pediatric 
research, identifies off-patent drugs that need to be studied for 
pediatric use. 

My remarks today provide an overview of the study and proper labeling 
of drugs for pediatric use under BPCA. I will focus on (1) the extent 
to which pediatric drug studies were being conducted under BPCA for on- 
patent drugs, (2) the extent to which pediatric drug studies were being 
conducted under BPCA for off-patent drugs, and (3) the impact of BPCA 
on the labeling of drugs for pediatric use and the process by which the 
labeling was changed. My remarks are based upon our report assessing 
the effect of BPCA on pediatric drug studies and labeling.[Footnote 9] 

In carrying out the work for our report, we collected and analyzed a 
variety of data from FDA, NIH, and FNIH about written requests and 
pediatric studies for both on-and off-patent drugs from January 2002 
through December 2005. Our work focused on actions regarding these 
drugs prior to 2006. To evaluate the impact of BPCA on the labeling of 
drugs for pediatric use and the process by which labeling was changed, 
we reviewed summaries of the labeling changes for drugs studied from 
the enactment of BPCA through 2005. In addition, to assist with our 
review in general, we interviewed officials from FDA, NIH, and FNIH. 
The work done for this statement was performed from September 2005 
through March 2007 in accordance with generally accepted government 
auditing standards. 

In summary, most of the on-patent drugs for which FDA requested 
pediatric drug studies under BPCA were being studied, but no studies 
resulted when the requests were declined by drug sponsors. Drug 
sponsors agreed to study 173 of the 214 on-patent drugs (81 percent) 
for which FDA issued written requests for pediatric drug studies from 
January 2002 through December 2005. Drug sponsors completed pediatric 
drug studies for 59 of the 173 accepted written requests--studies for 
the remaining 114 written requests were ongoing--and FDA made a 
pediatric exclusivity determination for 55 of those through December 
2005. Of those 55 written requests, 52 (95 percent) resulted in FDA 
granting pediatric exclusivity. In addition, of the 41 on-patent drugs 
that drug sponsors declined to study, FDA referred 9 to FNIH, which had 
not funded the study of any, as of December 2005. 

Few of the off-patent drugs identified by NIH as in need of study for 
pediatric use have been studied. By 2005, NIH had identified 40 off- 
patent drugs it recommended be studied for pediatric use. Through 2005, 
FDA issued written requests for 16 of these drugs, and all but one of 
these written requests were declined by drug sponsors. NIH funded 
pediatric drugs studies for 7 of the remaining 15 written requests 
declined by drug sponsors through December 2005. 

Almost all the drugs that have been granted pediatric exclusivity under 
BPCA--about 87 percent--have had important labeling changes as a result 
of pediatric drug studies conducted under BPCA, but the process for 
reviewing the study results and making these changes can be lengthy. 
The labeling of drugs was often changed because the pediatric drug 
studies revealed that children may have been exposed to ineffective 
drugs, ineffective dosing, overdosing, or previously unknown side 
effects. The review process took from 238 to 1,055 days when FDA 
required additional information to support changes in the drug 
labeling. 

Background: 

BPCA was enacted on January 4, 2002, to encourage drug sponsors to 
conduct pediatric drug studies.[Footnote 10] BPCA allows FDA to grant 
drug sponsors pediatric exclusivity--6 months of additional market 
exclusivity--in exchange for conducting and reporting on pediatric drug 
studies. BPCA also provides mechanisms for pediatric drug studies that 
drug sponsors decline to conduct. 

BPCA Process: 

The process for initiating pediatric drug studies under BPCA formally 
begins when FDA issues a written request to a drug sponsor to conduct 
pediatric drug studies for a particular drug. When a drug sponsor 
accepts the written request and completes the pediatric drug studies, 
it submits to FDA reports describing the studies and the study results. 
BPCA specifies that FDA generally has 90 days to review the study 
reports to determine whether the pediatric drug studies met the 
conditions outlined in the written request.[Footnote 11] If FDA 
determines that the pediatric drug studies conducted by the drug 
sponsor were responsive to the written request, it will grant a drug 
pediatric exclusivity regardless of the study findings.[Footnote 12] 
Figure 1 illustrates the process under BPCA. 

Figure 1: BPCA Process: 

[See PDF for image] 

Source: GAO> 

[A] If a drug sponsor of an off-patent drug does not respond to FDA's 
written request within 30 days, the written request is considered 
declined. Pediatric exclusivity is not granted to drugs where the drug 
sponsor declined the written request. 

[B] FDA has granted pediatric exclusivity in response to written 
requests for on-patent drugs only. Under certain circumstances FDA 
could grant pediatric exclusivity in response to a written request for 
an off-patent drug. 

[End of figure] 

BPCA Provisions for Pediatric Drug Studies Declined by Drug Sponsors: 

BPCA includes two provisions to further the study of drugs when drug 
sponsors decline written requests. FDA cannot extend pediatric 
exclusivity in response to written requests for any drugs for which the 
drug sponsors declined to conduct the requested pediatric drug studies. 

First, when drug sponsors decline written requests for studies of on- 
patent drugs, BPCA provides for FDA to refer the study of those drugs 
to FNIH for funding. FNIH, which is a nonprofit corporation and 
independent of NIH, supports the mission of NIH and advances research 
by linking private sector donors and partners to NIH programs. FNIH and 
NIH collaborate to fund certain projects. As of December 2005, FNIH had 
raised $4.13 million to fund pediatric drug studies under BPCA. 

Second, to further the study of off-patent drugs, NIH--in consultation 
with FDA and experts in pediatric research--develops a list of drugs, 
including off-patent drugs, which the agency believes need to be 
studied in children. NIH lists these drugs annually in the Federal 
Register. FDA may issue written requests for those drugs on the list 
that it determines to be most in need of study. If the drug sponsor 
declines or fails to respond to the written request, NIH can contract 
for, and fund, the pediatric drug studies. Drug sponsors generally 
decline written requests for off-patent drugs because the financial 
incentives are considerably limited. 

Making Labeling Changes under BPCA for On-Patent Drugs: 

Pediatric drug studies often reveal new information about the safety or 
effectiveness of a drug, which could indicate the need for a change to 
its labeling. Generally, the labeling includes important information 
for health care providers, including proper uses of the drug, proper 
dosing, and possible adverse events that could result from taking the 
drug. FDA may determine that the drug is not approved for use by 
children, which would then be reflected in any labeling changes. 

The agency refers to its review to determine the need for labeling 
changes as its scientific review. BPCA specifies that study results 
submitted as a supplemental new drug application--which, according to 
FDA officials, most are--are subject to FDA's general performance goals 
for a scientific review, which in this case is 180 days.[Footnote 13] 
FDA's process for reviewing study results submitted under BPCA for 
consideration of labeling changes is not unique to BPCA. FDA's action 
can include approving the application, determining that the application 
is approvable, or determining that the application is not approvable. A 
determination that an application is approvable may require that drug 
sponsors conduct additional analyses. Each time FDA takes action on the 
application, a review cycle is ended. 

Drug Sponsors Agreed to Study the Majority of On-Patent Drugs with 
Written Requests under BPCA, but No Studies Were Conducted When Drug 
Sponsors Declined the Written Requests: 

Most of the on-patent drugs for which FDA requested pediatric drug 
studies under BPCA were being studied, but no studies have resulted 
when the requests were declined by drug sponsors. From January 2002 
through December 2005, FDA issued 214 written requests for on-patent 
drugs to be studied under BPCA, and drug sponsors agreed to conduct 
pediatric drug studies for 173 (81 percent) of those.[Footnote 14] The 
remaining 41 written requests were declined. Of these 41, FDA referred 
9 written requests to FNIH for funding and FNIH had not funded any of 
those studies as of December 2005. 

Drug sponsors completed pediatric drug studies for 59 of the 173 
accepted written requests--studies for the remaining 114 written 
requests were ongoing--and FDA made pediatric exclusivity 
determinations for 55 of those through December 2005.[Footnote 15] Of 
those 55 written requests, 52 (95 percent) resulted in FDA granting 
pediatric exclusivity. Figure 2 shows the status of written requests 
issued under BPCA for the study of on-patent drugs, from January 2002 
through December 2005. 

Figure 2: Status of Written Requests Issued under BPCA for the Study of 
On-Patent Drugs, from January 2002 through December 2005: 

[See PDF for image] 

Source: GAO. 

Note: Written requests issued from January 2002 through December 2005 
include new written requests issued under BPCA combined with written 
requests originally issued under FDAMA but reissued under BPCA. 

[End of figure] 

Drugs were studied under BPCA for their safety and effectiveness in 
treating children for a wide range of diseases, including some that are 
common--such as asthma and allergies--and serious or life threatening 
in children--such as cancer, HIV, and hypertension. We found that the 
drugs studied under BPCA represented more than 17 broad categories of 
disease. The category that had the most drugs studied under BPCA was 
cancer, with 28 drugs. In addition, there were 26 drugs studied for 
neurological and psychiatric disorders, 19 for endocrine and metabolic 
disorders, 18 related to cardiovascular disease--including drugs 
related to hypertension--and 17 related to viral infections. Analyses 
of two national databases shows that about half of the 10 most 
frequently prescribed drugs for children were studied under BPCA. 

Through December 2005, drug sponsors declined written requests issued 
under BPCA for 41 on-patent drugs. FDA referred 9 of these 41 written 
requests (22 percent) to FNIH for funding,[Footnote 16] but as of 
December 2005, FNIH had not funded the study of any of these 
drugs.[Footnote 17] NIH has estimated that the cost of studying these 9 
drugs would exceed $43 million, but FNIH had raised only $4.13 million 
for pediatric drug studies under BPCA. 

Few Off-Patent Drugs Have Been Studied under BPCA: 

Few off-patent drugs identified by NIH as in need of study for 
pediatric use have been studied. By 2005, NIH had identified 40 off- 
patent drugs that it believed should be studied for pediatric use. 
Through 2005, FDA issued written requests for 16 of these drugs. All 
but 1 of these written requests were declined by drug sponsors. NIH 
funded pediatric drug studies for 7 of the remaining 15 written 
requests declined by drug sponsors through December 2005. 

NIH provided several reasons why it has not pursued the study of some 
off-patent drugs that drug sponsors declined to study. Concerns about 
the incidence of the disease that the drugs were developed to treat, 
the feasibility of study design, drug safety, and changes in the drugs' 
patent status have caused the agency to reconsider the merit of 
studying some of the drugs it identified as important for study in 
children.[Footnote 18] For example, in one case NIH issued a request 
for proposals to study a drug but received no responses. In other 
cases, NIH is awaiting consultation with pediatric experts to determine 
the potential for study. 

Further, NIH has not received appropriations specifically for funding 
pediatric drug studies under BPCA. NIH anticipates spending an 
estimated $52.5 million for pediatric drug studies associated with 7 
written requests issued by FDA from January 2002 through December 
2005.[Footnote 19] 

Most Drugs Granted Pediatric Exclusivity under BPCA Had Labeling 
Changes, but the Process for Making Changes Was Sometimes Lengthy: 

Most drugs that have been granted pediatric exclusivity under BPCA-- 
about 87 percent--have had labeling changes as a result of the 
pediatric drug studies conducted under BPCA. Pediatric drug studies 
conducted under BPCA showed that children may have been exposed to 
ineffective drugs, ineffective dosing, overdosing, or side effects that 
were previously unknown. However, the process for reviewing study 
results and completing labeling changes was sometimes lengthy, 
particularly when FDA required additional information from drug 
sponsors to support the changes. 

Of the 52 drugs studied and granted pediatric exclusivity under BPCA 
from January 2002 through December 2005, 45 (about 87 percent) had 
labeling changes as a result of the pediatric drug studies. In 
addition, 3 other drugs had labeling changes prior to FDA making a 
decision on granting pediatric exclusivity. FDA officials said that the 
pediatric drug studies conducted up to that time provided important 
safety information that should be reflected in the labeling without 
waiting until the full study results were submitted or pediatric 
exclusivity determined. 

Pediatric drug studies conducted under BPCA have shown that the way 
that some drugs were being administered to children potentially exposed 
them to an ineffective therapy, ineffective dosing, overdosing, or 
previously unknown side effects--including some that affect growth and 
development. The labeling for these drugs was changed to reflect these 
study results. For example, studies of the drug Sumatriptan, which is 
used to treat migraines, showed that there was no benefit derived from 
this drug when it was used in children. There were also certain serious 
adverse events associated with its use in children, such as vision loss 
and stroke, so the labeling was changed to reflect that the drug is not 
recommended for children under 18 years old. 

Other drugs have had labeling changes indicating that the drugs may be 
used safely and effectively by children in certain dosages or forms. 
Typically, this resulted in the drug labeling being changed to indicate 
that the drug was approved for use by children younger than those for 
whom it had previously been approved. In other cases, the changes 
reflected a new formulation of a drug, such as a syrup that was 
developed for pediatric use, or new directions for preparing the drug 
for pediatric use were identified in the pediatric drug studies 
conducted under BPCA. 

Although FDA generally completed its first scientific review of study 
results--including consideration of labeling changes--within its 180- 
day goal, the process for completing the review, including obtaining 
sufficient information to support and approve labeling changes, 
sometimes took longer. For the 45 drugs granted pediatric exclusivity 
that had labeling changes, it took an average of almost 9 months after 
study results were first submitted to FDA for the sponsor to submit and 
the agency to review all of the information it required and approve 
labeling changes. For 13 drugs (about 29 percent), FDA completed this 
scientific review process and approved labeling changes within 180 
days. It took from 181 to 187 days for the scientific review process to 
be completed and labeling changes to be approved for 14 drugs (about 31 
percent). For the remaining 18 drugs (about 40 percent), FDA took from 
238 to 1,055 days to complete the scientific review process and approve 
labeling changes. For 7 of those drugs, it took more than a year to 
complete the scientific review process and approve labeling changes. 

While the first scientific reviews were generally completed within 180 
days, it took 238 days or more for 18 drugs.[Footnote 20] For those 18 
drugs, FDA determined that it needed additional information from the 
drug sponsors in order to be able to approve the drugs for pediatric 
use. This often required that the drug sponsor conduct additional 
analyses or pediatric drug studies. FDA officials said they could not 
approve any changes to drug labeling until the drug sponsor provided 
this information. Drug sponsors sometimes took as long as 1 year to 
gather the additional necessary data and respond to FDA's 
request.[Footnote 21] 

Mr. Chairman, this concludes my prepared remarks. I would be pleased to 
respond to any questions that you or other members of the Subcommittee 
may have. 

For further information regarding this testimony, please contact Marcia 
Crosse at (202) 512-7119 or crossem@gao.gov. Contact points for our 
Offices of Congressional Relations and Public Affairs may be found on 
the last page of this testimony. Thomas Conahan, Assistant Director; 
Carolyn Feis Korman; and Cathleen Hamann made key contributions to this 
statement. 

(290642): 

FOOTNOTES 

[1] The drug "label" refers to written, printed, or graphic material 
placed on the drug container while drug "labeling" is much broader and 
includes all labels and other written, printed, or graphic materials on 
any container, wrapper, or materials accompanying the drug. 21 U.S.C. § 
321(k), (m). 

[2] FDA generally defines the pediatric population covered under BPCA 
as children from birth to 16 years old, though studies have included 
children as old as 18. 

[3] Provisions regarding pediatric studies of drugs are generally 
codified at 21 U.S.C. § 355a. Pub. L. No. 107-109, 115 Stat. 1408. The 
market exclusivity provisions of BPCA will sunset on October 1, 2007. 

[4] The value of 6 months additional marketing exclusivity is difficult 
to assess and depends on a number of factors for which data are not 
available. However, a recent study estimated that for some drugs, the 
benefit of 6 months of marketing exclusivity was quite large, while for 
others the return the drug sponsor received for pediatric exclusivity 
was less than the cost of the studies. See Jennifer S. Li, et al., 
"Economic Return of Clinical Trials Performed Under the Pediatric 
Exclusivity Program," JAMA, vol. 297, no. 5 (2007). 

[5] Drug sponsors can obtain additional market exclusivity or patent 
protection for drugs protected by patents, drugs designed to treat rare 
diseases, drugs consisting of new chemical entities, and already- 
marketed drugs approved for new uses. See, for example, 21 U.S.C. §§ 
355(j)(5)(F)(ii), (iii); 21 C.F.R. § 314.108 (2006). Pediatric 
exclusivity under BPCA attaches to an existing listed patent or any 
existing market exclusivity held by the drug sponsor. 

[6] For purposes of this statement, we refer to drugs that have patent 
protection or market exclusivity as on-patent and those whose patent 
protection or marketing exclusivity has ended as off-patent. This is 
the same terminology typically used by government agencies to describe 
the exclusivity status of a drug under BPCA. 

[7] FDA is responsible for issuing written requests for pediatric 
studies, determining whether a drug merits pediatric exclusivity as a 
result of those studies, and all steps in between. 

[8] FNIH is an independent, nonprofit corporation. The majority of 
funds that FNIH receives are from the private sector. Only a portion of 
these funds are available for FNIH to award to researchers to conduct 
studies related to BPCA. 

[9] GAO, Pediatric Drug Research: Studies Conducted under Best 
Pharmaceuticals for Children Act, GAO-07-557 (Washington, D.C.: Mar. 
22, 2007). 

[10] BPCA reauthorized and enhanced the pediatric exclusivity 
provisions of the Food and Drug Administration Modernization Act of 
1997 (FDAMA), Pub. L. No. 105-115, 111 Stat. 2296, which first 
established incentives for conducting pediatric drug studies--in the 
form of additional market exclusivity--and whose pediatric exclusivity 
provisions expired on January 1, 2002. We previously described how 
FDAMA was responsible for an increase in pediatric drug studies. GAO, 
Pediatric Drug Research: Substantial Increase in Studies of Drug for 
Children, But Some Challenges Remain, GAO-01-705T (Washington, D.C.: 
May 8, 2001). 

[11] Under certain circumstances, FDA could have only 60 days to review 
the study report to determine pediatric exclusivity. However, FDA 
officials told us that under BPCA, this has never happened. Otherwise, 
FDA has 90 days to determine if the studies fairly respond to the 
written request, were conducted in accordance with commonly accepted 
scientific principles and protocols, and were properly submitted. 

[12] Pediatric exclusivity applies to all approved uses of the drug, 
not just those studied in children. Therefore, if the studies find that 
the drug is not safe for use by children, the drug will still receive 
pediatric exclusivity and therefore extended market exclusivity for the 
adult uses of the drug. 

[13] Most drugs studied under BPCA have previously been approved for 
marketing in the United States, so a supplement to the original "new 
drug application" is submitted. BPCA requires that supplemental new 
drug applications submitted by drug sponsors be treated as "priority 
supplements." FDA's goal is to take action on priority supplements 
within 180 days. If the drug studied under BPCA was not previously 
approved for marketing in the United States, the application would be 
submitted as a new drug application. FDA has a performance goal to 
review nonpriority new drug applications in 10 months. 

[14] Some drugs have two written requests for a variety of reasons. In 
some cases, FDA may have requested that the drug sponsor study the 
effects of the drug on different diseases. In other cases, there could 
be two written requests for the same drug, issued to different drug 
sponsors for different dosage forms of the drug. In addition, FDA told 
us that the specified time period for studies to be completed elapsed 
for some written requests before the completion of studies, and the 
agency issued new written requests. In all of these situations, we 
counted each of these written requests separately. Therefore, there are 
more written requests than there are unique drugs with written 
requests. Of the 214 written requests issued by FDA, 68 were written 
requests first issued under BPCA. The remaining 146 written requests 
were originally issued under FDAMA and reissued under BPCA because drug 
sponsors had not responded to the written requests or completed the 
requested pediatric drug studies at the time that BPCA went into 
effect. 

[15] FDA had not completed its review of the study results to determine 
exclusivity prior to December 2005 for the remaining four drugs. 

[16] When a drug sponsor of an on-patent drug declines a written 
request, the agency must determine if there is a continuing need for 
information relating to the use of the drug in children. Reasons that 
FDA has concluded that there is not a continuing need include the drug 
was not yet approved, some part of the study was being performed by the 
drug sponsor or another party, the drug's patent ended, the risk- 
benefit assessment shifted, safe alternative therapies were already on 
the market even though the agency had issued the written request in 
hope of obtaining additional valuable information, another drug may 
have been approved or may soon be approved with a better safety record, 
or there is minimal use of the drug by children. 

[17] In April 2006, FNIH agreed to allocate all $4.13 million it had 
raised for pediatric drug studies under BPCA to fund half of the cost 
to study one on-patent day--baclofen. NIH expects the cost of the study 
of baclofen to be about $7.8 million over three years and NIH agreed to 
cover the costs of the study that exceed the contribution from FNIH. 
Because FNIH has committed all of its BPCA funds to the study of 
baclofen, there are no resources left for FNIH to fund the study of any 
other drugs. 

[18] Since its inception, no drug has been removed from the list 
published in the Federal Register, regardless of the feasibility or 
likelihood of it being studied. 

[19] The costs reported by NIH are estimates, which may change during 
the course of the studies. 

[20] FDA considers itself in conformance with its review goals even 
though the entire process often took longer than 180 days. 

[21] BPCA provides a dispute resolution process that FDA can use to 
resolve disagreements with drug sponsors regarding labeling of on- 
patent drugs where the only remaining issue concerns the labeling. FDA 
officials said they have never used this process because labeling has 
never been the only unresolved issue for those drugs for which the 
review period exceeded 180 days. Agency officials told us that 
reminding the drug sponsors that such a process exists has motivated 
drug sponsors to complete labeling change negotiations by reaching 
agreement with FDA.

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