Pediatric Drug Research: The Study and Labeling of Drugs for	 
Pediatric Use under the Best Pharmaceuticals for Children Act	 
(22-MAY-07, GAO-07-898T).					 
                                                                 
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.	 
-------------------------Indexing Terms------------------------- 
REPORTNUM:   GAO-07-898T					        
    ACCNO:   A69826						        
  TITLE:     Pediatric Drug Research: The Study and Labeling of Drugs 
for Pediatric Use under the Best Pharmaceuticals for Children Act
     DATE:   05/22/2007 
  SUBJECT:   Children						 
	     Drug testing					 
	     Drugs						 
	     Food and drug law					 
	     Labeling law					 
	     Patents						 
	     Pediatrics 					 
	     Pharmacological research				 
	     Policy evaluation					 
	     Research programs					 

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GAO-07-898T

   

     * [1]Background

          * [2]BPCA Process
          * [3]BPCA Provisions for Pediatric Drug Studies Declined by Drug
          * [4]Making Labeling Changes under BPCA for On-Patent Drugs

     * [5]Drug Sponsors Agreed to Study the Majority of On-Patent Drug
     * [6]Few Off-Patent Drugs Have Been Studied under BPCA
     * [7]Most Drugs Granted Pediatric Exclusivity under BPCA Had Labe

          * [8]Order by Mail or Phone

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

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.^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,^2 Congress passed the Best
Pharmaceuticals for Children Act (BPCA) in 2002 to provide marketing
incentives to drug sponsors for conducting pediatric drug studies.^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.^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.^5 Generally, pediatric exclusivity
can only be granted to those drugs that are on-patent--that is, those that
still have market exclusivity^6--and for which FDA has issued a written
request for pediatric drug studies.^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.

^1The 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. S
321(k), (m).

^2FDA 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.

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

^4The 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).

^5Drug 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. SS
355(j)(5)(F)(ii), (iii); 21 C.F.R. S 314.108 (2006). Pediatric exclusivity
under BPCA attaches to an existing listed patent or any existing market
exclusivity held by the drug sponsor.

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.^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.^9

6For 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.

^7FDA 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.

^8FNIH 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.

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.

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

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.^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

^10BPCA 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,
[10]GAO-01-705T (Washington, D.C.: May 8, 2001).

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.^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.^12 Figure 1 illustrates the process under BPCA.

^11Under 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.

^12Pediatric 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.

Figure 1: BPCA Process

aIf 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.

bFDA 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.

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.^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.^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.

^13Most 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.

^14Some 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.

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.^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.

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

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

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.

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,^16 but as of December 2005,
FNIH had not funded the study of any of these drugs.^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.

^16When 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.

^17In 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.

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.^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.^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.

^18Since 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.

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

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.^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.^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 [11][email protected] . 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)

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

^21BPCA 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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Highlights of [19]GAO-07-898T , a testimony before the Subcommittee on
Health, Committee on Energy and Commerce, House of Representatives

May 22, 2007

PEDIATRIC DRUG RESEARCH

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

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.

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.

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

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.

References

Visible links
   9. http://www.gao.gov/cgi-bin/getrpt?GAO-07-557
  10. http://www.gao.gov/cgi-bin/getrpt?GAO-01-705T
  19. http://www.gao.gov/cgi-bin/getrpt?GAO-07-898T
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