United States Government Accountability Office

GAO Testimony 

Before the Subcommittee on Health, 

Committee on Energy and Commerce, 

House of Representatives 

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 

For Release on Delivery

Expected at 10:00 a.m. EDT 

Tuesday, May 22, 2007

 

GAO-07-898T 
What GAO Found

United States Government Accountability Office

Why GAO Did This Study

Highlights

Accountability Integrity Reliability

May 22, 2007

PEDIATRIC DRUG RESEARCH 

The Study and Labeling of Drugs for 

Pediatric Use under the Best 

Pharmaceuticals for Children Act 

Highlights of GAO-07-898T, a testimony 

before the Subcommittee on Health, 

Committee on Energy and Commerce, 

House of Representatives

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) 

Source: GAO. 

Number of applications that pass through decision point

On-patent drugs

denied pediatric 

exclusivity

3

On-patent drugs

granted pediatric 

exclusivity

52

4

Exclusivity determination 

made by FDA through 

December 2005

55

Studies ongoing

through 

December 2005

114

Studies completed and results

submitted to FDA for review 

through December 2005

Written requests

not referred to 

FNIH for funding

32

Written requests

referred to 

FNIH for funding

Studies

not funded 

by FNIH

9

Studies

funded 

by FNIH

0

Written requests

declined by drug 

sponsors

214

On-patent written requests

issued by FDA from January 

2002 through December 2005

173

Written requests

accepted by drug 

sponsors

59

41

9

Exclusivity determination 

pending 

through 2005

X

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. 

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. 
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

 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.

Page 1 GAO-07-898T
exclusivity6

—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. 

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 

 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. 

Page 2 GAO-07-898T
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

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 

 9

GAO, Pediatric Drug Research: Studies Conducted under Best Pharmaceuticals for

Children Act, GAO-07-557 (Washington, D.C.: Mar. 22, 2007).

Page 3 GAO-07-898T
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. 

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. 

Background 

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, GAO-01-705T (Washington, D.C.: 

May 8, 2001). 

Page 4 GAO-07-898T
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. 

Page 5 GAO-07-898T
Figure 1: BPCA Process 

Source: GAO.

FDA decides whether to Sponsor conducts studies of drug.

further refer the drug for study.

Drug sponsor receives written request and determines

whether to accept or decline the written request.

Process ends.

FDA determines whether to issue a written request. The written request may be in response 

to a drug sponsor’s proposed pediatric study request or may be FDA initiated.

Process ends.

Drug sponsor may submit a proposed 

pediatric study request.

No written 

request is 

issued.

Written 

request is 

issued.

Written 

request is 

declined. a

Written 

request is 

accepted.

Written 

request is 

not referred.

Written request 

is referred.

Studies of 

drug are 

finished.

Sponsor submits study reports to FDA 

for pediatric exclusivity determination.

FDA grants

pediatric 

exclusivity.b

Process ends.

Pediatric 

exclusivity 

is denied.

Pediatric 

exclusivity 

is granted.

NIH develops and publishes

a list of drugs in need of 

study in children.

FNIH 

receives

referral 

for study 

of an onpatent 

drug.

NIH 

receives

referral 

for study 

of an offpatent 

drug.

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. 

Page 6 GAO-07-898T
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. 

BPCA Provisions for 

Pediatric Drug Studies 

Declined by Drug Sponsors 

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

Page 7 GAO-07-898T
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. 

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. 

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 

 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. 

Page 8 GAO-07-898T
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 onpatent 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. 

Page 9 GAO-07-898T
Figure 2: Status of Written Requests Issued under BPCA for the Study of On-Patent Drugs, from January 2002 through 

December 2005

Source: GAO.

X Number of applications that pass through decision point

On-patent drugs

denied pediatric 

exclusivity

3

On-patent drugs

granted pediatric 

exclusivity

52

4

Exclusivity determination 

made by FDA through 

December 2005

55

Studies ongoing

through 

December 2005

114

Studies completed and results

submitted to FDA for review 

through December 2005

Written requests

not referred to 

FNIH for funding

32

Written requests

referred to 

FNIH for funding

Studies

not funded 

by FNIH

9

Studies

funded 

by FNIH

0

Written requests

declined by drug 

sponsors

214

On-patent written requests

issued by FDA from January 

2002 through December 2005

173

Written requests

accepted by drug 

sponsors

59

41

9

Exclusivity determination 

pending 

through 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. 

Page 10 GAO-07-898T
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 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. 

Few Off-Patent Drugs 

Have Been Studied 

under BPCA 

 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. 

Page 11 GAO-07-898T
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 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. 

Most Drugs Granted 

Pediatric Exclusivity 

under BPCA Had 

Labeling Changes, but 

the Process for 

Making Changes Was 

Sometimes Lengthy 

 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. 

Page 12 GAO-07-898T
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. 

Page 13 GAO-07-898T
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 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. 

 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.

(290642) Page 14 GAO-07-898T
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