19–010

Calendar No. 547

107TH CONGRESS REPORT " SENATE ! 2d Session 107–300

AMENDING THE FEDERAL FOOD, DRUG, AND COSMETIC 

ACT TO REQUIRE LABELING CONTAINING INFORMATION 

APPLICABLE TO PEDIATRIC PATIENTS

OCTOBER 8, 2002.—Ordered to be printed 

Mr. KENNEDY, from the Committee on Health, Education, Labor, 

and Pensions, submitted the following 

R E P O R T 

together with 

ADDITIONAL VIEWS 

[To accompany S. 2394]

The Committee on Health, Education, Labor, and Pensions, to 

which was referred the bill (S. 2394) to amend the Federal Food, 

Drug, and Cosmetic Act to require labeling containing information 

applicable to pediatric patients, having considered the same, reports favorably thereon with an amendment and recommends that 

the bill (as amended) do pass.

CONTENTS 

Page 

I. Purpose and Summary of the Bill ................................................................ 1

II. Background and Need for the Legislation ................................................... 3

III. Legislative History and Committee Action .................................................. 8

IV. Explanation of the Legislation and Committee Views ............................... 10

V. Cost Estimate ................................................................................................. 12

VI. Application of Law to the Legislative Branch ............................................. 12

VII. Regulatory Impact Statement ....................................................................... 12

VIII. Section-by-Section Analysis .......................................................................... 12

IX. Additional Views ............................................................................................ 15

X. Changes in Existing Law .............................................................................. 17

I. PURPOSE AND SUMMARY OF THE BILL

To address a longstanding concern that only a small portion of 

prescription medications on the market have been tested and apVerDate 0ct 09 2002 16:54 Oct 18, 2002 Jkt 019010 PO 00000 Frm 00001 Fmt 6659 Sfmt 6602 E:\HR\OC\SR300.XXX SR300
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proved for use in children, the Food and Drug Administration 

(FDA) proposed its Pediatric Rule in 1997. FDA finalized the Pediatric Rule in 1998, and it became effective in 1999. That rule requires the manufacturers of certain new and marketed drugs and 

biological products to conduct studies and provide adequate labeling for the use of the products in children. The rule is an essential 

complement to the provisions in the Best Pharmaceuticals for Children Act (BPCA, Pub. L. 107–109), which provides a 6–month exclusivity period for completion of requested pediatric studies as 

well as additional mechanisms to assure that drugs are studied 

and appropriately labeled for pediatric uses. The Pediatric Rule is 

under legal challenge in Federal district court and under regulatory review. The committee has approved this legislation to eliminate the uncertainties surrounding the rule. 

1. THE LEGISLATION ‘‘CODIFIES’’ FDA’S PEDIATRIC RULE AND ENSURES

THAT THE RULE REMAINS IN EFFECT

The legislation amends the Federal Food, Drug, and Cosmetic 

Act (FFDCA) by adding a new section 505B, which codifies the essential provisions of FDA’s Pediatric Rule. For example, with respect to drugs and biological products that are not yet approved, 

the legislation provides that each new drug application under section 505 of the FFDCA or biologics license application under section 351 of the Public Health Service Act (PHSA) for a new active 

ingredient, new indication (except for an orphan drug indication), 

new dosage form, new dosing regimen, or new route of administration must contain data adequate to assess the safety and effectiveness of the drug or biological product for its claimed indications, 

and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. With respect 

to drugs and biological products that are already marketed, the legislation allows FDA, having made certain findings and under certain conditions, to require the product manufacturer to submit data 

on safety and effectiveness and dosing and administration, after 

having provided the holder with notice and an opportunity for written response and a meeting. 

Under the legislation, FDA is required to grant a full or partial 

waiver of the pediatric data requirement for a drug or biological 

product for certain reasons, including if necessary studies are impossible or highly impractical; if there is evidence strongly suggesting that the drug or biological product would be ineffective or 

unsafe in all pediatric age groups; or if the drug or biological product does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients, the drug or biological product 

is not likely to be used by a substantial number of pediatric patients, and the absence of adequate labeling would not pose significant risks to pediatric patients. Under the legislation, when the 

Secretary grants a full or partial waiver because there is evidence 

that the drug or biological product would be ineffective or unsafe 

in pediatric populations, the information must be included in the 

labeling for the drug or biological product. 

The legislation provides for meetings with a drug sponsor during 

the investigational new drug process to discuss plans and timelines 

of pediatric studies or requests for waiver or deferral of pediatric 

studies. In addition, the legislation provides that the FDA’s PediVerDate 0ct 09 2002 16:54 Oct 18, 2002 Jkt 019010 PO 00000 Frm 00002 Fmt 6659 Sfmt 6602 E:\HR\OC\SR300.XXX SR300
3

atric Rule, except to the extent it is inconsistent with section 505B, 

shall be considered to implement section 505B. 

2. THE LEGISLATION CLARIFIES THE INTERACTION OF PEDIATRIC RULE

WITH THE PEDIATRIC EXCLUSIVITY PROVISION WHEN APPLIED TO

ALREADY-MARKETED DRUGS

For already-marketed drugs, the legislation requires that, before 

FDA may invoke the Pediatric Rule (if it is applicable), FDA must 

ask the manufacturer to conduct the study voluntarily under section 505A of the FFDCA, which provides for 6 months of market 

exclusivity for completing pediatric studies, or section 409I of the 

PHSA and that the company does not agree or that FDA does not 

receive a response. This requirement is consistent with current 

FDA practice. The legislation also clarifies that it does not change 

the provisions in the BPCA that establish a process at NIH to contract for studies to gather pediatric information. The legislation 

further clarifies that use of the NIH contracting process does not 

preclude FDA from using the Pediatric Rule to require that a manufacturer study an already-marketed drug. 

3. THE LEGISLATION PROVIDES FOR APPROPRIATE ENFORCEMENT OF

THE REQUIREMENT TO SUBMIT TIMELY PEDIATRIC ASSESSMENTS

The legislation provides that a drug or biological product for 

which a pediatric assessment is not filed by the date specified by 

FDA is deemed misbranded and is subject to an injunction or seizure action, but is not subject to criminal proceedings, withdrawal 

of approval as a new drug, or revocation of its approved biologics 

license. 

4. THE LEGISLATION PROVIDES THAT IT DOES NOT ALTER FDA’S CUR- RENT AUTHORITY TO REQUIRE PEDIATRIC OR OTHER SUBPOPULATION STUDIES AND LABELING

The legislation states that section 505B does not affect whatever 

existing authority FDA has to require studies, in addition to those 

required under section 505B, of the safety and effectiveness of 

drugs and biological products in pediatric populations. It also states 

that FDA’s authority, if any, to require studies for specific populations other than the pediatric population shall be exercised under 

the FFDCA as in effect on the day before the date of enactment of 

the legislation. 

II. BACKGROUND AND NEED FOR THE LEGISLATION

Children suffer from many of the same diseases as adults and 

are often treated with the same medicines, yet only about 25 percent of today’s medicines have been studied and labeled for use in 

children. Dosing children based merely on their lower weight is 

often imprecise, since their bodies can metabolize medicines differently than adults. Some drugs may have different adverse side 

effects or toxicities in children than in adults, so estimating dosages for children from dosages found to be safe and effective in 

adults may not be appropriate. The lack of pediatric studies and labeling information may lead to unintended medical errors and 

place children at risk of being under-dosed or over-dosed with 

medication. The lack of age-appropriate formulations (e.g., liquid 

4

form) can also make it difficult to give children and infants prescribed amounts of a needed medication. 

Before 1997, regulatory efforts to address the lack of pediatric 

studies and insufficient labeling information had been largely unsuccessful. In 1979, the FDA first issued a rule requiring specific 

pediatric indications, if any, to be described under the ‘‘Indications 

and Usage’’ section of the label, with pediatric dose information included in the ‘‘Dosage and Administration’’ section. The rule also 

required that recommendations for pediatric use must be based on 

data from adequate and well-controlled studies in the pediatric 

population. The 1979 rule did not successfully encourage the pharmaceutical industry to conduct pediatric studies and appropriately 

label their products for children. 

Accordingly, in 1994, the FDA published a final rule requiring 

drug manufacturers to survey existing data and to determine 

whether it would support pediatric labeling, and if it did, to file a 

supplemental new drug application. FDA’s December 1994 Pediatric Plan sought to encourage the pharmaceutical industry to develop voluntarily pediatric data both during the drug development 

process and after marketing. Neither of these 1994 initiatives sufficiently increased the number of drugs with adequate pediatric labeling. 

In 1997, FDA proposed its Pediatric Rule, which it finalized in 

1998, and which became effective in 1999. The rule requires the 

manufacturers of certain new and marketed drugs and biological 

products to provide adequate labeling for certain uses of the products in children. 

Under FDA’s Pediatric Rule, each new drug application under 

section 505 of the FFDCA or biologics license application under section 351 of the PHSA for a new active ingredient, new indication 

(except indications for which orphan designation has been granted), 

new dosage form, new dosing regimen, or new route of administration must contain certain data. In particular, the application must 

contain data adequate to assess the safety and effectiveness of the 

drug or biological product for its claimed indications in all relevant 

pediatric subpopulations, and to support dosing and administration 

for each pediatric subpopulation for which the drug is safe and effective. 

The rule provides for deferred submission of these data when the 

drug or biological product is ready for approval in adults before pediatric studies are complete or if pediatric studies should be delayed until additional safety and effectiveness data are collected. A 

request for deferral must include certification of the grounds for delaying the studies, a description of the planned or ongoing studies, 

and evidence that the studies are being or will be conducted with 

due diligence and at the earliest possible time. 

Under the rule, FDA may grant a full waiver of the pediatric 

data requirement for a new drug or biological product for 3 reasons: (1) the product does not represent a meaningful therapeutic 

benefit over existing treatments for pediatric patients and it is not 

likely to be used by a substantial number of pediatric patients; (2) 

necessary studies are impossible or highly impractical, because, for 

example, the number of such patients is so small or geographically

dispersed; or (3) there is evidence strongly suggesting that the drug 

or biological product would be ineffective or unsafe in all pediatric 

5

age groups. Partial waivers are available with respect to a particular pediatric age group if any of these 3 reasons applies to that 

age group, or if the applicant can demonstrate that reasonable attempts to produce a pediatric formulation necessary for that age 

group have failed. A drug or biological product for which a full or 

partial waiver is granted because there is evidence that the product 

would be ineffective or unsafe in pediatric populations must be labeled with that information. 

Under the rule, pre-investigation new drug meetings may include 

a discussion of plans for studying the drug or biological product in 

pediatric populations. In addition, end-of-phase 2 meetings during 

the investigational new drug application process must address 

plans to assess pediatric safety and effectiveness, and ‘‘pre-NDA’’ and ‘‘pre-BLA’’ meetings include as a major purpose the identification of the status of ongoing or needed studies adequate to assess 

pediatric safety and effectiveness. 

With respect to an already-marketed drug or biological product 

that is used in a substantial number of pediatric patients or that 

provides a meaningful therapeutic benefit over existing treatments 

for pediatric patients and for which the absence of adequate pediatric labeling could pose significant risks to pediatric patients, the 

rule allows FDA in these compelling circumstances to require the 

product’s manufacturer to submit an application containing data 

adequate to assess whether the drug is safe and effective in pediatric populations for the drug’s approved indications, as well as 

adequate evidence to support dosage and administration in some or 

all pediatric populations, depending on the known or appropriate 

use of the drug in those pediatric subpopulations. FDA may require 

the manufacturer to develop a pediatric formulation for a drug 

product that represents a meaningful therapeutic benefit over existing treatments for pediatric populations for whom a pediatric 

formulation is necessary, unless the manufacturer demonstrates 

that reasonable attempts to produce a pediatric formulation necessary for that age group have failed. 

Under the rule, after notifying the manufacturer and offering the 

manufacturer an opportunity for a written response and a meeting, 

which may include an advisory committee meeting, FDA may issue 

such an order provided FDA finds that the absence of adequate labeling could pose significant risks to pediatric patients and that 

one of two additional conditions holds: (1) the drug or biological 

product is used in a substantial number of pediatric patients for 

the labeled indications, or (2) there is reason to believe that the 

drug or biological product would represent a meaningful therapeutic benefit over existing therapies for pediatric patients for 1 or 

more of the claimed indications. 

Once the conditions necessary to invoke the rule have been met, 

FDA may grant a full waiver of the pediatric data requirement for 

an already-marketed drug or biological product for 2 reasons: (1) 

necessary studies are impossible or highly impractical, because, for 

example, the number of such patients is so small or geographically 

dispersed, or (2) there is evidence strongly suggesting that the drug 

or biological product would be ineffective or unsafe in all pediatric 

age groups. Partial waivers are available with respect to a particular pediatric age group if either of these 2 reasons applies to 

that age group, or if the applicant can demonstrate that reasonable 

6

attempts to produce a pediatric formulation necessary for that age 

group have failed, or if each of the following three reasons applies: 

(1) the product does not represent a meaningful therapeutic benefit 

over existing treatments for patients in that age group, (2) it is not 

likely to be used by a substantial number of patients in that age 

group, and (3) the absence of adequate labeling could not pose significant risks to pediatric patients. A drug or biological product for 

which a full or partial waiver is granted because there is evidence 

that the product would be ineffective or unsafe in pediatric populations must be labeled with that information. 

Under the rule, a drug or biological product for which the manufacturer fails to submit the required supplemental application may 

be considered misbranded or an unapproved new drug or 

unlicenced biologic. The rule also defines ‘‘meaningful therapeutic 

benefit’’ to mean either (1) the drug would represent a significant 

improvement in the treatment, diagnosis, or prevention of a disease, compared to marketed products adequately labeled for that 

use in the relevant pediatric population; or (2) the drug is in a 

class of drugs or for an indication for which there is a need for additional therapeutic options. The rule includes four examples of improvement under the first definition: (1) evidence of increased effectiveness in treatment, prevention, or diagnosis of disease, (2) elimination or substantial reduction of a treatment-limiting drug reaction, (3) documented enhancement of compliance, or (4) evidence of 

safety and effectiveness in a new subpopulation. 

In sum, for new drugs and biological products with indications 

that should be tested in and labeled for children, the Pediatric Rule 

assures that they will be tested in and labeled for children when 

they are approved or, in the case of deferrals, shortly after approval. For already-marketed drugs and biological products, the 

rule gives FDA a means to require that they are tested in and labeled for children when doing so is important for children’s health. 

The Pediatric Rule works in tandem with pediatric exclusivity, 

which Congress enacted as the Better Pharmaceuticals for Children Act, part of the Food and Drug Administration Modernization 

Act of 1997 (Pub. L. 105–115). This act provided a market incentive 

of 6 months of additional exclusivity to drug companies for studies 

of medicines in children. The 6 month exclusivity period is added 

to any patent or exclusivity (such as orphan exclusivity or a 5- or 

3-year Hatch-Waxman exclusivity) on the drug. The exclusivity has 

the nature of the patent or exclusivity that it extends. Congress reauthorized the pediatric exclusivity provision in 2001 in the BPCA. 

In the BPCA, Congress also provided an off-patent research fund 

at the National Institutes of Health (NIH) for the study of off-patent drugs and a process using first the Foundation of the National 

Institutes of Health (Foundation) and then the research fund for 

the study of drugs for which the manufacturers have declined written requests to study the drug under the pediatric exclusivity provision. 

The Pediatric Rule is both broader and narrower than the pediatric exclusivity provision first enacted by Congress in 1997 and reauthorized by the BPCA in 2001. Most significantly, the rule is 

broader than pediatric exclusivity because the rule covers biological 

products while neither the pediatric exclusivity provision nor the 

7

provisions for contracting for pediatric studies at the Foundation 

and at NIH applies to biological products.

In addition, the Pediatric Rule is broader than pediatric exclusivity because it covers subsequent indications and pediatric subpopulations that pediatric exclusivity, with its associated contracting process at the Foundation and NIH, may not. For example, 

if FDA does not include studies of newborns and infants in a written request for a drug under the pediatric exclusivity provision, pediatric exclusivity is generally not available to ensure that the drug 

will be studied for these children, but FDA may use the rule to require studies in those pediatric subpopulations. Moreover, if the pediatric exclusivity provision has been applied to a drug and subsequently the drug’s manufacturer seeks approval for a new indication, pediatric exclusivity is generally not available to ensure that 

the new indication will be studied in children. FDA, however, may 

invoke the rule to require that the new indication is studied. 

The Pediatric Rule is narrower than pediatric exclusivity and its 

associated contracting process at the Foundation and NIH in some 

respects also. For example, the rule may only be used for an indication for which the drug is approved or approval is sought in adults, 

whereas FDA may also use pediatric exclusivity to request pediatric studies of an indication not approved for adult use. In addition, the rule applies only to drugs that will be used by a substantial number of pediatric patients or that will provide a meaningful 

therapeutic benefit for pediatric patients, whereas pediatric exclusivity applies to drugs for which information relating to the use of 

the drug in the pediatric population may produce health benefits 

in that population. 

Finally, for a drug or biological product for which approval is 

now being or will be sought, the rule ensures that children will be 

considered in the process of clinical development of the drug. This 

is true not merely because the rule requires that pediatric assessments must be performed for every new product, but also because 

the rule provides that significant meetings in the clinical development process—pre-investigation new drug meetings, end-of-phase 2 

meetings during the investigational new drug application process, 

and ‘‘pre-NDA’’ and ‘‘pre-BLA’’ meetings—address the need for pediatric studies of a drug. 

Even given these differences in scope, the Pediatric Rule and the 

pediatric exclusivity provision clearly work effectively together to 

ensure that a drug or biological product will be tested in and labeled for children when that is appropriate. When their scopes 

overlap, Congress provided in section 505A(h) of the FFDCA that 

pediatric studies required under the rule can also satisfy the requirements for market exclusivity. There are many drugs for which 

the rule and the incentive have worked together successfully to encourage a drug company to respond affirmatively to FDA’s request 

for pediatric studies. 

But the rule and pediatric exclusivity do not always both apply 

to a drug. It is those instances in which only the Pediatric Rule has 

assured the study and labeling of a drug for children that demonstrate most compellingly the need for the rule. FDA reports that, 

between April 1, 1999, when the rule first became effective, and 

March 31, 2002, 404 new drug applications and supplements fell 

within the scope of the rule. For approximately 266 of these drugs, 

8

manufacturers have submitted, or will be required to submit, studies in one or more pediatric age groups (the remaining drugs received complete waivers, typically for safety reasons in children or 

because the drug’s approved indication is not for a childhood disease). As of March 31, 2002, 94 submitted applications contained 

complete or partial pediatric use information. FDA attributes 48 of 

these submissions to the Pediatric Rule alone. By comparison, FDA 

reports that 57 drugs have been granted exclusivity and 8 have 

been denied exclusivity, with 35 of these drugs currently labeled for 

use in the pediatric population. It is therefore clear that the Pediatric Rule has made a substantial contribution to the slow but 

steady improvement in the pediatric labeling of drugs and biological products that has occurred since 1997, when Congress first provided for pediatric exclusivity and FDA first proposed the Pediatric 

Rule. The legislation assures that this progress will continue. 

III. LEGISLATIVE HISTORY AND COMMITTEE ACTION

On April 29, 2002, Senator Clinton, for herself and Senators 

DeWine, Dodd, Murray, and Kennedy, introduced S. 2394, to 

amend the Federal Food, Drug, and Cosmetic Act to require drug 

labeling that contains information applicable to pediatric patients. 

On August 1, 2002, the committee held an executive session to 

consider S. 2394. Senator Clinton offered an amendment for herself 

and Senators DeWine, Dodd, Gregg, and Frist that the committee 

accepted by unanimous voice vote. Also without objection, the committee directed that technical and conforming changes be made. 

The committee approved S. 2394, as amended, by unanimous voice 

vote. 

A. AMENDMENT ADOPTED BY UNANIMOUS VOICE VOTE DURING

EXECUTIVE SESSION

The committee adopted 1 amendment by unanimous voice vote. 

1. Senator Clinton offered an amendment for herself and Senators DeWine, Dodd, Gregg, and Frist that clarifies the interaction 

of the Pediatric Rule and the pediatric exclusivity provision provided under section 505A of the FFDCA with respect to drugs already approved under section 505 of the FFDCA. 

For already-marketed drugs, the legislation requires that, before 

FDA may invoke the Pediatric Rule (if it is applicable), FDA must 

ask the manufacturer to conduct the study voluntarily under section 505A of the FFDCA, which provides for 6 months of market 

exclusivity for completing pediatric studies, or section 409I of the 

PHSA and that the company does not agree or that FDA does not 

receive a response. This requirement is consistent with current 

FDA practice. The amendment also clarifies that the legislative 

provisions in S. 2394 do not change the provisions in the BPCA 

that establish a process for NIH to contract for studies to gather 

pediatric information. The amendment further clarifies that use of 

the NIH contracting process does not preclude the Secretary from 

using the authorities under the legislation to require that a manufacturer study an already-marketed drug. 

The committee intends that, with respect to a drug already approved under section 505 of the FFDCA, the Secretary seek needed 

pediatric information by first asking the sponsor under section 

9

505A(d) of the FFDCA and section 409I(c)(1) of the PHSA. Only if 

the company either does not agree or does not respond to these requests may the Secretary require the manufacturer to collect the 

needed pediatric information under an assessment for the drug 

under the legislation. Because the written request under section 

505A and the assessment under the legislation should seek the 

same pediatric information, the amendment describes the pediatric 

studies under the written request as being ‘‘related’’ to the assessment under the legislation. The rule, however, may only be invoked 

for assessments in pediatric subpopulations of approved indications 

for the drug. 

The committee intends for FDA to continue to issue broad written requests under section 505A of the FFDCA, section 409I of the 

PHSA, and the authorities of this legislation to capture the full 

scope of pediatric information desired, including for all uses of the 

drug in the pediatric population for which pediatric information 

may produce health benefits in that population. In the unusual circumstances when FDA makes an initial written request for pediatric studies of a drug under section 505A and FDA issues a subsequent request that the drug’s manufacturer accepts, FDA may, 

when appropriate, invoke the rule to require the completion of 

studies included in the first written request and not included in the 

second written request without again invoking section 505A, provided that the criteria specified in the rule are met. 

If the Secretary issues a written request for pediatric studies of 

a drug under section 505A(d) of the FFDCA and the recipient of 

the written request does not agree to conduct the studies, under 

section 505A(d)(4)(B) the Secretary must refer the drug for study 

to the Foundation for the National Institutes of Health established 

under section 499 of the PHSA. If the Secretary issues a written 

request for pediatric studies under section 409I(c) of the PHSA and 

the recipient of the written request does not agree to conduct the 

studies, section 409I(c)(2) requires the Secretary to issue a request 

for contract proposals to conduct the pediatric studies. As adequate 

funding is necessary for the contracting process to work effectively, 

the committee does not intend for the Secretary to issue requests 

for contract proposals without regard to the availability of funding 

needed for those proposals. At the same time, the committee also 

emphasizes that the Secretary should issue written requests under 

section 505A(d) or section 409I without regard for whether there 

are sufficient funds at the Foundation or NIH to fund the studies 

should the recipient of the written request not agree to conduct the 

studies. Therefore, insufficient funding to contract for studies 

under section 409I will not preclude the Secretary from requiring 

pediatric studies under the legislation. 

This amendment adds only one prohibition on the Secretary’s authority to invoke the Pediatric Rule, and that is the prohibition on 

use of the rule before the Secretary has asked the company to conduct the studies voluntarily and the company has either declined 

or failed to respond. Congress has provided several tools, including 

the contracting process, under the BPCA to see to it that needed 

pediatric studies are completed, but Congress never contemplated 

exhaustion of all the tools under BPCA before the Secretary can invoke the Pediatric Rule. This amendment makes clear that, so long 

as FDA has first asked a company to conduct the study of an alVerDate 0ct 09 2002 16:54 Oct 18, 2002 Jkt 019010 PO 00000 Frm 00009 Fmt 6659 Sfmt 6602 E:\HR\OC\SR300.XXX SR300
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ready-marketed drug voluntarily and the company does not agree 

or FDA has not received a response, FDA will then be able to invoke the rule. 

IV. EXPLANATION OF THE LEGISLATION AND COMMITTEE VIEWS

CodificatIon of FDA’s Pediatric Rule 

The legislation amends the FFDCA by adding a new section 

505B to codify FDA’s Pediatric Rule. 

The legislation assures that, when appropriate, new drugs and 

biological products will be studied for safety and effectiveness and 

dosing and administration in children before new active ingredients, new indications, new dosage forms, new dosing regimens, or 

new routes of administration are approved, unless a deferral or 

waiver is obtained. It also gives FDA the express statutory authority to require that already-marketed drugs and biological products 

be tested in children for approved indications if the agency finds, 

after certain conditions are met, that the absence of adequate labeling could pose significant risks to pediatric patients and that either 

(1) the drug or biological product is used for a substantial number 

of pediatric patients for the labeled indications, or (2) there is reason to believe that the drug or biological product would represent 

a meaningful therapeutic benefit over existing therapies for pediatric patents for 1 or more of the claimed indications. 

The legislation allows FDA to conclude that pediatric effectiveness may be extrapolated from studies in adults, usually supplemented with information about pediatric patients, if the course of 

a disease and the effects of a drug are sufficiently similar in adults 

and pediatric patients. The legislation also allows FDA, on its own 

initiative or that of an applicant, to defer submission of these data 

in those circumstances provided for in the Pediatric Rule. 

Under the legislation, FDA may grant a full or partial waiver of 

the pediatric assessment for a drug or biological product under certain conditions, including if (1) necessary studies are impossible or 

highly impractical, because, for example, the number of patients is 

so small or geographically dispersed (2) there is evidence strongly 

suggesting that the drug or biological product would be ineffective 

or unsafe in all pediatric age groups, or (3) the drug or biological 

product does not represent a meaningful therapeutic benefit over 

existing therapies for pediatric patients, the drug or biological 

product is not likely to be used by a substantial number of pediatric patients, and the absence of adequate labeling would not pose 

significant risks to pediatric patients. Because of a technical error, 

these waiver provisions differ from those in the Pediatric Rule. In 

particular, the first two of these conditions are those provided by 

the Pediatric Rule for full waivers for already-marketed drugs and 

biological products (with the third condition mirroring the finding 

FDA must make to require study of the drug or biological product, 

and available as a third condition for a partial waiver), and the Pediatric Rule provides each of these three conditions for a waiver for 

a new drug or biological product, except that the third condition 

lacks the ‘‘absence of adequate labeling’’ prong. The committee intends to correct this technical error before the full Senate acts on 

the legislation. Like the Pediatric Rule, the legislation requires 

that, when the Secretary grants a full or partial waiver because 

11

there is evidence that the drug or biological product would be ineffective or unsafe in pediatric populations, the information must be 

included in the labeling for the drug or biological product. 

The legislation provides that the FDA’s Pediatric Rule, except to 

the extent that it is inconsistent with section 505B, is considered 

to implement section 505B. As an example, the legislation provides 

for meetings with a drug sponsor during the investigational new 

drug process to discuss plans and timelines of pediatric studies or 

requests for waiver or deferral of pediatric studies. The committee 

regards the provisions in the Pediatric Rule regarding meetings to 

implement and be consistent with this provision on meetings in the 

legislation. In addition, the rule requires a pediatric use section in 

a new drug or biologic license application, as well as postmarketing 

reports directed at pediatric use issues. The committee regards 

these and other provisions of the Pediatric Rule to implement and 

be consistent with the legislation. 

The legislation includes no definition of meaningful therapeutic 

benefit, a term that identifies when a drug should be studied in 

children. The term is defined in the Pediatric Rule, however, and 

the committee considers that definition to be consistent with the 

legislation. Although the legislation includes no explicit exemption 

for orphan drugs, the committee views the current exemption in 

the Pediatric Rule for indications with orphan designations to be 

consistent with the legislation. 

Enforcement of FDA’s Pediatric Rule 

The legislation provides that a drug or biological product for 

which a pediatric assessment is not filed by the date specified by 

FDA may be considered misbranded and subject to an injunction 

or seizure action, but is not subject to criminal proceedings nor to 

withdrawal of approval as a new drug or revocation of its approved 

biologics license. 

Under FDA’s Pediatric Rule, a drug for which a pediatric assessment is not timely filed could also be considered an unapproved 

new drug, and a biological product for which a pediatric assessment is not timely filed could also be considered an unlicensed biologic. The committee considers this provision of the Pediatric Rule 

to be inconsistent with the legislation. In addition, unlike the legislation, the rule includes no provision limiting enforcement of the 

rule to injunction or seizure action. Nonetheless, the committee understands that FDA would only enforce the rule using its seizure 

or injunction authorities. This restriction in the legislation therefore has no effect on what actual FDA practice would be under the 

rule, but it does reflect the committee’s concern that neither criminal charges nor withdrawal of a drug from the market be used 

when a drug company violates the requirement to submit timely 

pediatric assessments. 

Current authority for studies in and labeling for pediatric and other 

subpopulations 

The legislation states that section 505B does not affect whatever 

existing authority FDA has to require studies, in addition to those 

required under section 505B, of the safety and effectiveness of 

drugs and biological products in pediatric populations. It also states 

that FDA’s authority, if any, to require studies for specific popuVerDate 0ct 09 2002 16:54 Oct 18, 2002 Jkt 019010 PO 00000 Frm 00011 Fmt 6659 Sfmt 6602 E:\HR\OC\SR300.XXX SR300
12

lations other than the pediatric population shall be exercised under 

the FFDCA as in effect on the day before the date of enactment of 

the legislation. 

The committee wants it to be clear that, with this legislation, it 

takes no view as to the existence or scope of current authority of 

FDA to require pediatric or other subpopulation studies. This limitation neither limits nor expands such authority, if it exists under 

current provisions in the FFDCA. The committee does regard the 

legislation as providing explicit statutory authority for FDA’s current Pediatric Rule, however, except insofar as that rule is inconsistent with this legislation, as described above. 

V. COST ESTIMATE

Due to time constraints the Congressional Budget Office estimate 

was not included in the report. When received by the committee, 

it will appear in the Congressional Record at a later time. 

VI. APPLICATION OF LAW TO THE LEGISLATIVE BRANCH

S. 2394 adds section 505B to the Federal Food, Drug, and Cosmetic Act to further improve the safety and efficacy of both drugs 

and biological products for children. As such, it has no application 

to the legislative branch. 

VII. REGULATORY IMPACT STATEMENT

The legislation repeats the major provisions of existing regulation, with only two exceptions. Although the Pediatric Rule is currently under legal challenge, the rule is currently in force, and 

FDA has affirmed its intention to continue implementing the rule, 

which has been in place since 1999. Therefore, this legislation is 

unlikely to increase the costs associated with the development of 

drugs and biological products. Accordingly, S. 2394 is not expected 

to increase costs to government or to drug manufacturers. 

VIII. SECTION-BY-SECTION ANALYSIS

Sec. 1. Pediatric labeling of drugs and biological products 

Section 1 amends the FFDCA by adding a new section 505B to 

codify FDA’s Pediatric Rule. With respect to drugs and biological 

products that are not yet approved, the legislation provides that 

each new drug application under section 505 of the FFDCA or biologics license application under section 351 of the PHSA for a new 

active ingredient, new indication (except for an orphan drug indication), new dosage form, new dosing regimen, or new route of administration must contain data adequate to assess the safety and 

effectiveness of the drug or biological product for its claimed indications, and to support dosing and administration for each pediatric 

subpopulation for which the product is safe and effective. FDA may 

conclude that pediatric effectiveness may be extrapolated from 

studies in adults, usually supplemented with information about pediatric patients, if the course of a disease and the effects of a drug 

are sufficiently similar in adults and pediatric patients. FDA, on its 

own initiative or that of an applicant, may defer submission of 

these data in certain circumstances, provided the applicant submits 

certain information to FDA. 

13

With respect to drugs and biological products that are already 

marketed, section 1 allows FDA, having made certain findings and 

under certain circumstances, to order the holder of an approved 

new drug application or biologics license application to submit data 

on safety and effectiveness and dosing and administration, after 

having provided the holder with notice and an opportunity for written response and a meeting, which may include an advisory committee meeting. To issue such an order, FDA must find that the absence of adequate labeling could pose significant risks to pediatric 

patients and that one of two additional conditions holds: (1) that 

the drug or biological product is used for a substantial number of 

pediatric patients for the labeled indications, or (2) that there is 

reason to believe that the drug or biological product would represent a meaningful therapeutic benefit over existing therapies for 

pediatric patents for 1 or more of the claimed indications. 

In addition, for already-marketed drugs, section 1 requires that, 

before FDA may invoke the Pediatric Rule (if it is applicable), FDA 

must ask the manufacturer to conduct the study voluntarily under 

section 505A of the FFDCA or section 409I of the PHSA and that 

the company does not agree or that FDA does not receive a response. Section 1 also clarifies that it does not change the provisions in the BPCA that establish a process at NIH to contract for 

studies to gather pediatric information. Section 1 further clarifies 

that use of the NIH contracting process does not preclude FDA 

from using the Pediatric Rule to require that a manufacturer study 

an already-marketed drug. Section 1 provides that the rule may 

only be invoked to study approved indications, even if the written 

request is broader. 

Section 1 provides that a drug or biological product for which a 

pediatric assessment is not filed by the date specified by FDA is 

deemed misbranded and is subject to an injunction or seizure action, but is not subject to criminal proceedings nor to withdrawal 

of approval as a new drug or revocation of its approved biologics 

license. 

Section 1 requires FDA to grant a full waiver of the pediatric 

data requirement for a drug or biological product if (1) necessary 

studies are impossible or highly impractical; (2) there is evidence 

strongly suggesting that the drug or biological product would be ineffective or unsafe in all pediatric age groups; or (3) the drug or biological product does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients, the drug or biological product is not likely to be used by a substantial number of 

pediatric patients, and the absence of adequate labeling would not 

pose significant risks to pediatric patients. Partial waivers are 

available for new drugs and biological products with respect to a 

particular pediatric subpopulation if any of these 3 reasons applies 

to that subpopulation, or if the applicant can demonstrate that reasonable attempts to produce a pediatric formulation necessary for 

that pediatric subpopulation have failed. Under section 1, when the 

Secretary grants a full or partial waiver because there is evidence 

that the drug or biological product would be ineffective or unsafe 

in pediatric populations, the information must be included in the 

labeling for the drug or biological product. 

Section 1 provides for meetings with a drug sponsor during the 

investigational new drug process to discuss plans and timelines of 

14

pediatric studies or requests for waiver or deferral of pediatric 

studies. In addition, section 1 provides that the FDA’s Pediatric 

Rule, except to the extent it is inconsistent with section 505B, shall 

be considered to implement section 505B. 

Finally, section 1 states that section 505B does not affect whatever existing authority FDA has to require studies, in addition to 

those required under section 505B, of the safety and effectiveness 

of drugs and biological products in pediatric populations. It also 

states that FDA’s authority, if any, to require studies for specific 

populations other than the pediatric population shall be exercised 

under the FFDCA as in effect on the day before the date of enactment of the legislation. 

Sec. 2. Technical correction

(15)

IX. ADDITIONAL VIEWS OF SENATORS GREGG AND FRIST

The incentives created by the BPCA and reauthorized in the Best 

Pharmaceuticals for Children Act (P.L. 107–109) to encourage new 

research into the proper use of medicines in children have been tremendously successful. In fact, in its January 2001 Status Report to 

Congress, the Food and Drug Administration (FDA) wrote: ‘‘The pediatric exclusivity provision has done more to generate clinical 

studies and useful prescribing information for the pediatric population than any other regulatory or legislative process to date.’’ As 

of August 31, 2002, FDA had issued 253 written requests for 580 

pediatric studies. In just over four years, the pediatric exclusivity 

incentive has resulted in the submission of pediatric studies for 60 

medicines used to treat a wide range of critical therapeutic areas, 

including juvenile rheumatoid arthritis (in which studies found 

that a higher dose was needed to treat pain in younger children 

than in adults), gastroesophageal reflux, hepatitis B, diabetes, 

heart disease, cancer, kidney disease, obsessive compulsive disorder, and many others. The pediatric testing incentive has also encouraged pharmaceutical companies to develop pediatric formulations (also resulting in better pediatric labeling information) for 

medicines used to treat HIV infection, malaria, seizures, asthma, 

and other serious diseases and conditions. Just as significantly, the 

pediatric exclusivity incentive that is the driving force behind these 

studies has resulted in increased investments in pediatric training 

and research infrastructure to support current and future pediatric 

research. 

The Pediatric Rule cannot, and should not, work alone. Without 

the broader incentives provided by the Best Pharmaceuticals for 

Children Act, the rule alone would not be nearly as effective in encouraging research and providing important information regarding 

the use of pharmaceuticals in children. For example, under the 

rule, the FDA can only require pediatric studies for a claimed indication and cannot require the study of pediatric diseases that differ 

from the claimed or approved indication. For example, juvenile 

rheumatoid arthritis is a different disease than osteoarthritis and 

rheumatoid arthritis in adults. Therefore, if those adult indications 

are the only approved or claimed indications, the rule may not be 

invoked to encourage testing for children with the juvenile rheumatoid arthritis. Other diseases and infections that affect 

newborns and other pediatric populations but not adults include: 

bronchopulmonary dysplasia, croup, and bronchiolitis. While certain types of cancer affect adults but not children, medicines used 

to treat such adult cancers may prove to be promising treatments 

for different cancers that uniquely affect children (such as Wilms 

tumor and neuroblastoma). 

Earlier this year, the pediatric exclusivity incentive was reauthorized with provisions to address off-patent drugs and certain onVerDate 0ct 09 2002 16:54 Oct 18, 2002 Jkt 019010 PO 00000 Frm 00015 Fmt 6604 Sfmt 6604 E:\HR\OC\SR300.XXX SR300
16

patent drugs for which written requests are declined. The bipartisan support that Congress and two administrations have shown 

for the pediatric testing incentive makes clear that FDA should 

continue its policy (as stated in the preamble to the rule) of only 

invoking the Pediatric Rule in ‘‘compelling circumstances’’ and 

should continue to grant deferrals, as appropriate, rather than 

allow the Pediatric Rule’s testing mandate to delay the availability 

of new therapies in adults.

BILL FRIST. 

JUDD GREGG.

(17)

X. CHANGES IN EXISTING LAW

In compliance with rule XXVI paragraph 12 of the Standing 

Rules of the Senate, the following provides a print of the statute 

or the part or section thereof to be amended or replaced (existing 

law proposed to be omitted is enclosed in black brackets, new matter is printed in italic, existing law in which no change is proposed 

is shown in roman): 

* * * * * * *

FEDERAL FOOD, DRUG, AND COSMETIC ACT 

* * * * * * *

NEW DRUGS

SEC. 505. (a) No person shall introduce or deliver for introduction 

into interstate commerce any new drug, unless an approval of an 

application filed pursuant to subsection (b) or (j) is effective with 

respect to such drug. 

(b)(1) Any person may file with the Secretary an application with 

respect to any drug subject to the provisions of subsection (a). Such 

persons shall submit to the Secretary as a part of the application 

(A) full reports of investigations which have been made to show 

whether or not such drug is safe for use and whether such drug 

is effective in use; (B) a full list of the articles used as components 

of such drug; (C) a full statement of the composition of such drug; 

(D) a full description of the methods used in, and the facilities and 

controls used for, the manufacture, processing, and packing of such 

drug; (E) such samples of such drug and of the articles used as 

components thereof as the Secretary may require; øand (F)¿ (F)

specimens of the labeling proposed to be used for such drugø.¿, and 

(G) any assessments required under section 505B. The applicant 

shall file with the application the patent number and the expiration date of any patent which claims the drug for which the applicant submitted the application or which claims a method of using 

such drug and with respect to which a claim of patent infringement 

could reasonably be asserted if a person not licensed by the owner 

engaged in the manufacture use, or sale of the drug. If an application is filed under this subsection for a drug and a patent which 

claims such drug or a method of using such drug is issued after the 

filing date but before approval of the application, the applicant 

shall amend the application to include the information required by 

the preceding sentence. Upon approval of the application, the Secretary shall publish information submitted under the two preceding 

sentences. The Secretary shall, in consultation with the Director of 

the National Institutes of Health and with representatives of the 

drug manufacturing industry, review and develop guidance, as apVerDate 0ct 09 2002 16:54 Oct 18, 2002 Jkt 019010 PO 00000 Frm 00017 Fmt 6604 Sfmt 6604 E:\HR\OC\SR300.XXX SR300
18

propriate, on the inclusion of women and minorities in clinical 

trials required by clause (A). 

* * * * * * *

SEC. 505A. [21 U.S.C. 355a] PEDIATRIC STUDIES OF DRUGS. 

(a) DEFINITIONS.— ***

(b) MARKET EXCLUSIVITY FOR NEW DRUGS.—If, prior to approval 

of an application that is submitted under section 505(b)(1), the Secretary determines that information relating to the use of a new 

drug in the pediatric population may produce health benefits in 

that population, the Secretary makes a written request for pediatric studies (which shall include a timeframe for completing such 

studies), and such studies are completed within any such timeframe and the reports thereof submitted in accordance with subsection (d)(2) or accepted in accordance with subsection (d)(3)—

(1)(A)(i) * * *

* * * * * * *

(2)(A) if the drug is the subject of—

(i) a listed patent for which a certification has been submitted under subsection (b)(2)(A)(ii) or (j)(2)(A)(vii)(II) of 

section 505 and for which pediatric studies were submitted 

prior to the expiration of the patent (including any patent 

extensions); or 

(ii) a listed patent for which a certification has been submitted under subsections (b)(2)(A)(iii) or (j)(2)(A)(vii)(III) of 

section 505, 

the period during which an application may not be approved under 

section 505(c)(3) or section ø505(j)(4)(B)¿ shall be extended by a period of six months after the date the patent expires (including any 

patent extensions); or 

(B) if the drug is the subject of a listed patent for which a certification has been submitted under subsection (b)(2)(A)(iv) or 

(j)(2)(A)(vii)(IV) of section 505, and in the patent infringement litigation resulting from the certification the court determines that the 

patent is valid and would be infringed, the period during which an 

application may not be approved under section 505(c)(3) or section 

ø505(j)(4)(B)¿ shall be extended by a period of six months after the 

date the patent expires (including any patent extensions). 

* * * * * * *

(c) MARKET EXCLUSIVITY FOR ALREADY-MARKETED DRUGS.—If the 

Secretary determines that information relating to the use of an approved drug in the pediatric population may produce health benefits in that population and makes a written request to the holder 

of an approved application under section 505(b)(1) for pediatric 

studies (which shall include a timeframe for completing such studies), the holder agrees to the request, the studies are completed 

within such timeframe, and the reports thereof submitted in accordance with subsection (d)(2) or accepted an in accordance with 

subsection (d)(3)—

(1)(A)(i) * * *

* * * * * * *

(2)(A) if the drug is the subject of—

19

(i) a listed patent for which a certification has been submitted under subsection (b)(2)(A)(ii) or (j)(2)(A)(vii)(II) of 

section 505 and for which pediatric studies were submitted 

prior to the expiration of the patent (including any patent 

extensions); or 

(ii) a listed patent for which a certification has been submitted under subsection (b)(2)(A)(iii) or (j)(2)(A)(vii)(III) of 

section 505, 

the period during which an application may not be approved under 

section 505(c)(3) or section ø505(j)(4)(B)¿ 505(j)(5)(B) shall be extended by a period of six months after the date the patent expires 

(including any patent extensions); or 

(B) if the drug is the subject of a listed patent for which a 

certification has been submitted under subsection (b)(2)(A)(iv) 

or (j)(2)(A)(vii)(IV) of section 505, and in the patent infringement litigation resulting from the certification the court determines that the patent is valid and would be infringed, the period during which an application may not be approved under 

section 505(c)(3) or section ø505(j)(4)(B)¿ 505(j)(5)(B) shall be 

extended by a period of six months after the date the patent 

expires (including any patent extensions). 

* * * * * * *

(h) RELATIONSHIP TO øREGULATIONS¿ PEDIATRIC STUDY REQUIREMENTS.—Notwithstanding any other provision of law, if any pediatric study is required øpursuant to regulations promulgated by 

the Secretary¿ by a provision of law (including a regulation) other 

than this section and such study meets the completeness, timeliness, and other requirements of this section, such study shall be 

deemed to satisfy the requirement for market exclusivity pursuant 

to this section. 

* * * * * * *

SEC. 505B. PEDIATRIC LABELING OF DRUGS AND BIOLOGICAL PRODUCTS. 

(a) NEW DRUGS AND BIOLOGICAL PRODUCTS.—

(1) IN GENERAL.—A person that submits an application (or 

supplement to an application)—

(A) under section 505 for a new active ingredient, new indication, new dosage form, new dosing regimen, or new 

route of administration; or 

(B) under section 351 of the Public Health Service Act (42 

U.S.C. 262) for a biological product license; 

shall submit with the application the assessments described in 

paragraph (2). 

(2) ASSESSMENTS.—

(A) IN GENERAL.—The assessments referred to in paragraph (1) shall contain data, gathered using appropriate 

formulations, that are adequate—

(i) to assess the safety and effectiveness of the drug, 

or the biological product licensed under section 351 of 

the Public Health Service Act (42 U.S.C. 262), for the 

claimed indications in all relevant pediatric subpopulations; and 

20

(ii) to support dosing and administration for each 

pediatric subpopulation for which the drug, or the biological product licensed under section 351 of the Public 

Health Service Act (42 U.S.C. 262), is safe and effective. 

(B) SIMILAR COURSE OF DISEASE OR SIMILAR EFFECT OF

DRUG OR BIOLOGICAL PRODUCT.—If the course of the disease 

and the effects of the drug are sufficiently similar in adults 

and pediatric patients, the Secretary may conclude that pediatric effectiveness can be extrapolated from adequate and 

well-controlled studies in adults, usually supplemented 

with other information obtained in pediatric patients, such 

as pharmacokinetic studies. 

(3) DEFERRAL.—On the initiative of the Secretary or at the request of the applicant, the Secretary may defer submission of 

some or all assessments required under paragraph (1) until a 

specified date after approval of the drug or issuance of the license for a biological product if—

(A) the Secretary finds that—

(i) the drug or biological product is ready for approval for use in adults before pediatric studies are 

complete; or 

(ii) pediatric studies should be delayed until additional safety or effectiveness data have been collected; 

and 

(B) the applicant submits to the Secretary—

(i) a certified description of the planned or ongoing 

studies; and 

(ii) evidence that the studies are being conducted or 

will be conducted with due diligence. 

(b) MARKETED DRUGS AND BIOLOGICAL PRODUCTS.—

(1) IN GENERAL.—After providing notice and an opportunity 

for written response and a meeting, which may include an advisory committee meeting, the Secretary may by order require the 

holder of an approved application relating to a drug under section 505 or the holder of a license for a biological product under 

section 351 of the Public Health Service Act (42 U.S.C. 262) to 

submit by a specified date the assessments described in subsection (a) if the Secretary finds that—

(A)(i) the drug or biological product is used for a substantial number of pediatric patients for the labeled indications, and 

(ii) the absence of adequate labeling could pose significant risks to pediatric patients; or 

((B)(i) there is reason to believe that the drug or biological product would represent a meaningful therapeutic benefit over existing therapies for pediatric patients for 1 or 

more of the claimed indications; and 

(ii) the absence of adequate labeling could pose significant risk to pediatric patients. 

(2) RELATIONSHIP TO OTHER PEDIATRIC PROVISIONS.—

(A) NO ASSESSMENT WITHOUT WRITTEN REQUEST.—No assessment may be required under paragraph (1) for a drug 

21

subject to an approved application under section 505 unless—

(i) the Secretary has issued a written request for related pediatric studies under section 505A(d) or section 

409I of the Public Health Service Act; and 

(ii)(I) if the request was made under section 

505A(d)—

(aa) the recipient of the written request does not 

agree to the request; or 

(bb) the Secretary does not receive a response as 

specified under section 505A(d)(4)(A); or 

(II) if the request was made under section 409I of the 

Public Health Service Act—

(aa) the recipient of the written request does not 

agree to the request; or 

(bb) the Secretary does not receive a response as 

specified under section 409I(c)(2) of that Act. 

(B) NO EFFECT ON OTHER AUTHORITY.—Nothing in this 

subsection shall be construed to alter any requirement 

under section 505A(d)(4) or section 409I of the Public 

Health Service Act. Subject to paragraph (2)(A), nothing in 

this subsection, section 505A(d)(4), or section 409I or 499 of 

the Public Health Service Act shall be construed to preclude 

the Secretary from exercising the authority of the Secretary 

under this subsection. 

(c) DELAY IN SUBMISSION OF ASSESSMENTS.—If a person delays 

the submission of assessments relating to a drug or biological product beyond a date specified in subsection (a) or (b)—

(1) the drug of biological product—

(A) shall be deemed to be misbranded; 

(B) shall be subject to action under sections 302 and 304; 

and 

(C) shall not be subject to action under section 303; and 

(2) the delay shall not be the basis for a proceeding to withdraw approval for a drug under section 505(e) or revoke the license for a biological product under section 351 of the Public 

Health Service Act (42 U.S.C. 262). 

(d) WAIVERS.—

(1) FULL WAIVER.—At the request of an applicant, the Secretary shall grant a full waiver, as appropriate, of the requirement to submit assessments under subsection (a) or (b) if—

(A) necessary studies are impossible or highly impracticable; 

(B) there is evidence strongly suggesting that the drug or 

biological product would be ineffective or unsafe in all pediatric age groups; or 

(C)(i) the drug or biological product—

(I) does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients; and 

(II) is not likely to be used for a substantial number 

of pediatric patients; and 

(ii) the absence of adequate labeling would not pose significant risks to pediatric patients. 

22

(2) PARTIAL WAIVER.—At the request of an applicant, the Secretary shall grant a partial waiver, as appropriate, of the requirement to submit assessments under subsection (a) with respect to a specific pediatric subpopulation if— (A) any of the grounds stated in paragraph (1) applies to 

that subpopulation; or 

(B) the applicant demonstrates that reasonable attempts 

to produce a pediatric formulation necessary for that subpopulation have failed. 

(3) LABELING REQUIREMENT.—If the Secretary grants a full or 

partial waiver because there is evidence that a drug or biological product would be ineffective or unsafe in pediatric populations, the information shall be included in the labeling for the 

drug or biological product. 

(e) MEETINGS.—The Secretary shall meet at appropriate times in 

the investigational new drug process with the sponsor to discuss 

background information that the sponsor shall submit on plans and 

timelines for pediatric studies, or any planned request for waiver or 

deferral of pediatric studies. 

* * * * * * *

PUBLIC HEALTH SERVICES ACT 

* * * * * * *

SEC. 351. (a)(1) No person shall introduce or deliver for introduction into interstate commerce any biological product unless—*** (2)(A) The Secretary shall establish, by regulation, requirements 

for the approval, suspension, and revocation of biologics licenses.

(B) PEDIATRIC STUDIES.—A person that submits an application 

for a license under this paragraph shall submit to the Secretary as 

part of the application any assessments required under section 505B 

of the Federal Food, Drug, and Cosmetic Act. 

ƒ(B)≈ (C) The Secretary shall approve a biologics license application—***

* * * * * * *

Æ