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                                                       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 
approved 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 
deferralof pediatric studies. In addition, the legislation 
provides that the FDA's Pediatric 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 CURRENT 
   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 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 geographicallydispersed; 
or (3) 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 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 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 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, 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 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 already-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 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 processto 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 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.
    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.
    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 andeffectiveness 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 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

            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 on-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.

                       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; [and 
(F)] (F) specimens of the labeling proposed to be used for such 
drug[.], 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 appropriate, 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 [505(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 [505(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--
                  (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 [505(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 [505(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 [Regulations] Pediatric Study 
Requirements.--Notwithstanding any other provision of law, if 
any pediatric study is required [pursuant 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
                          (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 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.
          (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 thereis 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.
    [(B)] (C) The Secretary shall approve a biologics license 
application--* * *

           *       *       *       *       *       *       *