[Congressional Record Volume 149, Number 43 (Tuesday, March 18, 2003)]
[Senate]
[Pages S3897-S3900]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]

      By Mr. DeWINE (for himself, Mrs. Clinton, Mr. Gregg, Mr. Dodd, 
        and Mr. Kennedy):
  S. 650. A bill to amend the Federal Food, Drug, and Cosmetic Act to 
authorize the Food and Drug Administration to require certain research 
into drugs used in pediatric patients; to the Committee on Health, 
Education, Labor, and Pensions.
  Mr. DeWINE. Mr. President, I rise today to talk about a very 
important subject--one that affects parents, doctors, hospitals, nurses 
and our children each and every day. The subject that I am talking 
about is the safety and efficacy of the medicines that doctors give our 
children when they are sick.
  Nearly six years ago, I was astonished to learn that close to 80 
percent of drugs on the market were not tested for use in children--
yet, doctors were prescribing these drugs to our children. Doctors had 
no choice but to prescribe these drugs for children if they thought the 
medicines would be helpful. And, sometimes the medicines did help--
sometimes a child's pain was relieved, or a child would be able to 
breathe easier or digest food better because of the medicines the 
doctors prescribed them. But, even when the drugs do work, an anxious 
feeling remains among doctors and parents about whether these medicines 
are safe for children. How are doctors and parents to know for certain 
which medicines will work if they haven't been tested for safety and 
efficacy in children?
  There are many examples, of situations where drugs have been 
misprescribed for children because doctors simply weren't aware of the 
effects these drugs would have on kids. For example, the drug, 
Neurontin, which is used to treat chronic pain, was given to children 
without being properly tested, and doctors eventually learned they were 
under-dosing children by 50 percent. That means children were suffering 
from pain because they were being under-dosed. They weren't being given 
the proper dose of medication to relieve their pain.
  Another drug, Lithium, which has been prescribed to treat bipolar 
disorder since 1940 was never tested for long-term use in children 
until just a few months ago. This is an example of a drug that doctors 
have been prescribing ``off-label'' for years, and only now we are 
finally getting some evidence of its effect in children. According to 
doctors, the testing of Lithium revealed important information because 
children who suffer from bipolar disorder cycle between mania and 
depression quicker than adults, and they can even have signs of both at 
the same time. Unlike adults, they don't have periods of normalcy. 
Doctors now know that Lithium can be used to treat bipolar disorder in 
children.
  Doctors have taken a chance in prescribing medicines for children. 
Doctors tell parents to cut a pill in half or in quarters so it can be 
given to a child. Doctors use the best information they have to 
determine how much or what kind of medicines to give a child. That is 
all they can do when the medicines children need have not been tested 
for their use.
  Doctors and pediatricians should not be left to guess how much 
medicine our children should receive. And, parents shouldn't have to 
feel anxious or question whether the half a pill that's been ground up 
and put in applesauce will still be effective in treating their child--
or whether it's even safe for their child to take.
  It's been over a year now since the Senate passed and the President 
signed into law the Best Pharmaceuticals for Children's Act. As many of 
my colleagues know, that law has been part of a solution--but just a 
part of a solution--to address the problem I just mentioned. The law 
provides a six-month patent extension to pharmaceutical companies in 
exchange for the testing of medicines in children. And, for as long as 
the bill has been law, the Food and Drug Administration is reporting 
its success in ensuring that more medicines are tested for use in 
children. With the incentive provided by Best Pharmaceuticals, 
companies are seeing the value of studying their drugs in children and 
are applying for the patent extension.
  But, the Best Pharmaceuticals incentive cannot work alone to ensure 
that medicines in children do not go untested. The incentive in the 
Best Act was never intended to work alone. When the Best Act became 
law, there was already a rule on the books that helped ensure that no 
medicine used to treat children, including vaccines or other biologics, 
would go untested. Back in 1997, the Food and Drug Administration 
proposed what is known today as the Pediatric Rule. The Pediatric Rule 
allowed FDA to require that the drugs the agency felt are important for 
children are safe, effective, and properly labeled for children.
  Unfortunately, the Pediatric Rule has come under legal challenge, 
with a District Court ruling just a few months ago stating that FDA 
lacked the statutory authority to require pediatric studies. This was a 
troubling step backward for children's health--a troubling step at a 
time when 75 percent of the medicines on the market still aren't tested 
and labeled for pediatric use. We've made some improvements from the 80 
percent of medicines on the market, but 75 percent is still too much. 
Without the Pediatric Rule, new medicines and biologics coming onto the 
market are not required to be tested for use in children. Congress 
needs to make sure that the FDA continues to have every tool--that 
includes the market incentives and the pediatric rule--available to 
them to ensure that drugs for children are tested for safety and 
efficacy and that they are labeled properly.
  Everyday that a drug manufacturer chooses not to participate in the 
incentive program, the number of medicines

[[Page S3898]]

that go untested for use in children increases. Everyday that we don't 
have the Pediatric Rule, we sacrifice our children's safety. Medicines 
that are used by children should be tested for safety and efficacy. 
That is why Senators Clinton, Gregg, Dodd, and Kennedy and I are 
introducing a bill today--the Pediatric Research Equity Act--that would 
ensure that the Pediatric Rule continues to work alongside the Best 
Act, so that children will remain on safe footing when it comes to the 
testing of the medications they use.

  Congress needs to make sure the Pediatric Rule stays in place, 
because right now, the Pediatric Rule and the Best Act incentive work 
together to ensure that drugs are tested for use in children. As I said 
already, the Best Act was never intended to substitute the rule, but 
rather to reinforce and work with the rule. For example, the Pediatric 
Rule may be invoked in instances where pediatric information is 
essential, but the patent exclusivity is no longer available.
  The Pediatric Rule also applies to biologics, whereas the Best 
Pharmaceuticals does not. A significant portion of therapeutics used in 
children, including many cancer treatments, are biological products 
(products that include a live agent). Because Best Pharmaceuticals does 
not apply to biologics, the Pediatric Rule is the only way to ensure 
pediatric labeling.
  Finally, the Best Pharmaceuticals is voluntary. For any number of 
reasons, including insufficient sales, a manufacturer may choose not to 
conduct the testing necessary to receive additional exclusivity under 
the Best Act. But, just because a drug manufacturer chooses not to 
study the drug in children does not mean that drug is not critical to 
the proper treatment of our children. Without the Pediatric Rule, there 
is no way to guarantee that a drug that is used in the pediatric 
population is tested for children's use.
  With the establishment of the Pediatric Rule and the financial 
incentives of the Best Pharmaceuticals law, there has been a dramatic 
increase in the number of studies that have been undertaken. Let me 
quote from the Government's Response to Plaintiff's Notice of 
Reauthorization of FDA Modernization Act. This is the document that the 
government filed to defend the lawsuit against the Rule: ``These two 
options [the Best Pharmaceuticals for Children Act and the Pediatric 
Rule] have resulted in a number of drugs being labeled for use in 
pediatric populations. As of March 31, 2002, 94 applications containing 
complete or partial pediatric use information had been submitted to the 
agency. Of these 94 applications, 45 are attributable to the statutory 
exclusivity provisions. FDA attributes 48 of the 94 applications to the 
authority of the pediatric rule alone.''
  The bill that my colleagues and I are introducing today would help 
maintain that progress--not erode it. Our bill would provide the FDA 
with the authority it needs to ensure that the medicines children take 
are studied for safety and efficacy. And, our bill would give FDA this 
authority in a way so that it does not conflict with the incentives 
provided in the Best Pharmaceuticals Act.
  Our bill would preserve the waiver and deferral process, so that drug 
companies can get waivers or deferrals for a range of legitimate 
reasons. Drug companies could get a waiver or deferral of studies for 
safety or ethical concerns. A drug company could get a waiver or 
deferral if the pediatric testing would interfere with the drug's 
availability for adults.
  Ultimately, though, our bill would help make certain that children 
are no longer a therapeutic afterthought by ensuring that all new drugs 
are studied for pediatric use at the time a drug comes to market. This 
would put children on a level playing field with adults for the first 
time. Our children deserve no less, and I encourage my colleagues to 
join in support of this legislation.
  I ask unanimous consent that the text of the bill be printed in the 
Record.
  There being no objection, the bill was ordered to be printed in the 
Record, as follows:

                                 S. 650

       Be it enacted by the Senate and House of Representatives of 
     the United States of America in Congress assembled,

     SECTION 1. SHORT TITLE.

       This Act may be cited as the ``Pediatric Research Equity 
     Act of 2003''.

     SEC. 2. RESEARCH INTO PEDIATRIC USES FOR DRUGS AND BIOLOGICAL 
                   PRODUCTS.

       (a) In General.--Subchapter A of chapter V of the Federal 
     Food, Drug, and Cosmetic Act (21 U.S.C. 351 et seq.) is 
     amended by inserting after section 505A the following:

     ``SEC. 505B. RESEARCH INTO PEDIATRIC USES FOR 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 new active ingredient, new indication, 
     new dosage form, new dosing regimen, or new route of 
     administration;

     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 for each age group for which the assessment is 
     required, that are adequate--
       ``(i) to assess the safety and effectiveness of the drug or 
     the biological product 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 is safe and effective.
       ``(B) Similar course of disease or similar effect of drug 
     or biological product.--
       ``(i) In general.--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.
       ``(ii) Extrapolation between age groups.--A study may not 
     be needed in each pediatric age group if data from 1 age 
     group can be extrapolated to another age group.
       ``(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;
       ``(ii) pediatric studies should be delayed until additional 
     safety or effectiveness data have been collected; or
       ``(iii) there is another appropriate reason for deferral; 
     and
       ``(B) the applicant submits to the Secretary--
       ``(i) certification of the grounds for deferring the 
     assessments;
       ``(ii) a description of the planned or ongoing studies; and
       ``(iii) evidence that the studies are being conducted or 
     will be conducted with due diligence and at the earliest 
     possible time.
       ``(4) Waivers.--
       ``(A) Full waiver.--On the initiative of the Secretary or 
     at the request of an applicant, the Secretary shall grant a 
     full waiver, as appropriate, of the requirement to submit 
     assessments for a drug or biological product under this 
     subsection if the applicant certifies and the Secretary finds 
     that--
       ``(i) necessary studies are impossible or highly 
     impracticable (because, for example, the number of patients 
     is so small or the patients are geographically dispersed);
       ``(ii) there is evidence strongly suggesting that the drug 
     or biological product would be ineffective or unsafe in all 
     pediatric age groups; or
       ``(iii) 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 in a substantial number of 
     pediatric patients.

       ``(B) Partial waiver.--On the initiative of the Secretary 
     or at the request of an applicant, the Secretary shall grant 
     a partial waiver, as appropriate, of the requirement to 
     submit assessments for a drug or biological product under 
     this subsection with respect to a specific pediatric age 
     group if the applicant certifies and the Secretary finds 
     that--
       ``(i) necessary studies are impossible or highly 
     impracticable (because, for example, the number of patients 
     in that age group is so small or patients in that age group 
     are geographically dispersed);
       ``(ii) there is evidence strongly suggesting that the drug 
     or biological product would be ineffective or unsafe in that 
     age group;
       ``(iii) the drug or biological product--

       ``(I) does not represent a meaningful therapeutic benefit 
     over existing therapies for pediatric patients in that age 
     group; and
       ``(II) is not likely to be used by a substantial number of 
     pediatric patients in that age group; or

       ``(iv) the applicant can demonstrate that reasonable 
     attempts to produce a pediatric

[[Page S3899]]

     formulation necessary for that age group have failed.
       ``(C) Pediatric formulation not possible.--If a waiver is 
     granted on the ground that it is not possible to develop a 
     pediatric formulation, the waiver shall cover only the 
     pediatric groups requiring that formulation.
       ``(D) 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.
       ``(b) Marketed Drugs and Biological Products.--
       ``(1) In general.--After providing notice in the form of a 
     letter and an opportunity for written response and a meeting, 
     which may include an advisory committee meeting, the 
     Secretary may (by order in the form of a letter) require the 
     holder of an approved application for 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)(2) 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 risks to pediatric patients.
       ``(2) Waivers.--
       ``(A) Full waiver.--At the request of an applicant, the 
     Secretary shall grant a full waiver, as appropriate, of the 
     requirement to submit assessments under this subsection if 
     the applicant certifies and the Secretary finds that--
       ``(i) necessary studies are impossible or highly 
     impracticable (because, for example, the number of patients 
     in that age group is so small or patients in that age group 
     are geographically dispersed); or
       ``(ii) there is evidence strongly suggesting that the drug 
     or biological product would be ineffective or unsafe in all 
     pediatric age groups.
       ``(B) Partial waiver.--At the request of an applicant, the 
     Secretary shall grant a partial waiver, as appropriate, of 
     the requirement to submit assessments under this subsection 
     with respect to a specific pediatric age group if the 
     applicant certifies and the Secretary finds that--
       ``(i) necessary studies are impossible or highly 
     impracticable (because, for example, the number of patients 
     in that age group is so small or patients in that age group 
     are geographically dispersed);
       ``(ii) there is evidence strongly suggesting that the drug 
     or biological product would be ineffective or unsafe in that 
     age group;
       ``(iii)(I) the drug or biological product--

       ``(aa) does not represent a meaningful therapeutic benefit 
     over existing therapies for pediatric patients in that age 
     group; and
       ``(bb) is not likely to be used in a substantial number of 
     pediatric patients in that age group; and

       ``(II) the absence of adequate labeling could not pose 
     significant risks to pediatric patients; or
       ``(iv) the applicant can demonstrate that reasonable 
     attempts to produce a pediatric formulation necessary for 
     that age group have failed.
       ``(C) Pediatric formulation not possible.--If a waiver is 
     granted on the ground that it is not possible to develop a 
     pediatric formulation, the waiver shall cover only the 
     pediatric groups requiring that formulation.
       ``(D) 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.
       ``(3) 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 a 
     related pediatric study under section 505A(c) of this Act or 
     section 409I of the Public Health Service Act (42 U.S.C. 
     284m);
       ``(ii)(I) if the request was made under section 505A(c)--

       ``(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 (42 U.S.C. 284m)--

       ``(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; and

       ``(iii)(I) the Secretary certifies under subparagraph (B) 
     that there are insufficient funds under sections 409I and 499 
     of the Public Health Service Act (42 U.S.C. 284m, 290b) to 
     conduct the study; or
       ``(II) the Secretary publishes in the Federal Register a 
     certification that certifies that--

       ``(aa) no contract or grant has been awarded under section 
     409I or 499 of the Public Health Service Act (42 U.S.C. 284m, 
     290b); and
       ``(bb) not less than 270 days have passed since the date of 
     a certification under subparagraph (B) that there are 
     sufficient funds to conduct the study.

       ``(B) No agreement to request.--Not later than 60 days 
     after determining that no holder will agree to the written 
     request (including a determination that the Secretary has not 
     received a response specified under section 505A(d) of this 
     Act or section 409I of the Public Health Service Act (42 
     U.S.C. 284m), the Secretary shall certify whether the 
     Secretary has sufficient funds to conduct the study under 
     section 409I or 499 of the Public Health Service Act (42 
     U.S.C. 284m, 290b), taking into account the prioritization 
     under section 409I.
       ``(c) Meaningful Therapeutic Benefit.--For the purposes of 
     paragraph (4)(A)(iii)(I) and (4)(B)(iii)(I) of subsection (a) 
     and paragraphs (1)(B)(i) and (2)(B)(iii)(I)(aa) of subsection 
     (b), a drug or biological product shall be considered to 
     represent a meaningful therapeutic benefit over existing 
     therapies if the Secretary estimates that--
       ``(1) if approved, the drug or biological product would 
     represent a significant improvement in the treatment, 
     diagnosis, or prevention of a disease, compared with marketed 
     products adequately labeled for that use in the relevant 
     pediatric population; or
       ``(2) the drug or biological product is in a class of 
     products or for an indication for which there is a need for 
     additional options.
       ``(d) Submission of Assessments.--If a person fails to 
     submit an assessment described in subsection (a)(2), or a 
     request for approval of a pediatric formulation described in 
     subsection (a) or (b), in accordance with applicable 
     provisions of subsections (a) and (b)--
       ``(1) the drug or biological product that is the subject of 
     the assessment or request may be considered misbranded and 
     subject to relevant enforcement action (except that the drug 
     or biological product shall not be subject to action under 
     section 303); but
       ``(2) the failure to submit the assessment or request shall 
     not be the basis for a proceeding--
       ``(A) to withdraw approval for a drug under section 505(e); 
     or
       ``(B) to revoke the license for a biological product under 
     section 351 of the Public Health Service Act (42 U.S.C. 262).
       ``(e) Meetings.--Before and during the investigational 
     process for a new drug or biological product, the Secretary 
     shall meet at appropriate times with the sponsor of the new 
     drug or biological product to discuss--
       ``(1) information that the sponsor submits on plans and 
     timelines for pediatric studies; or
       ``(2) any planned request by the sponsor for waiver or 
     deferral of pediatric studies.
       ``(f) Scope of Authority.--Nothing in this section provides 
     to the Secretary any authority to require a pediatric 
     assessment of any drug or biological product, or any 
     assessment regarding other populations or uses of a drug or 
     biological product, other than the pediatric assessments 
     described in this section.
       ``(g) Orphan Drugs.--Unless the Secretary requires 
     otherwise by regulation, this section does not apply to any 
     drug for an indication for which orphan designation has been 
     granted under section 526.''.
       (b) Conforming Amendments.--
       (1) Section 505(b)(1) of the Federal Food, Drug, and 
     Cosmetic Act (21 U.S.C. 355(b)(1)) is amended in the second 
     sentence--
       (A) by striking ``and (F)'' and inserting ``(F)''; and
       (B) by striking the period at the end and inserting ``, and 
     (G) any assessments required under section 505B.''.
       (2) Section 505A(h) of the Federal Food, Drug, and Cosmetic 
     Act (21 U.S.C. 355a(h)) is amended--
       (A) in the subsection heading, by striking ``Regulations'' 
     and inserting ``Pediatric Research Requirements''; and
       (B) by striking ``pursuant to regulations promulgated by 
     the Secretary'' and inserting ``by a provision of law 
     (including a regulation) other than this section''.
       (3) Section 351(a)(2) of the Public Health Service Act (42 
     U.S.C. 262(a)(2)) is amended--
       (A) by redesignating subparagraph (B) as subparagraph (C); 
     and
       (B) by inserting after subparagraph (A) the following:
       ``(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.''.

     SEC. 3. TECHNICAL AND CONFORMING AMENDMENTS.

       (a) Abbreviated New Drug Application.--Section 505A of the 
     Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a) is 
     amended in subparagraphs (A) and (B) of subsection (b)(2) and 
     subparagraphs (A) and (B) of subsection (c)(2) by striking 
     ``505(j)(4)(B)'' and inserting ``505(j)(5)(B)''.
       (b) Pediatric Advisory Committee.--
       (1) Section 505A(i)(2) of the Federal Food, Drug, and 
     Cosmetic Act (21 U.S.C. 355a(i)(2)) is amended by striking 
     ``Advisory Subcommittee of the Anti-Infective Drugs'' each 
     place it appears.
       (2) Section 14 of the Best Pharmaceuticals for Children Act 
     (42 U.S.C. 284m note; Public Law 107-109) is amended--
       (A) in the section heading, by striking ``PHARMACOLOGY'';
       (B) in subsection (a), by striking ``(42 U.S.C. 217a),'' 
     and inserting (42 U.S.C. 217a) or other appropriate 
     authority,'';

[[Page S3900]]

       (C) in subsection (b)--
       (i) in paragraph (1), by striking ``and in consultation 
     with the Director of the National Institutes of Health''; and
       (ii) in paragraph (2), by striking ``and 505A'' and 
     inserting ``505A, and 505B''; and
       (D) by striking ``pharmacology'' each place it appears and 
     inserting ``therapeutics''.
       (3) Section 15(a)(2)(A) of the Best Pharmaceuticals for 
     Children Act (115 Stat. 1419) is amended by striking 
     ``Pharmacology''.
       (4) Section 16(1)(C) of the Best Pharmaceuticals for 
     Children Act (21 U.S.C. 355a note; Public Law 107-109) is 
     amended by striking ``Advisory Subcommittee of the Anti-
     Infective Drugs''.
       (5) Section 17(b)(1) of the Best Pharmaceuticals for 
     Children Act (21 U.S.C. 355b(b)(1)) is amended in the second 
     sentence by striking ``Advisory Subcommittee of the Anti-
     Infective Drugs''.
       (6) Paragraphs (8), (9), and (11) of section 409I(c) of the 
     Public Health Service Act (42 U.S.C. 284m(c)) are amended by 
     striking ``Advisory Subcommittee of the Anti-Infective 
     Drugs'' each place it appears.

     SEC. 4. EFFECTIVE DATE.

       (a) In General.--This Act and the amendments made by this 
     Act take effect October 17, 2002.
       (b) No Limitation of Authority.--Neither the lack of 
     guidance or regulations to implement this Act or the 
     amendments made by this Act nor the pendency of the process 
     for issuing guidance or regulations shall limit the authority 
     of the Secretary of Health and Human Services under, or defer 
     any requirement under, this Act or those amendments.
                                 ______