[Congressional Record Volume 149, Number 110 (Wednesday, July 23, 2003)]
[Senate]
[Pages S9811-S9819]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]
PEDIATRIC RESEARCH EQUITY ACT OF 2003
Mr. DeWINE. Mr. President, I ask unanimous consent the Senate proceed
to the immediate consideration of calendar 183, S. 650.
The PRESIDING OFFICER. The clerk will report the bill by title.
The legislative clerk read as follows:
A bill (S. 650) 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.
There being no objection, the Senate proceeded to consider the
bill which had been reported from the Committee on Health, Education,
Labor, and Pensions, with amendments, as follows:
[Strike the part shown in black brackets and insert the
part shown in italic.]
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 S9812]]
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.''.] 526.
``(h) Integration With Other Pediatric Studies.--The
authority under this section shall remain in effect so long
as an application subject to this section may be accepted for
filing by the Secretary on or before the date specified in
section 505A(n).''.
(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.
[[Page S9813]]
(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,'';
(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.
Mr. DeWINE. Mr. President, I rise this evening in support of the
passage of this bill, the pediatric rule. Passage of this bill will be
a very important step in protecting the health of our children. This
bill will help keep the pediatric rule in place to help ensure the
drugs we give our children when they are sick are actually tested for
use by our children. The tragic reality is there are medicines on the
market today that are being used by and prescribed for our Nation's
children that are oftentimes not being tested for their use. It has
been that way for years and years.
For many years, doctors have had to take a chance when prescribing
medicines for our kids. Doctors have literally had to tell parents to
cut the pill in half or in quarters to be given to a child. The doctors
have used the best information they have to literally guess how much
medicine to give a child. That is all they could do with the medicines;
they have had to guess.
Quite frankly, these medicines have been overprescribed,
underprescribed, or maybe not prescribed at all when they should have
been prescribed. For example, recently the drug Paxil, which is an
antidepressant, has been prescribed without being tested in children at
all. Many people have heard of this drug. Many people have heard of the
beneficial effects for adults with anxiety and panic disorders. What
people did not know, what doctors did not know, was what we have
recently found out. Recently the British Government has warned doctors
to stop prescribing this drug for children, warning that the medicine
increased the risk of suicide or suicidal thinking among children with
depression. This action, in turn, spurred the FDA to conduct its own
investigation into the safety of this drug for younger patients,
resulting in a similar warning to physicians here in the United States:
Don't prescribe this drug for children.
That is just one example. We have page after page of examples of
drugs that have been prescribed to children in the past and once we
then tested them, once the protocols were done, the testing was done,
lo and behold, we found they were more effective for children than we
thought. Sometimes they were not effective, sometimes the
prescriptions, the amount, the dosage that had been used was too much,
sometimes not enough.
The facts are these. As we all know, children are not just miniature
adults. You can't just take the weight and just reduce the dosage. Kids
react differently. That is why it is so important to have the testing
done. Yet when Senator Chris Dodd and I first started on this cause, 5
or 6 years ago, 80 percent of the drugs that came on the market had
never been tested for children at all.
It has been over a year now since this Senate passed and the
President signed into law the Best Pharmaceuticals for Children Act.
The Best Act was a bill that followed the Better Pharmaceuticals for
Children Act, which we passed a few years before that. That law, the
Best Pharmaceuticals for Children Act, was part of the solution, just
part of the solution to address the problem of getting medicines tested
for use by children.
That law provides, as its predecessor bill did, a 6-month patent
extension to pharmaceutical companies in exchange for the testing of
medicines in children. That was a voluntary law and it has worked
pretty well. For as long as the bill has been law--its predecessor was
law--the Food and Drug Administration reported success in ensuring that
more medicines are tested for use in children. With this economic
incentive by this Best Pharmaceutical and Better Pharmaceutical bill in
place, companies are seeing the value of studying their drugs in
children and are applying for the patent extension, and children are
benefiting.
But the Best Pharmaceuticals incentive cannot work alone. It was
never intended to work alone to ensure that medicines for children are
properly tested for their use. In order to ensure that no medicines
needed to treat children, including vaccines or other biologics, would
go untested, the FDA, in 1997, proposed what is known as the Pediatric
Rule, a companion rule. The Pediatric Rule allowed the FDA to require
that drugs deemed important for children be tested for their safety,
for their effectiveness, and that they be properly, then, labeled for
children.
Unfortunately--and this is what brings us to the Senate floor tonight
to consider this bill--the Pediatric Rule came under legal challenge
and was, in fact, overturned in court in October 2002, last year, by a
district court. That court ruled that the FDA lacked the statutory
authority to require pediatric studies.
What the court said was it was incumbent upon Congress to fix it.
That is why we are here tonight. This was a troubling step backward for
children's health, considering that today 75 percent of the medicines
on the market still, even with the Better Pharmaceutical bill and the
Best Pharmaceutical bill, still 75 percent of the medicines on the
market today are not tested and labeled for pediatric use.
Without the Pediatric Rule in place, without the necessary authority
provided to the FDA, new medicines and biologics coming onto the market
are not required to be tested for use in kids. Since that court
decision on October 17, 2002, the FDA has indicated that over 300
medicines either have applications pending or incomplete studies
pending, and that unless the Pediatric Rule stays in place these will
all be lost. Many more, hundreds more will be lost in the future.
Pediatricians will not know how to prescribe these drugs in the future
or whether to prescribe them at all.
That is why Senator Clinton, Senator Dodd, and myself introduced the
bill that we hope to pass tonight. It is a bill that would codify a
significant piece of the Pediatric Rule to assure that it stays in
place and ensures that children will remain on safe footing when it
comes to the testing of the medications that they use.
Furthermore, we need to keep the Pediatric Rule in place right now
because the Pediatric Rule and incentives work together to ensure that
drugs are tested for use in children.
The Best Pharmaceuticals for Children Act, as I said already, was
never intended to be a substitute for 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 incentive is no longer available.
The Pediatric Rule also applies to biologics, whereas the Best
Pharmaceutical bill does not. A significant portion of therapeutics
used in children, including many cancer treatments or biological
products--by that, of course, we mean products that include a live
agent. Because the Best Pharmaceutical law does not apply to biologics,
the Pediatric Rule is the only way to ensure proper and effective
pediatric labeling.
Finally, the Best Pharmaceutical Act is voluntary. For any number of
reasons, including insufficient sales, a manufacturer simply may choose
to
[[Page S9814]]
not conduct the necessary testing to receive additional exclusivity
under the ``Best'' law, and when that happens and the drug is not
tested for kids, children are the losers. But just because a drug
manufacturer chooses not to study the drug in children does not mean
that the drug is not critical to the proper care of your children and
my children or grandchildren. Without the Pediatric Rule that is in
front of us today, 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 Pharmaceutical law, which will go with this,
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 the Government filed to defend the lawsuit against the
rule.
These two options--Best Pharmaceuticals for Children Act
and the Pediatric Rule--have resulted in a number of drugs
being labeled for use in pediatric applications. As of March
31, 2001, 94 applications containing complete or partial
pediatric use and information have been submitted to the
agency. Of these 94 applications, 45 are attributable to the
statutory exclusivity provision. FDA attributes 48 of the 94
applications to the authority of the pediatric rule alone.
So you can see how the two must work together, how important the rule
is. Our legislation is a step toward assuring this progress that we
have made so far will not erode. Our bill, as amended, provides that
the FDA may only impose the pediatric study requirement for already-
marketed drugs when the pediatric exclusivity incentive provisions fail
to yield necessary pediatric information. This means that for already-
marketed drugs, drugs that the FDA has already approved and are already
on the drugstore shelf, before FDA can require a company to study the
drug for use in children, the incentive provisions of the Best
Pharmaceuticals law have to be used first. So the drug manufacturer has
to choose to use the incentive provisions first, before FDA can invoke
the pediatric study requirement.
Our bill also preserves the waiver and deferral process so that drug
companies can get waivers or deferrals for a range of legitimate
reasons. Waivers are a simple concept.
Drugs, such as those used to treat Alzheimer's disease--those drugs
that would not be used in children at all--obviously should not be
tested for use in children. Those drug manufacturers would be allowed
to waive the pediatric drug study requirement.
Deferrals are similar. For drug manufacturers who require additional
time to complete the drug study or need to get additional information
in the adult population before beginning to study the drug in children
can, in consultation with the FDA, defer the pediatric drug studies
until a later date.
Again, I am very pleased that my colleagues have agreed to pass our
bill. It is a vital step toward ensuring that children are no longer a
therapeutic afterthought.
Our bill puts children on a level playing field with adults for the
first time.
Before I yield the floor, I would like to take this opportunity to
thank the many people who have worked diligently to draft this bill and
to help get it passed. I would like to thank Majority Leader Frist and
Senators Clinton, Dodd, Gregg, Kennedy, and Murray for their leadership
on this issue. Without their support, this bill would not be a reality.
I would also like to thank Abby Kral of my staff for her dedication
and hard work on this issue--she spent an unbelievable amount of time
on it--as well as Christina Ho from Senator Clinton's Staff, Ben
Berwick with Senator Dodd, Vince Ventimiglia with Senator Gregg's
Staff, and David Dorsey with Senator Kennedy.
Finally, I would like to recognize two groups that provided my staff
and the staff of the HELP Committee with invaluable comments and
insights--the American Academy of Pediatrics and the Elizabeth Glaser
Pediatric AIDS Foundation.
Thank you all for your efforts and commitment to protecting our
children's health and safety.
Mr. KENNEDY. Mr. President, this important bill guarantees that drugs
and biological products used for children are tested and labeled for
children. It helps assure that the miracle cures of today can be
administered to our children in safe and effective ways.
I commend Senators Gregg, Clinton, DeWine, and Dodd for their
effective and tireless leadership to see this important legislation
through the Senate. And it is endorsed by the American Academy of
Pediatrics, the Elizabeth Glaser Pediatric AIDS Foundation, the March
of Dimes, and many other organizations dedicated to children's health.
Under this legislation, drug companies will be required to prove that
their drugs and biological products are safe and effective for their
intended use in children. For too long, drug companies have tested
their products only in adults. For years, companies only rarely tested
their drugs in children, unless the drug's use was for a juvenile
disease. For other drugs, the label simply said that the product had
not been shown to be safe and effective in children. To use such drugs
on our children was a medical gamble.
Fortunately, that practice began to change 6 years ago. In 1997,
Congress authorized 6 months of ``pediatric exclusivity''--6 months of
additional life of a drug patent if the company had studied the drug in
children. The extra patent protection was a valuable economic incentive
for drug companies to study their drugs on children, and it has been
very successful in achieving that goal.
In 1998, FDA issued its Pediatric Rule, which allowed the agency to
require a drug company to test and label certain drugs for children.
The patent exclusivity can be used once to study a drug. But the FDA
rule can be used more than once, if needed, such as when the studies
requested under exclusivity do not include studies in infants or
newborns. In some cases, studies in older children are needed before
studies can even be designed for younger children and newborn infants.
The rule can be used to require testing for biological products,
which are not eligible for the extra patent exclusivity. The rule can
also be used when a drug company decides not to seek extra patent
exclusivity and does not study a drug in children.
Unfortunately, a Federal district court held that FDA does not have
the statutory authority to issue the Pediatric Rule. Although the
American Academy of Pediatrics and the Elizabeth Glaser Pediatric AIDS
Foundation are appealing this decision, and we hope for their quick
success, the Senate has now passed this legislation to correct the
situation.
With this legislation, the essential protections of the rule will be
codified in law: There will be a presumption that newly approved
applications for new active ingredients, new indications, new dosage
forms, new dosing regimens, or new routes of administration for drugs
and biological products will include assessments of safety and
effectiveness for all relevant pediatric subpopulations. These
assessments will support dosing and administration using a pediatric
formulation for all pediatric subpopulations in which the product is
safe and effective. This will be a huge step forward for children, and
will put them on an equal footing with adults.
In addition, many products already on the market have meaningful
therapeutic benefit to children or may be used for a substantial number
of children. However, the absence of adequate labeling in these
products poses significant risks to pediatric patients. This
legislation will allow FDA to require such products to be studied in
children for its approved indication. The bill requires that FDA must
first provide an opportunity for these studies to be conducted under
the provisions of the Best Pharmaceuticals for Children Act. However,
if a product's manufacturer does not agree promptly to perform such
studies voluntarily, and if funds are not sufficient so that the NIH or
the Foundation for the NIH does not contract or issue a grant for
conduct of the studies within a set period of time, FDA may invoke the
authority in this legislation to require the studies. Although FDA
never used this authority under its Pediatric Rule, we expect FDA to
use it as necessary to ensure that drugs and biological products that
are already approved are studied in children when other mechanisms to
get them studied fail.
[[Page S9815]]
This legislation, with the managers' amendment, provides FDA with
clear enforcement authority to bring a seizure or injunction action
when a company fails to submit a required pediatric assessment. That
failure alone will make the drug or biological product misbranded.
This legislation, with the managers' amendment, clarifies that
assessments required under FDA's Pediatric Rule that have not yet been
submitted to FDA, whether deferred until after approval or not, are
assessments required under this legislation. The legislation therefore
ensures that hundreds of assessments that FDA required under its rule
will be completed for the benefit of the Nation's children.
Although this legislation is a giant step forward for children, I
can't help but express my disappointment that its requirements are tied
to the pediatric exclusivity provision that sunsets in 2007. Adults are
guaranteed that new drugs will be reviewed for safety and effectiveness
for them before they are approved by the FDA. Our Nation's children
deserve no less. They should not have to come back in 4 years to plead
for the right to safe and effective medicines.
Again, I commend my colleagues for reaching bipartisan agreement on
this important initiative for children. I urge the House to act
promptly to pass this bill so that children may quickly be protected by
this legislation.
Mr. DeWINE. Mr. President, I ask unanimous consent that the committee
amendment be agreed to, the Gregg amendment be agreed to, that the
bill, as amended, be read a third time and passed, the motion to
reconsider be laid upon the table, and that any statements and
colloquies relating to the bill be printed in the Record.
The PRESIDING OFFICER. Without objection, it is so ordered.
The committee amendment was agreed to.
The amendment (No. 1360) was agreed to, as follows:
amendment no. 1360
On page 14, line 18, after ``misbranded'', insert ``solely
because of that failure''.
On page 19, strike lines 5 and 6 and insert the following:
(a) In General.--Subject to subsection (b), this Act and
the amendments made by this Act take effect on the date of
enactment of this Act.
(b) Applicability to New Drugs and Biological Products.--
(1) In general.--Subsection (a) of section 505B of the
Federal Food, Drug, and Cosmetic Act (as added by section 2)
shall apply to an application described in paragraph (1) of
that subsection submitted to the Secretary of Health and
Human Services on or after April 1, 1999.
(2) Waivers and deferrals.--
(A) Waiver or deferral granted.--If, with respect to an
application submitted to the Secretary of Health and Human
Services between April 1, 1999, and the date of enactment of
this Act, a waiver or deferral of pediatric assessments was
granted under regulations of the Secretary then in effect,
the waiver or deferral shall be a waiver or deferral under
subsection (a) of section 505B of the Federal Food, Drug, and
Cosmetic Act, except that any date specified in such a
deferral shall be extended by the number of days that is
equal to the number of days between October 17, 2002, and the
date of enactment of this Act.
(B) Waiver and deferral not granted.--If, with respect to
an application submitted to the Secretary of Health and Human
Services between April 1, 1999, and the date of enactment of
this Act, neither a waiver nor deferral of pediatric
assessments was granted under regulations of the Secretary
then in effect, the person that submitted the application
shall be required to submit assessments under subsection
(a)(2) of section 505B of the Federal Food, Drug, and
Cosmetic Act on the date that is the later of--
(i) the date that is 1 year after the date of enactment of
this Act; or
(ii) such date as the Secretary may specify under
subsection (a)(3) of that section;
unless the Secretary grants a waiver under subsection (a)(4)
of that section.
On page 19, line 7, strike ``(b)'' and insert ``(c)''.
pediatrics research authority
Mr. GREGG. Mr. President, I rise to speak to a managers' amendment to
S. 650, the Pediatric Research Equity Act. This amendment makes
improvements to the legislation as reported out of the Committee on
Health, Education, Labor and Pensions in June. Because these
improvements were made after the committee report was filed, this
statement is intended to serve as the committee's views on the amended
legislation. This statement was shared with the other committee members
and has their concurrence.
Mr. KENNEDY. Mr. President, the Democratic sponsors of the bill and I
concur with this statement.
Mr. GREGG. Mr. President, the purpose of this legislation is to
provide FDA with statutory authority to require pediatric studies in
specified circumstances. In October 2002, a Federal district court held
that existing law did not provide FDA the authority to issue a
regulation requiring pediatric studies for drugs marketed to adults but
important to children. Although this decision is being appealed, this
legislation will provide the agency with definitive statutory authority
to require pediatric studies of new and already marketed drugs and
biologics in the circumstances specified in the legislation and to
enforce any violations of those requirements in Federal court. This has
always been the intent of S. 650. After the legislation was marked up
in committee, the managers of the bill agreed to amend the language in
section 505B(d) to make this intent even clearer.
The enforcement mechanism in section 505B(d) provides that 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) under the new law, ``the drug or biological
product that is the subject of the assessment or request may be
considered misbranded solely because of such failure.'' This language
confers on the Secretary authority to bring a misbranding action where
a violation has occurred.
The committee has used the language ``may be considered''
(misbranded) rather than the traditional ``shall be deemed to be''
(misbranded) that is used in other provisions of the Federal Food, Drug
and Cosmetic Act in order to emphasized that the Secretary may exercise
traditional enforcement discretion in deciding whether to bring such an
action. The Committee recognizes that the Secretary retains that
discretion under other provisions of current law that use the ``shall''
formulation. Nevertheless, the Committee intends for this authority to
be interpreted by the courts and to be implemented by FDA in a manner
consistent with the agency's enforcement authorities in current law
that use the ``shall'' formulation.
As is true with other provisions of current law, once the Secretary
decides to initiate an enforcement action under section 505B(d), no
formal finding or other proceeding is required. Moreover, it is not
necessary for the Secretary to identify any other misbranding authority
in the act. The new authority conferred by section 505B(d)
is sufficient. For example, the failure of a sponsor to submit
pediatric studies in accordance with the requirements of the
legislation alone would be a sufficient basis to prosecute an action in
federal district court.
The managers of the bill have agreed to the extraordinary retroactive
application of the provisions of the new research authority in order to
avoid even greater potential harm to children through the loss of
research and agency resources should assessments, waivers, and
deferrals under the Pediatric Rule be considered invalid following the
recent district court decision invalidating the rule. This application
should not be considered approval of the agency's interpretation of its
authority nor disagreement of the court's ruling. In the extraordinary
situation at hand, the managers' amendment modifies the effective date
provision of the legislation to ensure a seamless transition of the
pediatric study requirement from the Pediatric rule to this
legislation. The intent is that waivers and deferrals of the study
requirement previously granted under the rule be deemed to be in effect
under the legislation. A sponsor that received a deferral under the
rule would have the original deferral date extended by the number of
days between October 17, 2002, and the date of enactment of this
legislation.
A sponsor that submitted an application in the time period between
April 1, 1999, and the date of enactment of this legislation that was
not granted a waiver or deferral under the rule would be required to
submit pediatric assessments unless granted a waiver by FDA. However,
no submission by a sponsor would be due until 12 months after the date
of enactment of this legislation or until a date specified by FDA under
section 505B(a)(3), whichever is later.
Mr. KENNEDY. Mr. President, Although I and the Democratic sponsors
[[Page S9816]]
of the bill disagree with the chairman's view that the agency lacked
the authority to promulgate the Pediatric Rule and his view that the
Federal district court ruling invalidating the rule was correct, we do
agree with the chairman's statements regarding the need to apply the
requirements of this legislation retroactively to ensure that no
pediatric studies are lost in the transition from the rule to this
legislation.
Mr. GREGG. Mr. President, S. 650 provides FDA the statutory authority
to require that new and already marketed drugs and biological products
be studied in children in specified circumstances. This authority is
intended to work in a complementary fashion with pediatric exclusivity.
With regard to already marketed products, S. 650 provides that FDA
require pediatric testing only after pediatric exclusivity and the
National Institutes of Health grant and contract provisions contained
in sections 409I and 499 of the Public Health service Act have failed
to produce the necessary studies. However, nothing in S. 650 requires
FDA to wait until the voluntary mechanisms have failed or been
exhausted before invoking the pediatric studies requirement for new
drug applications under section 505 of the Federal Food, drug and
Cosmetic Act or biological license applications under section 351 of
the Public Health service Act. On the contrary, S. 650 creates the
presumption that new drugs and biologics will be studied before
approval unless a waiver or deferral is granted.
Mr. KENNEDY. Mr. President, I agree with the Senator. Does he agree
as well, that, in accordance with the plain language of the
legislation, FDA shall grant a waiver of the requirement to submit
pediatric assessments only if the applicant certifies and the Secretary
finds that the conditions specified in 505B(a)(4) and 505B(b)(2) exist?
By using the word ``including'' before listing the circumstances under
which FDA shall grant a full or partial waiver in the committee report
for S. 650, the committee does not intend that any conditions or
circumstances other than those specifically stated in 505B(a)(4) and
505B(b)(2) serve as the basis for FDA granting a full or partial waiver
of the requirements of the legislation.
Mr. GREGG. Mr. President, I do, and I thank the Senator for his work
on this bill and the report.
The bill (S. 650), as amended, was read the third time and passed 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 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
[[Page S9817]]
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 solely
because of that failure 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.
``(h) Integration With Other Pediatric Studies.--The
authority under this section shall remain in effect so long
as an application subject to this section may be accepted for
filing by the Secretary on or before the date specified in
section 505A(n).''.
(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,'';
(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.--Subject to subsection (b), this Act and
the amendments made by this Act take effect on the date of
enactment of this Act.
(b) Applicability to New Drugs and Biological Products.--
(1) In general.--Subsection (a) of section 505B of the
Federal Food, Drug, and Cosmetic Act (as added by section 2)
shall apply to an application described in paragraph (1) of
that subsection submitted to the Secretary of Health and
Human Services on or after April 1, 1999.
(2) Waivers and deferrals.--
(A) Waiver or deferral granted.--If, with respect to an
application submitted to the Secretary of Health and Human
Services
[[Page S9818]]
between April 1, 1999, and the date of enactment of this Act,
a waiver or deferral of pediatric assessments was granted
under regulations of the Secretary then in effect, the waiver
or deferral shall be a waiver or deferral under subsection
(a) of section 505B of the Federal Food, Drug, and Cosmetic
Act, except that any date specified in such a deferral shall
be extended by the number of days that is equal to the number
of days between October 17, 2002, and the date of enactment
of this Act.
(B) Waiver and deferral not granted.--If, with respect to
an application submitted to the Secretary of Health and Human
Services between April 1, 1999, and the date of enactment of
this Act, neither a waiver nor deferral of pediatric
assessments was granted under regulations of the Secretary
then in effect, the person that submitted the application
shall be required to submit assessments under subsection
(a)(2) of section 505B of the Federal Food, Drug, and
Cosmetic Act on the date that is the later of--
(i) the date that is 1 year after the date of enactment of
this Act; or
(ii) such date as the Secretary may specify under
subsection (a)(3) of that section;
unless the Secretary grants a waiver under subsection (a)(4)
of that section.
(c) 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.
Mr. DODD. Mr. President, I rise today to applaud my colleagues for
passing the Pediatric Research Equity Act of 2003, and to thank all of
those who have worked so hard on this issue. This legislation
represents a truly bipartisan compromise, and I deeply appreciate the
commitment to this issue shown by Senators DeWine, Clinton, Gregg, and
Kennedy. I also acknowledge the invaluable role played by the American
Academy of Pediatrics and the Elizabeth Glaser Pediatric AIDS
Foundation.
Quite simply, this legislation will make our children safer. It will
ensure that they have access to prescription drugs that have been
properly evaluated for their use. It will remove the guesswork often
done by pediatricians about what drugs are appropriate for a child, and
in what dosages. And it will accomplish all of this by codifying into
statutory language a tool that has already been shown to be effective:
the Pediatric Rule.
The Pediatric Rule went into effect in April of 1999 and was intended
to work in conjunction with a voluntary incentives program that
Congress passed in 1997 and was reauthorized last year. Both the
incentives program and the rule were put into place to address an unmet
need that had potentially serious consequences to the health of
children.
Children are not just small versions of adults when it comes to
drugs. Some drugs that are completely safe for adults may be very
harmful to children. In addition, some needed drugs are not available
in a formulation that a child can take, such as a liquid or chewable
tablet. Finally, the appropriate dosage for a child cannot be
determined simply by extrapolating from adults. Yet, until the rule and
the incentives program were enacted, this is exactly what pediatricians
were forced to do. Roughly 75 percent of all prescription drugs on the
market today have never been properly tested for safe use by children.
As a result, children have suffered needlessly. For example, new
tests on the epilepsy drug Neurontin have shown that higher dosages
than expected are needed for children under 5. For years, pediatricians
simply believed that Neurontin was a drug that was ineffective for
children.
In 1997, Congress enacted legislation, introduced by Senator DeWine
and myself, to provide drug companies with an economic incentive to
test their products to ensure their safety in children. This was
followed by enactment of the Pediatric Rule in 1999, which worked with
the incentive by giving the Food and Drug Administration (FDA) the
authority to require that drugs and biologics important to children be
tested and formulated for their use.
Working as complements to each other, the rule and the incentive
provided tremendous results. Between April 1999 and March 2002,
research was completed on the safety and effectiveness in children of
roughly 100 days. These medicines were for the treatment of, among
other things, HIV/AIDS, diabetes, asthma pain and arthritis. In
addition, studies of hundreds more drugs are in the pipeline.
But continued success of this magnitude is dependent on the existence
of both the rule and the incentive program. FDA has stated that
approximately half of the completed studies were due to the authority
provided by the Pediatric Rule.
Unfortunately, in October of last year, the U.S. District Court for
the District of Columbia ruled that FDA does not have the authority to
enforce the rule. This decision represented a step backwards for
children's health. We can hardly afford to do without the rule when we
still do not have necessary information for kids for a majority of the
medicines on the market.
The legislation that we passed today will give the FDA clear
authority to require that drugs be tested and formulated for children.
Companies should continue to have access to voluntary incentives, but
the rule must be in place to ensure that as many products as possible
are studied for use in children.
For example, the rule captures a class of products, specifically
biologics, for which market exclusivity incentives do not apply. There
are a number of biologic products used to treat cancer in children for
which information about their specific use--safety and efficacy--in
kids would be vital. Only the rule would apply here.
The rule can also be applied as needed during the life of a drug as
more information is required. For example, if a new use of a drug is
discovered and safety or dosing information for that new use is needed.
Exclusivity can only be applied once, even if an important new use for
a product is found. Also, because the incentives are voluntary, for any
number of reasons a manufacturer may choose not to conduct the
necessary testing. Without the rule there is no way to guarantee that a
drug that may be critically important to children's health is tested.
I would be remiss if I did not mention one provision in this
legislation with which I disagree. As a result of this provision, the
authority that we clearly provide to FDA with this bill will sunset in
2007. While I believe that FDA has the authority to enforce the rule
even without this legislation, that has clearly been called into
question given the District Court ruling. Therefore, it is imperative
that we unequivocally and permanently provide the FDA with statutory
authority to require pediatric testing. Unfortunately, as it now stands
that critical authority will expire in 2007 unless reauthorized.
It is my view that such a reauthorization should not be necessary. We
take it for granted that studies will be done to assure that the drugs
that adults use are safe and effective. Why should the assumption be
any different for children? FDA should always have the authority to
make sure that the drugs that kids use have been tested for their use.
This is not something that Congress should have to reauthorize every 5
years. Kids should not have to come back to Congress every 5 years to
fight for the basic right to safe drugs.
Despite my concern with the sunset provision, I strongly support this
bill. The voluntary program has been a huge success, but its
limitations can be addressed by passage of this legislation. Simply
put, taking any tool off the table that promotes pediatric testing is
at odds with our overarching goal of ensuring that medicines are safe
and available for our children. That is why we must protect the rule
and ensure that our efforts for kids will not be diminished. The
Pediatric Research Equity Act of 2003 will do exactly that.
I sincerely hope that the House will pass this bill as soon as
possible, preferably without any changes so that we can send it to the
President to be signed into law without delay.
Mrs. CLINTON. Mr. President, I rise to mark the passage on the Senate
floor of a bill, S. 650, that will assure the safety and efficacy of
medicines for children, and address a problem that pediatricians,
parents, and children's advocates have worked on for decades. A great
deal of work went into this bill. So many hardworking, dedicated
Senators made the effort on a bipartisan basis to come together around
this important issue. In particular I want to thank Senators DeWine,
Dodd, Gregg, and Kennedy. Senators DeWine and Dodd and I now have
worked on pediatric research for many years, and we
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will continue to be around to work on behalf of children, who, without
dedicated advocates like Senators DeWine and Dodd, would not have a
political voice.
Last year this bill was passed out of committee but held up on the
floor toward the end of session. Unfortunately, that meant no backstop
was in place to assure the continuation of a minimum baseline
protection for children when last October, a District Court judge
struck down the 1998 FDA Pediatric Rule, based on his view that
Congress did not intend to charge FDA with making sure our children are
protected. Today, we pass legislation to clarify that FDA authority to
assure safe, effective medicines for children is exactly what we
intend.
This bill was the product of compromise. We all worked hard and made
concessions on all sides to craft the language the Senate was able to
pass today. Some of us would have preferred a strong, permanent
assurance for children, and not a sunset of these crucial protections
in 2007. Indeed, because the purpose of this legislation was to address
the uncertainty caused by the court-triggered lapse of pediatric
studies, not codify such a lapse into statute, I cannot support the
sunset provision.
But others may have wished to change other aspects of the bill. So we
were able to give on each side for the sake of moving forward on a
central accomplishment providing FDA with undisputed, unencumbered
authority to require and enforce studies of whether medicines important
for children are also safe and effective for children. Our managers'
amendment and the colloquy we submitted today reinforce that as the
goal we all share here today in passing this language.
I want to take a moment to bring special attention to the amount of
work and cooperation that the chair and ranking member of Senate Health
Education, Labor, and Pensions Committee have dedicated to this bill,
both last Congress and this Congress. Senator Gregg and Senator
Kennedy, and both their staffs, Vince Ventimiglia, and David Dorsey
have lent their expertise and their time to this issue. Senator
DeWine's staff, Abby Kral, and Senator Dodd's staff, Ben Berwick this
year, Debra Barrett last year, have been more dedicated than anyone on
this issue.
I particularly want to acknowledge the outside experts who have
devoted so much time to advocating on behalf of children and making
this proposal a reality. The American Academy of Pediatricians, Elaine
Vining here in DC and all the pediatricians across the country, have
been championing this issue for so long. Also, Mark Isaac and Jeanne
Ireland at the Elizabeth Glaser Pediatric AIDS Foundation have been
tireless in their efforts. The children's hospitals, and so many others
cannot be thanked enough. We would not be here today without their
passionate advocacy. I also appreciate working with Phrma to get to
this point and hope to continue to work with them in order to move this
bill quickly into law.
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