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U.S. Code as of:
01/19/04
Section 355a. Pediatric studies of drugs
(a) Definitions
As used in this section, the term "pediatric studies" or
"studies" means at least one clinical investigation (that, at the
Secretary's discretion, may include pharmacokinetic studies) in
pediatric age groups (including neonates in appropriate cases) in
which a drug is anticipated to be used.
(b) Market exclusivity for new drugs
If, prior to approval of an application that is submitted under
section 355(b)(1) of this title, the Secretary determines that
information relating to the use of a new drug in the pediatric
population may produce health benefits in that population, the
Secretary makes a written request for pediatric studies (which
shall include a timeframe for completing such studies), and such
studies are completed within any such timeframe and the reports
thereof submitted in accordance with subsection (d)(2) of this
section or accepted in accordance with subsection (d)(3) of this
section -
(1)(A)(i) the period referred to in subsection (c)(3)(D)(ii) of
section 355 of this title, and in subsection (j)(5)(F)(ii) of
such section, is deemed to be five years and six months rather
than five years, and the references in subsections (c)(3)(D)(ii)
and (j)(5)(F)(ii) of such section to four years, to forty-eight
months, and to seven and one-half years are deemed to be four and
one-half years, fifty-four months, and eight years, respectively;
or
(ii) the period referred to in clauses (iii) and (iv) of
subsection (c)(3)(D) of such section, and in clauses (iii) and
(iv) of subsection (j)(5)(F) of such section, is deemed to be
three years and six months rather than three years; and
(B) if the drug is designated under section 360bb of this title
for a rare disease or condition, the period referred to in
section 360cc(a) of this title is deemed to be seven years and
six months rather than seven years; and
(2)(A) if the drug is the subject of -
(i) a listed patent for which a certification has been
submitted under subsection (b)(2)(A)(ii) or (j)(2)(A)(vii)(II)
of section 355 of this title and for which pediatric studies
were submitted prior to the expiration of the patent (including
any patent extensions); or
(ii) a listed patent for which a certification has been
submitted under subsections (b)(2)(A)(iii) or
(j)(2)(A)(vii)(III) of section 355 of this title,
the period during which an application may not be approved under
section 355(c)(3) of this title or section 355(j)(5)(B) of this
title shall be extended by a period of six months after the date
the patent expires (including any patent extensions); or
(B) if the drug is the subject of a listed patent for which a
certification has been submitted under subsection (b)(2)(A)(iv)
or (j)(2)(A)(vii)(IV) of section 355 of this title, and in the
patent infringement litigation resulting from the certification
the court determines that the patent is valid and would be
infringed, the period during which an application may not be
approved under section 355(c)(3) of this title or section
355(j)(5)(B) of this title shall be extended by a period of six
months after the date the patent expires (including any patent
extensions).
(c) Market exclusivity for already-marketed drugs
If the Secretary determines that information relating to the use
of an approved drug in the pediatric population may produce health
benefits in that population and makes a written request to the
holder of an approved application under section 355(b)(1) of this
title for pediatric studies (which shall include a timeframe for
completing such studies), the holder agrees to the request, the
studies are completed within any such timeframe, and the reports
thereof are submitted in accordance with subsection (d)(2) of this
section or accepted in accordance with subsection (d)(3) of this
section -
(1)(A)(i) the period referred to in subsection (c)(3)(D)(ii) of
section 355 of this title, and in subsection (j)(5)(F)(ii) of
such section, is deemed to be five years and six months rather
than five years, and the references in subsections (c)(3)(D)(ii)
and (j)(5)(F)(ii) of such section to four years, to forty-eight
months, and to seven and one-half years are deemed to be four and
one-half years, fifty-four months, and eight years, respectively;
or
(ii) the period referred to in clauses (iii) and (iv) of
subsection (c)(3)(D) of such section, and in clauses (iii) and
(iv) of subsection (j)(5)(F) of such section, is deemed to be
three years and six months rather than three years; and
(B) if the drug is designated under section 360bb of this title
for a rare disease or condition, the period referred to in
section 360cc(a) of this title is deemed to be seven years and
six months rather than seven years; and
(2)(A) if the drug is the subject of -
(i) a listed patent for which a certification has been
submitted under subsection (b)(2)(A)(ii) or (j)(2)(A)(vii)(II)
of section 355 of this title and for which pediatric studies
were submitted prior to the expiration of the patent (including
any patent extensions); or
(ii) a listed patent for which a certification has been
submitted under subsection (b)(2)(A)(iii) or
(j)(2)(A)(vii)(III) of section 355 of this title,
the period during which an application may not be approved under
section 355(c)(3) of this title or section 355(j)(5)(B) of this
title shall be extended by a period of six months after the date
the patent expires (including any patent extensions); or
(B) if the drug is the subject of a listed patent for which a
certification has been submitted under subsection (b)(2)(A)(iv)
or (j)(2)(A)(vii)(IV) of section 355 of this title, and in the
patent infringement litigation resulting from the certification
the court determines that the patent is valid and would be
infringed, the period during which an application may not be
approved under section 355(c)(3) of this title or section
355(j)(5)(B) of this title shall be extended by a period of six
months after the date the patent expires (including any patent
extensions).
(d) Conduct of pediatric studies
(1) Agreement for studies
The Secretary may, pursuant to a written request from the
Secretary under subsection (b) or (c) of this section, after
consultation with -
(A) the sponsor of an application for an investigational new
drug under section 355(i) of this title;
(B) the sponsor of an application for a new drug under
section 355(b)(1) of this title; or
(C) the holder of an approved application for a drug under
section 355(b)(1) of this title,
agree with the sponsor or holder for the conduct of pediatric
studies for such drug. Such agreement shall be in writing and
shall include a timeframe for such studies.
(2) Written protocols to meet the studies requirement
If the sponsor or holder and the Secretary agree upon written
protocols for the studies, the studies requirement of subsection
(b) or (c) of this section is satisfied upon the completion of
the studies and submission of the reports thereof in accordance
with the original written request and the written agreement
referred to in paragraph (1). In reaching an agreement regarding
written protocols, the Secretary shall take into account adequate
representation of children of ethnic and racial minorities. Not
later than 60 days after the submission of the report of the
studies, the Secretary shall determine if such studies were or
were not conducted in accordance with the original written
request and the written agreement and reported in accordance with
the requirements of the Secretary for filing and so notify the
sponsor or holder.
(3) Other methods to meet the studies requirement
If the sponsor or holder and the Secretary have not agreed in
writing on the protocols for the studies, the studies requirement
of subsection (b) or (c) of this section is satisfied when such
studies have been completed and the reports accepted by the
Secretary. Not later than 90 days after the submission of the
reports of the studies, the Secretary shall accept or reject such
reports and so notify the sponsor or holder. The Secretary's only
responsibility in accepting or rejecting the reports shall be to
determine, within the 90 days, whether the studies fairly respond
to the written request, have been conducted in accordance with
commonly accepted scientific principles and protocols, and have
been reported in accordance with the requirements of the
Secretary for filing.
(4) Written request to holders of approved applications for drugs
that have market exclusivity
(A) Request and response
If the Secretary makes a written request for pediatric
studies (including neonates, as appropriate) under subsection
(c) of this section to the holder of an application approved
under section 355(b)(1) of this title, the holder, not later
than 180 days after receiving the written request, shall
respond to the Secretary as to the intention of the holder to
act on the request by -
(i) indicating when the pediatric studies will be
initiated, if the holder agrees to the request; or
(ii) indicating that the holder does not agree to the
request.
(B) No agreement to request
(i) Referral
If the holder does not agree to a written request within
the time period specified in subparagraph (A), and if the
Secretary determines that there is a continuing need for
information relating to the use of the drug in the pediatric
population (including neonates, as appropriate), the
Secretary shall refer the drug to the Foundation for the
National Institutes of Health established under section 290b
of title 42 (referred to in this paragraph as the
"Foundation") for the conduct of the pediatric studies
described in the written request.
(ii) Public notice
The Secretary shall give public notice of the name of the
drug, the name of the manufacturer, and the indications to be
studied made in a referral under clause (i).
(C) Lack of funds
On referral of a drug under subparagraph (B)(i), the
Foundation shall issue a proposal to award a grant to conduct
the requested studies unless the Foundation certifies to the
Secretary, within a timeframe that the Secretary determines is
appropriate through guidance, that the Foundation does not have
funds available under section 290b(j)(9)(B)(i) (!1) of title 42
to conduct the requested studies. If the Foundation so
certifies, the Secretary shall refer the drug for inclusion on
the list established under section 284m of title 42 for the
conduct of the studies.
(D) Effect of subsection
Nothing in this subsection (including with respect to
referrals from the Secretary to the Foundation) alters or
amends section 331(j) of this title or section 552 of title 5
or section 1905 of title 18.
(E) No requirement to refer
Nothing in this subsection shall be construed to require that
every declined written request shall be referred to the
Foundation.
(F) Written requests under subsection (b)
For drugs under subsection (b) of this section for which
written requests have not been accepted, if the Secretary
determines that there is a continuing need for information
relating to the use of the drug in the pediatric population
(including neonates, as appropriate), the Secretary shall issue
a written request under subsection (c) of this section after
the date of approval of the drug.
(e) Delay of effective date for certain application
If the Secretary determines that the acceptance or approval of an
application under section 355(b)(2) or 355(j) of this title for a
new drug may occur after submission of reports of pediatric studies
under this section, which were submitted prior to the expiration of
the patent (including any patent extension) or the applicable
period under clauses (ii) through (iv) of section 355(c)(3)(D) of
this title or clauses (ii) through (iv) of section 355(j)(5)(F) of
this title, but before the Secretary has determined whether the
requirements of subsection (d) of this section have been satisfied,
the Secretary shall delay the acceptance or approval under section
355(b)(2) or 355(j) of this title until the determination under
subsection (d) of this section is made, but any such delay shall
not exceed 90 days. In the event that requirements of this section
are satisfied, the applicable six-month period under subsection (b)
or (c) of this section shall be deemed to have been running during
the period of delay.
(f) Notice of determinations on studies requirement
The Secretary shall publish a notice of any determination that
the requirements of subsection (d) of this section have been met
and that submissions and approvals under subsection (b)(2) or (j)
of section 355 of this title for a drug will be subject to the
provisions of this section.
(g) Limitations
A drug to which the six-month period under subsection (b) or (c)
of this section has already been applied -
(1) may receive an additional six-month period under subsection
(c)(1)(A)(ii) of this section for a supplemental application if
all other requirements under this section are satisfied, except
that such a drug may not receive any additional such period under
subsection (c)(2) of this section; and
(2) may not receive any additional such period under subsection
(c)(1)(B) of this section.
(h) Relationship to pediatric research requirements
Notwithstanding any other provision of law, if any pediatric
study is required by a provision of law (including a regulation)
other than this section and such study meets the completeness,
timeliness, and other requirements of this section, such study
shall be deemed to satisfy the requirement for market exclusivity
pursuant to this section.
(i) Labeling supplements
(1) Priority status for pediatric supplements
Any supplement to an application under section 355 of this
title proposing a labeling change pursuant to a report on a
pediatric study under this section -
(A) shall be considered to be a priority supplement; and
(B) shall be subject to the performance goals established by
the Commissioner for priority drugs.
(2) Dispute resolution
(A) Request for labeling change and failure to agree
If the Commissioner determines that an application with
respect to which a pediatric study is conducted under this
section is approvable and that the only open issue for final
action on the application is the reaching of an agreement
between the sponsor of the application and the Commissioner on
appropriate changes to the labeling for the drug that is the
subject of the application, not later than 180 days after the
date of submission of the application -
(i) the Commissioner shall request that the sponsor of the
application make any labeling change that the Commissioner
determines to be appropriate; and
(ii) if the sponsor of the application does not agree to
make a labeling change requested by the Commissioner, the
Commissioner shall refer the matter to the Pediatric Advisory
Committee.
(B) Action by the Pediatric Advisory Committee
Not later than 90 days after receiving a referral under
subparagraph (A)(ii), the Pediatric Advisory Committee shall -
(i) review the pediatric study reports; and
(ii) make a recommendation to the Commissioner concerning
appropriate labeling changes, if any.
(C) Consideration of recommendations
The Commissioner shall consider the recommendations of the
Pediatric Advisory Committee and, if appropriate, not later
than 30 days after receiving the recommendation, make a request
to the sponsor of the application to make any labeling change
that the Commissioner determines to be appropriate.
(D) Misbranding
If the sponsor of the application, within 30 days after
receiving a request under subparagraph (C), does not agree to
make a labeling change requested by the Commissioner, the
Commissioner may deem the drug that is the subject of the
application to be misbranded.
(E) No effect on authority
Nothing in this subsection limits the authority of the United
States to bring an enforcement action under this chapter when a
drug lacks appropriate pediatric labeling. Neither course of
action (the Pediatric Advisory Committee process or an
enforcement action referred to in the preceding sentence) shall
preclude, delay, or serve as the basis to stay the other course
of action.
(j) Dissemination of pediatric information
(1) In general
Not later than 180 days after the date of submission of a
report on a pediatric study under this section, the Commissioner
shall make available to the public a summary of the medical and
clinical pharmacology reviews of pediatric studies conducted for
the supplement, including by publication in the Federal Register.
(2) Effect of subsection
Nothing in this subsection alters or amends section 331(j) of
this title or section 552 of title 5 or section 1905 of title 18.
(k) Clarification of interaction of market exclusivity under this
section and market exclusivity awarded to an applicant for
approval of a drug under section 355(j) of this title
If a 180-day period under section 355(j)(5)(B)(iv) of this title
overlaps with a 6-month exclusivity period under this section, so
that the applicant for approval of a drug under section 355(j) of
this title entitled to the 180-day period under that section loses
a portion of the 180-day period to which the applicant is entitled
for the drug, the 180-day period shall be extended from -
(1) the date on which the 180-day period would have expired by
the number of days of the overlap, if the 180-day period would,
but for the application of this subsection, expire after the
6-month exclusivity period; or
(2) the date on which the 6-month exclusivity period expires,
by the number of days of the overlap if the 180-day period would,
but for the application of this subsection, expire during the
six-month exclusivity period.
(l) Prompt approval of drugs under section 355(j) of this title
when pediatric information is added to labeling
(1) General rule
A drug for which an application has been submitted or approved
under section 355(j) of this title shall not be considered
ineligible for approval under that section or misbranded under
section 352 of this title on the basis that the labeling of the
drug omits a pediatric indication or any other aspect of labeling
pertaining to pediatric use when the omitted indication or other
aspect is protected by patent or by exclusivity under clause
(iii) or (iv) of section 355(j)(5)(F) of this title.
(2) Labeling
Notwithstanding clauses (iii) and (iv) of section 355(j)(5)(F)
of this title, the Secretary may require that the labeling of a
drug approved under section 355(j) of this title that omits a
pediatric indication or other aspect of labeling as described in
paragraph (1) include -
(A) a statement that, because of marketing exclusivity for a
manufacturer -
(i) the drug is not labeled for pediatric use; or
(ii) in the case of a drug for which there is an additional
pediatric use not referred to in paragraph (1), the drug is
not labeled for the pediatric use under paragraph (1); and
(B) a statement of any appropriate pediatric
contraindications, warnings, or precautions that the Secretary
considers necessary.
(3) Preservation of pediatric exclusivity and other provisions
This subsection does not affect -
(A) the availability or scope of exclusivity under this
section;
(B) the availability or scope of exclusivity under section
355 of this title for pediatric formulations;
(C) the question of the eligibility for approval of any
application under section 355(j) of this title that omits any
other conditions of approval entitled to exclusivity under
clause (iii) or (iv) of section 355(j)(5)(F) of this title; or
(D) except as expressly provided in paragraphs (1) and (2),
the operation of section 355 of this title.
(m) Report
The Secretary shall conduct a study and report to Congress not
later than January 1, 2001, based on the experience under the
program established under this section. The study and report shall
examine all relevant issues, including -
(1) the effectiveness of the program in improving information
about important pediatric uses for approved drugs;
(2) the adequacy of the incentive provided under this section;
(3) the economic impact of the program on taxpayers and
consumers, including the impact of the lack of lower cost generic
drugs on patients, including on lower income patients; and
(4) any suggestions for modification that the Secretary
determines to be appropriate.
(n) Sunset
A drug may not receive any 6-month period under subsection (b) or
(c) of this section unless -
(1) on or before October 1, 2007, the Secretary makes a written
request for pediatric studies of the drug;
(2) on or before October 1, 2007, an application for the drug
is accepted for filing under section 355(b) of this title; and
(3) all requirements of this section are met.
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