US CODE: Title 21,355a. 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.

§ 355a. Pediatric studies of drugs