U.S Code last checked for updates: May 26, 2024
§ 355c.
Research into pediatric uses for drugs and biological products
(a)
New drugs and biological products
(1)
In general
(A)
General requirements
Except with respect to an application for which subparagraph (B) applies, a person that submits, on or after September 27, 2007, an application (or supplement to an application) for a drug—
(i)
under section 355 of this title for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration; or
(ii)
under section 262 of title 42 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).
(B)
Certain molecularly targeted cancer indications
A person that submits, on or after the date that is 3 years after August 18, 2017, an original application for a new active ingredient under section 355 of this title or section 262 of title 42, shall submit with the application reports on the investigation described in paragraph (3) if the drug or biological product that is the subject of the application is—
(i)
intended for the treatment of an adult cancer; and
(ii)
directed at a molecular target that the Secretary determines to be substantially relevant to the growth or progression of a pediatric cancer.
(2)
Assessments
(A)
In general
The assessments referred to in paragraph (1)(A) 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
(ii)
Extrapolation between age groups
(iii)
Information on extrapolation
(3)
Molecularly targeted pediatric cancer investigation
(A)
In general
(B)
Extrapolation of data
(C)
Deferrals and waivers
(4)
Deferral
(A)
In general
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)(A) or reports on the investigation required under paragraph (1)(B) until a specified date after approval of the drug or issuance of the license for a biological product if—
(i)
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
(ii)
the applicant submits to the Secretary—
(I)
certification of the grounds for deferring the assessments or reports on the investigation;
(II)
a pediatric study plan as described in subsection (e);
(III)
evidence that the studies are being conducted or will be conducted with due diligence and at the earliest possible time; and
(IV)
a timeline for the completion of such studies.
(B)
Deferral extension
(i)
In general
On the initiative of the Secretary or at the request of the applicant, the Secretary may grant an extension of a deferral approved under subparagraph (A) for submission of some or all assessments required under paragraph (1)(A) or reports on the investigation required under paragraph (1)(B) if—
(I)
the Secretary determines that the conditions described in subclause (II) or (III) of subparagraph (A)(i) continue to be met; and
(II)
the applicant submits a new timeline under subparagraph (A)(ii)(IV) and any significant updates to the information required under subparagraph (A)(ii).
(ii)
Timing and information
(C)
Annual review
(i)
In general
On an annual basis following the approval of a deferral under subparagraph (A), the applicant shall submit to the Secretary the following information:
(I)
Information detailing the progress made in conducting pediatric studies.
(II)
If no progress has been made in conducting such studies, evidence and documentation that such studies will be conducted with due diligence and at the earliest possible time.
(III)
Projected completion date for pediatric studies.
(IV)
The reason or reasons why a deferral or deferral extension continues to be necessary.
(ii)
Public availability
Not later than 90 days after the submission to the Secretary of the information submitted through the annual review under clause (i), the Secretary shall make available to the public in an easily accessible manner, including through the Internet Web site of the Food and Drug Administration—
(I)
such information;
(II)
the name of the applicant for the product subject to the assessment or investigation;
(III)
the date on which the product was approved; and
(IV)
the date of each deferral or deferral extension under this paragraph for the product.
(5)
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 or reports on the investigation 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 or reports on the investigation 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
(D)
Labeling requirement
(b)
Marketed drugs and biological products
(1)
In general
The Secretary may (by order in the form of a letter) require the sponsor or holder of an approved application for a drug under section 355 of this title or the holder of a license for a biological product under section 262 of title 42 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)
adequate pediatric labeling could confer a benefit on pediatric patients;
(B)
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; or
(C)
the absence of adequate pediatric labeling could pose a risk 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
(D)
Labeling requirement
(3)
Effect of subsection
(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) 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 determines that—
(1)
if approved, the drug or biological product could represent an 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 and reports on the investigation
If a person fails to submit a required assessment described in subsection (a)(2) or the investigation described in subsection (a)(3), fails to meet the applicable requirements in subsection (a)(4), or fails to submit a request for approval of a pediatric formulation described in subsection (a) or (b), in accordance with applicable provisions of subsections (a) and (b), the following shall apply:
(1)
Beginning 270 days after July 9, 2012, the Secretary shall issue a non-compliance letter to such person informing them of such failure to submit or meet the requirements of the applicable subsection. Such letter shall require the person to respond in writing within 45 calendar days of issuance of such letter. Such response may include the person’s request for a deferral extension if applicable. Such letter and the person’s written response to such letter shall be made publicly available on the Internet Web site of the Food and Drug Administration 60 calendar days after issuance, with redactions for any trade secrets and confidential commercial information. If the Secretary determines that the letter was issued in error, the requirements of this paragraph shall not apply. The Secretary shall inform the Pediatric Advisory Committee of letters issued under this paragraph and responses to such letters.
(2)
The drug or biological product that is the subject of an assessment described in subsection (a)(2) or the investigation described in subsection (a)(3), applicable requirements in subsection (a)(4), or request for approval of a pediatric formulation, 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 333 of this title), but such failure shall not be the basis for a proceeding—
(A)
to withdraw approval for a drug under section 355(e) of this title; or
(B)
to revoke the license for a biological product under section 262 of title 42.
(e)
Pediatric study plans
(1)
In general
(2)
Timing; content; meetings
(A)
Timing
An applicant shall submit the initial pediatric study plan under paragraph (1)—
(i)
before the date on which the applicant submits the assessments under subsection (a)(2) or the investigation described in subsection (a)(3); and
(ii)
not later than—
(I)
60 calendar days after the date of the end-of-Phase 2 meeting (as such term is used in section 312.47 of title 21, Code of Federal Regulations, or successor regulations); or
(II)
such other time as may be agreed upon between the Secretary and the applicant.
Nothing in this section shall preclude the Secretary from accepting the submission of an initial pediatric study plan earlier than the date otherwise applicable under this subparagraph.
(B)
Content of initial pediatric study plan
The initial pediatric study plan shall include—
(i)
an outline of the pediatric study or studies that the applicant plans to conduct (including, to the extent practicable study objectives and design, age groups, relevant endpoints, and statistical approach);
(ii)
any request for a deferral, partial waiver, or waiver under this section, if applicable, along with any supporting information; and
(iii)
other information specified in the regulations promulgated under paragraph (7).
(C)
Meetings
The Secretary—
(i)
shall meet with the applicant—
(I)
if requested by the applicant with respect to a drug or biological product that is intended to treat a serious or life-threatening disease or condition, to discuss preparation of the initial pediatric study plan, not later than the end-of-Phase 1 meeting (as such term is used in section 312.82(b) of title 21, Code of Federal Regulations, or successor regulations) or within 30 calendar days of receipt of such request, whichever is later;
(II)
to discuss the initial pediatric study plan as soon as practicable, but not later than 90 calendar days after the receipt of such plan under subparagraph (A); and
(III)
to discuss the bases for the deferral under subsection (a)(4) or a full or partial waiver under subsection (a)(5);
(ii)
may determine that a written response to the initial pediatric study plan is sufficient to communicate comments on the initial pediatric study plan, and that no meeting under clause (i)(II) is necessary; and
(iii)
if the Secretary determines that no meeting under clause (i)(II) is necessary, shall so notify the applicant and provide written comments of the Secretary as soon as practicable, but not later than 90 calendar days after the receipt of the initial pediatric study plan.
(3)
Agreed initial pediatric study plan
(4)
Deferral and waiver
(5)
Amendments to the agreed initial pediatric study plan
(6)
Internal committee
(7)
Required rulemaking
(f)
Review of pediatric study plans, assessments, deferrals, deferral extensions, and waivers
(1)
Review
(2)
Activity by committee
(3)
Documentation of committee action
(4)
Review of pediatric study plans, assessments, deferrals, deferral extensions, and waivers
(5)
Retrospective review of pediatric assessments, deferrals, and waivers
(6)
Tracking of assessments and labeling changes
The Secretary, in consultation with the committee referred to in paragraph (1), shall track and make available to the public in an easily accessible manner, including through posting on the Web site of the Food and Drug Administration—
(A)
the number of assessments conducted under this section;
(B)
the specific drugs and biological products and their uses assessed under this section;
(C)
the types of assessments conducted under this section, including trial design, the number of pediatric patients studied, and the number of centers and countries involved;
(D)
aggregated on an annual basis—
(i)
the total number of deferrals and deferral extensions requested and granted under this section and, if granted, the reasons for each such deferral or deferral extension;
(ii)
the timeline for completion of the assessments;
(iii)
the number of assessments completed and pending; and
(iv)
the number of postmarket non-compliance letters issued pursuant to subsection (d), and the recipients of such letters;
(E)
the number of waivers requested and granted under this section and, if granted, the reasons for the waivers;
(F)
the number of pediatric formulations developed and the number of pediatric formulations not developed and the reasons any such formulation was not developed;
(G)
the labeling changes made as a result of assessments conducted under this section;
(H)
an annual summary of labeling changes made as a result of assessments conducted under this section for distribution pursuant to subsection (h)(2);
(I)
an annual summary of information submitted pursuant to subsection (a)(4)(C); and
(J)
the number of times the committee referred to in paragraph (1) made a recommendation to the Secretary under paragraph (4) regarding priority review, the number of times the Secretary followed or did not follow such a recommendation, and, if not followed, the reasons why such a recommendation was not followed.
(g)
Labeling changes
(1)
Dispute resolution
(A)
Request for labeling change and failure to agree
If, on or after September 27, 2007, the Commissioner determines that a sponsor and the Commissioner have been unable to reach agreement on appropriate changes to the labeling for the drug that is the subject of the application or supplement, not later than 180 days after the date of the submission of the application or supplement that receives a priority review or 330 days after the date of the submission of an application or supplement that receives a standard review—
(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 does not agree within 30 days after the Commissioner’s request 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
(D)
Misbranding
(E)
No effect on authority
(2)
Other labeling changes
(h)
Dissemination of pediatric information
(1)
In general
(2)
Dissemination of information regarding labeling changes
(3)
Effect of subsection
(i)
Adverse event reporting
(1)
Reporting in first 18-month period
(2)
Reporting in subsequent periods
(3)
Preservation of authority
(4)
Effect
(j)
Scope of authority
(k)
Relation to orphan drugs
(1)
In general; exemption for orphan indications
(2)
Applicability despite orphan designation of certain indications
(l)
New active ingredient
(1)
Non-interchangeable biosimilar biological product
(2)
Interchangeable biosimilar biological product
(m)
List of primary molecular targets
(1)
In general
Within one year of August 18, 2017, the Secretary shall establish and update regularly, and shall publish on the internet website of the Food and Drug Administration—
(A)
a list of molecular targets considered, on the basis of data the Secretary determines to be adequate, to be substantially relevant to the growth and progression of a pediatric cancer, and that may trigger the requirements under this section; and
(B)
a list of molecular targets of new cancer drugs and biological products in development for which pediatric cancer study requirements under this section will be automatically waived.
(2)
Consultation
(3)
Rule of construction
Nothing in paragraph (1) shall be construed—
(A)
to require the inclusion of a molecular target on the list published under such paragraph as a condition for triggering the requirements under subsection (a)(1)(B) with respect to a drug or biological product directed at such molecular target; or
(B)
to authorize the disclosure of confidential commercial information, as prohibited under section 331(j) of this title or section 1905 of title 18.
(June 25, 1938, ch. 675, § 505B, as added Pub. L. 108–155, § 2(a), Dec. 3, 2003, 117 Stat. 1936; amended Pub. L. 110–85, title IV, § 402(a), Sept. 27, 2007, 121 Stat. 866; Pub. L. 111–148, title VII, § 7002(d)(2), Mar. 23, 2010, 124 Stat. 816;
cite as: 21 USC 355c