Research into pediatric uses of drugs; additional authorities of Food and Drug Administration regarding molecularly targeted cancer drugs

(a)

In general

(1)

Authority regarding investigation of novel combination drugs

Section 505B(a)(1)(B) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355c(a)(1)(B)) is amended, in the matter preceding clause (i), by inserting after Public Health Service Act, the following: or an application under such section 505 or such section 351 for a drug or biological product that contains a novel combination of two or more active ingredients (subject to paragraph (3)(B)(iii)).(2)

Additional active ingredient for application drug; limitation regarding novel-combination application drug

Section 505B(a)(3) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355c(a)(3)) is amended—(A)by redesignating subparagraphs (B) and (C) as subparagraphs (C) and (D), respectively; and(B)by striking subparagraph (A) and inserting the following:

(A)

In general

For purposes of paragraph (1)(B), the investigation described in this paragraph is (as determined by the Secretary) a molecularly targeted pediatric cancer investigation of—(i)the drug or biological product for which the application referred to in such paragraph is submitted; or(ii)the active ingredient or ingredients of such drug or biological product in combination with—(I)an active ingredient of a drug for which an approved application under section 505(j) is in effect or an active ingredient of a biological product for which an approved application under section 351(k) of the Public Health Service Act is in effect, which drug or biological product is determined by the Secretary to be the standard of care for treating a pediatric cancer;(II)an active ingredient of a drug for which an approved application under section 505(b) is in effect to treat an adult cancer, or an active ingredient of a biological product for which an approved application under section 351(a) of the Public Health Service Act is in effect to treat an adult cancer, which approved application is held by the same person submitting the application referred to in paragraph (1)(B); or(III)an active ingredient of a drug or biological product for which there is in effect an exemption for investigational use under section 505(i), which drug or biological product is under such exemption being studied jointly by the person submitting the application referred to in paragraph (1)(B) and by another person pursuant to an agreement between such persons.(B)

Additional requirements

(i)

Design of investigation

A molecularly targeted pediatric cancer investigation referred to in subparagraph (A) shall be designed to yield clinically meaningful pediatric study data, gathered using appropriate formulations for each age group for which the study is required, regarding dosing, safety, and preliminary efficacy.(ii)

Purpose of investigation

The purpose of a molecularly targeted pediatric cancer investigation referred to in subparagraph (A) shall be—(I)in the case of such an investigation conducted with respect to a drug or biological product referred to in clause (i) of such subparagraph, to inform potential pediatric labeling of the drug or biological product for which the application referred to in paragraph (1)(B) is submitted; and(II)in the case of such an investigation conducted with respect to a combination of active ingredients described to in clause (ii) of such subparagraph, to assist in determining the relevance of its molecular target to the growth or progression of a pediatric cancer.(iii)

Limitation regarding investigation of novel combination

For purposes of paragraph (1)(B), a novel combination is a combination of two or more active ingredients for which an application under section 505 of this Act or section 351 of the Public Health Service Act for such combination has not previously been approved. A pediatric investigation under this paragraph of such novel combination is required only if each of the active ingredients in the combination has been approved under such section 505 or such section 351 to treat an adult cancer.(iv)

Preclinical data

The Secretary may require that reports on an investigation required pursuant to paragraph (1)(B) shall include the results of all preclinical studies on which the decision to conduct such investigation was based.(v)

Rule of construction regarding inactive ingredients

With respect to a combination of active ingredients referred to in subparagraph (A)(ii), such subparagraph may not be construed as addressing the use of inactive ingredients with such combination.

(3)

Clarifying applicability of certain provisions

Section 505B(a)(3) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355c(a)(3)), as amended by paragraph (2), is further amended by adding at the end the following:

(E)

Internal committee review; labeling changes; dissemination of information; adverse events; scope of authority

Subsections (f) through (j) shall apply with respect to investigations described in this paragraph to the same extent and in the same manner as such subsections apply with respect to the assessments required under paragraph (1)(A), except that subsection (g) does not apply with respect to an investigation referred to in subparagraph (A)(ii) of this paragraph.

(4)

Conforming amendments

Section 505B(a) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355c(a)) is amended—(A)in paragraph (3)(C), as redesignated by paragraph (2)(A) of this subsection, by striking investigations described in this paragraph and inserting investigations referred to in subparagraph (A)(i);(B)in paragraph (3)(D), as redesignated by paragraph (2)(A) of this subsection, by striking the assessments under paragraph (2)(B) and inserting the assessments required under paragraph (1)(A); and(C)in paragraph (5)(D), by inserting before the period at the end the following: , except this subparagraph is not applicable to an investigation referred to in paragraph (3)(A)(ii).(b)

Authority regarding preclinical studies

Section 505B(a)(1) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355c(a)(1)), as amended by subsection (a)(1), is further amended by adding at the end the following:

(C)

Preclinical studies generally

(i)

In general

With respect to an application for an exemption for investigational use under section 505(i) for a drug or biological product that is intended for the treatment of an adult cancer, the Secretary may require, as a condition of permitting the exemption to go into effect, that the sponsor involved enter into an agreement with the Secretary to conduct not more than two preclinical studies of the drug or biological product in order to assist in determining the relevance of its molecular target to the growth or progression of a pediatric cancer. (ii)

Timeframe for preclinical studies

With respect to the drug or biological product involved, an agreement under clause (i) for a preclinical study shall specify the date by which an initial plan for the study will be submitted to the Secretary except that the Secretary may not require the submission of such plan any earlier than one year after the exemption referred to in clause (i) goes into effect. The results of the preclinical study shall be submitted to the Secretary in accordance with a timeframe to which the Secretary and the sponsor involved have agreed. Such timeframe shall provide for deferrals equivalent to deferrals under paragraph (4).

(c)

Applicability

The amendments made by this section apply with respect to any application under section 505(i) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(i)), any application under section 505 of such Act (21 U.S.C. 355), and any application under section 351(a) of the Public Health Service Act (42 U.S.C. 262), that is submitted on or after the expiration of the 3-year period beginning on the date of the enactment of this Act.