II 

110TH CONGRESS 

1ST SESSION S. 993 

To improve pediatric research. 

IN THE SENATE OF THE UNITED STATES 

MARCH 27, 2007 

Mrs. CLINTON (for herself and Mr. DODD) introduced the following bill; which 

was read twice and referred to the Committee on Health, Education, 

Labor, and Pensions 

A BILL 

To improve pediatric research. 

1 Be it enacted by the Senate and House of Representa2 tives of the United States of America in Congress assembled, 

3 SECTION 1. SHORT TITLE. 

4 This Act may be cited as the ‘‘Pediatric Research Im5 provement Act’’. 

6 SEC. 2. PEDIATRIC FORMULATIONS, EXTRAPOLATIONS, 

7 AND DEFERRALS. 

8 Section 505B(a) of the Federal Food, Drug, and Cos9 metic Act (21 U.S.C. 355c(a)) is amended— 

10 (1) in paragraph (4)(C), by adding at the end 

11 the following: ‘‘An applicant seeking either a partial 


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1 or full waiver shall submit to the Secretary docu2 mentation detailing why a pediatric formulation can3 not be developed, and, if the waiver is granted, the 

4 applicant’s submission shall promptly be made avail5 able to the public in an easily accessible manner, in6 cluding through posting on the website of the Food 

7 and Drug Administration’’; 

8 (2) in paragraph (2)(B), by adding at the end 

9 the following: 

10 ‘‘(iii) INFORMATION ON EXTRAPO11 LATION.—A brief documentation of the sci12 entific data supporting the conclusion 

13 under clauses (i) and (ii) shall be included 

14 in the medical review that is collected as 

15 part of the application under section 505 

16 or section 351 of the Public Health Service 

17 Act.’’; and 

18 (3) by striking paragraph (3) and inserting the 

19 following: 

20 ‘‘(3) DEFERRAL.— 

21 ‘‘(A) IN GENERAL.—On the initiative of 

22 the Secretary or at the request of the applicant, 

23 the Secretary may defer submission of some or 

24 all assessments required under paragraph (1) 

25 until a specified date after approval of the drug 


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1 or issuance of the license for a biological prod2 uct if— 

3 ‘‘(i) the Secretary finds that— 

4 ‘‘(I) the drug or biological prod5 uct is ready for approval for use in 

6 adults before pediatric studies are 

7 complete; 

8 ‘‘(II) pediatric studies should be 

9 delayed until additional safety or ef10 fectiveness data have been collected; 

11 or 

12 ‘‘(III) there is another appro13 priate reason for deferral; and 

14 ‘‘(ii) the applicant submits to the Sec15 retary— 

16 ‘‘(I) certification of the grounds 

17 for deferring the assessments; 

18 ‘‘(II) a description of the planned 

19 or ongoing studies; 

20 ‘‘(III) evidence that the studies 

21 are being conducted or will be con22 ducted with due diligence and at the 

23 earliest possible time; and 

24 ‘‘(IV) a timeline for the comple25 tion of such studies. 


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1 ‘‘(B) ANNUAL REVIEW.— 

2 ‘‘(i) IN GENERAL.—On an annual 

3 basis following the approval of a deferral 

4 under subparagraph (A), the applicant 

5 shall submit to the Secretary the following 

6 information: 

7 ‘‘(I) Information detailing the 

8 progress made in conducting pediatric 

9 studies. 

10 ‘‘(II) If no progress has been 

11 made in conducting such studies, evi12 dence and documentation that such 

13 studies will be conducted with due 

14 diligence and at the earliest possible 

15 time. 

16 ‘‘(ii) PUBLIC AVAILABILITY.—The in17 formation submitted through the annual 

18 review under clause (i) shall promptly be 

19 made available to the public in an easily 

20 accessible manner, including through the 

21 website of the Food and Drug Administra22 tion.’’. 


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1 SEC. 3. IMPROVING AVAILABILITY OF PEDIATRIC DATA 

2 FOR ALREADY MARKETED PRODUCTS. 

3 Section 505B(b) of the Federal Food, Drug, and Cos4 metic Act (21 U.S.C. 355c(b)) is amended— 

5 (1) by striking paragraph (1) and inserting the 

6 following: 

7 ‘‘(1) IN GENERAL.—After providing notice in 

8 the form of a letter, or a written request under sec9 tion 505A that was declined by the sponsor or hold10 er, and an opportunity for written response and a 

11 meeting, which may include an advisory committee 

12 meeting, the Secretary may (by order in the form of 

13 a letter) require the sponsor or holder of an ap14 proved application for a drug under section 505 or 

15 the holder of a license for a biological product under 

16 section 351 of the Public Health Service Act (42 

17 U.S.C. 262) to submit by a specified date the assess18 ments described in subsection (a)(2) and the written 

19 request, as appropriate, if the Secretary finds that— 

20 ‘‘(A)(i) the drug or biological product is 

21 used for a substantial number of pediatric pa22 tients for the labeled indications; and 

23 ‘‘(ii) adequate pediatric labeling could con24 fer a benefit on pediatric patients; 

25 ‘‘(B) there is reason to believe that the 

26 drug or biological product would represent a 


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1 meaningful therapeutic benefit over existing 

2 therapies for pediatric patients for 1 or more of 

3 the claimed indications; or 

4 ‘‘(C) the absence of adequate pediatric la5 beling could pose a risk to pediatric patients.’’; 

6 (2) in paragraph (2)(C), by adding at the end 

7 the following: ‘‘An applicant seeking either a partial 

8 or full waiver shall submit to the Secretary docu9 mentation detailing why a pediatric formulation can10 not be developed, and, if the waiver is granted, the 

11 applicant’s submission shall promptly be made avail12 able to the public in an easily accessible manner, in13 cluding through posting on the website of the Food 

14 and Drug Administration.’’; and 

15 (3) by striking paragraph (3). 

16 SEC. 4. REVIEW OF PEDIATRIC ASSESSMENTS; ADVERSE 

17 EVENT REPORTING; STRIKE OF SUNSET; LA18 BELING CHANGES; AND PEDIATRIC ASSESS19 MENTS. 

20 Section 505B of the Federal Food, Drug, and Cos21 metic Act (21 U.S.C. 355c) is amended— 

22 (1) by striking subsection (h); 

23 (2) by redesignating subsection (f) as sub24 section (k); 


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1 (3) by redesignating subsection (g) as sub2 section (l); and 

3 (4) by inserting after subsection (e) the fol4 lowing: 

5 ‘‘(f) REVIEW OF PEDIATRIC ASSESSMENT REQUESTS, 

6 PEDIATRIC ASSESSMENTS, DEFERRALS, AND WAIVERS.— 

7 ‘‘(1) REVIEW.—The Secretary shall create an 

8 internal committee to review all pediatric assessment 

9 requests issued under this section, all pediatric as10 sessments conducted under this section, and all de11 ferral and waiver requests made pursuant to this 

12 section. Such internal committee shall include indi13 viduals with the following expertise: 

14 ‘‘(A) Pediatrics. 

15 ‘‘(B) Biopharmacology. 

16 ‘‘(C) Statistics. 

17 ‘‘(D) Drugs and drug formulations. 

18 ‘‘(E) Pediatric ethics. 

19 ‘‘(F) Legal issues. 

20 ‘‘(G) Appropriate expertise pertaining to 

21 the pediatric product under review. 

22 ‘‘(H) 1 or more experts from the Office of 

23 Pediatric Therapeutics. 

24 ‘‘(I) Other individuals as designated by the 

25 Secretary. 


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1 ‘‘(2) REVIEW OF REQUESTS FOR PEDIATRIC AS2 SESSMENTS, DEFERRALS, AND WAIVERS.—All writ3 ten requests for a pediatric assessment issued pursu4 ant to this section and all requests for deferrals and 

5 waivers from the requirement to conduct a pediatric 

6 assessment under this section shall be reviewed and 

7 approved by the committee established under para8 graph (1). 

9 ‘‘(3) REVIEW OF ASSESSMENTS.—The com10 mittee established under paragraph (1) shall review 

11 all assessments conducted under this section to de12 termine whether such assessments meet the require13 ments of this section. 

14 ‘‘(4) TRACKING OF ASSESSMENTS AND LABEL15 ING CHANGES.—The committee established under 

16 paragraph (1) is responsible for tracking and mak17 ing public in an easily accessible manner, including 

18 through posting on the website of the Food and 

19 Drug Administration— 

20 ‘‘(A) the number of assessments conducted 

21 under this section; 

22 ‘‘(B) the specific drugs and drug uses as23 sessed under this section; 

24 ‘‘(C) the types of assessments conducted 

25 under this section, including trial design, the 


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1 number of pediatric patients studied, and the 

2 number of centers and countries involved; 

3 ‘‘(D) the total number of deferrals re4 quested and granted under this section, and, if 

5 granted, the reasons for such deferrals, the 

6 timeline for completion, and the number com7 pleted and pending by the specified date, as 

8 outlined in subsection (a)(3); 

9 ‘‘(E) the number of waivers requested and 

10 granted under this section, and, if granted, the 

11 reasons for the waivers; 

12 ‘‘(F) the number of pediatric formulations 

13 developed and the number of pediatric formula14 tions not developed and the reasons any such 

15 formulations were not developed; 

16 ‘‘(G) the labeling changes made as a result 

17 of assessments conducted under this section; 

18 ‘‘(H) an annual summary of labeling 

19 changes made as a result of assessments con20 ducted under this section for distribution pursu21 ant to subsection (i)(2); and 

22 ‘‘(I) an annual summary of the informa23 tion submitted pursuant to subsection 

24 (a)(3)(B). 

25 ‘‘(g) LABELING CHANGES.— 


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1 ‘‘(1) PRIORITY STATUS FOR PEDIATRIC SUP2 PLEMENT.—Any supplement to an application under 

3 section 505 and section 351 of the Public Health 

4 Service Act proposing a labeling change as a result 

5 of any pediatric assessments conducted pursuant to 

6 this section— 

7 ‘‘(A) shall be considered a priority supple8 ment; and 

9 ‘‘(B) shall be subject to the performance 

10 goals established by the Commissioner for pri11 ority drugs. 

12 ‘‘(2) DISPUTE RESOLUTION.— 

13 ‘‘(A) REQUEST FOR LABELING CHANGE

14 AND FAILURE TO AGREE.—If the Commissioner 

15 determines that a sponsor and the Commis16 sioner have been unable to reach agreement on 

17 appropriate changes to the labeling for the drug 

18 that is the subject of the application or supple19 ment, not later than 180 days after the date of 

20 the submission of the application or supple21 ment— 

22 ‘‘(i) the Commissioner shall request 

23 that the sponsor make any labeling change 

24 that the Commissioner determines to be 

25 appropriate; and 


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1 ‘‘(ii) if the sponsor does not agree to 

2 make a labeling change requested by the 

3 Commissioner, the Commissioner shall 

4 refer the matter to the Pediatric Advisory 

5 Committee. 

6 ‘‘(B) ACTION BY THE PEDIATRIC ADVISORY

7 COMMITTEE.—Not later than 90 days after re8 ceiving a referral under subparagraph (A)(ii), 

9 the Pediatric Advisory Committee shall— 

10 ‘‘(i) review the pediatric study reports; 

11 and 

12 ‘‘(ii) make a recommendation to the 

13 Commissioner concerning appropriate la14 beling changes, if any. 

15 ‘‘(C) CONSIDERATION OF RECOMMENDA16 TIONS.—The Commissioner shall consider the 

17 recommendations of the Pediatric Advisory 

18 Committee and, if appropriate, not later than 

19 30 days after receiving the recommendation, 

20 make a request to the sponsor of the applica21 tion or supplement to make any labeling 

22 changes that the Commissioner determines to 

23 be appropriate. 

24 ‘‘(D) MISBRANDING.—If the sponsor, with25 in 30 days after receiving a request under subVerDate Aug 31 2005 03:29 Mar 30, 2007 Jkt 059200 PO 00000 Frm 00011 Fmt 6652 Sfmt 6201 E:\BILLS\S993.IS S993

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1 paragraph (C), does not agree to make a label2 ing change requested by the Commissioner, the 

3 Commissioner may deem the drug that is the 

4 subject of the application or supplement to be 

5 misbranded. 

6 ‘‘(E) NO EFFECT ON AUTHORITY.—Noth7 ing in this subsection limits the authority of the 

8 United States to bring an enforcement action 

9 under this Act when a drug lacks appropriate 

10 pediatric labeling. Neither course of action (the 

11 Pediatric Advisory Committee process of an en12 forcement action referred to in the preceding 

13 sentence) shall preclude, delay, or serve as the 

14 basis to stay the other course of action. 

15 ‘‘(3) OTHER LABELING CHANGES.—If the Sec16 retary makes a determination that a pediatric as17 sessment conducted under this section does not dem18 onstrate that the drug that is the subject of such as19 sessment is safe and effective, the Secretary shall 

20 order the label of such product to include informa21 tion about the results of the assessment and a state22 ment of the Secretary’s determination. 

23 ‘‘(h) DISSEMINATION OF PEDIATRIC INFORMA24 TION.— 


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1 ‘‘(1) IN GENERAL.—Not later than 180 days 

2 after the date of submission of a pediatric assess3 ment under this section, the Commissioner shall 

4 make available to the public in an easily accessible 

5 manner the medical, statistical, and clinical pharma6 cology reviews of such pediatric assessments and 

7 shall post such assessments on the website of the 

8 Food and Drug Administration. 

9 ‘‘(2) DISSEMINATION OF INFORMATION RE10 GARDING LABELING CHANGES.—The Secretary shall 

11 require that the sponsors of the assessments that re12 sult in labeling changes that are reflected in the an13 nual summary developed pursuant to subsection 

14 (f)(4)(H) distribute such information to physicians 

15 and other health care providers. 

16 ‘‘(3) EFFECT OF SUBSECTION.—Nothing in this 

17 subsection shall alter or amend section 301(j) of this 

18 Act or section 552 of title 5, United States Code, or 

19 section 1905 of title 18, United States Code. 

20 ‘‘(i) ADVERSE EVENT REPORTING.— 

21 ‘‘(1) REPORTING IN YEAR 1.—During the 1- 

22 year period beginning on the date a labeling change 

23 is made pursuant to subsection (g), the Secretary 

24 shall ensure that all adverse event reports that have 

25 been received for such drug (regardless of when such 


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1 report was received) are referred to the Office of Pe2 diatric Therapeutics. In considering the report, the 

3 Director of such Office shall provide for the review 

4 of the report by the Pediatric Advisory Committee, 

5 including obtaining any recommendations of such 

6 committee regarding whether the Secretary should 

7 take action under this Act in response to such re8 port. 

9 ‘‘(2) REPORTING IN SUBSEQUENT YEARS.—Fol10 lowing the 1-year period described in paragraph (1), 

11 the Secretary shall, as appropriate, provide the Of12 fice of Pediatric Therapeutics with a report regard13 ing pediatric adverse events for a drug for which a 

14 pediatric study was conducted under this section. In 

15 considering the report, the Director of such Office 

16 may provide for the review of the report by the Pedi17 atric Advisory Committee, including obtaining any 

18 recommendation of such Committee regarding 

19 whether the Secretary should take action in response 

20 to such report.’’. 

21 SEC. 5. MEANINGFUL THERAPEUTIC BENEFIT. 

22 Section 505B(c) of the Federal Food, Drug, and Cos23 metic Act (21 U.S.C. 355c) is amended— 

24 (1) by striking ‘‘estimates’’ and inserting ‘‘de25 termines’’; and 


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1 (2) by striking ‘‘would’’ and inserting ‘‘could’’. 

2 SEC. 6. REPORTS. 

3 (a) IOM STUDY.—Section 505B of the Federal Food, 

4 Drug, and Cosmetic Act (21 U.S.C. 355c), as amended 

5 by section 4, is further amended by adding after sub6 section (l), the following: 

7 ‘‘(m) INSTITUTE OF MEDICINE STUDY.— 

8 ‘‘(1) IN GENERAL.—Not later than 3 years 

9 after the date of enactment of the Pediatric Re10 search Improvement Act, the Secretary shall con11 tract with the Institute of Medicine to conduct a 

12 study and report to Congress regarding the pediatric 

13 studies conducted pursuant to this section since 

14 1997. 

15 ‘‘(2) CONTENT OF STUDY.—The study under 

16 paragraph (1) shall review and assess— 

17 ‘‘(A) pediatric studies conducted pursuant 

18 to this section since 1997 and labeling changes 

19 made as a result of such studies; and 

20 ‘‘(B) the use of extrapolation for pediatric 

21 subpopulations, the use of alternative endpoints 

22 for pediatric populations, neonatal assessment 

23 tools, number and type of pediatric adverse 

24 events, and ethical issues in pediatric clinical 

25 trials. 


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1 ‘‘(3) REPRESENTATIVE SAMPLE.—The Institute 

2 of Medicine may devise an appropriate mechanism to 

3 review a representative sample of studies conducted 

4 pursuant to this section from each review division 

5 within the Center for Drug Evaluation and Research 

6 and the Center for Biologics Evaluation and Re7 search in order to make the required assessment.’’. 

8 (b) PREA REPORT.—The Pediatric Research Equity 

9 Act of 2003 (Public Law 108–155) is amended by adding 

10 at the end the following: 

11 ‘‘SEC. 5. REPORT. 

12 ‘‘Not later than September 1, 2010, the Comptroller 

13 General of the United States, in consultation with the Sec14 retary of Health and Human Services, shall submit to 

15 Congress a report that addresses the effectiveness of sec16 tion 505B of the Federal Food, Drug, and Cosmetic Act 

17 (21 U.S.C. 355a) in ensuring that medicines used by chil18 dren are tested and properly labeled, including— 

19 ‘‘(1) the number and importance of drugs for 

20 children that are being tested as a result of this pro21 vision and the importance for children, health care 

22 providers, parents, and others of labeling changes 

23 made as a result of such testing; 

24 ‘‘(2) the number and importance of drugs for 

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1 withstanding the provisions of this Act, and possible 

2 reasons for the lack of testing; and 

3 ‘‘(3) the number of drugs for which testing is 

4 being done and labeling changes required, including 

5 the date labeling changes are made and which label6 ing changes required the use of the dispute resolu7 tion process established pursuant to the amendments 

8 made by this Act, together with a description of the 

9 outcomes of such process, including a description of 

10 the disputes and the recommendations of the Pedi11 atric Advisory Committee.’’. 

12 SEC. 7. TECHNICAL CORRECTIONS. 

13 Section 505B(a)(2)(B)(ii) of the Federal Food, Drug, 

14 and Cosmetic Act (21 U.S.C. 355c(a)(2)(B)(ii)) is amend15 ed by striking ‘‘one’’ and inserting ‘‘1’’. 

Æ 


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