II 

114TH CONGRESS 

1ST SESSION S. 1767 

To amend the Federal Food, Drug, and Cosmetic Act with respect to 

combination products, and for other purposes. 

IN THE SENATE OF THE UNITED STATES 

JULY 15, 2015 

Mr. ISAKSON (for himself, Mr. CASEY, and Mr. ROBERTS) introduced the following bill; which was read twice and referred to the Committee on 

Health, Education, Labor, and Pensions 

A BILL 

To amend the Federal Food, Drug, and Cosmetic Act with 

respect to combination products, and for other purposes. 

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 ‘‘Combination Product 

5 Regulatory Fairness Act of 2015’’. 

6 SEC. 2. DEVICE DEFINITION. 

7 Section 201(h) of the Federal Food, Drug, and Cos8 metic Act (21 U.S.C. 321(h)) is amended— 

9 (1) by redesignating subparagraphs (1), (2), 

10 and (3) as clauses (A), (B), and (C), respectively; 

mstockstill on DSK4VPTVN1PROD with BILLS

2 

•S 1767 IS

1 (2) by striking ‘‘(h)’’ and inserting ‘‘(h)(1)’’; 

2 and 

3 (3) by adding at the end the following: 

4 ‘‘(2)(A) Before determining that an article does not 

5 meet the definition of a device under this paragraph, the 

6 Secretary shall provide to the sponsor of the article com7 petent and reliable scientific rationale that— 

8 ‘‘(i) cites any scientific evidence relied upon to 

9 support the rationale; and 

10 ‘‘(ii) supports such determination. 

11 ‘‘(B) If the Secretary makes a determination de12 scribed in clause (A)— 

13 ‘‘(i) the sponsor of the article may propose a 

14 nonclinical or clinical study, limited to not more data 

15 than necessary to establish the significance, if any, 

16 of the chemical action in achieving the primary in17 tended purpose of the article; and 

18 ‘‘(ii) the Secretary and the sponsor of the arti19 cle shall collaborate in good faith to reach agree20 ment, within a reasonable time not to exceed 90 

21 days, on the design of such study. 

22 ‘‘(C) The data resulting from a study conducted 

23 under clause (B) shall inform the classification of the arti24 cle.’’. 

mstockstill on DSK4VPTVN1PROD with BILLS

3 

•S 1767 IS

1 SEC. 3. COMBINATION PRODUCTS. 

2 Section 503(g) of the Federal Food, Drug, and Cos3 metic Act (21 U.S.C. 353(g)) is amended— 

4 (1) by redesignating paragraphs (2) through 

5 (5) as paragraphs (6) through (9), respectively; 

6 (2) by striking ‘‘(g)(1)’’ and all that follows 

7 through the end of paragraph (1) and inserting the 

8 following: 

9 ‘‘(g)(1)(A) The Secretary shall, in accordance with 

10 this subsection, assign an agency center to regulate prod11 ucts that constitute a combination of a drug, device, or 

12 biological product (referred to in this subsection as the 

13 ‘lead center’). 

14 ‘‘(B) The Secretary shall conduct the premarket re15 view of any combination product, whenever possible, under 

16 a single application using existing premarket review au17 thorities. 

18 ‘‘(C) The Secretary shall determine the primary mode 

19 of action of the combination product. If the Secretary de20 termines that the primary mode of action is that of— 

21 ‘‘(i) a drug (other than a biological product), 

22 the agency center charged with premarket review of 

23 drugs shall have primary jurisdiction; 

24 ‘‘(ii) a device, the agency center charged with 

25 premarket review of devices shall have primary juris26 diction; or 

mstockstill on DSK4VPTVN1PROD with BILLS

4 

•S 1767 IS

1 ‘‘(iii) a biological product, the agency center 

2 charged with premarket review of biological products 

3 shall have primary jurisdiction. 

4 ‘‘(D) In determining the primary mode of action of 

5 a combination product, the Secretary shall not determine 

6 that the primary mode of action is that of a drug or bio7 logical product solely because the combination product has 

8 any chemical action within or on the human body. 

9 ‘‘(E) If the Secretary disagrees with the conclusions 

10 of the sponsor on the primary mode of action of the com11 bination product, the Secretary shall provide a competent 

12 and reliable scientific rationale to the product sponsor that 

13 cites any scientific evidence relied upon to support the de14 cision. 

15 ‘‘(F) For purposes of this paragraph— 

16 ‘‘(i) the term ‘primary mode of action’ means 

17 the single mode of action of a combination product 

18 that provides the most important therapeutic action 

19 of the combination product; and 

20 ‘‘(ii) the term ‘most important therapeutic ac21 tion’ means the mode of action expected to make the 

22 greatest contribution to the overall intended thera23 peutic effects of the combination product. 

24 ‘‘(2)(A) The sponsor of a combination product may 

25 submit a combination product review plan (referred to in 

mstockstill on DSK4VPTVN1PROD with BILLS

5 

•S 1767 IS

1 this subsection as a ‘CPRP’) for the combination product, 

2 and may request a meeting prior to submission of the 

3 CPRP, to establish clarity and certainty for the sponsor 

4 regarding the standards and requirements applicable to— 

5 ‘‘(i) the review of safety and effectiveness, or 

6 substantial equivalence, of the combination product; 

7 ‘‘(ii) a postmarket modification of the combina8 tion product; or 

9 ‘‘(iii) good manufacturing practices for the com10 bination product. 

11 ‘‘(B) Not later than 60 days after the sponsor of a 

12 combination product submits a proposed CPRP, including 

13 a revision to a previously proposed or approved CPRP, 

14 the Secretary shall review the CPRP and— 

15 ‘‘(i) if the Secretary determines that the CPRP 

16 is appropriate to ensure adequate review of the safe17 ty and effectiveness, or substantial equivalence, of 

18 the combination product— 

19 ‘‘(I) approve the CPRP; and 

20 ‘‘(II) issue to the sponsor a response indi21 cating such approval; or 

22 ‘‘(ii) if the Secretary finds that the CPRP does 

23 not meet the standard specified in clause (i)— 

24 ‘‘(I) decline to approve the CPRP; and 

mstockstill on DSK4VPTVN1PROD with BILLS

6 

•S 1767 IS

1 ‘‘(II) issue to the sponsor a response indi2 cating that the Secretary has declined such ap3 proval and specifying any deficiencies in the 

4 proposed CPRP. 

5 ‘‘(C)(i) In the case of a CPRP that the Secretary de6 clines to approve under subparagraph (B)(ii), unless the 

7 sponsor submitting such CPRP determines a meeting is 

8 not necessary, the Secretary shall, not later than 30 days 

9 after submitting a response under such subparagraph, 

10 meet with such sponsor to discuss the CPRP. 

11 ‘‘(ii) A meeting under clause (i) shall— 

12 ‘‘(I) include any necessary experts from the rel13 evant agency centers; and 

14 ‘‘(II) coordinate the advice of such experts. 

15 ‘‘(D) The sponsor or applicant shall provide informa16 tion necessary for discussion and agreement on the level 

17 of evidence necessary to ensure adequate review of the 

18 safety and effectiveness, or substantial equivalence, of the 

19 combination product. 

20 ‘‘(E) Not later than 30 days after the date on which 

21 a meeting is held under subparagraph (A)(i), the minutes 

22 of such meeting shall be prepared by the sponsor and 

23 made available to the Secretary. 

24 ‘‘(F) Any agreement that is reached between the Sec25 retary and a sponsor or applicant through a meeting held 

mstockstill on DSK4VPTVN1PROD with BILLS

7 

•S 1767 IS

1 under subparagraph (A)(i) shall be reduced to writing by 

2 the sponsor or applicant, and, once approved by the Sec3 retary, made part of the administrative record by the Sec4 retary within 60 days of such meeting. 

5 ‘‘(G) An agreement described in subparagraph (F) 

6 shall not be changed after approval of the agreement, ex7 cept— 

8 ‘‘(i) with the written agreement of the sponsor 

9 or applicant; or 

10 ‘‘(ii) pursuant to a decision, made in accordance 

11 with subparagraph (H) by the director of the review12 ing division of the lead center, in consultation with 

13 consulting centers and the Office, that a substantial 

14 scientific issue essential to determining the safety or 

15 effectiveness, or substantial equivalence, of the com16 bination product has been identified. 

17 ‘‘(H) With respect to a decision under subparagraph 

18 (G)(ii), the Secretary shall provide notice, within 2 busi19 ness days of such decision, to the sponsor of the combina20 tion product and an opportunity for a meeting to take 

21 place not later than 14 calendar days after issuing such 

22 notice, at which— 

23 ‘‘(i) the director of the reviewing division of the 

24 lead center, staff from the consulting agency centers, 

mstockstill on DSK4VPTVN1PROD with BILLS

8 

•S 1767 IS

1 representatives of the Office, and the sponsor will be 

2 present; and 

3 ‘‘(ii) the director of the reviewing division of the 

4 lead center will document the scientific issue in5 volved. 

6 ‘‘(3) For purposes of conducting the premarket re7 view of a combination product that contains an approved 

8 constituent product described in paragraph (4), the Sec9 retary may require only that the sponsor of such combina10 tion product submit to the Secretary data or information 

11 that— 

12 ‘‘(A) the Secretary determines is necessary to 

13 assess the specific safety and effectiveness questions 

14 and incremental risks posed by the combination 

15 product, using a risk-based approach and taking into 

16 account any prior finding of safety and efficacy or 

17 substantial equivalence for the approved constituent 

18 product; and 

19 ‘‘(B) is not duplicative of data or information 

20 included in an application or other material sub21 mitted to the Secretary in connection with the ap22 proved constituent product. 

23 ‘‘(4) For purposes of paragraph (3), an approved con24 stituent product is— 

mstockstill on DSK4VPTVN1PROD with BILLS

9 

•S 1767 IS

1 ‘‘(A) a drug constituent part of a combination 

2 product being reviewed in a single application under 

3 section 515 or 510(k), provided such drug con4 stituent part was previously approved under section 

5 505 and such application complies with subpara6 graph (A) of paragraph (5) and is subject to sub7 paragraphs (D) and (E) of such paragraph; 

8 ‘‘(B) a device constituent part approved under 

9 section 515 that is referenced by the sponsor and 

10 which is available for use by the Secretary under 

11 section 520(h)(4); or 

12 ‘‘(C) any constituent part that was previously 

13 approved, cleared, or licensed under section 505, 

14 510(k), or 515 of this Act or section 351 of the 

15 Public Health Service Act, for which the sponsor has 

16 a right of reference or which is otherwise available 

17 for consideration by the Secretary under this Act or 

18 the Public Health Service Act. 

19 ‘‘(5)(A) If an application is submitted under section 

20 515 or 510(k) for a combination product containing as 

21 a constituent part an approved drug— 

22 ‘‘(i) the application shall include the certifi23 cation or statement required pursuant section 

24 505(b)(2); and 

mstockstill on DSK4VPTVN1PROD with BILLS

10 

•S 1767 IS

1 ‘‘(ii) the applicant shall provide notice as re2 quired pursuant to section 505(b)(3). 

3 ‘‘(B) For purposes of this paragraph, the term ‘ap4 proved drug’ means a drug— 

5 ‘‘(i) that was previously approved under section 

6 505; 

7 ‘‘(ii) for which full reports of investigations that 

8 have been made to show whether such drug is safe 

9 for use and whether such drug is effective in use— 

10 ‘‘(I) are relied upon by the applicant sub11 mitting the application described in subpara12 graph (A); and 

13 ‘‘(II) were not conducted by or for such 

14 applicant; and 

15 ‘‘(iii) with respect to which, the applicant sub16 mitting the application described in subparagraph 

17 (A) has not obtained a right of reference or use from 

18 the person by or for whom the investigations were 

19 conducted. 

20 ‘‘(C) The following provisions shall apply with respect 

21 an application described in subparagraph (A): 

22 ‘‘(i) Subparagraphs (A), (B), (C), and (D) of 

23 section 505(c)(3). 

24 ‘‘(ii) Clauses (ii), (iii), and (iv) of section 

25 505(c)(3)(E). 

mstockstill on DSK4VPTVN1PROD with BILLS

11 

•S 1767 IS

1 ‘‘(iii) Paragraphs (b) and (c) of section 505A. 

2 ‘‘(iv) Section 505E(a). 

3 ‘‘(v) Section 527(a). 

4 ‘‘(D) Notwithstanding section 520(h)(4)(A)(i), infor5 mation contained in an application for premarket approval 

6 filed with the Secretary pursuant to section 515(c) may 

7 not be used to approve any application submitted under 

8 section 515 or 510(k) for a combination product con9 taining as a constituent part a drug previously approved 

10 under section 505 unless— 

11 ‘‘(i) the application includes the certification or 

12 statement referenced in subparagraph (A); 

13 ‘‘(ii) the applicant provides notice as described 

14 in subparagraph (A); and 

15 ‘‘(iii) the Secretary’s approval of such applica16 tion is subject to the provisions specified in subpara17 graph (C). 

18 ‘‘(E) An application for a combination product de19 scribed in subparagraph (A) or (D) shall be considered 

20 an application submitted under Section 505(b)(2) solely 

21 for purposes of section 271(e)(2)(A) of the Patent Act.’’; 

22 (3) in paragraph (8) (as redesignated by para23 graph (1))— 

24 (A) in subparagraph (C)— 

mstockstill on DSK4VPTVN1PROD with BILLS

12 

•S 1767 IS

1 (i) by amending clause (i) to read as 

2 follows: 

3 ‘‘(i) In carrying out this subsection, the Office shall 

4 ensure timely and effective premarket reviews involving 

5 more than one agency center by— 

6 ‘‘(I) overseeing the timeliness and alignment of 

7 reviews; and 

8 ‘‘(II) coordinating reviews.’’; 

9 (ii) in clause (ii), by inserting ‘‘and 

10 alignment’’ after ‘‘the timeliness’’ each 

11 place it appears; and 

12 (iii) by adding at the end the fol13 lowing new clauses: 

14 ‘‘(iii) The Office shall ensure that the lead center be 

15 the primary point of contact for the sponsor of the prod16 uct. The Office shall also coordinate communications to 

17 and from any consulting agency center involved in such 

18 premarket review. Agency communications and commit19 ments, to the extent consistent with other provisions of 

20 law and the requirements of all affected agency centers, 

21 from the lead center shall be binding on all other centers 

22 involved in the review. 

23 ‘‘(iv) The Office shall, with respect to the premarket 

24 review of a combination product— 

mstockstill on DSK4VPTVN1PROD with BILLS

13 

•S 1767 IS

1 ‘‘(I) ensure that any meeting between the Food 

2 and Drug Administration and the sponsor of the 

3 product is attended by each agency center involved 

4 in the review, as appropriate; 

5 ‘‘(II) require that each consulting agency center 

6 has completed its premarket review and provided the 

7 results of such review to the lead center within time8 frames that allow the lead center to meet the review 

9 goals established pursuant to the most recent au10 thorization or reauthorization of parts 2, 3, 7, and 

11 8, as applicable, of subchapter C of title VII; and 

12 ‘‘(III) ensure that each consulting agency cen13 ter complies with the guidance described in clause 

14 (vi) and other relevant regulations, guidances, and 

15 policies. 

16 ‘‘(v) Not later than 10 days after the receipt by an 

17 agency center of an application under section 505, 510(k), 

18 or 520 of this Act, or under section 351 of the Public 

19 Health Service Act, for a combination product or an appli20 cation for investigational use of a combination product 

21 under section 505(i) or 520(g), the agency center shall 

22 inform the Office of such receipt. 

23 ‘‘(vi) Not later than 2 years after the date of enact24 ment of the Combination Product Regulatory Fairness Act 

25 of 2015, the Secretary shall issue final guidance that demstockstill on DSK4VPTVN1PROD with BILLS

14 

•S 1767 IS

1 scribes the responsibilities of each agency center regarding 

2 its review of combination products, including each center’s 

3 role in evaluating evidence development and review under 

4 a risk-based approach, dispute resolution, labeling, prod5 uct usability assessments, and human factors testing. The 

6 Office shall, after soliciting public comment, review and 

7 update the guidance at least biannually and specify in 

8 such updated guidance the reasons for updates.’’; 

9 (B) in subparagraph (E)— 

10 (i) by striking clause (i) and inserting 

11 the following new clause: 

12 ‘‘(i) During the review process, any dispute regarding 

13 the substance, timeliness, review process, requirements, or 

14 alignment of the premarket review may be presented to 

15 the Office for resolution and the Office shall convene the 

16 relevant parties and resolve conflicts not later than 90 

17 days after the date on which the Office receives written 

18 notice of such conflicts.’’; and 

19 (ii) in clause (ii), by striking ‘‘During 

20 the review process, any dispute regarding 

21 the substance of the premarket review’’ 

22 and inserting ‘‘Any remaining dispute’’; 

23 (C) in subparagraph (F), in the first sen24 tence— 

mstockstill on DSK4VPTVN1PROD with BILLS

15 

•S 1767 IS

1 (i) by inserting ‘‘or which involves de2 termining the safety or efficacy of a com3 ponent of a combination product’’ after 

4 ‘‘assignment of combination products to 

5 agency centers’’; and 

6 (ii) by inserting ‘‘and with the guid7 ance described in subparagraph (C)(vi).’’ 

8 before the period at the end; and 

9 (D) in subparagraph (G)— 

10 (i) in clause (ii), by striking ‘‘and’’ at 

11 the end; 

12 (ii) in clause (iii), by striking the pe13 riod at the end and inserting a semicolon; 

14 and 

15 (iii) by adding at the end the fol16 lowing new clauses: 

17 ‘‘(iv) identifying the percentage of combination 

18 products for which a dispute resolution, with respect 

19 to premarket review, was requested by the combina20 tion product’s sponsor; and 

21 ‘‘(v) identifying the percentage of meetings be22 tween the Food and Drug Administration and the 

23 sponsor of a combination product at which all of the 

24 centers participating in the review of the combinamstockstill on DSK4VPTVN1PROD with BILLS

16 

•S 1767 IS

1 tion product were in attendance, in accordance with 

2 subparagraph (C)(iv)(I).’’; 

3 (4) in paragraph (9) (as redesignated by para4 graph (1)), by adding at the end the following: 

5 ‘‘(D) The terms ‘premarket review’ and ‘re6 views’ include all activities of the Food and Drug 

7 Administration conducted prior to approval or clear8 ance of an application or notification submitted 

9 under section 505, 510(k), 515, or 520 of this Act 

10 or under section 351 of the Public Health Service 

11 Act, including with respect to investigational use of 

12 the product.’’; and 

13 (5) by adding at the end the following: 

14 ‘‘(10) RULE OF CONSTRUCTION.—Nothing in this 

15 subsection shall be construed as prohibiting a sponsor, at 

16 the sponsor’s discretion, from submitting separate applica17 tions for the constituent parts of a combination product, 

18 unless the Secretary determines that a single application 

19 is necessary to ensure the safety and effectiveness, or sub20 stantial equivalence, as applicable, of the combination 

21 product.’’. 

Æ 

mstockstill on DSK4VPTVN1PROD with BILLS