[Congressional Bills 114th Congress]
[From the U.S. Government Publishing Office]
[S. 1767 Introduced in Senate (IS)]

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.

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

SECTION 1. SHORT TITLE.

    This Act may be cited as the ``Combination Product Regulatory 
Fairness Act of 2015''.

SEC. 2. DEVICE DEFINITION.

    Section 201(h) of the Federal Food, Drug, and Cosmetic Act (21 
U.S.C. 321(h)) is amended--
            (1) by redesignating subparagraphs (1), (2), and (3) as 
        clauses (A), (B), and (C), respectively;
            (2) by striking ``(h)'' and inserting ``(h)(1)''; and
            (3) by adding at the end the following:
    ``(2)(A) Before determining that an article does not meet the 
definition of a device under this paragraph, the Secretary shall 
provide to the sponsor of the article competent and reliable scientific 
rationale that--
            ``(i) cites any scientific evidence relied upon to support 
        the rationale; and
            ``(ii) supports such determination. 
    ``(B) If the Secretary makes a determination described in clause 
(A)--
            ``(i) the sponsor of the article may propose a nonclinical 
        or clinical study, limited to not more data than necessary to 
        establish the significance, if any, of the chemical action in 
        achieving the primary intended purpose of the article; and
            ``(ii) the Secretary and the sponsor of the article shall 
        collaborate in good faith to reach agreement, within a 
        reasonable time not to exceed 90 days, on the design of such 
        study.
    ``(C) The data resulting from a study conducted under clause (B) 
shall inform the classification of the article.''.

SEC. 3. COMBINATION PRODUCTS.

    Section 503(g) of the Federal Food, Drug, and Cosmetic Act (21 
U.S.C. 353(g)) is amended--
            (1) by redesignating paragraphs (2) through (5) as 
        paragraphs (6) through (9), respectively;
            (2) by striking ``(g)(1)'' and all that follows through the 
        end of paragraph (1) and inserting the following:
    ``(g)(1)(A) The Secretary shall, in accordance with this 
subsection, assign an agency center to regulate products that 
constitute a combination of a drug, device, or biological product 
(referred to in this subsection as the `lead center').
    ``(B) The Secretary shall conduct the premarket review of any 
combination product, whenever possible, under a single application 
using existing premarket review authorities.
    ``(C) The Secretary shall determine the primary mode of action of 
the combination product. If the Secretary determines that the primary 
mode of action is that of--
            ``(i) a drug (other than a biological product), the agency 
        center charged with premarket review of drugs shall have 
        primary jurisdiction;
            ``(ii) a device, the agency center charged with premarket 
        review of devices shall have primary jurisdiction; or
            ``(iii) a biological product, the agency center charged 
        with premarket review of biological products shall have primary 
        jurisdiction.
    ``(D) In determining the primary mode of action of a combination 
product, the Secretary shall not determine that the primary mode of 
action is that of a drug or biological product solely because the 
combination product has any chemical action within or on the human 
body.
    ``(E) If the Secretary disagrees with the conclusions of the 
sponsor on the primary mode of action of the combination product, the 
Secretary shall provide a competent and reliable scientific rationale 
to the product sponsor that cites any scientific evidence relied upon 
to support the decision.
    ``(F) For purposes of this paragraph--
            ``(i) the term `primary mode of action' means the single 
        mode of action of a combination product that provides the most 
        important therapeutic action of the combination product; and
            ``(ii) the term `most important therapeutic action' means 
        the mode of action expected to make the greatest contribution 
        to the overall intended therapeutic effects of the combination 
        product.
    ``(2)(A) The sponsor of a combination product may submit a 
combination product review plan (referred to in this subsection as a 
`CPRP') for the combination product, and may request a meeting prior to 
submission of the CPRP, to establish clarity and certainty for the 
sponsor regarding the standards and requirements applicable to--
            ``(i) the review of safety and effectiveness, or 
        substantial equivalence, of the combination product;
            ``(ii) a postmarket modification of the combination 
        product; or
            ``(iii) good manufacturing practices for the combination 
        product.
    ``(B) Not later than 60 days after the sponsor of a combination 
product submits a proposed CPRP, including a revision to a previously 
proposed or approved CPRP, the Secretary shall review the CPRP and--
            ``(i) if the Secretary determines that the CPRP is 
        appropriate to ensure adequate review of the safety and 
        effectiveness, or substantial equivalence, of the combination 
        product--
                    ``(I) approve the CPRP; and
                    ``(II) issue to the sponsor a response indicating 
                such approval; or
            ``(ii) if the Secretary finds that the CPRP does not meet 
        the standard specified in clause (i)--
                    ``(I) decline to approve the CPRP; and
                    ``(II) issue to the sponsor a response indicating 
                that the Secretary has declined such approval and 
                specifying any deficiencies in the proposed CPRP.
    ``(C)(i) In the case of a CPRP that the Secretary declines to 
approve under subparagraph (B)(ii), unless the sponsor submitting such 
CPRP determines a meeting is not necessary, the Secretary shall, not 
later than 30 days after submitting a response under such subparagraph, 
meet with such sponsor to discuss the CPRP.
    ``(ii) A meeting under clause (i) shall--
            ``(I) include any necessary experts from the relevant 
        agency centers; and
            ``(II) coordinate the advice of such experts.
    ``(D) The sponsor or applicant shall provide information necessary 
for discussion and agreement on the level of evidence necessary to 
ensure adequate review of the safety and effectiveness, or substantial 
equivalence, of the combination product.
    ``(E) Not later than 30 days after the date on which a meeting is 
held under subparagraph (A)(i), the minutes of such meeting shall be 
prepared by the sponsor and made available to the Secretary.
    ``(F) Any agreement that is reached between the Secretary and a 
sponsor or applicant through a meeting held under subparagraph (A)(i) 
shall be reduced to writing by the sponsor or applicant, and, once 
approved by the Secretary, made part of the administrative record by 
the Secretary within 60 days of such meeting.
    ``(G) An agreement described in subparagraph (F) shall not be 
changed after approval of the agreement, except--
            ``(i) with the written agreement of the sponsor or 
        applicant; or
            ``(ii) pursuant to a decision, made in accordance with 
        subparagraph (H) by the director of the reviewing division of 
        the lead center, in consultation with consulting centers and 
        the Office, that a substantial scientific issue essential to 
        determining the safety or effectiveness, or substantial 
        equivalence, of the combination product has been identified.
    ``(H) With respect to a decision under subparagraph (G)(ii), the 
Secretary shall provide notice, within 2 business days of such 
decision, to the sponsor of the combination product and an opportunity 
for a meeting to take place not later than 14 calendar days after 
issuing such notice, at which--
            ``(i) the director of the reviewing division of the lead 
        center, staff from the consulting agency centers, 
        representatives of the Office, and the sponsor will be present; 
        and
            ``(ii) the director of the reviewing division of the lead 
        center will document the scientific issue involved.
    ``(3) For purposes of conducting the premarket review of a 
combination product that contains an approved constituent product 
described in paragraph (4), the Secretary may require only that the 
sponsor of such combination product submit to the Secretary data or 
information that--
            ``(A) the Secretary determines is necessary to assess the 
        specific safety and effectiveness questions and incremental 
        risks posed by the combination product, using a risk-based 
        approach and taking into account any prior finding of safety 
        and efficacy or substantial equivalence for the approved 
        constituent product; and
            ``(B) is not duplicative of data or information included in 
        an application or other material submitted to the Secretary in 
        connection with the approved constituent product.
    ``(4) For purposes of paragraph (3), an approved constituent 
product is--
            ``(A) a drug constituent part of a combination product 
        being reviewed in a single application under section 515 or 
        510(k), provided such drug constituent part was previously 
        approved under section 505 and such application complies with 
        subparagraph (A) of paragraph (5) and is subject to 
        subparagraphs (D) and (E) of such paragraph;
            ``(B) a device constituent part approved under section 515 
        that is referenced by the sponsor and which is available for 
        use by the Secretary under section 520(h)(4); or
            ``(C) any constituent part that was previously approved, 
        cleared, or licensed under section 505, 510(k), or 515 of this 
        Act or section 351 of the Public Health Service Act, for which 
        the sponsor has a right of reference or which is otherwise 
        available for consideration by the Secretary under this Act or 
        the Public Health Service Act.
    ``(5)(A) If an application is submitted under section 515 or 510(k) 
for a combination product containing as a constituent part an approved 
drug--
            ``(i) the application shall include the certification or 
        statement required pursuant section 505(b)(2); and
            ``(ii) the applicant shall provide notice as required 
        pursuant to section 505(b)(3).
    ``(B) For purposes of this paragraph, the term `approved drug' 
means a drug--
            ``(i) that was previously approved under section 505;
            ``(ii) for which full reports of investigations that have 
        been made to show whether such drug is safe for use and whether 
        such drug is effective in use--
                    ``(I) are relied upon by the applicant submitting 
                the application described in subparagraph (A); and
                    ``(II) were not conducted by or for such applicant; 
                and
            ``(iii) with respect to which, the applicant submitting the 
        application described in subparagraph (A) has not obtained a 
        right of reference or use from the person by or for whom the 
        investigations were conducted.
    ``(C) The following provisions shall apply with respect an 
application described in subparagraph (A):
            ``(i) Subparagraphs (A), (B), (C), and (D) of section 
        505(c)(3).
            ``(ii) Clauses (ii), (iii), and (iv) of section 
        505(c)(3)(E).
            ``(iii) Paragraphs (b) and (c) of section 505A.
            ``(iv) Section 505E(a).
            ``(v) Section 527(a).
    ``(D) Notwithstanding section 520(h)(4)(A)(i), information 
contained in an application for premarket approval filed with the 
Secretary pursuant to section 515(c) may not be used to approve any 
application submitted under section 515 or 510(k) for a combination 
product containing as a constituent part a drug previously approved 
under section 505 unless--
            ``(i) the application includes the certification or 
        statement referenced in subparagraph (A);
            ``(ii) the applicant provides notice as described in 
        subparagraph (A); and
            ``(iii) the Secretary's approval of such application is 
        subject to the provisions specified in subparagraph (C).
    ``(E) An application for a combination product described in 
subparagraph (A) or (D) shall be considered an application submitted 
under Section 505(b)(2) solely for purposes of section 271(e)(2)(A) of 
the Patent Act.'';
            (3) in paragraph (8) (as redesignated by paragraph (1))--
                    (A) in subparagraph (C)--
                            (i) by amending clause (i) to read as 
                        follows:
    ``(i) In carrying out this subsection, the Office shall ensure 
timely and effective premarket reviews involving more than one agency 
center by--
            ``(I) overseeing the timeliness and alignment of reviews; 
        and
            ``(II) coordinating reviews.'';
                            (ii) in clause (ii), by inserting ``and 
                        alignment'' after ``the timeliness'' each place 
                        it appears; and
                            (iii) by adding at the end the following 
                        new clauses:
    ``(iii) The Office shall ensure that the lead center be the primary 
point of contact for the sponsor of the product. The Office shall also 
coordinate communications to and from any consulting agency center 
involved in such premarket review. Agency communications and 
commitments, to the extent consistent with other provisions of law and 
the requirements of all affected agency centers, from the lead center 
shall be binding on all other centers involved in the review.
    ``(iv) The Office shall, with respect to the premarket review of a 
combination product--
            ``(I) ensure that any meeting between the Food and Drug 
        Administration and the sponsor of the product is attended by 
        each agency center involved in the review, as appropriate;
            ``(II) require that each consulting agency center has 
        completed its premarket review and provided the results of such 
        review to the lead center within timeframes that allow the lead 
        center to meet the review goals established pursuant to the 
        most recent authorization or reauthorization of parts 2, 3, 7, 
        and 8, as applicable, of subchapter C of title VII; and
            ``(III) ensure that each consulting agency center complies 
        with the guidance described in clause (vi) and other relevant 
        regulations, guidances, and policies.
    ``(v) Not later than 10 days after the receipt by an agency center 
of an application under section 505, 510(k), or 520 of this Act, or 
under section 351 of the Public Health Service Act, for a combination 
product or an application for investigational use of a combination 
product under section 505(i) or 520(g), the agency center shall inform 
the Office of such receipt.
    ``(vi) Not later than 2 years after the date of enactment of the 
Combination Product Regulatory Fairness Act of 2015, the Secretary 
shall issue final guidance that describes the responsibilities of each 
agency center regarding its review of combination products, including 
each center's role in evaluating evidence development and review under 
a risk-based approach, dispute resolution, labeling, product usability 
assessments, and human factors testing. The Office shall, after 
soliciting public comment, review and update the guidance at least 
biannually and specify in such updated guidance the reasons for 
updates.'';
                    (B) in subparagraph (E)--
                            (i) by striking clause (i) and inserting 
                        the following new clause:
    ``(i) During the review process, any dispute regarding the 
substance, timeliness, review process, requirements, or alignment of 
the premarket review may be presented to the Office for resolution and 
the Office shall convene the relevant parties and resolve conflicts not 
later than 90 days after the date on which the Office receives written 
notice of such conflicts.''; and
                            (ii) in clause (ii), by striking ``During 
                        the review process, any dispute regarding the 
                        substance of the premarket review'' and 
                        inserting ``Any remaining dispute'';
                    (C) in subparagraph (F), in the first sentence--
                            (i) by inserting ``or which involves 
                        determining the safety or efficacy of a 
                        component of a combination product'' after 
                        ``assignment of combination products to agency 
                        centers''; and
                            (ii) by inserting ``and with the guidance 
                        described in subparagraph (C)(vi).'' before the 
                        period at the end; and
                    (D) in subparagraph (G)--
                            (i) in clause (ii), by striking ``and'' at 
                        the end;
                            (ii) in clause (iii), by striking the 
                        period at the end and inserting a semicolon; 
                        and
                            (iii) by adding at the end the following 
                        new clauses:
            ``(iv) identifying the percentage of combination products 
        for which a dispute resolution, with respect to premarket 
        review, was requested by the combination product's sponsor; and
            ``(v) identifying the percentage of meetings between the 
        Food and Drug Administration and the sponsor of a combination 
        product at which all of the centers participating in the review 
        of the combination product were in attendance, in accordance 
        with subparagraph (C)(iv)(I).'';
            (4) in paragraph (9) (as redesignated by paragraph (1)), by 
        adding at the end the following:
            ``(D) The terms `premarket review' and `reviews' include 
        all activities of the Food and Drug Administration conducted 
        prior to approval or clearance of an application or 
        notification submitted under section 505, 510(k), 515, or 520 
        of this Act or under section 351 of the Public Health Service 
        Act, including with respect to investigational use of the 
        product.''; and
            (5) by adding at the end the following:
    ``(10) Rule of Construction.--Nothing in this subsection shall be 
construed as prohibiting a sponsor, at the sponsor's discretion, from 
submitting separate applications for the constituent parts of a 
combination product, unless the Secretary determines that a single 
application is necessary to ensure the safety and effectiveness, or 
substantial equivalence, as applicable, of the combination product.''.
                                 <all>