II 

Calendar No. 425 

114TH CONGRESS 

2D SESSION S. 185 

To create a limited population pathway for approval of certain antibacterial 

drugs. 

IN THE SENATE OF THE UNITED STATES 

JANUARY 16, 2015 

Mr. HATCH (for himself, Mr. BENNET, Ms. AYOTTE, Mr. ISAKSON, Mr. KIRK, 

Mr. CARPER, and Mr. BLUMENTHAL) introduced the following bill; which 

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

Labor, and Pensions 

APRIL 18, 2016 

Reported by Mr. ALEXANDER, with an amendment 

[Strike out all after the enacting clause and insert the part printed in italic] 

A BILL 

To create a limited population pathway for approval of 

certain antibacterial drugs. 

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 ‘‘Promise for Antibiotics 

5 and Therapeutics for Health Act’’ or the ‘‘PATH Act’’. 


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1 SEC. 2. LIMITED POPULATION PATHWAY FOR ANTI2 BACTERIAL DRUGS. 

3 Section 506 of the Federal Food, Drug, and Cosmetic 

4 Act (21 U.S.C. 356) is amended— 

5 (1) by transferring subsection (e) so that it ap6 pears before subsection (f); and 

7 (2) by adding at the end the following: 

8 ‘‘(g) LIMITED POPULATION PATHWAY FOR ANTI9 BACTERIAL DRUGS.— 

10 ‘‘(1) IN GENERAL.—The Secretary shall estab11 lish a program under which the Secretary may, at 

12 the request of a sponsor, approve an antibacterial 

13 drug, alone or in combination with one or more 

14 drugs, as a limited population antibacterial drug, 

15 upon a determination that such drug is intended to 

16 treat a serious or life-threatening disease, condition, 

17 or infection and address an unmet medical need for 

18 such disease, condition, or infection within an identi19 fiable limited population. 

20 ‘‘(2) LIMITED POPULATION PATHWAY.— 

21 ‘‘(A) IN GENERAL.—The sponsor of an 

22 antibacterial drug that the Secretary deter23 mines to be eligible for approval as a limited 

24 population antibacterial drug shall be required 

25 to demonstrate the safety and effectiveness of 

26 such drug, as required under section 505(d) or 


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1 section 351(a) of the Public Health Service Act, 

2 for the intended use of the drug. The Secretary 

3 shall determine the safety and effectiveness of 

4 an antibacterial drug under the limited popu5 lation pathway for antibacterial drugs in ac6 cordance with subparagraph (B). An anti7 bacterial drug shall be eligible for approval 

8 under the limited population pathway only upon 

9 the request of the sponsor. 

10 ‘‘(B) CONSIDERATIONS.— 

11 ‘‘(i) BENEFIT-RISK PROFILE.—The 

12 Secretary’s determination of safety and ef13 fectiveness of a limited population anti14 bacterial drug shall reflect the benefit-risk 

15 profile of the drug in the intended limited 

16 population, taking into account the sever17 ity, rarity, or prevalence of the infection 

18 the drug is intended to treat and the avail19 ability or lack of alternative treatment for 

20 such infection. Approval of a drug under 

21 the limited population antibacterial drug 

22 pathway shall not be denied due to a lack 

23 of evidence to fully establish a favorable 

24 benefit-risk profile in a population that is 


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1 broader than the intended limited popu2 lation. 

3 ‘‘(ii) TYPES OF EVIDENCE.—In deter4 mining whether to approve a drug under 

5 the limited population pathway, the Sec6 retary— 

7 ‘‘(I) shall rely on sufficient evi8 dence, which may include traditional 

9 endpoints, alternate endpoints, or a 

10 combination of traditional and alter11 nate endpoints, and, as appropriate, 

12 small clinical data sets; and 

13 ‘‘(II) may rely on supplemental 

14 data, including preclinical evidence, 

15 pharmacologic or pathophysiologic evi16 dence, nonclinical susceptibility, phar17 macokinetic data, and other such con18 firmatory evidence as the Secretary 

19 determines appropriate. 

20 ‘‘(3) REQUIREMENTS.—With respect to a drug 

21 approved through the limited population pathway, 

22 the Secretary shall require— 

23 ‘‘(A) the labeling of such antibacterial 

24 drug, such as through a logo or other means, 

25 to indicate that the drug has been approved for 


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1 use only in a limited population and that the 

2 safety and efficacy of the drug has been dem3 onstrated only with respect to such limited pop4 ulation; and 

5 ‘‘(B) the sponsor to submit copies of all 

6 promotional materials related to the limited 

7 population antibacterial drug, at least 30 days 

8 prior to dissemination of the materials. 

9 ‘‘(4) OTHER PROGRAMS.—A sponsor of a drug 

10 that seeks approval of a drug through the limited 

11 population pathway for antibacterial drugs may also 

12 seek approval of such drug under subsections (a), 

13 (b), and (c), and sections 505E and 524. 

14 ‘‘(5) GUIDANCE.—Not later than 18 months 

15 after the date of enactment of the Promise for Anti16 biotics and Therapeutics for Health Act, the Sec17 retary shall issue draft guidance describing criteria, 

18 processes, and other general considerations for dem19 onstrating the safety and effectiveness of limited 

20 population antibacterial drugs and how the pathway 

21 can be expanded to other therapeutic areas in addi22 tion to antibacterial infections. The Secretary may 

23 approve antibacterial drugs through such limited 

24 population pathway prior to issuing guidance under 

25 this paragraph. 


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1 ‘‘(6) POSTAPPROVAL MONITORING PROGRAMS

2 FOR ANTIBACTERIAL DRUGS.—The Secretary, in 

3 consultation with the Commissioner and other rel4 evant heads of agencies, shall conduct postapproval 

5 monitoring programs to study how antibacterial 

6 drugs approved through the pathway under this sub7 section are used and to monitor changes in bacterial 

8 resistance to drugs, including drugs approved under 

9 this pathway. 

10 ‘‘(7) ADVICE.—The Secretary shall provide 

11 prompt advice to the sponsor of a drug for which the 

12 sponsor seeks approval through the limited popu13 lation pathway for antibacterial drugs to enable the 

14 sponsor to plan a development program to obtain the 

15 necessary data for approval of such drug through 

16 the limited population pathway for antibacterial 

17 drugs and to conduct any additional studies that 

18 would be required to gain approval of such drug for 

19 use in a broader population. 

20 ‘‘(8) TERMINATION OF LIMITATIONS.—If, after 

21 approval of a drug through the limited population 

22 pathway for antibacterial drugs, the Secretary ap23 proves a broader indication for such drug for which 

24 the sponsor applies under section 505(b) or section 

25 351 of the Public Health Service Act, the Secretary 


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1 may remove any postmarketing conditions, including 

2 requirements with respect to labeling and review of 

3 promotional materials under paragraph (3) and 

4 postapproval monitoring under paragraph (6), appli5 cable to the approval of the drug through the limited 

6 population pathway for antibacterial drugs. 

7 ‘‘(9) RULES OF CONSTRUCTION.— 

8 ‘‘(A) STANDARDS OF EVIDENCE AND AU9 THORITY OF SECRETARY.—Nothing in this sub10 section shall be construed to alter the standards 

11 of evidence applicable to the review and ap12 proval of a drug under this Act or the Public 

13 Health Service Act, or to modify or limit the 

14 authority of the Secretary to approve or mon15 itor drugs pursuant to this Act or the Public 

16 Health Service Act as authorized prior to the 

17 date of enactment of the Promise for Anti18 biotics and Therapeutics for Health Act. 

19 ‘‘(B) PRESCRIBING AUTHORITY.—Nothing 

20 in this subsection shall be construed to restrict 

21 the prescribing of antibiotics or other products, 

22 including drugs approved under the limited pop23 ulation pathway, by health care professionals, 

24 or to limit the practice of health care. 


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1 ‘‘(10) EXPANSION OF PATHWAY.—Beginning on 

2 October 1, 2016, the limited population pathway for 

3 antibiotic drugs may be expanded to apply to ap4 proval of other drugs intended to treat a serious or 

5 life-threatening illness. The approval of such drugs 

6 shall be subject to the considerations and require7 ments described in this subsection, unless the Sec8 retary delivers a report to Congress prior to that 

9 date explaining why such pathway should not be 

10 used for other therapeutic areas in addition to anti11 bacterial infections.’’. 

12 SECTION 1. SHORT TITLE. 

13 This Act may be cited as the ‘‘Promise for Antibiotics 

14 and Therapeutics for Health Act’’ or the ‘‘PATH Act’’. 

15 SEC. 2. ANTIBACTERIAL RESISTANCE MONITORING. 

16 Section 319E of the Public Health Service Act (42 

17 U.S.C. 247d-5) is amended— 

18 (1) by redesignating subsections (f) and (g) as 

19 subsections (k) and (l), respectively; and 

20 (2) by inserting after subsection (e), the fol21 lowing: 

22 ‘‘(f) MONITORING AT FEDERAL HEALTH CARE FACILI23 TIES.—The Secretary shall encourage reporting on aggre24 gate antibacterial drug use and bacterial resistance to anti25 bacterial drugs and the implementation of antibiotic stewVerDate Sep 11 2014 22:05 Apr 18, 2016 Jkt 059200 PO 00000 Frm 00008 Fmt 6652 Sfmt 6203 E:\BILLS\S185.RS S185

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1 ardship programs by health care facilities of the Depart2 ment of Defense, the Department of Veterans Affairs, and 

3 the Indian Health Service and shall provide technical as4 sistance to the Secretary of Defense and the Secretary of 

5 Veterans Affairs, as appropriate and upon request. 

6 ‘‘(g) REPORT ON ANTIBACTERIAL RESISTANCE IN HU7 MANS AND USE OF ANTIBACTERIAL DRUGS.—Not later 

8 than 1 year after the date of enactment of this subsection, 

9 and annually thereafter, the Secretary shall prepare and 

10 make publically available data and information con11 cerning— 

12 ‘‘(1) aggregate national and regional trends of 

13 bacterial resistance in humans to antibacterial drugs, 

14 including those approved under section 506(g) of the 

15 Federal Food, Drug, and Cosmetic Act; 

16 ‘‘(2) antibacterial stewardship, which may in17 clude summaries of State efforts to address bacterial 

18 resistance in humans to antibacterial drugs and anti19 bacterial stewardship; and 

20 ‘‘(3) coordination between the Director of the 

21 Centers for Disease Control and Prevention and the 

22 Commissioner of Food and Drugs with respect to the 

23 monitoring of— 

24 ‘‘(A) any applicable resistance under para25 graph (1); and 


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1 ‘‘(B) drugs approved under section 506(g) of 

2 the Federal Food, Drug, and Cosmetic Act. 

3 ‘‘(h) INFORMATION RELATED TO ANTIBIOTIC STEW4 ARDSHIP PROGRAMS.—The Secretary shall, as appropriate, 

5 disseminate guidance, educational materials, or other ap6 propriate materials related to the development and imple7 mentation of evidence-based antibiotic stewardship pro8 grams or practices at health care facilities, such as nursing 

9 homes and other long-term care facilities, ambulatory sur10 gical centers, dialysis centers, and community and rural 

11 hospitals. 

12 ‘‘(i) SUPPORTING STATE-BASED ACTIVITIES TO COM13 BAT ANTIBACTERIAL RESISTANCE.—The Secretary shall 

14 continue to work with State and local public health depart15 ments on statewide or regional programs related to anti16 bacterial resistance. Such efforts may include activities to 

17 related to— 

18 ‘‘(1) identifying patterns of bacterial resistance 

19 in humans to antibacterial drugs; 

20 ‘‘(2) preventing the spread of bacterial infections 

21 that are resistant to antibacterial drugs; and 

22 ‘‘(3) promoting antibiotic stewardship. 

23 ‘‘(j) ANTIBACTERIAL RESISTANCE AND STEWARDSHIP

24 ACTIVITIES.— 


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1 ‘‘(1) IN GENERAL.—For the purposes of sup2 porting stewardship activities, examining changes in 

3 bacterial resistance, and evaluating the effectiveness of 

4 section 506(g) of the Federal Food, Drug, and Cos5 metic Act, the Secretary shall— 

6 ‘‘(A) provide a mechanism for facilities to 

7 report data related to their antimicrobial stew8 ardship activities (including analyzing the out9 comes of such activities); and 

10 ‘‘(B) evaluate— 

11 ‘‘(i) antimicrobial resistance data 

12 using a standardized approach; and 

13 ‘‘(ii) trends in the utilization of drugs 

14 approved under such section 506(g) with re15 spect to patient populations. 

16 ‘‘(2) USE OF SYSTEMS.—The Secretary shall use 

17 available systems, including the National Healthcare 

18 Safety Network or other systems identified by the Sec19 retary, to fulfill the requirements or conduct activities 

20 under this section. 

21 ‘‘(3) AVAILABILITY OF DATA.—The Secretary 

22 shall make the data collected pursuant to this sub23 section public. Nothing in this subsection shall be con24 strued as authorizing the Secretary to disclose any in25 formation that is a trade secret or confidential inforVerDate Sep 11 2014 22:05 Apr 18, 2016 Jkt 059200 PO 00000 Frm 00011 Fmt 6652 Sfmt 6203 E:\BILLS\S185.RS S185

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1 mation subject to section 552(b)(4) of title 5, United 

2 States Code, or section 1905 of title 18, United States 

3 Code.’’. 

4 SEC. 3. LIMITED POPULATION PATHWAY FOR ANTI5 BACTERIAL DRUGS. 

6 Section 506 of the Federal Food, Drug, and Cosmetic 

7 Act (21 U.S.C. 356) is amended— 

8 (1) by transferring subsection (e) so that it ap9 pears before subsection (f); and 

10 (2) by adding at the end the following: 

11 ‘‘(g) LIMITED POPULATION PATHWAY FOR ANTI12 BACTERIAL DRUGS.— 

13 ‘‘(1) IN GENERAL.—The Secretary may approve 

14 an antibacterial drug, alone or in combination with 

15 one or more other drugs, as a limited population drug 

16 pursuant to this subsection only if— 

17 ‘‘(A) the drug is intended to treat a serious 

18 or life-threatening infection in a limited popu19 lation of patients with unmet needs; 

20 ‘‘(B) the standards for approval under sec21 tion 505(c) and (d), or the standards for licen22 sure under section 351 of the Public Health 

23 Service Act, as applicable, are met; and 


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1 ‘‘(C) the Secretary receives a written request 

2 from the sponsor to approve the drug as a lim3 ited population drug pursuant to this subsection. 

4 ‘‘(2) BENEFIT-RISK CONSIDERATION.—The Sec5 retary’s determination of safety and effectiveness of a 

6 limited population antibacterial drug shall reflect the 

7 benefit-risk profile of the drug in the intended limited 

8 population, taking into account the severity, rarity, 

9 or prevalence of the infection the drug is intended to 

10 treat and the availability or lack of alternative treat11 ment in such limited population. Such drug may be 

12 approved under this subsection notwithstanding a 

13 lack of evidence to fully establish a favorable benefit14 risk profile in a population that is broader than the 

15 intended limited population. 

16 ‘‘(3) ADDITIONAL REQUIREMENTS.—A drug ap17 proved under this subsection shall be subject to the re18 quirements of this paragraph, in addition to any 

19 other applicable requirements of this Act: 

20 ‘‘(A) LABELING.—To indicate that the safe21 ty and effectiveness of a drug approved under 

22 this subsection has been demonstrated only with 

23 respect to a limited population— 

24 ‘‘(i) all labeling and advertising of an 

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1 section shall contain the statement ‘Limited 

2 Population’ in a prominent manner and 

3 adjacent to, and not more prominent 

4 than— 

5 ‘‘(I) the proprietary name of such 

6 drug, if any; or 

7 ‘‘(II) if there is no proprietary 

8 name, the established name of the drug, 

9 if any, as defined in section 503(e)(3), 

10 or for drugs which are biological prod11 ucts, the proper name, as defined by 

12 regulation; and 

13 ‘‘(ii) the prescribing information for 

14 such antibacterial drug required by section 

15 201.57 of title 21, Code of Federal Regula16 tions (or any successor regulation) shall 

17 also include the following statement: ‘This 

18 drug is indicated for use in a limited and 

19 specific population of patients.’. 

20 ‘‘(B) PROMOTIONAL MATERIAL.—The spon21 sor of an antibacterial drug subject to this sub22 section shall submit to the Secretary copies of all 

23 promotional materials related to such drug at 

24 least 30 calendar days prior to dissemination of 

25 the materials. 


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1 ‘‘(4) OTHER PROGRAMS.—A sponsor of a drug 

2 that seeks approval of a drug under this subsection for 

3 antibacterial drugs may also seek designation or ap4 proval, as applicable, of such drug under other appli5 cable sections or subsections of this Act of the Public 

6 Health Service Act. 

7 ‘‘(5) GUIDANCE.—Not later than 18 months after 

8 the date of enactment of the Promise for Antibiotics 

9 and Therapeutics for Health Act, the Secretary shall 

10 issue draft guidance describing criteria, processes, 

11 and other general considerations for demonstrating 

12 the safety and effectiveness of limited population anti13 bacterial drugs. The Secretary shall publish final 

14 guidance within 18 months of the close of the public 

15 comment period on such draft guidance. The Sec16 retary may approve antibacterial drugs under this 

17 subsection prior to issuing guidance under this para18 graph. 

19 ‘‘(6) ADVICE.—The Secretary shall provide 

20 prompt advice to the sponsor of a drug for which the 

21 sponsor seeks approval under this subsection for anti22 bacterial drugs to enable the sponsor to plan a devel23 opment program to obtain the necessary data for ap24 proval of such drug under this subsection for anti25 bacterial drugs and to conduct any additional studies 


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1 that would be required to gain approval of such drug 

2 for use in a broader population. 

3 ‘‘(7) TERMINATION OF LIMITATIONS.—If, after 

4 approval of a drug under this subsection, the Sec5 retary approves a broader indication for such drug 

6 for which the sponsor applies under section 505(b) or 

7 section 351(a) of the Public Health Service Act, the 

8 Secretary may remove any postmarketing conditions, 

9 including requirements with respect to labeling and 

10 review of promotional materials under paragraph (3), 

11 applicable to the approval of the drug under this sub12 section. 

13 ‘‘(8) RULES OF CONSTRUCTION.—Nothing in this 

14 subsection shall be construed to alter the authority of 

15 the Secretary to approve drugs pursuant to this Act 

16 and section 351 of the Public Health Service Act, in17 cluding the standards of evidence, and applicable con18 ditions, for approval under such Acts, the standards 

19 of approval of a drug under this Act or the Public 

20 Health Service Act, or to alter the authority of the 

21 Secretary to monitor drugs pursuant to this Act or 

22 the Public Health Service Act. 

23 ‘‘(9) REPORTING AND ACCOUNTABILITY.— 

24 ‘‘(A) BIANNUAL REPORTING.—The Secretary 

25 shall report to Congress not less often than once 


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1 every 2 years on the number of requests for ap2 proval, and the number of approvals, of an anti3 bacterial drug under this subsection. 

4 ‘‘(B) GAO REPORT.—Not later than Decem5 ber 2021, the Comptroller General of the United 

6 States shall report on the coordination of activi7 ties required under section 319E of the Public 

8 Health Service Act, a review of such activities, 

9 and the extent to which the use of the pathway 

10 established under this subsection has streamlined 

11 premarket approval for antibacterial drugs for 

12 limited populations, if such pathway has func13 tioned as intended, if such pathway has helped 

14 provide for safe and effective treatment for pa15 tients, if such premarket approval would be ap16 propriate for other categories of drugs, and if the 

17 authorities under this subsection have affected 

18 antibiotic resistance.’’. 

19 SEC. 4. PRESCRIBING AUTHORITY. 

20 Nothing in this Act, or an amendment made by this 

21 Act, shall be construed to restrict the prescribing of anti22 bacterial drugs or other products, including drugs approved 

23 under section 506(g) of the Federal Food, Drug, and Cos24 metic Act (21 U.S.C. 356(g)), by health care professionals, 

25 or to limit the practice of health care. 


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Calendar No. 425 

114TH CONGRESS 

2D SESSION S. 185 

A BILL 

To create a limited population pathway for approval 

of certain antibacterial drugs. 

APRIL 18, 2016 

Reported with an amendment 


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