[House Hearing, 114 Congress]
[From the U.S. Government Publishing Office]




    COMBATING SUPERBUGS: U.S. PUBLIC HEALTH RESPONSES TO ANTIBIOTIC 
                               RESISTANCE

=======================================================================

                                HEARING

                               BEFORE THE

              SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS

                                 OF THE

                    COMMITTEE ON ENERGY AND COMMERCE
                        HOUSE OF REPRESENTATIVES

                    ONE HUNDRED FOURTEENTH CONGRESS

                             SECOND SESSION

                               __________

                             JUNE 14, 2016

                               __________

                           Serial No. 114-153



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                    COMMITTEE ON ENERGY AND COMMERCE

                          FRED UPTON, Michigan
                                 Chairman
JOE BARTON, Texas                    FRANK PALLONE, Jr., New Jersey
  Chairman Emeritus                    Ranking Member
ED WHITFIELD, Kentucky               BOBBY L. RUSH, Illinois
JOHN SHIMKUS, Illinois               ANNA G. ESHOO, California
JOSEPH R. PITTS, Pennsylvania        ELIOT L. ENGEL, New York
GREG WALDEN, Oregon                  GENE GREEN, Texas
TIM MURPHY, Pennsylvania             DIANA DeGETTE, Colorado
MICHAEL C. BURGESS, Texas            LOIS CAPPS, California
MARSHA BLACKBURN, Tennessee          MICHAEL F. DOYLE, Pennsylvania
  Vice Chairman                      JANICE D. SCHAKOWSKY, Illinois
STEVE SCALISE, Louisiana             G.K. BUTTERFIELD, North Carolina
ROBERT E. LATTA, Ohio                DORIS O. MATSUI, California
CATHY McMORRIS RODGERS, Washington   KATHY CASTOR, Florida
GREGG HARPER, Mississippi            JOHN P. SARBANES, Maryland
LEONARD LANCE, New Jersey            JERRY McNERNEY, California
BRETT GUTHRIE, Kentucky              PETER WELCH, Vermont
PETE OLSON, Texas                    BEN RAY LUJAN, New Mexico
DAVID B. McKINLEY, West Virginia     PAUL TONKO, New York
MIKE POMPEO, Kansas                  JOHN A. YARMUTH, Kentucky
ADAM KINZINGER, Illinois             YVETTE D. CLARKE, New York
H. MORGAN GRIFFITH, Virginia         DAVID LOEBSACK, Iowa
GUS M. BILIRAKIS, Florida            KURT SCHRADER, Oregon
BILL JOHNSON, Ohio                   JOSEPH P. KENNEDY, III, 
BILLY LONG, Missouri                     Massachusetts
RENEE L. ELLMERS, North Carolina     TONY CARDENAS, California
LARRY BUCSHON, Indiana
BILL FLORES, Texas
SUSAN W. BROOKS, Indiana
MARKWAYNE MULLIN, Oklahoma
RICHARD HUDSON, North Carolina
CHRIS COLLINS, New York
KEVIN CRAMER, North Dakota

              Subcommittee on Oversight and Investigations

                        TIM MURPHY, Pennsylvania
                                 Chairman
DAVID B. McKINLEY, West Virginia     DIANA DeGETTE, Colorado
  Vice Chairman                        Ranking Member
MICHAEL C. BURGESS, Texas            JANICE D. SCHAKOWSKY, Illinois
MARSHA BLACKBURN, Tennessee          KATHY CASTOR, Florida
H. MORGAN GRIFFITH, Virginia         PAUL TONKO, New York
LARRY BUCSHON, Indiana               JOHN A. YARMUTH, Kentucky
BILL FLORES, Texas                   YVETTE D. CLARKE, New York
SUSAN W. BROOKS, Indiana             JOSEPH P. KENNEDY, III, 
MARKWAYNE MULLIN, Oklahoma               Massachusetts
RICHARD HUDSON, North Carolina       GENE GREEN, Texas
CHRIS COLLINS, New York              PETER WELCH, Vermont
KEVIN CRAMER, North Dakota           FRANK PALLONE, Jr., New Jersey (ex 
JOE BARTON, Texas                        officio)
FRED UPTON, Michigan (ex officio)
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
                             C O N T E N T S

                              ----------                              
                                                                   Page
Hon. Tim Murphy, a Representative in Congress from the 
  Commonwealth of Pennsylvania, opening statement................     1
    Prepared statement...........................................     3
Hon. Diana DeGette, a Representative in Congress from the state 
  of Colorado, opening statement.................................     4
Hon. Fred Upton, a Representative in Congress from the State of 
  Michigan, opening statement....................................     6
    Prepared statement...........................................     7
Hon. David B. McKinley, a Representative in Congress from the 
  State of West Virginia, opening statement......................     8
    Prepared statement...........................................     8
Hon. Frank Pallone, Jr., a Representative in Congress from the 
  State of New Jersey, opening statement.........................     9

                               Witnesses

Beth Bell, Director, National Center for Emerging and Zoonotic 
  Infectious Disease, Centers for Disease Control................    12
    Prepared statement...........................................    14
Janet Woodcock, Director, Center for Drug Evaluation and 
  Research, Food and Drug Administration.........................    21
    Prepared statement...........................................    23
Richard J. Hatchett, Acting Director, Biomedical Advanced 
  Research And Development Authority.............................    34
    Prepared statement...........................................    36
Dennis M. Dixon, Division of Microbiology and Infectious 
  Diseases, National Institute of Allergy and Infectious 
  Diseases, National Institutes of Health........................    45
    Prepared statement...........................................    47

                           Submitted Material

Committee memorandum.............................................    79

 
    COMBATING SUPERBUGS: U.S. PUBLIC HEALTH RESPONSES TO ANTIBIOTIC 
                               RESISTANCE

                              ----------                              


                         TUESDAY, JUNE 14, 2016

                  House of Representatives,
      Subcommittee on Oversight and Investigations,
                          Committee on Energy and Commerce,
                                                    Washington, DC.
    The subcommittee met, pursuant to call, at 10:00 a.m., in 
room 2322, Rayburn House Office Building, Hon. Tim Murphy 
(chairman of the subcommittee) presiding.
    Present: Representatives Murphy, McKinley, Burgess, 
Blackburn, Bucshon, Flores, Brooks, Mullin, Hudson, Collins, 
Upton (ex officio), DeGette, Schakowsky, Castor, Tonko, Clarke, 
Kennedy, Green, and Pallone (ex officio).
    Staff Present: Gary Andres, Staff Director; Emily Felder, 
Counsel, Oversight and Investigations; Jay Gulshen, Staff 
Assistant; Brittany Havens, Oversight Associate, Oversight and 
Investigations; Charles Ingebretson, Chief Counsel, Oversight 
and Investigations; Alan Slobodin, Deputy Chief Counsel, 
Oversight; Dylan Vorbach, Deputy Press Secretary; Jeff Carroll, 
Minority Staff Director; Tiffany Guarascio, Minority Deputy 
Staff Director and Chief Health Advisor; Chris Knauer, Minority 
Oversight Staff Director; Una Lee, Minority Chief Oversight 
Counsel; Elizabeth Letter, Minority Professional Staff Member; 
and Andrew Souvall, Minority Director of Communications, 
Outreach and Member Services.

   OPENING STATEMENT OF HON. TIM MURPHY, A REPRESENTATIVE IN 
         CONGRESS FROM THE COMMONWEALTH OF PENNSYLVANIA

    Mr. Murphy. Good morning, meeting here of the Energy and 
Commerce Subcommittee on Oversight and Investigations. I do 
want to announce to members this hearing is here and not in 
Room 2123. I just want you to know. I was there, you were not. 
It was a very powerful, moving----
    Mr. Upton. There was a very long line of folks to get in.
    Mr. Murphy. There was, so I figured it must be this 
hearing, but my apologies. It happens.
    So this is a hearing on U.S. public health response to 
antibiotic resistance. The subcommittee convenes this hearing 
today to examine public health responses to the challenge of 
antibiotic-resistant superbugs. One of the world's most 
pressing health problems is the emergence of bacterial 
infections that are resistant to antibiotics. And according to 
the Centers for Disease Control and Prevention, each year, 2 
million Americans become sick with antibiotic-resistant 
infections, and of that, about 23,000 die. Globally, some 
institutions estimate up to 700,000 die each year from 
antibiotic-resistant infections, and without action, the 
researchers estimate 10 million people will die per year by 
2050 from drug-resistant infections.
    The World Health Organization has declared that humanity is 
on the precipice of a post-antibiotic era where common 
infections may once again be lethal because bacteria have 
become resistant to the antibiotics existing to treat them.
    The antibiotic-resistance threat just got greater. Last 
month, a woman in my home State of Pennsylvania was diagnosed 
with an E. coli infection that had a rare gene called MCR-1, a 
new kind of superbug never before seen in the United States. 
Medical professionals were alarmed for two reasons. One, this 
new superbug is resistant to colistin, an antibiotic of last 
resort, which is used when no other antibiotics can fight the 
infection. And two, this MCR-1 gene can move from one bacteria 
to another. Eventually, MCR-1 could emerge with another 
superbug that is resistant to all antibiotics except for 
colistin and form an unstoppable superbug.
    In response to the discovery of the MCR-1 gene, CDC 
Director Dr. Tom Frieden commented that the medicine cabinet is 
empty for some patients. It is the end of the road unless we 
act urgently. If this threat is not stopped, minor infections 
may become life-threatening and treatment for diseases such as 
cancer, diabetes, or routine surgeries will be at risk.
    Fortunately, the end of the road is not here yet, and 
Congress and Federal agencies are working diligently to counter 
the effects of antibiotic resistance. These efforts confront 
the two main contributors to the spread of antibiotic 
resistance: the overprescription of antibiotics and the lack of 
new antibiotic development.
    Since the discovery of penicillin in the early 20th 
century, almost every type of bacteria has become less 
responsive to antibiotics. As soon as an antibiotic goes into 
wide use among the general public, bacteria evolve to become 
resistant.
    A study published last month in the Journal of the American 
Medical Association, known as JAMA, found that nearly a third 
of antibiotics prescribed in doctors' offices, emergency rooms 
and hospital-based clinics in the United States are not needed. 
This amounts to nearly 47 million unnecessary prescriptions 
given out each year. That is 47 million unnecessary 
prescriptions each year. And the number in this report most 
likely undercount the use of antibiotics because the data did 
not include urgent care clinics, retail pharmacies, dentist 
offices, and prescriptions given over the phone by nurse 
practitioners and physician assistants.
    To combat antibiotic overuse, the CDC has partnered with 
the FDA to advocate for antibiotic stewardship programs in 
health care facilities throughout the United States. The CDC 
has issued guidelines about how hospitals can minimize 
inappropriate or excessive use of antibiotics, which could help 
reduce antibiotic overprescription. Reducing the inappropriate 
use of antibiotics will help, but it can only slow the spread 
of antibiotic-resistant bacteria, new antibiotics, and 
alternative therapies must be developed.
    Despite the need for antibiotic development, as of March 
2016 there were only 37 new antibiotics in development, and 
just 13 were in phase 3 clinical trials. These drugs would 
potentially address many resistant bacteria, but they are not 
enough. To combat this, in February of this year the Biomedical 
Advanced Research and Development Authority, known as BARDA, 
has collaborated with NIH to establish a biopharmaceutical 
accelerator that will support research and development to 
incentivize antibacterial drug development. This accelerator 
will, one, fund development of antibacterial products; and two, 
quickly move successful drug candidates through early 
development; three, provide business and drug development 
guidance; and four, decrease barriers to research and 
development of antibiotics.
    The CDC, FDA, NIH, and BARDA have and continue to make 
significant and ongoing contributions to implement the National 
Action Plan for Combating Antibiotic-Resistant Bacteria 
released last year, which outlines steps to implement a 
national strategy to combat antibiotic resistance. 
Additionally, Congress has increased funding for these 
initiatives by 57 percent over last fiscal year for a total of 
more than $375 million.
    Despite these promising developments, we are facing a 
public health challenge, and we need to ensure that the Federal 
Government is taking the appropriate action to protect the 
American public.
    So I want to thank the witnesses for appearing here today 
before the subcommittee. I look forward to hearing all of your 
testimony on this very, very important issue.
    [The prepared statement of Mr. Murphy follows:]

                 Prepared statement of Hon. Tim Murphy

    The subcommittee convenes this hearing today to examine 
public health responses to the challenge of antibiotic 
resistant ``superbugs.''
    One of the world's most pressing health problems is the 
emergence of bacterial infections that are resistant to 
antibiotics.
    According to the Centers for Disease Control and 
Prevention, each year 2 million Americans become sick every 
year with antibiotic-resistant infections, and of that about 
23,000 die.
    Globally, some institutions estimate up to 700,000 die each 
year from antibiotic resistant infections. Without action, the 
researchers estimate 10 million people will die per year by 
2050 from drug resistant infections.
    The World Health Organization has declared that humanity is 
on the precipice of a ``post-antibiotic era,'' where common 
infections may once again be lethal because bacteria have 
become resistant to the antibiotics existing to treat them.
    The antibiotic-resistance threat just got greater. Last 
month, a woman in my home state of Pennsylvania was diagnosed 
with an E. coli infection that had a rare gene called MCR-1, a 
new kind of superbug never before seen in the United States.
    Medical professionals were alarmed for two reasons. One, 
this new superbug is resistant to colistin [Co--liss--tin], an 
antibiotic of last resort which is used when no other 
antibiotics can fight the infection.
    Two, this MCR-1 gene can move from one bacteria to another. 
Eventually, MCR-1 could merge with another superbug that is 
resistant to all antibiotics, except for colistin, and form an 
unstoppable superbug.
    In response to the discovery of the MCR-1 gene, CDC 
Director Dr. Tom Frieden commented that ``the medicine cabinet 
is empty for some patients . . . . It is the end of the road 
unless we act urgently.'' If the threat is not stopped, minor 
infections may become life threatening and treatment for 
disease such as cancer, diabetes or routine surgeries will be 
at risk.
    Fortunately, the end of the road is not here yet. Congress 
and Federal agencies are working diligently to counter the 
effects of antibiotic resistance.
    These efforts confront the two main contributors to the 
spread of antibiotic resistance: The over-prescription of 
antibiotics and the lack of new antibiotic development.
    Since the discovery of penicillin in the early 20th 
century, almost every type of bacteria has become less 
responsive to antibiotics. As soon as an antibiotic goes in to 
wide use among the general public, bacteria evolve to become 
resistant.
    A study published last month in the Journal of the American 
Medical Association (JAMA) found that nearly a third of 
antibiotics prescribed in doctors' offices, emergency rooms, 
and hospital-based clinics in the United States are not needed. 
This amounts to nearly 47 million unnecessary prescriptions 
given out each year.
    And the numbers in this report most likely undercount the 
use of antibiotics, because the data did not include urgent 
care clinics, retail pharmacies, dentists' offices, and 
prescriptions given over the phone, and by nurse practitioners 
and physician assistants.
    To combat antibiotic over-use, the CDC has partnered with 
FDA to advocate for antibiotic ``stewardship'' programs in 
health care facilities throughout the United States. The CDC 
has issued guidelines about how hospitals can minimize 
inappropriate or excessive use of antibiotics, which could help 
reduce antibiotic over-prescription.
    Reducing the inappropriate use of antibiotics will help, 
but it can only slow the spread of antibiotic resistant 
bacteria. New antibiotics and alternative therapies must be 
developed.
    Despite the need for antibiotic development, as of March 
2016, there were only 37 new antibiotics in development. Just 
13 were in phase 3 clinical trials. These drugs would 
potentially address many resistant bacteria--but they are not 
enough.
    To combat this, in February of this year, the Biomedical 
Advanced Research and Development Authority (BARDA) has 
collaborated with NIH to establish a ``Biopharmaceutical 
Accelerator'' that will support research and development to 
incentivize antibacterial drug development. This Accelerator 
will (1) fund development of antibacterial products, (2) 
quickly move successful drug candidates through early 
development, (3) provide business and drug development 
guidance, and (4) decrease barriers to research and development 
of antibiotics.
    The CDC, FDA, NIH, and BARDA have, and continue to make, 
significant and ongoing contributions to implement the National 
Action Plan for Combating Antibiotic-Resistant Bacteria 
released last year, which outlines steps to implement a 
national strategy to combat antibiotic resistance.
    Additionally, Congress has increased funding for these 
initiatives by 57 percent over last fiscal year, for a total of 
more than $375 million.
    Despite these promising developments, we are facing a 
public health challenge and we need to ensure that the federal 
government is taking the appropriate action to protect the 
American public.
    I would like to thank the witnesses for appearing before 
the Subcommittee today and I look forward to hearing your 
testimony on this very important issue.

    Mr. Murphy. I now recognize the Ranking Member of the 
subcommittee, Ms. DeGette of Colorado, for 5 minutes.
     And I now recognize the ranking member of the 
subcommittee, Ms. DeGette of Colorado, for 5 minutes.

 OPENING STATEMENT OF HON. DIANA DEGETTE, A REPRESENTATIVE IN 
              CONGRESS FROM THE STATE OF COLORADO

    Ms. DeGette. Thank you so much, Mr. Chairman. This is a 
really important hearing. We have been worried for quite some 
time here in Congress and at the agencies about the risk of 
resistant antibiotics. And this report last month about the 
superbug has been quite concerning to all of us.
    The bacterium's resistance to colistin is particularly 
concerning because in this country physicians use colistin as 
the treatment of last resort when other antibiotics are no 
longer effective. Public health experts fear that this gene 
could jump to other bacteria that are already resistant to most 
other antibiotics.
    Here is another observation about Dr. Frieden. He said, 
``It basically shows that the end of the road isn't very far 
away for antibiotics, that we may be in a situation where we 
have patients in our intensive care units or patients getting 
urinary tract infections for which we do not have 
antibiotics.''
    Obviously, we are all concerned about this, and I know all 
the witnesses and the members share this concern. We really 
don't want to revert to a time when physicians no longer have 
the tools to treat infections. Even common and once easily 
treated infections could once again prove life-threatening.
    That this newest superbug has emerged on our home turf 
should not surprise us. Public health and infectious disease 
experts have been sounding the alarm for years. But I hope that 
this new discovery will lend urgency to efforts to monitor and 
fight antibiotic resistance.
    The CDC has reported for decades that overuse of 
antibiotics and poor hygiene practices in hospitals and other 
inpatient health care settings contribute to the formation of 
drug-resistant bacteria. For example, studies showed that 30 to 
50 percent of antibiotics prescribed in hospitals were 
unnecessary or inappropriate. Public health experts have 
similarly warned us about overprescribing of antibiotics in 
outpatient settings. A recent Pew study, for example, found 
that about 30 percent of all outpatient office visits in the 
U.S. resulted in the prescribing of an antibiotic, but 30 
percent of those, which is almost 50, 5-0 million prescriptions 
are unnecessary.
    Now, in the last decade these issues have received 
increased attention and funding, but as our witnesses will 
testify today, there is still far more to do. And I want to 
hear from our witnesses in particular in two different areas. 
The first one is antibiotic stewardship programs, which can 
both decrease the spread of infections and reduce the 
inappropriate use of antibiotics.
    We need to improve public health education to ensure that 
patients and physicians understand how and when antibiotics 
should be prescribed. We need such stewardship programs both in 
health care facilities like hospitals and also in communities. 
I am hoping I can hear from our witnesses about antibiotic 
stewardship and whether we are seeing positive outcomes from 
current efforts.
    I also am interested to see how antibiotic stewardship 
programs can result in more appropriate and effective use of 
antibiotics in animals. I think more needs to be done to shed a 
light on these issues, and I am interested to see what the 
witnesses will have to say. I do wish that we had a witness 
from the USDA because antibiotic overuse in animals is a really 
big problem.
    The second area I want to hear about is the development of 
new antibiotics, diagnostics, and even vaccines to address the 
issue of antibiotic resistance. All of these agencies today 
play a critical role in the development of new drugs and other 
tools.
    I can't lose the opportunity to talk about our wonderful 
bill that Chairman Upton and I have cosponsored, along with all 
the other members of this subcommittee. Earlier this year, the 
21st Century Cures Act passed out of the Energy and Commerce 
Committee unanimously and was then passed by the full House on 
an overwhelming basis. The bill includes the text of the 
Antibiotic Development to Advance Patient Treatment Act, or 
ADAPT Act. This is a really important bill that was originally 
cosponsored by Congressman Green and Congressman Shimkus, and 
it creates a new FDA approval pathway for limited population 
antibacterial drugs.
    This legislation is designed to provide an approval process 
for drugs that affect a limited population of patients with 
serious or life-threatening infections or for drugs that fill 
an unmet need. We really need to pass the ADAPT Act. The 
easiest way to do this is of course for the Senate to pass the 
21st Century Cures bill, and frankly, we keep hearing 
assurances that this will be happening any day. So maybe this 
urgent issue can be used to help enact this important law into 
law.
    So, Mr. Chairman, I really want to thank you for having 
this hearing. It is an important one. And I want to thank our 
witnesses again for coming today, and I yield back.
    Mr. Murphy. The gentlelady yields back. I now recognize the 
chairman of the full committee, Mr. Upton, for 5 minutes.

   OPENING STATEMENT OF HON. FRED UPTON, A REPRESENTATIVE IN 
              CONGRESS FROM THE STATE OF MICHIGAN

    Mr. Upton. Well, thank you, Mr. Chairman.
    So today, we gather to discuss the U.S. public health 
response to antibiotic resistance in light of the recent 
discovery of a new superbug. This superbug gene was first 
discovered by Chinese and British researchers in pigs, raw 
pork, and in a small number of folks in China in November of 
last year, but a recent case of course of the woman in 
Pennsylvania with the E. coli is the first discovery of this 
rare gene known as MCR here in the U.S.
    A headline in the Post captured the urgency: ``The superbug 
that doctors have been dreading just reached the U.S.'' 
Concerns about this new threat are real indeed and they are 
being felt in Michigan and throughout the country.
    The detection of this new antibiotic-resistant gene is very 
troubling because it signals the potential arrival of an 
unstoppable superbug. The gene is resistant to a last-report 
antibiotic and has the ability to move from one bacterium to 
another. While MCR-1 on its own is treatable by other 
antibiotics, disease experts tell us that the fear is not if 
but when this gene transfers and merges with another superbug 
that is resistant to all other antibiotics. This would create 
the nightmare scenario of a bacterial infection that cannot be 
stopped with any known antibiotic treatment.
    The continuing evolution of bacteria, the overprescription 
of antibiotics, and the lack of new antibiotic development have 
all contributed to the problem. Our understanding of the MCR-1 
gene is growing by the day, but there are still many questions 
that remain to be answered before we can be assured that we are 
doing everything that we can to protect the American people 
from this superbug and future challenges that arise from 
antibiotic resistance.
    The questions include how did the bug get here to the U.S.? 
Where did it come from? How does it spread? Are we prepared for 
an outbreak of antibiotic-resistant bacterium? What is the 
Federal Government's plan to confront the public health 
challenge? In addition to our concerns about this particular 
superbug, we need to take a look at antibiotic resistance as a 
whole. And in response to the discovery of MCR gene in 
Pennsylvania, Dr. Frieden commented that it basically shows us 
that the end of the road isn't very far away for antibiotics. 
If that is true, minor bacterial infections could suddenly 
become fatal.
    So we need to evaluate antibiotic development and assess 
where the science is, what barriers exist. How do we promote 
the discovery of new antibiotics? And as my good friend and 
colleague Ms. DeGette said, through the GAIN Act of 2012 and 
the ADAPT Act, which is part of 21st Century Cures, this 
committee has made a good number of strides to foster and 
encourage the development of new antibiotics that can fight the 
superbugs. In the meantime, we need to take appropriate 
measures such as antibiotic stewardship program to ensure that 
the antibiotics that already exist are being prescribed 
appropriately.
    [The prepared statement of Mr. Upton follows:]

                 Prepared statement of Hon. Fred Upton

    Today, we gather to discuss the U.S. public health response 
to antibiotic resistance in light of the recent discovery of a 
new superbug.
    This superbug gene was first discovered by Chinese and 
British researchers in pigs, raw pork, and in a small number of 
people in China in November last year, but a recent case of a 
woman in Pennsylvania with E. coli is the first discovery of 
this rare gene, known as MCR-1, in the United States. A 
headline in The Washington Post captured the urgency--``The 
superbug that doctors have been dreading just reached the 
U.S.'' Concerns about this new threat are real, and they are 
being felt in Michigan and throughout the country.
    The detection of this new antibiotic-resistant gene is 
troubling because it signals the potential arrival of an 
unstoppable superbug. This gene is resistant to a last-resort 
antibiotic and has the ability to move from one bacterium to 
another. While MCR-1 on its own is treatable by other 
antibiotics, disease experts tell us the fear is not if, but 
when, this gene transfers and merges with another superbug that 
is resistant to all other antibiotics. This would create the 
nightmare scenario of a bacterial infection that cannot be 
stopped with any known antibiotic treatment.
    The continuing evolution of bacteria, the over-prescription 
of antibiotics, and the lack of new antibiotic development have 
all contributed to this problem. Our understanding of the MCR-1 
gene is growing by the day, but there are still many questions 
that remain to be answered before we can be assured that we are 
doing everything that we can to protect the American people 
from this superbug and future challenges that arise from 
antibiotic-resistance.
    The questions include: How did the bug get to the United 
States? Where did it come from? How does it spread? Are we 
prepared for an outbreak of an antibiotic-resistant bacterium? 
What is the federal government's plan to confront this public 
health challenge?
    In addition to our concerns about this particular superbug, 
we need to take a look at antibiotic resistance as a whole. In 
response to the discovery of the MCR-1 gene in the Pennsylvania 
case, the CDC Director, Dr. Tom Frieden, commented that ``[i]t 
basically shows us that the end of the road isn't very far away 
for antibiotics.'' If that is true, minor bacterial infections 
could suddenly become fatal.
    We need to evaluate antibiotic development and assess where 
the science is, what barriers exist, and how we can promote the 
discovery of new antibiotics. Through the GAIN Act in 2012, and 
the ADAPT Act which is part of 21st Century Cures, this 
committee has made numerous strides to foster and encourage the 
development of new antibiotics that can fight these superbugs.
    In the meantime, we need to take appropriate measures, such 
as antibiotic stewardship programs, to ensure that antibiotics 
that already exist are being prescribed appropriately.
    We thank the experts joining us this morning to discuss the 
federal response to this superbug and how antibiotic resistance 
is being addressed both as a nation and globally. The last 
thing we can afford is looking back to today, and wishing we 
had done more.

    Mr. Upton. I appreciate the testimony and the dialogue with 
our experts, and I yield back to Mr. McKinley.

 OPENING STATEMENT OF HON. DAVID B. MCKINLEY, A REPRESENTATIVE 
          IN CONGRESS FROM THE STATE OF WEST VIRGINIA

    Mr. McKinley. Thank you, Mr. Chairman.
    Antibiotics, it is my understanding--I am the engineer in 
the room, not the practicing physician, but my understanding is 
that the antibiotics are not effective against viruses, and 
this seems to be a good scientific fact from which to begin 
with. But yet in America you have heard the statistics. A third 
of the antibiotics are overprescribed by doctors. The CDC said 
that 47 million prescriptions were unnecessarily prescribed or 
inappropriately prescribed for cases that don't respond to the 
antibiotics.
    And then the other point it comes down to is that we only 
represent 5 percent of the population in the world, so we have 
got 95 percent of the world out there--in many respects we know 
there are 20 nations in Europe and we know Mexico gives you 
antibiotics over the counter. And that tends to get to a point 
where we are probably going to overprescribe or they are going 
to be inappropriately used and our body will be able to build 
up resistance to that as a result of this inappropriate use for 
that.
    And then we go to this, fast-forward to today with the 
woman in Pennsylvania. The interesting part is going to be how 
we are going to respond to that because how did she get it and 
what are we going to do to respond to that? So watching the 
time frame with this, we don't know if these antibiotics are 
used to help will even be effective in the future because of 
this overuse, overprescription.
    [The prepared statement of Mr. McKinley follows:]

              Prepared statement of Hon. David B. McKinley

    Thank you, Mr. Chairman, and thank you for holding this 
hearing on this important public health challenge.
    When we think about superbugs, or antibiotic resistant 
bacteria, we think about two different categories: what we 
know, and what we don't know.
    We know that doctors and patients alike are partially to 
blame for the over-use of antibiotics. Doctors prescribe 
antibiotics when they are not necessary, and patients ask for 
antibiotics, thinking they will make them better, faster.
    We know that antibiotics are becoming less effective in 
treating bacterial infections, because bacteria are evolving to 
become resistant. This will make it harder to treat not only 
common infections, such as strep throat, but also more serious 
conditions like cancer.
    Patients fighting cancer undergo treatment that damages the 
immune system, which makes them more susceptible to infections. 
The same is true for organ transplant patients.
    We know that the current crop of antibiotics in development 
and clinical trials are not sufficient. Researchers are 
starting to examine alternative therapies, other than 
antibiotics, to treat bacterial infections.
    Now, on to what we don't know. We don't know how the 
dangerous MCR-1 gene came into the United States. We don't know 
how the woman in Pennsylvania contracted the MCR-1 gene, since 
she had not traveled outside the United States recently, and 
tests did not find the gene in her close family and friends.
    We don't know how long it will take for the MCR-1 gene to 
transfer to bacteria that are resistant to all other 
antibiotics to create bacteria that cannot be treated with 
existing antibiotics. And when that happens, we don't know how 
far or how quickly it will spread, and how doctors will treat 
it.
    Fortunately, Congress and Federal agencies are taking 
action, and they did not wait until this MCR-1 gene showed up. 
Over the last several years, the Federal government has ramped 
up its efforts to surveil and track these dangerous bacteria so 
that scientists and medical professionals can be as prepared as 
possible to confront these threats.
    The CDC has led the coordinated effort between the DOD and 
the USDA to respond to the discovery of the MCR-1 gene. The 
USDA has also been investigating the source of the MCR-1 gene, 
and discovered the gene in a pig in the United States. The USDA 
is currently working to identify the source of that gene as 
well.
    Through the National Antimicrobial Resistance Monitoring 
System, the FDA, CDC, and USDA all conduct research on bacteria 
found in food, animals, and humans. These surveillance methods 
track the bacteria and determine how resistance arises and 
transfers between bacteria.
    Also, as part of a National Action Plan, CDC is ramping up 
its network of regional and local labs to track the spread of 
the MCR-1 gene and other new forms of antibiotic resistance.
    The more we know about these superbugs--where they are, how 
they become resistant, and how they are transmitted to humans--
the more we can prepare as a nation to combat these challenges.
    Thank you to our witnesses for testifying today, and I look 
forward to a productive conversation.

    Mr. McKinley. So I am looking forward to your testimony 
today, and I yield back the balance of my time to Dr. Burgess.
    Mr. Burgess. I thank the gentleman for yielding. And I do 
want to thank our panelists for being here today. And I am most 
interested in knowing how you all are going to be working 
together on an interagency basis to see that we achieve the 
goals. I would like to hear from you perhaps some of your 
thoughts on what the legislative branch might do in addition to 
getting the Cures bill passed over in the other body.
    And then finally, there was a significant amount of money 
made available in this area last December, and I would like to 
hear from each of you how that money has been allocated and 
utilized and as to whether or not you thought it had been of 
any benefit.
    Thank you, Mr. Chairman. I will yield back.
    Mr. Murphy. Thank you. I now recognize the ranking member 
of the full committee, Mr. Pallone, for 5 minutes.

OPENING STATEMENT OF HON. FRANK PALLONE, JR., A REPRESENTATIVE 
            IN CONGRESS FROM THE STATE OF NEW JERSEY

    Mr. Pallone. Thank you, Mr. Chairman.
    Antibiotic resistance is a significant domestic and global 
threat to both public health and national security, and I am 
glad we are taking the opportunity to examine this issue. I 
want to begin by emphasizing that antibiotics are incredibly 
valuable tools that have made once-fatal infections easily 
treatable, and antibiotics have transformed our health care 
system.
    But as the use of antibiotics has spread, the threat posed 
by antibiotic-resistant bacteria or superbugs has grown. For 
that effective, coordinated, and decisive government action, we 
risk entering into a post-antibiotic world where common 
infections could once again become life-threatening.
    The recent discovery of the MCR-1 gene on a colistin-
resistant strain of the E. coli bacteria signals that this day 
is closer than it has ever been before. We see alarming 
statistics about the rates of overprescribing of antibiotics 
both for unnecessary and inappropriate use. At the same time, 
we have seen that drug manufacturers are unable to produce 
enough new drugs to meet this threat. There is no question that 
our arsenal of effective antibiotics is dangerously low today 
as a result of antibiotic resistance, and it is a dire 
situation.
    That said, I am encouraged by the attention and funding we 
have placed on antibiotic resistance in recent years. Last 
year, the White House unveiled its National Action Plan for 
Combating Antibiotic-Resistant Bacteria, which sets forth 
ambitious goals to fight antibiotic resistance. All the 
agencies before us today play critical roles in that effort. In 
fiscal year 2016, we are devoting over $830 million to fighting 
antibiotic resistance, and President Obama has requested $1.1 
billion towards this effort for fiscal year 2017. And these are 
important investments.
    But in order for us to effectively address antibiotic 
resistance we need to make this a priority for the foreseeable 
future. This is not an issue we can address for a few years and 
then ignore. Antibiotic resistance is a reality of nature. 
Bacteria begin to mutate and develop resistance as soon as a 
new antibiotic begins to be used. We must develop long-term 
strategies and guarantee long-term funding to fight antibiotic 
resistance, and once we have begun implementing those 
strategies and ramping up funding, we must follow through on 
our commitments.
    It is also important to emphasize that this is a global 
threat. It is not enough to address resistance here in the 
United States and hope that it will keep us protected. And from 
a global perspective, we must recognize that we are only as 
strong as our weakest link. In some places, antibiotics are 
used sparingly in the United States are available over the 
counter. In many countries, a lack of hygiene, sanitation, and 
basic infection control in medical settings results in 
increased antibiotic consumption.
    If we do not want these superbugs here in the United 
States, we need to stop them from developing both here and 
abroad, and we must also improve global surveillance of 
antibiotic-resistant bacteria and antibiotic consumption. 
Stopping the spread of antibiotic-resistant bacteria is a 
global threat, and therefore, solutions must be global in 
nature.
    So I just want to thank the witnesses, look forward to the 
promising work at each of your agencies and how we in Congress 
can be your partners in moving forward. And I yield my 
remaining time to Mr. Green of Texas.
    Mr. Green. Thank you, Mr. Chairman. Thanks to our ranking 
member for yielding to me.
    As said before, researchers have found a person in the 
United States carrying bacteria resistance to antibiotics of 
last resort, an alarming development that could mean the end of 
the road for antibiotics. For years, scientific leaders across 
the globe have been warning if we don't take swift, aggressive 
action, a post-antibiotic era in which modern medicine we take 
for granted is no longer safe because we will not be able to 
control infection from childbirth, in surgery, to dialysis and 
chemotherapy. Even simple cuts and wounds could be at increased 
risk of turning fatal without effective antibiotic treatments.
    Alarmingly, at a time when resistance is rising, a pipeline 
for new antibiotics has dried up. Resistance can and must be 
slowed, but it cannot be stopped, and we need new classes of 
antibiotics to combat drug-resistant antibiotics.
    The public value of antibiotics is difficult to 
overestimate, yet there is a widening acknowledged market fail 
when it comes to antibiotics. We need meaningful research 
incentives, strong public-private partnerships, and flexible 
clinical trials. That is why not only myself but our committee 
championed the ADAPT Act. It passed in the 21st Century Cures. 
It would enable the FDA to work with sponsors and reduce 
regulatory barriers to antibiotic drug development.
    ADAPT offers one tool Congress can enact to address the 
lack of effective treatments against superbugs. I look forward 
to hearing more about that proposal and other ideas Congress 
should consider in the ongoing efforts to address this public 
health crisis.
    And again, I will yield back my 14 seconds.
    Mr. Murphy. The gentleman yields back.
    I ask unanimous consent that the members' written opening 
statements be introduced into the record. And without 
objections, the documents will be entered into the record.
    I would now like to introduce the witnesses of our first 
panel for today's hearing. The first witness on today's panel 
is Dr. Beth Bell. Dr. Bell is a Director of the National Center 
for Emerging and Zoonotic Infectious Diseases with the CDC.
    We would also like to welcome again Dr. Janet Woodcock. Dr. 
Woodcock is currently Director of the FDA's Center for Drug 
Evaluation and Research.
    Our third witness on today's panel is Dr. Richard Hatchett. 
Dr. Hatchett is currently serving as acting director for the 
Biomedical Advanced Research and Development Authority within 
HHS Office of the Assistant Secretary for Preparedness and 
Response.
    Our final witness is Dr. Dennis Dixon. Dr. Dixon joins us 
from the NIAID's Division of Microbiology and Infectious 
Diseases.
    I would like to thank all the witnesses for appearing 
before the subcommittee today. You are all aware that the 
committee is holding an investigative hearing, and when doing 
so has the practice of taking testimony under oath. Do any of 
you have an objection to taking testimony under oath?
    The chair then advises that you are under the rules of the 
House and the rules of the committee you are entitled to be 
advised by counsel. Do any of you desire to be advised by 
counsel during the testimony today?
    Seeing no request for that, in that case, will you all 
please rise, raise your right hand, and I will swear you in.
    [Witnesses sworn.]
    Mr. Murphy. Thank you. All the witnesses have answered in 
the affirmative, and you are now under oath and subject to the 
penalties set forth in title 18, section 1001 of the United 
States Code.
    I will have you each give a 5-minute summary of your 
written statement. Please pay attention to the timing and turn 
the microphone on and bring it as close to your mouth as you 
can. Thank you. You may begin, Dr. Bell. You are recognized for 
5 minutes.

  STATEMENTS OF DR. BETH BELL, DIRECTOR, NATIONAL CENTER FOR 
 EMERGING AND ZOONOTIC INFECTIOUS DISEASE, CENTERS FOR DISEASE 
    CONTROL; DR. JANET WOODCOCK, DIRECTOR, CENTER FOR DRUG 
  EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION; DR. 
   RICHARD J. HATCHETT, ACTING DIRECTOR, BIOMEDICAL ADVANCED 
   RESEARCH AND DEVELOPMENT AUTHORITY; AND DENNIS M. DIXON, 
  DIVISION OF MICROBIOLOGY AND INFECTIOUS DISEASES, NATIONAL 
    INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NATIONAL 
                      INSTITUTES OF HEALTH

                   STATEMENT OF DR. BETH BELL

    Dr. Bell. Thank you. Good morning, Chairman Murphy, Ranking 
Member DeGette, and members of the subcommittee. I am Dr. Beth 
Bell, director of the National Center for Emerging and Zoonotic 
Infectious Diseases at the Centers for Disease Control and 
Prevention. And thank you for the opportunity to testify before 
you today.
    CDC works 24/7 to save lives and protect people against 
health threats, including the threat of potentially untreatable 
infections. With support from Congress, CDC is working to 
improve the Nation's capacity to detect, respond, and prevent 
antibiotic-resistant threats in health care settings and across 
communities to protect Americans and save lives.
    Using the resources provided by Congress in fiscal year 
2016, CDC is working on four fronts to support transformative 
improvements in our national capability to identify and respond 
to antibiotic resistance. First, CDC will invest the largest 
portion of this funding in our 50 states, six largest cities, 
and Puerto Rico. CDC will support state activities to improve 
the detection and prevention of AR infections transmitted 
across health care and community settings. These are just-in-
time investments as the pace and challenges of antibiotic 
resistance are accelerating and every state needs capacity to 
take appropriate action.
    Second, CDC's antibiotic resistance lab network will 
provide infrastructure and lab capacity through seven regional 
labs across the country. These labs will be able to detect 
resistant organisms recovered from human samples and new forms 
of antibiotic resistance. CDC will also provide support for 
labs in all States to test for CRE, the nightmare bacteria.
    Third, CDC's Advanced Molecular Detection initiative is 
another important tool in our efforts to identify and solve 
more outbreaks faster. Because of innovations developed through 
this AMD initiative, CDC will be able to scale up whole genome 
sequencing of multiple foodborne pathogens to better understand 
foodborne antibiotic resistance patterns. Through the National 
Antimicrobial Resistance Monitoring System, NARMS, sequences 
from animals, from retail meat, and from humans will be 
compared to identify new ways of preventing human infections.
    Finally, our ability to reduce antibiotic resistance will 
depend in part on improving antibiotic use, and we are working 
towards that through better measurement, through expansion of 
stewardship programs, and through educational campaigns.
    The administration's budget request for fiscal year 2017 
includes an increase of $40 million for year 2 of CDC's 
Antibiotic Resistance Solutions initiative. And so in fiscal 
year 2017, in addition to sustaining AR capacity started in 
'16, CDC will expand state antibiotic resistance prevention 
programs to better respond to outbreaks, to improve 
prescribing, and prevent antibiotic-resistant infections across 
all health care settings.
    These collective investments have a direct impact on the 
response to AR threats, including the emergence of the MCR-1 
gene in the United States. In May, Department of Defense 
scientists announced the first discovery of the MCR-1 gene in 
bacteria isolated from a person in the United States. Although 
there is not an immediate threat to the public or the current 
health of this patient, this is an important development for 
the United States. The antibiotic colistin is used as a rescue 
drug to treat patients with multidrug-resistant infections like 
CRE.
    The MCR-1 gene makes bacteria resistant to colistin. The 
gene exists on a plasmid, which is a small piece of DNA that is 
capable of moving from one bacterium to another, spreading 
antibiotic resistance among bacterial species. The presence of 
the MCR-1 gene and its ability to share its colistin resistance 
with other bacteria such as CRE raises the possibility of a 
bacteria that is resistant to every antibiotic.
    USDA also discovered MCR-1 in E. coli isolates collected 
from two different pig intestines. By comparing the DNA 
sequences of all three isolates, Federal scientists have 
determined that the isolates from the pigs are different from 
that from the human.
    Yesterday, CDC issued an alert to proactively notify 
states, hospitals, and clinical laboratories about the 
availability of new detection tools for MCR-1 and to reiterate 
recommendations for infection prevention, environmental 
cleaning, and reporting to public health.
    The identification of MCR-1 vividly illustrates our 
domestic and global challenges of antibiotic resistance. MCR-1 
was first identified in China in November of last year, and in 
less than 6 months has been identified in a human and two 
animals in the United States. Antibiotic use anywhere can 
potentially affect any one of us.
    The emergence and reemergence of health threats, including 
those caused by antibiotic-resistant bacteria, is something we 
can expect to continue to see in the future. If we lose 
antibiotics, we could lose the ability to effectively treat 
sepsis and to provide the care to cancer patients, to organ 
transplant recipients, or burn and trauma victims.
    So thank you again for the opportunity to appear before you 
today, and I look forward to the opportunity to answer your 
questions.
    [The prepared statement of Beth Bell follows:]
    
   
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    Mr. Murphy. Thank you. Dr. Woodcock, you are recognized for 
5 minutes.

                STATEMENT OF DR. JANET WOODCOCK

    Dr. Woodcock. Thank you for holding a hearing on this 
critical topic.
    FDA is involved in many fronts in the fight against 
resistant organisms. We're participating actively in the CARB 
initiative and collaborating internationally and also of course 
with our Federal partners represented here. Our Center for 
Veterinary Medicine oversees animal drugs. They have received 
commitments from the manufacturers are medically important 
antibiotics to submit supplements by the end of the year. As a 
result of this, these drugs will have to be prescribed by a 
veterinarian and can't be used for growth promotion purposes.
    Our Center for Devices and Radiologic Health regulates in 
vitro diagnostics or test kits, including antimicrobial 
susceptibility tests and diagnostics. They're seeing a growing 
pipeline of rapid diagnostic tests under development. This is 
very good news. These tests are intended to identify if a 
person has a bacterial infection or--versus a virus or has 
bacteria circulating in the blood or even rapidly diagnose 
certain types of resistant organisms. So we hope these 
development programs are successful.
    They also plan to issue guidance on what they call 
coordinated development of susceptibility tests. So as we have 
new antimicrobials approved by Center for Drugs, we could have 
susceptibility tests also available that could be interpreted 
by clinicians.
    Our Center for Biologics regulates vaccines. We know that 
prevention is a best approach to disease, and of course there 
are some vaccines for microbial diseases, and we would hope 
that more are going to be developed.
    The Center for Drug Evaluation and Research that I head 
regulates antimicrobials. We've seen the percent of infections 
treated by common antibiotics shrink over time, as everybody's 
been saying, as resistance grows. CDER's been actively 
implementing the GAIN Act that Congress passed several years 
ago. We've granted 107 qualified infectious disease product 
designations to 63 different molecules. The designated products 
can receive fast-track designation, and they get a priority 
review. On approval, they receive additional 5 years of market 
exclusivity, so this is an incentive of course. Five designated 
antibacterial drugs and one antifungal drug have been approved 
since GAIN was enacted.
     We continue to work on streamlining drug development. 
We've issued guidelines. We're trying to lower the barriers, 
but many of the barriers, as I'm sure we'll discuss, are either 
scientific or economic barriers to new antimicrobials.
    Now, there are further efforts going on in lowering the 
barriers. I really commend BARDA who is exploring the use of a 
master common protocol. We're working with them, novel ways of 
studying these that lower the barriers and make some types of 
studies actually feasible.
    The 21st Century Cures bill that was passed in the House 
contains provisions for the limited population use provision, 
and the Senate PATH Act does mirror that. We're also very 
interested in the issue of antimicrobial break points and the 
use of a more rapid and agile method for changing the break 
point designations.
    Finally, though, drug development in this area remains 
fragile and weak. The incentives that have been put in place 
apparently are not enough to overcome the scientific challenges 
that the industry faces in finding new targets and developing 
these and then actually making money on them. Much more needs 
to be done, I think, to address this threat across all the 
groups represented here, but the drug development area in 
particular needs further examination.
    Thank you.
    [The prepared statement of Janet Woodcock follows:]
    
    
  
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    Mr. Murphy. Thank you, Dr. Woodcock.
    I now recognize Dr. Hatchett for 5 minutes.

              STATEMENT OF DR. RICHARD J. HATCHETT

    Dr. Hatchett. Good morning, Chairman Murphy, Ranking Member 
DeGette, and members of the committee. Thank you for inviting 
me to testify about our efforts to combat antibiotic-resistant 
bacteria. I am Dr. Richard Hatchett, acting director of the 
Biomedical Advanced Research and Development Authority within 
the Office of the Assistant Secretary for Preparedness and 
Response.
    BARDA was established in December 2006 to support the 
advanced research development and procurement of medical 
countermeasures against chemical, biological, radiological, and 
nuclear threats, pandemic influenza, and emerging diseases such 
as Ebola and Zika.
    In 2010, BARDA initiated its Broad Spectrum Antimicrobials 
program, or the BSA program that I'll refer to, and in 2016, 
Congress awarded BARDA substantial new funding specifically to 
combat antibiotic-resistant bacteria. The BSA program was 
established to support the development of new classes of 
antibiotics for both biodefense and commercial applications. 
Under the auspices of the program, we now manage seven public-
private partnerships and a pipeline of nine antibacterials.
    BARDA's objectives have been to revitalize the antibiotic 
pipeline, emphasize programs that address the immediate public 
health threat of multidrug-resistant organisms, and enhance our 
biodefense capabilities. We have achieved notable success. Our 
portfolio is quite mature at this point. Five BARDA products 
are in phase 3 clinical development, and two have completed the 
pivotal studies required for FDA approval.
    Several products show promise for the treatment of 
infections due to carbapenem-resistant Enterobacteriaceae or 
CRE, one of the most urgent threats that we face, and a few 
have shown in vitro activity against bacteria harboring the 
MCR-1 colistin-resistance gene recently identified in a patient 
in Pennsylvania.
    And we are working with our international partners. One of 
our partnerships has facilitated groundbreaking coordination of 
funding with the EU's Innovative Medicines Initiative to speed 
the development of a drug called aztreonam-avibactam.
    BARDA also supports the development of improved clinical 
diagnostics. Without better diagnostics to guide antibiotic 
therapy, it will be difficult to prevent the emergence of 
resistant bacteria. BARDA would thus support a diverse set of 
tools to differentiate viral and bacterial infections, identify 
resistant infections in the physician's office, and measure 
antimicrobial susceptibility. BARDA aims to simplify genetic 
sequencing tools so that they can be used in clinical 
laboratories for the evaluation of resistant infections.
    Finally, BARDA and NIH will offer a $20 million prize for 
the development of truly novel diagnostics for drug-resistant 
bacteria. We will be announcing more details about this prize 
later this year.
    To achieve these goals, BARDA employs innovative 
partnership models. Within HHS, BARDA has pioneered the use of 
portfolio partnerships that can advance multiple drug 
candidates simultaneously. BARDA has established these flexible 
cost-sharing business partnerships using our other transaction 
authority. We have found that portfolio-based funding reduces 
risk by allowing for the reallocation of resources across 
activities and among drug candidates as technical and business 
risks materialize.
    Clearly, the early-stage antimicrobial pipeline is too 
thin. To enrich it, BARDA and NIAID are working together to 
establish an initiative we are calling the CARB accelerator. 
Innovation frequently occurs in small biotechnology companies 
and in academic laboratories with limited resources and 
expertise to move product candidates forward. In such 
circumstances, promising early-stage candidates often fail to 
advance. The accelerator will serve as an incubator for new 
products and explicitly seeks to improve success rates in the 
early-stage antibiotic pipeline.
    BARDA will launch the accelerator in 2016 and support the 
program for at least 5 years while NIAID will provide an array 
of product development support services. Both entities will 
collaborate in managing the program and its investments through 
a joint oversight committee. Stay tuned. We certainly will have 
a lot more to report on this initiative in coming years.
    In summary, as new forms of antibiotic resistance continue 
to spread worldwide, the prospect of bacterial strains 
resistant to all available antibiotics can no longer be 
ignored. Developing new tools for diagnosing and treating drug-
resistant bacteria will be essential to preserving the practice 
of modern medicine.
    ASPR and its partners play a critical role in leading the 
charge against such threats, and we look forward to working 
with Congress to address the global challenge of antimicrobial 
resistance. I look forward to addressing your questions.
    [The prepared statement of Richard J. Hatchett follows:]
    
  
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    Mr. Murphy. Thank you, Doctor.
    Now, Dr. Dixon, you are recognized for 5 minutes.

                  STATEMENT OF DENNIS M. DIXON

    Mr. Dixon. Thank you, Mr. Chairman, Ranking Member 
DeGette----
    Mr. Murphy. Make sure the microphone is on and pulled close 
to you, OK?
    Mr. Dixon. Mr. Chairman, Ranking Member DeGette, and 
members of the subcommittee, thank you for the opportunity to 
discuss antibiotic resistance, a serious and growing global 
health threat. I am Dr. Dennis Dixon, and I serve as chief of 
the Bacteriology and Mycology Branch in the National Institute 
of Allergy and Infectious Diseases.
    The NIAID is the lead institute at the NIH for research on 
infectious diseases, including research on antibiotic 
resistance. NIAID's longstanding research efforts in this area 
aim to understand the molecular basis of antibiotic resistance, 
as well as to develop specific and sensitive diagnostics, 
vaccines to prevent infections, and to partner with 
pharmaceutical industry companies in the development of novel 
and improved treatments.
    The recent detection in the U.S. of bacteria resistant to 
colistin, an antibiotic of last resort, reminds us of the 
urgent challenge of drug resistance and the need to address its 
underlying causes. Fortunately, this particular bacterial 
strain was treatable by other antibiotics. However, the threat 
remains that this type of resistance could emerge in other 
bacteria resistant to most antibiotics making them untreatable 
with currently available drugs.
    Through our research mission, NIAID plays a critical role 
in the administration's national strategy and action plan on 
Combating Antibiotic-Resistant Bacteria or CARB. NIAID's 
antibiotic resistance research portfolio includes basic 
research on how bacteria develop resistance and cause disease; 
translational research to develop diagnostics, therapeutics, 
and vaccines; and clinical research to evaluate antibacterial 
products and strategies.
    Additional funding provided by Congress in fiscal year 2016 
for CARB have been instrumental to our efforts. NIAID-supported 
basic research provides the foundational knowledge essential 
for the development of vaccines to prevent antibiotic-resistant 
infections and therapeutics to treat them.
    As part of the CARB initiative, NIAID supports genome 
sequencing for a national database of antibiotic-resistant 
bacteria. This database, developed by NIH in collaboration with 
FDA and CDC, will provide a comprehensive resource for 
surveillance, epidemiology, and basic research into the 
mechanisms of antibiotic resistance.
    NIAID also facilitates product development by providing 
nonmonetary support to researchers, including genome sequences, 
access to clinical specimens, drug screening, and animal model 
testing. These resources provided much-needed support for the 
field and help to reduce the risk for product developers.
    We also provide clinical trials capacity for evaluating new 
antibacterial products and strategies through our Antibacterial 
Resistance Leadership Group and other clinical trial networks 
for clinical research on antibiotic resistance. We are 
currently in the process of expanding this infrastructure.
    NIAID is also pursuing the development of point-of-care 
diagnostic tests critical to determining which drugs will be 
effective against given infections and recently awarded funding 
for research projects that develop rapid, sensitive, and 
specific diagnostic tools.
    NIAID is working to discover better treatments to treat 
antibiotic-resistant infections by screening new compounds and 
optimizing the use of existing drugs. NIAID recently awarded 
funding for research projects to develop nontraditional 
therapeutics for bacterial infections and funds clinical 
studies testing new formulations, dosing regimens, or 
combination therapies of currently licensed drugs such as 
colistin.
    In summary, NIAID is committed to a robust and 
comprehensive research effort to address antibiotic resistance 
and is fostering collaborations with partners in academia, 
industry, and the Federal Government. NIAID will continue 
support promising research to develop and test new antibiotics 
as well as methods to prevent the further spread of antibiotic 
resistance.
    Thank you for bringing attention to this important topic. 
I'd be pleased to answer any questions.
    [The prepared statement of Dennis M. Dixon follows:]
    

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    Mr. Murphy. I thank all the panel for their comments here. 
I am going to recognize myself for 5 minutes of questions.
    On September 20 of 2000, then CDC director Dr. Jeffrey 
Koplan testified before Senate Appropriations Subcommittee on 
Labor, HHS, and Education on the emerging national and global 
problems of antimicrobial resistance and the response by CDC. 
And at that hearing the CDC unveiled its plan that targeted 
drug resistance. In particular, Dr. Koplan testified that a key 
part of this plan was developing a national campaign to improve 
physician prescribing practices and educate parents and 
patients about the proper use of antibiotics.
    Dr. Bell, despite the CDC's campaign as well as the efforts 
of others, the overprescribing of antibiotics still exists. So 
why did the overprescribing and overuse of antibiotics continue 
even with the CDC's campaign?
    Dr. Bell. Thank you very much, Mr. Chairman.
    The campaign that I think you're referring to is a campaign 
which is called Get Smart, and this is something that we've 
been working on for quite some time. But actually, we've had 
quite a bit of impact. Actually, we've been able to show 
decline. The Get Smart campaign was really focused on 
outpatient prescribing. And while we are very concerned about 
the continued overuse of antibiotics in outpatients, we've 
actually seen considerable improvements over the years and 
they've been able to show an impact of the Get Smart program.
    Antibiotic overprescribing and stewardship is a complex 
issue, and we really need to attack it on many different 
fronts. The Get Smart and outpatient facilities is just one 
piece of the puzzle, and we've been really redoubling our 
efforts in the area of stewardship over the last few years 
releasing guidelines for stewardship programs and essential 
elements for hospitals and for long-term care facilities.
    Mr. Murphy. Do you see trends changing, that it is getting 
through to physicians because----
    Dr. Bell. Well, we now know that there are about 40 percent 
of hospitals in the United States that have all the elements of 
a stewardship program, and we've set a target of 100 percent of 
inpatient facilities by 2020. There are a lot of positive 
developments. I think----
    Mr. Murphy. But go back to that number of the huge----
    Dr. Bell. Yes.
    Mr. Murphy [continuing]. Amount of prescriptions written 
every year----
    Dr. Bell. Yes.
    Mr. Murphy [continuing]. That shouldn't be. So that doesn't 
sound like it is working to me. I just want to know what else--
we are here to help you.
    Dr. Bell. Yes.
    Mr. Murphy. We are all on the same team here. I know the 
White House Action Plan at Combating Antibiotic-Resistant 
Bacteria----
    Dr. Bell. Yes.
    Mr. Murphy [continuing]. It is there. How is that going to 
be different? What do we see that is really going to get 
through to people this time?
    Dr. Bell. Well, we really I think are just over the last 
few years really attacking this on lots of different fronts. As 
I said, the initial Get Smart program was really an educational 
campaign focused in one area, and now we have many different 
modalities. We've been collaborating very effectively also with 
CMS, with the American Hospital Association. CMS will be 
developing conditions of participation both for hospitals and 
long-term care that will require----
    Mr. Murphy. Will this also--excuse me.
    Dr. Bell. Excuse me.
    Mr. Murphy. I have to jump in because we are short on time.
    Dr. Bell. Oh, sorry.
    Mr. Murphy. Will this also include--and I ask the 
panelists. Will this also include information for patients?
    Dr. Bell. Yes----
    Mr. Murphy. I mean, let's face it. People go to the doctor 
and say I want a prescription. He says, well, you have got a 
virus, it is not going to work; I want it anyways. And doctors 
now especially because they get rated on----
    Dr. Bell. Yes.
    Mr. Murphy [continuing]. Were you treated satisfactorily 
and hospitals then get dinged. They don't get paid as much.
    Dr. Bell. Yes.
    Mr. Murphy. And I have heard time and time again hospitals 
say, look, we are afraid of these ratings and so they will show 
up in Web sites, everything else. So what are we doing to 
combat that?
    Dr. Bell. I appreciate your point. And we have been 
developing a lot of educational campaigns focused on patients. 
And I think you're right. Our objective would be for patients, 
when they go to the doctor and the doctor wants to prescribe an 
antibiotic, the patient says why do I need this antibiotic? 
Please explain that to me. And we do really need a sea change, 
and we're certainly working in lots of different ways to 
educate the patient. The patient really is pivotal in terms of 
solving this problem.
    Mr. Murphy. Dr. Woodcock, it is always good to see you. Why 
haven't we developed rapid diagnostic testing for bacterial 
infections yet? And can you tell us about some of the 
commercial and technical impediments here?
    Dr. Woodcock. Well, it's just harder than it sounds. There 
are a few. We have strep test, and that's great, OK, so there's 
something where people can differentiate quickly and put people 
at ease perhaps that they don't have--don't need an antibiotic, 
an outpatient setting, right? The technology is advancing, as I 
said in my oral statement. The Center for Devices is seeing 
technologies come along in the development pipeline so we 
expect over the next several years we will see more rapid 
diagnostic tests in a variety of settings.
    It's urgent that we try to find some that differentiate 
bacterial and virus infections. People are working on 
expression profiles that you can do a blood test and make that 
determination, and then you could reassure the patient you 
don't have a bacterial infection. And that would be very 
helpful.
    Mr. Murphy. Thank you. I see I am out of time so I will 
recognize Ms. DeGette for 5 minutes.
    Ms. DeGette. Thank you, Mr. Chairman.
    As I said in my opening, I want to talk about how we can 
incentivize development of new antibiotics, and as we heard, 
earlier this year BARDA and NIAID collaborated to establish the 
Combating Antibiotic-Resistant Bacteria, or CARB, by a 
pharmaceutical accelerator. So, Dr. Hatchett, I am wondering if 
you can tell me very briefly why this program is important.
    Dr. Hatchett. Well, thank you, Ms. DeGette for the 
question. As I said in my opening testimony, BARDA is very 
concerned. We do currently have a mature portfolio of 
antibiotics that are close to achieving licensure, but we are 
concerned that the upstream pipeline is very weak----
    Ms. DeGette. Right.
    Dr. Hatchett [continuing]. And that reflects the 
progressive disinvestment over several decades by 
biopharmaceutical firms not viewing antibiotics as providing 
sufficient return on investment.
    The goal of the biopharmaceutical accelerator will be in 
collaboration with our partners at NIAID, and we've worked very 
closely with them to structure the accelerator to support that 
early development, bring resources and capabilities to early-
stage innovators and help them move rapidly through the 
development process and advance those products hopefully to a 
point where they can transition to direct support for it.
    Ms. DeGette. Thank you. And, Dr. Woodcock, I want to follow 
up on this because when you testified before this committee in 
2014 about 21st Century Cures, you talked about this issue of 
lack of commercial incentives for drug developers and that 
being a reason why we don't have new investigational drugs. Can 
you quickly update us on what the situation is since 2014 with 
this? Do we have some promising drugs in the pipeline? Are we 
fixing some of these commercial issues?
    Dr. Woodcock. There are some promising drugs in the 
pipeline, but the pipeline is still very fragile. And what we 
need is not just a few superstars here. We need a full panoply 
of investment in the research, the basic science, the drug 
discovery and drug development that lasts, as Dr. Hatchett just 
said, over decades because we don't just need a few 
antimicrobials, we need a whole continuing----
    Ms. DeGette. Range. Range.
    Dr. Woodcock [continuing]. Platform and range of them for a 
wide variety of diseases, and we're just not seeing that, not 
all of the ones under development are going to succeed. And 
that's true of all drug development.
    Ms. DeGette. So Chairman Murphy and I got a letter 
yesterday from the Infectious Disease Society of America, and 
that organization said in their letter that the administration 
promised to release a report and recommendations on economic 
incentives for antibiotics, but the reported recommendations 
have not been released. I am wondering what the status of that 
report is and when it will be released.
    Dr. Woodcock. I don't know. It's not under my purview, but 
we can get back to you.
    Ms. DeGette. I wish you would, thanks, because maybe that 
can help illuminate--yes, Dr. Hatchett?
    Dr. Hatchett. I just want to mention that Secretary Burwell 
did ask the Presidential Advisory Committee on Combating 
Antibiotic-Resistant Bacteria to look explicitly at the issue 
of necessary economic incentives for the development of 
antibiotics. That letter was sent to the committee at the end 
of March, so they are actively undertaking that review.
    Ms. DeGette. All right. Does anybody here know what this 
report is and when we are going to get it?
    Dr. Hatchett. The report was an internal report at the 
White House, and I don't know the status of it. You'll have to 
address the question to them.
    Ms. DeGette. Dr. Dixon, can you talk to me about the 
clinical trials that are going on on strategies for using 
existing drugs more effectively?
    Mr. Dixon. Absolutely. Thank you for the question. And it 
is important not only to develop new drugs but to optimize the 
ones we have left. And in fact, we have a clinical trial 
underway with colistin because we don't know how long it will 
be before we run out of use of colistin. But knowing how to use 
it wisely----
    Ms. DeGette. Right.
    Mr. Dixon [continuing]. Will reduce the risk of emergence 
of resistance.
    Ms. DeGette. OK.
    Mr. Dixon. So we have looked at how the body metabolizes 
colistin--in other words, the pharmacokinetics--to maximize the 
presence of drug in the blood and maximize the activity of the 
drug and minimize the emergence of resistance. And so we have 
completed a study there that helped to inform better dosing of 
colistin----
    Ms. DeGette. Right.
    Mr. Dixon [continuing]. And we're now looking at colistin 
alone versus colistin in combination with another drug for 
carbapenem-resistant Enterobacteriaceae, or CRE, and other 
resistant pathogens.
    Ms. DeGette. Thank you.
    Mr. Dixon. And so----
    Ms. DeGette. Thank you very much. I want to ask Dr. Bell a 
quick question about why improved diagnostics are an important 
part of addressing the threat of antibiotics resistance.
    Dr. Bell. Yes, thank you. As we've been talking, the issue 
of stewardship is so pivotal to addressing this whole issue of 
antibiotic resistance, and improved diagnostics, having the 
capability to be able to differentiate between a viral 
infection and a bacterial infection right there when the 
patient is sitting in front of you would be a really important 
tool that would help us in all of our stewardship efforts. So 
we really do hope that diagnostics that can at least perform 
that basic function will be something that'll be available----
    Ms. DeGette. Thank you.
    Dr. Bell [continuing]. Relatively soon.
    Ms. DeGette. Thank you so much, Mr. Chairman. I yield back.
    Mr. McKinley [presiding]. Thank you. I recognize myself for 
5 minutes.
    This discussion reminds me a little bit of some of the 
environmental issues we have been dealing with over the last 5 
years. The fact that we only represent such a small part, 5 
percent of the population of the world, yet we consume so much 
of our energy, and what Gina McCarthy from the EPA there other 
day said that it makes no difference what we do; it is what 
happens around the world is what is really going to affect the 
environment, so notwithstanding all the issues that we have 
done in rules and regulations.
    So my question goes back to my opening statement, was when 
with 95 percent of the rest of the world perhaps 
overprescribing antibiotics and we don't know what is happening 
in some other nations around the world. We know 20 nations at 
least and Mexico are over-the-counter for antibiotics. This 
global issue, what should we be doing? We can solve it here, 
but if indeed the patients, people are coming in that have drug 
resistance to our antibiotics, what do we do? So if the four of 
you could just give me a sense. This fight is a global fight, 
not a United States. Please, Dr. Bell.
    Dr. Bell. Thank you. Yes, you're absolutely right. This is 
definitely a global fight. These microbes move around the 
world, and we have to look at this from a global perspective.
    So we are working in a number of different areas. So, first 
of all, we do have a number of really excellent collaborations 
with the Europeans and the Transatlantic Task Force for 
Antimicrobial Resistance, which allows us to share information 
very quickly, develop common standards, and also pool our 
resources to help other countries around the world. That's a 
very effective collaboration.
    The World Health Organization is actually getting serious 
about antibiotic resistance. The World Health Assembly has 
passed several resolutions with all nations basically 
committing to do something about antibiotic use. So we have to 
do everything we can to support them----
    Mr. McKinley. But even with our education----
    Dr. Bell [continuing]. And we are----
    Mr. McKinley [continuing]. We are still at----
    Dr. Bell. That's right. It's a hard problem. And we haven't 
solved it here----
    Mr. McKinley [continuing]. Forty percent, so even with our 
education level here----
    Dr. Bell. That's right. It's a hard problem.
    Mr. McKinley [continuing]. I am troubled about other areas, 
emerging nations----
    Dr. Bell. Yes.
    Mr. McKinley [continuing]. What is happening. So please 
continue.
    Dr. Bell. I think----
    Mr. McKinley. I am not sure I am buying into all the 
educational part of it. I am trying to figure out what the 
other solution is.
    Dr. Bell. Yes. No, I think there are many parts of this. It 
can't just be education, you're absolutely right. There have to 
be national policies and there has to be national legislation 
that supports this sort of antibiotic stewardship around the 
world. And as I say, I think that there is a fair amount of 
interest in that.
    We've been working also a lot on improving detection so 
that at least we know what's emerging where, and this is 
something that----
    Mr. McKinley. Let----
    Dr. Bell. Go ahead. I'm sorry.
    Mr. McKinley. Let's go to that point.
    Dr. Bell. Yes.
    Mr. McKinley. Are there nations that are more prone to have 
problems that we need to deal with----
    Dr. Bell. Well----
    Mr. McKinley [continuing]. Around the world? Because we are 
not all equal so----
    Dr. Bell. No, we're not all equal, and there certainly are 
some countries that do have already a significant problem with, 
for example, bacteria that are resistant to all antibiotics. 
Colistin that we've been talking a lot about here is actually 
used quite a bit more to treat human infections in other parts 
of the world, in India, for example, because there are 
unfortunately a large number of patients that show up in 
intensive care units, for example, that are infected with 
bacteria that are resistant to all other antibiotics. So this 
is a larger problem in some other parts of the world. There are 
some hot spots. And this issue of detection and focusing on the 
hot spots and knowing where the hot spots are is something that 
we've been working on.
    The Global Health Security Initiative includes antibiotic 
resistance as one of the areas that the countries have agreed 
to focus on so----
    Mr. McKinley. Should we be spending more of our monies 
overseas to try to work those problems out over there?
    Dr. Bell. Well, I think that we--it would be not wise for 
us not to focus on our local problem here. If we don't know 
what's going on here, we're not going to be able to protect 
Americans. We have to be doing both because we have to be both 
strengthening our ability to prevent and detect and respond in 
the United States while at the same time supporting global 
efforts.
    Mr. McKinley. OK. So two quick questions. One, Colistin, is 
that a reasonably marketable, affordable drug or is this 
something----
    Dr. Bell. No, colistin is a very old antibiotic. It's been 
around for a long time. As a physician, I hate to prescribe 
colistin to patients. And actually in any country doctors 
really don't want to use it. It has a lot of potential side 
effects. It has kidney toxicity, it has brain toxicity. So it 
really is a last-resort antibiotic.
    Mr. McKinley. I am afraid my time is expired, but thank you 
very much for your responses.
    If I could, next line of questioning from Mr. Pallone, 5 
minutes.
    Mr. Pallone. Thank you, Mr. Chairman.
    I wanted to ask each of you a question about investment in 
fighting antibiotic resistance, so I am going to go through 
quickly so I can get to each of you.
    In the last few years, we have seen increased investment in 
this fight. The President released the National Action Plan for 
Combating Antibiotic-Resistant Bacteria in March of last year 
with ambitious goals for many Federal departments and agencies. 
And I am encouraged by the over $830 million we directed toward 
this effort in fiscal year 2016. And the President, as you 
know, has requested $1.1 billion for fiscal year 2017 for 
antibiotic resistance.
    So let me start with Dr. Bell. In your prepared testimony, 
you noted that CDC has received $160 million in fiscal year 
2016 to implement the National Action Plan noting that, ``These 
resources are transforming how our nation tackles and slows 
antibiotic resistance comprehensively, efficiently, and 
systematically.''
    So just tell me, how will the increased investment 
requested for the next fiscal year build on this capacity, and 
why is sustained investment critically important to our success 
in combating antibiotic resistance?
    Dr. Bell. Thank you. So antibiotic resistance is a problem 
in communities, so a lot of our funding in 2016, for which we 
are very grateful to Congress, is being used to fund states and 
large cities to build their capacity to detect and to respond 
and to prevent. And so the additional funding in 2017 will go 
towards being able to go even further in that regard. So we'll 
be able to fund more states to have the kind of antibiotic-
resistant prevention programs. We'll be able to strengthen our 
laboratory networks so that we can look for more types of 
antibiotic-resistant organisms. And in general, we'll be able 
to take the kind of investments that we're making in 2016 to 
more states and to a higher level.
    Mr. Pallone. Thank you. Dr. Dixon, in your testimony you 
noted that the additional funding for fiscal year 2016 has been 
instrumental to NIH efforts. Again, why is sustained investment 
in fighting antibiotic resistance critical to your agency?
    Mr. Dixon. Thank you for the question. We appreciate the 
additional funding, and we're applying that to such key 
resources as the National Sequence Database that will inform 
the sequences and tracking genes like the MCR-1 and others; and 
diagnosis and going particularly after the problem of 
diagnostics, which could certainly help to reduce the 
overprescribing whether or not you have a bacterial infection 
or a viral infection; advancing basic translational and 
clinical research overall, fundamentally addresses the problems 
that can help to identify new candidate drugs, new candidate 
vaccines, and new candidate diagnostics. And to close up, just 
to say that we are contributing with BARDA the $20 million 
diagnostics prize to try and draw key manufacturers into the 
space.
    Mr. Pallone. Well, thank you. So, Dr. Hatchett, you work 
with industry to bring new antibiotics to market. How is 
sustained investment important to your work, and what message 
does that send to your private partners? The same question.
    Dr. Hatchett. Yes, I was going to say. Let me address the 
question of the value of the funding----
    Mr. Pallone. Sure. Sure.
    Dr. Hatchett [continuing]. For BARDA. As I mentioned, we 
established our Broad Spectrum Antimicrobials program in 2010. 
We did that with funding that was provided by Congress for 
biodefense purposes. And so we were very diligent in making 
sure that every antibiotic that we were developing had a 
biodefense application. For better or worse, what that meant 
was that we had to develop broad spectrum antimicrobials, which 
are part of the problem that has contributed to the spread of 
resistance because of the overuse of broad spectrum 
antimicrobials.
    The funding that Congress provided in 2016 is specifically 
dedicated to the problem of antimicrobial resistance, and it 
allows us to think in much more nuanced ways about how we can 
build up an armamentarium to treat patients who have 
antibiotic-resistant bacteria so we can make investments in 
vaccines, we can make investments in monoclonal antibodies and 
alternative therapies. So strategically, it's very important.
    In 2016, we are making a number of investments. You've 
heard about the CARB accelerator. That's a major investment 
this year. You've heard about the diagnostics prize. We're also 
going to be expanding our portfolio partnership this year. All 
of those efforts are going to take years to mature and to 
convince our industry partners to enter into partnerships with 
us in an area that they have traditionally viewed as not 
providing an adequate return on investment. They have to see 
that sustained commitment of funding over many, many years and 
recognize that the government is a reliable partner.
    Mr. Pallone. Thank you. I am out of time for you, Dr. 
Woodcock. Sorry. Thank you, Mr. Chairman.
    Mr. McKinley. Thank you. And next, Dr. Burgess from Texas 
for 5 minutes.
    Mr. Burgess. Thank you, Mr. Chairman.
    Probably of all the members on this committee I have 
prescribed the most doses of antibiotics. Dr. Bucshon, who was 
here, is actually significantly younger than I am, so I think I 
probably have seniority on his as far as the doses of 
antibiotics.
    And it is worth considering just a couple of historic notes 
as we talk about this, 1929, Sir Alexander Fleming noticed the 
zone of inhibition around a mole that had grown on his agar 
plate, and that led to the development of what we now know as 
penicillin. But it was really 15 years later when the Pfizer 
Corporation figured out how to manufacture this on a large 
scale so literally making this wonder drug, which previously 
was kind of a parlor trick, making it available to the masses 
and having it available to treat our soldiers on the days that 
they stormed the beaches at Normandy, thus resulting in 
significantly lower loss of life and limb from those soldiers 
who took that beach on that heroic day.
    My grandfather practiced obstetrics. He was an academic 
physician. He unfortunately died in 1940 so he practiced 
obstetrics in the pre-antibiotic days, and I always kind of 
look at that with kind of wonder and amazement. Here was an 
individual that chose a profession before the development of 
good anesthesia, blood banks, and most of all, antibiotics 
because anyone who has practiced obstetrics knows that without 
the ability to prescribe good antibiotics and antibiotics that 
work well, our ability to fix problems has become severely 
limited. So we want the antibiotics that we have available to 
continue to work, and we want them to work well.
    The JAMA article that was referenced is of interest, and I 
thank the staff for pulling it for me so quickly. And just 
glancing through it, it seems like pharyngitis, otitis media, 
and sinusitis are the illnesses or the diagnoses that sort of 
achieve the lion's share of the antibiotic prescriptions. And 
easy to be critical of the doctors and practitioners who are 
prescribing those antibiotics, but let us not forget that 130 
years before penicillin was discovered, the father of our 
country succumbed to an illness that was treatable by 
penicillin, a complication of pharyngitis, tonsillitis, that 
led to a peritonsillar abscess and ultimately took his life. So 
bacterial diseases are interwoven within our country's history 
for the last, what, 85 years, have become part of the story of 
American medicine.
    Dr. Dixon, let me just ask you because this is such an 
unusual situation with this woman that had the infection. She 
had an Enterobacter infection? Is that correct? Do I understand 
the story correctly?
    Mr. Dixon. I think you do. It might be better of Dr. Bell, 
who followed that case and did the case study, could talk about 
the clinical workup of that individual.
    Mr. Burgess. So how in the world did you find this plasmid 
or this gene that was so unusual? Was there something about 
this patient's presentation that said we better look for this 
rare gene?
    Dr. Bell. No. Actually, this story really begins with--it's 
sort of a case study in how beefing up surveillance can really 
make a big difference in terms of prevention and response. So 
since we first heard about this MCR-1 identification in China, 
all of us in the Federal partners, including the Department of 
Defense, have been looking for evidence of this gene. And so 
the Department of Defense has a surveillance system where 
patients with bacterial infections or isolates within their 
system that have certain characteristics--in this case, show 
resistance to some of the extended spectrum beta lactamases--
are shuttled eventually to the Walter Reed where they fully 
characterize these unusual isolates. And it was in the context 
of that that this was actually--that this was identified.
    Mr. Burgess. But there was nothing in the patient's 
clinical course or her diagnostic presentation that said, oh, 
boy, we better be looking for this one needle in the haystack?
    Dr. Bell. No, that's right, there wasn't. And actually, 
just to clarify that this bacteria actually is not a pan-
resistant bacteria. So the bacteria that infected this patient 
is actually treatable by some antibiotics, and the patient 
herself is actually fine. Indeed, in our field investigation 
and follow-up we've been able to verify that she no longer has 
that bacteria in her urine.
    Mr. Burgess. Well, that is good news, but I guess the other 
question that comes up is how do you know this hasn't occurred 
on other occasions----
    Dr. Bell. Absolutely.
    Mr. Burgess [continuing]. In all of the vast number----
    Dr. Bell. We----
    Mr. Burgess [continuing]. Of specimens----
    Dr. Bell. Right.
    Mr. Burgess [continuing]. That aren't subject to that type 
of scrutiny?
    Dr. Bell. We do not know, and I think that's to the point 
about what are we doing with the investments that are available 
to us because of Congress' appropriation is that we are going 
to be--and this is one of the things I think we've been 
concerned about for a long time, that, for example, the CDC 
being the only lab in the country that can actually look for 
some of these unusual types of resistance, that's not a good 
state of affairs. And with the additional investments, we're 
going to be able to have a much more robust system for 
systematically looking for these and for looking for other and 
new, more emerging forms of resistance. In terms of responding 
to this finding, that's really the first thing that we want to 
do. We need to figure out how bit a problem this is----
    Mr. Burgess. Yes.
    Dr. Bell [continuing]. As you say, Congressman.
    Mr. Burgess. Right. Thank you, Mr. Chairman. I will yield 
back. Maybe we will have time for a second round.
    Mr. McKinley. Our next is Congressman Green from Texas for 
5 minutes.
    Mr. Green. Thank you, Mr. Chairman.
    Antibiotic resistance is a significant public health 
challenge, and we need think creatively to address it. And I 
want to hear from our witnesses today about the regulatory and 
scientific challenge in developing new antibiotics, especially 
focused on what we can do to tackle them.
    Dr. Hatchett, what are some of the challenges facing 
manufacturers in the antibiotics market?
    Dr. Hatchett. Thank you for the question, Congressman 
Green. Certainly there are scientific challenges, and I may 
turn to my colleague Dr. Dixon to let him address the 
scientific challenges. I'm just a dumb oncologist so this is 
not my field, but I do understand the medicinal chemistry 
particularly for gram-negative bacteria, which are some of the 
bacteria that we are most concerned about is particularly 
challenging.
    From where I'm sitting, I think the biggest challenges 
relate to the economic incentives in fact to convince companies 
to make the long-term investment to do the development. But 
that wasn't your question.
    Mr. Green. But what I was trying to get at is that we have 
both scientific challenges but we also have financial 
challenges because vaccines are not the next miracle drug. In 
some cases it could be.
    But, Dr. Woodcock, would you like to add anything on the 
issue between----
    Dr. Woodcock. Well, I do believe that----
    Mr. Green [continuing]. The economics and the scientific--
--
    Dr. Woodcock. I've talked to some of the large 
pharmaceutical companies. In the past they have run very broad 
scientific discovery programs and discovery means they're 
looking for antimicrobials, OK, they're trying to find 
candidates. And these programs have failed. So down at the 
science level, this is hard, and I think this is where NIAID's 
investment in the science of determining what are the bacteria 
like and how do they generate resistance and what is very 
important to advance that science because this is a hard area 
to develop drugs in.
    Mr. Green. Thank you. Dr. Hatchett, these next questions 
are for you. Is BARDA exploring any new ways to incentivize 
development of these new antibiotics and other therapeutics?
    Dr. Hatchett. Yes, sir, we are. I mentioned our use of our 
other transaction authority that Congress granted to us in the 
Pandemic and All-Hazards Preparedness Act. And that allows us 
to work with companies, particularly large companies that have 
multiple products in their pipeline. And so we can invest in 
their entire pipeline as opposed to making a specific 
investment in a single product.
    That approach has attracted a great deal of attention from 
large pharmaceutical partners. We have two of those portfolio 
partnerships now, one with GSK, one with AstraZeneca, a number 
of others are actually in negotiations. The companies find it 
very attractive because it allows them to keep a focus on the 
development of anti-infectives in a way that makes economic 
sense to them. So that's very important.
    There is an emerging consensus about economic incentives, 
that it's going to require both a combination of traditional 
what we call push incentives or investments in R&D, R&D 
contracts, as well as pull incentives, the market-entry 
incentives. If you make it to market, there's a guaranteed 
market, a guaranteed return on investment, potentially a prize.
    Mr. Green. OK. That brings us to the GAIN Act from last 
Congress and the ADAPT Act in this Congress, both individually 
but also as part of the 21st Century Cures. Envision a scenario 
where more adaptive clinical trials may be used to help drug 
developers seeking to create the next antibiotic drug effective 
against drug-resistant bacteria. Dr. Woodcock, can you tell me 
your thoughts on how the pathway laid out in ADAPT might 
benefit drug companies in the pursuit of the new novel 
antibiotics?
    Dr. Woodcock. Certainly. Well, after a candidate is 
discovered and it's for a resistant organism, then you have 
another scientific problem of how do you find these people who 
are infected who are maybe scattered around and then test the 
drug in them when they're critically ill and they need to be 
treated right away. And so doing these clinical trials, even 
small clinical programs are extremely challenging. And of 
course we want the drug to be used in the most resistant 
organisms, so we want it to be tested there to see if it works. 
But those are hard to find. And so you have this big problem.
    And we are interested in having a limited development 
program where you'd really have a great deal more uncertainty, 
but you wouldn't use the drug for sinusitis and otitis media 
and so forth. This would be signaled that there was only a 
limited amount of information, but the drug could be used in 
these desperate situations. And that pathway, we think, would 
be a reasonable pathway to make the drug available but with a 
stewardship signal.
    Mr. Green. OK. Thank you, Mr. Chairman. I know I am out of 
time, but, Dr. Burgess, I have sinus troubles and every once in 
a while I get an infection. I will not call you for a 
prescription.
    Mr. Burgess. Flonase, bubba.
    Mr. Green. I already take everything else.
    Mr. McKinley. All right. The chair recognizes Mr. Collins 
from New York for 5 minutes.
    Mr. Collins. Thank you, Mr. Chairman. I want to thank the 
witnesses as well. It has always been a concern to many of us, 
but maybe to answer a question that I know goes through a lot 
of families when our kids say I have got an infection, I need 
an antibiotic. And many moms and dads say, well, no, if you 
take these antibiotics, you will become antibiotic resistant, 
and some day when you are older and you really need one, it is 
not going to work.
    Contrasted to what we are talking about today is it is not 
a person who becomes antibiotic resistant, which is kind of 
this old wives' tale versus there are bugs that are figuring 
out a way to become antibiotic resistant. And a person getting 
one of those bugs, even if they have never taken an antibiotic 
in their life, has the same risk. Would that be a fair----
    Dr. Woodcock. Yes.
    Mr. Collins [continuing]. Summary?
    Dr. Woodcock. Yes, Congressman. If I could use that----
    Mr. Collins. Yes.
    Dr. Woodcock [continuing]. Myself, it would be helpful. 
That's--no, that's absolutely right. And that's part of the 
point about how antibiotic resistance is really a problem for 
everybody because it's not an individual that develops 
resistance. It's the bacteria. And these bacteria are 
constantly replicating and they share genetic material and they 
spread around the community. So this is exactly--your 
explanation is exactly correct. And I've often thought we need 
a better term than resistance because people think that applies 
to them, and actually----
    Mr. Collins. As a person.
    Dr. Woodcock [continuing]. It doesn't. It applies to the 
microbe itself. So again, we've oftentimes thought, you know, 
perhaps we need a better way to explain this to break that old 
idea----
    Mr. Collins. Well, sure. I mean----
    Dr. Woodcock [continuing]. That it's a person.
    Mr. Collins [continuing]. You can actually have in a family 
someone who should take an antibiotic, but because of this 
misconception----
    Dr. Woodcock. Yes.
    Mr. Collins [continuing]. The parents are saying, no, no, 
no, no.
    Dr. Woodcock. Yes.
    Mr. Collins. We are going to fight this for a few days, 
fight this for a week----
    Dr. Woodcock. Yes.
    Mr. Collins [continuing]. Because we don't want you to 
become antibiotic resistant.
    Dr. Woodcock. Yes, you're absolutely right. I mean, 
antibiotics, as we've heard are--you know, they're a treasure 
and they're incredibly important and we need to--when we talk 
about stewardship, we don't mean don't use antibiotics. We mean 
use the right antibiotic at the right dose for the right 
duration for the right indication. And it is a very important 
part of our message.
    Mr. Collins. Well, I think that is. That is why these 
hearings can be important.
    Now, I have got a question for Dr. Dixon. I understand at 
Washington State University--and maybe this will translate to 
Dr. Woodcock--but I understand they have like an e-bandaid, an 
electromagnetic thing that they are going to put on someone, 
they pass the electric current through, they have now 
determined that is producing hydrogen peroxide. And if they 
control this, they have gotten some interesting results as a 
way to treat bacterial infections and wounds without 
antibiotics. Are you familiar with some of that, and do you 
have a comment on--I know it sounds a little sci-fi-ish, but it 
actually seems to have some possibilities.
    Mr. Dixon. I understand the question. I'm not familiar with 
that particular example. It is entirely consistent, though, 
with our approach of looking at things other than traditional 
drugs, so we're looking at exploiting the host immunity a 
better way. We're exploiting things like bacteriophage. We're 
exploring things like microbiota using microbial ecology to 
outcompete and prevent infections and other alternative 
approaches that don't provoke the emergence of resistance.
    Mr. Collins. Yes, I think it makes a lot of sense sometimes 
to----
    Mr. Dixon. Absolutely.
    Mr. Collins [continuing]. Actually think out of the box, 
and if you had a chance, you should maybe look into this. It 
was Washington State University last November, about 6 months 
ago. The results sounded very encouraging because instead of by 
guess and by golly, they finally figured out why electric 
currents sometimes work and sometimes didn't, and it was 
controlling the process and it all came down to the hydrogen 
peroxide at a level of consistency that would say, on Shark 
Tank, this one might get funded. Who knows?
    Mr. Dixon. Absolutely. A lot of exciting things going on 
out there.
    Mr. Collins. So question for you, Dr. Woodcock. Let's say 
something like this happens. Now, this is an electrical 
therapeutic if you will. It is not a ``drug.'' What role would 
the FDA have, and would you have to run clinical trials like it 
would be a drug or is there something else when it is almost 
like a device or something instead of a drug?
    Dr. Woodcock. Well, there has to be a determination first 
whether it's a drug or device, and we have a process that's 
been set up by Congress, an office that sorts that out and what 
has to be done to study it. It depends on whether it's a 
device, a medical device or a drug, and those are appropriate 
to the two different kinds of----
    Mr. Collins. Being one or the other, it would still have to 
go through your agency for approval----
    Dr. Woodcock. Yes.
    Mr. Collins [continuing]. Final signoff if you will.
    Dr. Woodcock. These type of therapeutics, whether they're 
devices or drugs, are regulated by the FDA.
    Mr. Collins. OK. And no idea what this one would be, but I 
think all of us are encouraged there may be in this high-tech 
world we live in now something other than antibiotics. At the 
same time, we have got to keep searching, and it is kind of an 
all-of-the-above search if you will. Thank you for your 
testimony. My time is expired and I yield back, Mr. Chairman.
    Mr. McKinley. Thank you. And I now recognize for the next 
round of questions Ms. Castor from Florida for 5 minutes.
    Ms. Castor. Thank you, Mr. Chairman. Thank you all for your 
expert testimony today.
    I want to return to the discussion of how we tackle this 
internationally, as Mr. McKinley focused on, because no single 
country like the U.S. can do this alone. We are so 
interconnected now. People travel. You said microbes travel, 
animals travel, food travels.
    In July of 2014, the U.K. commissioned a study on the 
global problem of antimicrobial resistance. The study concluded 
that we must be concerned about drug resistance globally if we 
expect to be safe at home. An important theme discussed in the 
report is that infectious diseases profoundly affect poorer 
countries due to unsanitary living conditions. Unsanitary 
conditions, the report says, ``act as a catalyst of rapid 
person-to-person spread, which can lead to an increase in the 
use and overuse of antibiotics.''
    Dr. Bell, what effect do poor living conditions and access 
to clean food and water have on the spread of infectious 
diseases, and how can poor sanitation contribute to the overuse 
of antibiotics?
    Dr. Bell. Yes, thank you. This is unfortunately very much 
the case that--and you could imagine how, if you think about 
our prevention strategies in terms of infection control and in 
terms of hygiene how countries where people really just don't 
have the option of this sort of hygiene that we can--the level 
that we can establish here in the United States, but this does 
contribute to spread. And we see this in many countries around 
the world.
    I think one of the things that we've learned is that I 
think it makes sense to sort of break some of this down in 
order to approach it. And infection control in hospitals, for 
example, is one component that we've really been working now 
with a lot of countries to at least improve infection control 
in facilities. If we see that, a lot of the most resistant 
bacteria are in facilities. We've been working with a number of 
countries in India, in West Africa--you heard with Ebola that's 
not about antibiotic resistance, but we certainly saw what the 
importance of infection control was.
    Ms. Castor. So when poor countries address problems such as 
sanitation, access to clean water and infections in their 
medical facilities--this is basic--that helps reduce antibiotic 
resistance. And what more can be done then? We have so many 
fantastic nonprofit organizations, academics, churches, the 
developed world. What else can that group be doing to reduce 
the spread of infection?
    Dr. Bell. Yes, you're absolutely right. And actually, I'll 
go back again to Ebola while that isn't a resistant organism. 
In our work in West Africa to improve infection control, we 
used many nongovernmental organizations, church groups, and 
other sorts of nongovernmental groups as trainers, as 
extenders, and as groups that can stay in the area and help the 
ministries of health and the hospitals with infection control.
    Ms. Castor. So some experts have said and the U.K. report 
said and I think Mr. McKinley had said what needs to be done. 
They emphasized kind of some global organizing, collaborative 
or campaign. How could we go about such an effort?
    Dr. Bell. The World Health Organization actually is in the 
process of organizing such a campaign, and while we all need to 
participate in that and provide some leadership.
    Ms. Castor. So that would include tackling the over-the-
counter prescriptions of antibiotics? The U.K. study reported 
that in parts of Southern and Eastern Europe, 20 to 30 percent 
of antibiotics are consumed without a prescription, and in 
parts of Africa, the figure rises to 100?
    Dr. Bell. Yes. That's definitely part of what we have to 
tackle.
    Ms. Castor. OK. And then, Dr. Woodcock, Internet sales of 
antibiotics is a huge problem that this committee has 
documented extensively. You have testified before this 
committee multiple times on the use of Internet drugs. What 
role does FDA believe that Internet drug sales have on drug 
resistance across the globe?
    Dr. Woodcock. I don't think we know in the United States. 
We intercept some packages and so forth. Most of the ones that 
we intercept are not antimicrobials. But certainly that could 
play a role. But I think that's something that's very difficult 
to get your hands around because, again, it's an international 
problem. Some of these are counterfeit, and that often plays a 
big role, especially in places like Africa or potentially even 
here because they don't have the right amount in there but they 
may have a low amount of antimicrobial in them, which then 
promotes the generation of resistance. So the free flow of 
antimicrobials, whether from over-the-counter use or through 
the Internet, is a potentially continuing large problem and 
very difficult to manage.
    Ms. Castor. Thank you very much.
    Mr. Burgess [presiding]. The chair thanks the gentlelady. 
The gentlelady yields back. The chair recognizes the gentlelady 
from Tennessee 5 minutes for questions.
    Mrs. Blackburn. Thank you, Mr. Chairman.
    And I appreciate the patience you all have had with us this 
morning as we are running up and down to committees, hearings 
going on at the same time. So we have been in and out and you 
have been patient.
    Dr. Hatchett, I want to come to you. Going back into 
February BARDA established the accelerator to support and 
research and development--and of course as we have worked on 
21st Century Cures, we have been so interested in that, and 
then looking at the candidates that you were going to 
accelerate through this program with the drugs and vaccines and 
diagnostics and move that into development. And for us then 
moving it on to commercialization and into the mainstream.
    I would like it if you could take just a minute and talk a 
little bit about the specific candidates that you all have put 
in that, about some of the vaccines or the microbials, some of 
the alternative therapies that you are reviewing in that 
program.
    Dr. Hatchett. Yes, ma'am. Thank you for the question. Just 
to be clear, the accelerator has not been established yet. We 
put out the solicitation earlier this year, and we have 
received the proposals. We had a good response, and we actually 
are in the process of negotiating with the lead candidates 
right now. So we haven't----
    Mrs. Blackburn. OK.
    Dr. Hatchett [continuing]. Made the award----
    Mrs. Blackburn. When you say a good response, quantify that 
for me a little bit.
    Dr. Hatchett. We had a pre-proposal conference where we had 
a--I don't remember the specific number, and I'm under oath, 
but I can get it for you.
    Mrs. Blackburn. That would be great.
    Dr. Hatchett. But we ended up with five proposals, which 
really aggregated--actually some of the people that came to the 
pre-proposal conference met each other and then decided to 
partner, which made the proposals stronger. So I believe we had 
five proposals. And one of the requirements of--I don't think 
it was a requirement, but we requested it. It was that people 
making a proposal to us could leverage the U.S. Government 
funding by gaining access to additional funding either from 
other funders or other venture capital entities, for example, 
that was going to be viewed as a positive. And fortunately, we 
had tremendous success with that, so we think when we make the 
final award, actually our investment, which this year could be 
as much as $30 million----
    Mrs. Blackburn. OK.
    Dr. Hatchett [continuing]. May serve as a catalyst for 
additional investment coming in from other funders, even other 
countries that may be interested because of the way we've 
structured it. The--Ms. Castor mentioned the July 2014 U.K. 
study that was put together and led by Jim O'Neill, who was the 
former CEO of Goldman Sachs, and one of the recommendations of 
that study was to create a global innovation fund for 
antibiotic development. And actually, the United Kingdom and 
China have already made contributions of about $50 million to 
such a fund.
    We think the accelerator will certainly bring in that level 
of funding. We are committed to providing up to $250 million 
for the accelerator over the next 5 years, and that could be a 
major, major catalyst for international collaboration to 
support this early-stage development.
    Mrs. Blackburn. OK. And what is your expectation once you 
are able to populate the accelerator basically? Then how long 
do you think it will be before we begin to see next-generation 
products that are ready to go to the marketplace?
    Dr. Hatchett. So the accelerator, as I mentioned earlier, 
we are partnering very closely with our colleagues at NIAID. 
And NIAID has a full suite of what we call product development 
support services that can help innovators in the early stage 
accelerate their development. Our funding will allow those 
innovators to accelerate their timelines for bringing these 
products forward, and so we may be able to shorten the 
timelines. If those innovators were left to their own devices 
and left to the vagaries of the capital markets, it might take 
them many years to bring those products to the point that they 
would be ready for advanced development. The things that are in 
the accelerator are not going to pop out of the accelerator 
right into the marketplace. They're going to be brought to the 
stage of clinical development----
    Mrs. Blackburn. Right. We----
    Dr. Hatchett [continuing]. Which could take several years.
    Mrs. Blackburn. We understand that, but we----
    Dr. Hatchett. Right.
    Mrs. Blackburn. When we look at some of these drugs that 
are taking 10 years, 12 years to get through the process, and 
you look at the entire compendium and you look at what goes on 
with them, the innovators working with the FDA, our hope is 
that we are going to see your process work and help to push 
this to the marketplace sooner, that there will be some 
efficiencies. We know you have got some challenges, but we are 
hopeful there will be some efficiencies in moving it forward.
    Dr. Hatchett. Ours too, ma'am. The perhaps relevant 
example--its slightly different scale of urgency--but when we 
have had to respond to events like the Ebola epidemic----
    Mrs. Blackburn. Yes.
    Dr. Hatchett [continuing]. Or to the pandemic in 2009, we 
were able to push things forward with incredible velocity and 
so shorten normal development time frames. It might be 5, 7, 10 
years down to even, you know, 9 months, a year, 2 years----
    Mrs. Blackburn. OK.
    Dr. Hatchett. I'm not promising----
    Mrs. Blackburn. That is helpful.
    Dr. Hatchett [continuing]. That we can do that with the 
accelerator----
    Mrs. Blackburn. Right.
    Dr. Hatchett [continuing]. But that's the idea.
    Mrs. Blackburn. That is helpful. That is what we want to 
hear. Thank you. I yield back.
    Mr. Burgess. The gentlelady yields back. The chair thanks 
the gentlelady.
    And the chair recognizes the gentleman from New York, Mr. 
Tonko, for 5 minutes, please.
    Mr. Tonko. Thank you, Mr. Chair.
    My good friend and colleague, Representative Louise 
Slaughter, to my knowledge the only microbiologist in Congress, 
has been raising alarm bells for quite some time about the 
excessive use of antibiotics in our farm animals and feedstock.
    I know that the FDA has shared similar concerns about 
antibiotic use and resistance in farm animals. In fact, FDA's 
Center for Veterinary Medicine has developed a multipronged 
effort to limit or reverse resistance arising from the use of 
antibiotics in food-producing animals.
    Dr. Woodcock, I understand that FDA's efforts to control 
antibiotic use in farm animals are not entirely in your 
wheelhouse given where you sit in the agency. However, can you 
walk us through what FDA is doing to address the nexus between 
antibiotic resistance and the overuse of antibiotics at the 
farm?
    Dr. Woodcock. Yes. As I said in my oral testimony, the 
Center for Veterinary medicine has sought commitments from the 
manufacturers of animal drugs that have important medical uses, 
and they have all committed to submit supplements that would 
basically change these drugs to prescription only. And that 
means they would not be used for growth promotion purposes, and 
they would need to be prescribed by a veterinarian. The Center 
for Veterinary Medicine expects this to occur at the end of the 
year, the supplement submission. And so soon after that the 
changeover could be accomplished is my understanding.
    Mr. Tonko. And with that in mind, in any way are we making 
progress in overuse of antibiotics in our food supplies?
    Dr. Woodcock. That I can't answer but we could get back to 
you on that.
    Mr. Tonko. Thank you. I would appreciate that. And, Dr. 
Woodcock, how are we tracking how much and what kinds of 
antibiotics food producers are using, and who is in charge of 
that effort? And just what is being done?
    Dr. Woodcock. Well, in speaking to the Center for 
Veterinary medicine, I understand that tracking down to that 
level is difficult right now. We don't have a billing system 
similar to what we have for human drugs where we understand 
what prescriptions are issued for what animals and so forth. So 
my understanding is that that's a difficult set of information 
to find out.
    Mr. Tonko. And I understand that one concern of regulators 
is that antibiotics have been used extensively for feed 
production purposes and not only for therapeutic purposes. So 
can you describe how antibiotics have been misused in that 
regard?
    Dr. Woodcock. Well, there's been a long tradition as I 
understand--I'm not a veterinarian--but I understand there's 
been a long tradition of using certain amounts of 
antimicrobials preventively or in food that--in feed for the 
animals that results in some growth acceleration of the 
animals. And it's not treating an infection or anything like 
that. It's simply to put it in the feed and then the growth 
accelerates. And of course they're being produced as food 
animals, and so that is an economic benefit. That type of use 
is what's been addressed by the step that the Center for 
Veterinary Medicine is taking.
    Mr. Tonko. And what are FDA and USDA planning to do to 
address that aspect of the problem?
    Dr. Woodcock. Well, we expect the manufacturers will honor 
their commitments. They will submit supplements, and these will 
be changed. They cannot be used for growth-promoting purposes, 
these medically important antibiotics.
    Mr. Tonko. Are there any other efforts that can be made by 
FDA to control the use of antibiotics in our food supplies?
    Dr. Woodcock. Well, I think there's always more that can be 
done, and I also believe that the norm system is very important 
and probably needs to continue to be strengthened. I think the 
value of surveillance just can't be overestimated because we 
need to know what's going on and at every level, from 
production all the way through to the food itself, that 
monitoring is extremely important for us to know what's going 
on.
    Mr. Tonko. I take the efforts obviously are very important 
to the public----
    Dr. Woodcock. Yes.
    Mr. Tonko [continuing]. And we are at least pleased to hear 
that there is that kind of review being conducted, but I would 
love to see efforts go forward to make certain that there is 
every bit of safety and consumer-oriented response so that we 
can move forward progressively.
    Dr. Woodcock. Thank you.
    Mr. Tonko. With that, I yield back.
    Mr. Burgess. The gentleman yields back. The chair thanks 
the gentleman.
    The chair recognizes the gentleman from Oklahoma, Mr. 
Mullin, 5 minutes for questions, please.
    Mr. Mullin. Well, I don't know about the antibiotics in 
cattle, but I live on a farm and I am on three different 
antibiotics as we speak. I literally just got off Bactrim and I 
am on a Z-Pak and I have got another one that was prescribed to 
me yesterday. And so to say that they are overprescribed, I 
thank the Lord for them, but I will probably say you are 
accurate on that.
    With that being said, the University of Oklahoma has done a 
phenomenal job on trying to close the gap on what they call the 
superbug, and they recently developed a new antibiotic to go 
after what a lot of people refer to as MRSA or a staph 
infection. But even with all that development, Dr. Woodcock, 
despite the recent success at the University of Oklahoma, are 
there concerns that new drugs aren't being developed quickly 
enough to help close this gap?
    Dr. Woodcock. Yes. There are major concerns because the 
microbes are kind of like the criminals. They're always one 
step ahead of us, right, and if you expose people and you 
expose the bacteria to an antimicrobial, some of them will 
develop resistance. So we need a robust pipeline.
    We have approved a number of antibacterials recently for 
MRSA infections, new ones, but the general pipeline of 
antimicrobials is not robust. It's very fragile. We don't just 
need very targeted antimicrobials, we need a broad set of 
antimicrobials for the future. And that's still not happening, 
although there--you know, certainly there are discoveries being 
made.
    Mr. Mullin. So with the current crop of antibiotics out 
there, do you see where we are going to be able to catch up or 
we are going to continue to stay behind or get farther behind?
    Dr. Woodcock. I think we need to be very concerned because 
it's not the work of a year to catch up, it's the work of 
decades. And these development programs--Dr. Burgess mentioned 
Pfizer earlier; they're no longer in the space of development. 
These development programs were terminated by lots of companies 
several decades ago.
    Mr. Mullin. Due to?
    Dr. Woodcock. Lack of economic incentives and the fact that 
at that time there was of course a broad range of 
antimicrobials available. And even though we could foresee 
resistance occurring in the future, the return on investment 
wasn't there compared to, say, cancer or other fields.
    Mr. Mullin. Well, Dr. Woodcock, how long does it take, say, 
a company that is wanting to develop this, how long does it 
take them from when they start to when they can probably bring 
a product to the market?
    Dr. Woodcock. If you start from discovery, probably 10 
years.
    Mr. Mullin. At the cost of what?
    Dr. Woodcock. The estimates are very controversial. Many 
people have said between $1 billion and $2 billion for a new 
molecular entity.
    Mr. Mullin. So is there a way to speed this up? I mean, if 
we are behind because, my goodness, I can understand why a 
company would be hesitant to invest $1-2 million on an----
    Dr. Woodcock. Billion.
    Mr. Mullin. Billion, I am sorry, $1-2 billion on an 
antibiotic and it takes 10 years to bring it to market and the 
success rate is, I am sure, pretty low. Do you know what the 
success rate is on that?
    Dr. Woodcock. For antimicrobials, it's--if you start from 
discovery, it's going to be one in many thousands, OK----
    Mr. Mullin. One in many thousands, so----
    Dr. Woodcock. You start into entry into the clinic, it 
might be 1 in 10.
    Mr. Mullin. So what is the incentive for a company to do 
this? I mean, I am thinking as a business owner I am going, OK, 
I am going to invest $1-2 billion and I am going to have 1 out 
of 1,000--let's just use that number--of a chance of it 
actually coming to market. Is there an incentive? Is there a 
way to bring this number down? Is there a way to help improve 
that?
    Dr. Woodcock. Well, I would also add that we would urge you 
as a business owner once you develop this drug to make sure 
it's used very narrowly and not widely used because otherwise 
resistance would develop.
    Mr. Mullin. Well, I agree with that, but you have got to 
get your money back.
    Dr. Woodcock. I understand that.
    Mr. Mullin. I mean, $1-2 billion----
    Dr. Woodcock. I'm just saying that's the market--that's the 
return-on-investment problem. What Dr. Hatchett and Dr. Dixon 
have been talking about are Federal Government efforts to 
accelerate this pipeline and ease the barriers to getting so it 
doesn't cost so much and the success rate could be higher.
    Mr. Mullin. Is the FDA looking into this to help ease those 
barriers, help speed that process up? Because we can all tell 
this is going to be a major problem, and so it seems like we 
should be working together on this.
    Dr. Woodcock. Oh, yes. And we've been doing things for 
years. We have issued a number of new guidances on new 
pathways. We're working with outside public-private 
partnerships on new end points, different ways to study the 
drugs, and then what was mentioned earlier, the limited 
population use that's in the 21st Century Cures would be 
another way of streamlining the development programs.
    Mr. Mullin. Dr. Woodcock, thank you. I am out of time.
    Mr. Burgess. The gentleman yields back. The chair thanks 
the gentleman.
    The chair recognizes the gentlelady from Illinois, Ms. 
Schakowsky, 5 minutes for questions.
    Ms. Schakowsky. This is exactly the conversation that I 
have been wanting to get into.
    Dr. Woodcock, in conclusion you say ``It is virtually 
undisputed that we are facing a public health crisis because of 
the rise of serious resistant infections and the simultaneous 
decline in R&D in this area.'' What I am hearing is that there 
is not enough profit in addressing this problem. And that sets 
my hair on fire. If this is a worldwide public health issue and 
the reason that we cannot make progress is because--as have 
been called--our industry partners are unwilling to do that 
because there is not enough money, then it seems to me exactly 
the space then that government needs to step in and deal with 
this.
    I just don't understand the word ``incentives''--and there 
may be other ways besides money. I don't know. But what are we 
talking about here, that these companies are getting out of the 
business, that the Pfizers are getting out of the business. 
There is just not enough dough here when at some point this 
could be just a worldwide problem of the bug that is going to 
kill, I don't know, millions of people. Somebody answer me.
    Dr. Bell. Well, I would say there are two problems. One is 
it's very hard to discover and develop these----
    Ms. Schakowsky. Right.
    Dr. Bell [continuing]. OK, scientifically. And then once 
you get them on the market, we're going to--everyone will ask 
them is don't sell them, OK, don't sell them very much because 
they're too valuable to waste on--that was the paradigm in the 
past, and that's why antimicrobials are so overprescribed, OK, 
is they were used for minor infections----
    Ms. Schakowsky. Well, can I----
    Dr. Bell [continuing]. And viruses----
    Ms. Schakowsky [continuing]. Interrupt for a second? I 
think one of the other issues that contributes to that problem 
is TV advertising of drugs, which has created an atmosphere 
among consumers that I am in charge of my health, I am going to 
go to my doctor, I am going to say what I want, I will find a 
way to get that drug. I just wanted to add that. I think that 
is part of the culture that contributes to this problem. 
Anybody?
    Dr. Hatchett. Thank you. It's a critically important 
question. And I have seen an estimate that the market for 
antibiotics in the United States is about $40 billion. But of 
that $40 billion for that market, only about $4-5 billion is 
for drugs that are unpatented. So any new drug that enters the 
market enters a market where there are dozens of competing 
generic antibiotics. And so the new entries can't charge a 
premium unless they can fully differentiate themselves from all 
of the other antibiotics that are on the market. And so it 
suppresses the ability to achieve profit for a new drug.
    And you've heard the estimates of what it costs to bring a 
new drug to market, and so companies, to recoup their 
investment over many, many years have to see opportunities in 
the marketplace that they can achieve that return even almost 
just to a breakeven.
    The model that BARDA has implemented in other areas where 
the market is failing to deliver public health requirements so 
against agents of bioterrorism or pandemic influenza, for 
example, we over the past decade have evolved a model where we 
provide substantial advanced research and development funding 
for products that have reached the stage of clinical 
development. So these are things that are being tested in human 
clinical trials. We also provide a market entry incentive, a 
pull incentive in terms of a procurement of the product. So for 
something that we're developing for bioterrorism, we then buy a 
large quantity of it and put it into the strategic national 
stockpile so a person working under it has a guaranteed market 
commitment.
    And the other thing that we provide, which is very, very 
critical, we found this to be extremely critical is we provide 
access to a core of experts on all aspects of product 
development who can assist potentially smaller companies that 
don't have all of this expertise in-house and to access to 
product development infrastructure. And so it's a multi-legged 
stood in terms of the support that we provide.
    It wasn't until we put all of those components together for 
our bioterrorism threats, for pandemic influenza threats that 
we really started to see our program succeed. We think many of 
those elements are going to be required to overcome these 
adverse market courses that are leading to disinvestments.
    Ms. Schakowsky. Well, I hope that bottom line isn't that we 
have to look at the bottom line of for-profit companies to 
figure out whether we are going to protect the health of this 
planet.
    Mr. Burgess. The gentlelady yields back.
    Let me if I could, I would like to ask a follow-up question 
because the Center for Medicare and Medicaid services yesterday 
put out a relatively lengthy proposed rule on the stewardship 
program. You have had a chance to familiarize yourself with the 
proposed rule that CMS put out. Now, the question is, once 
again, do we get the right balance between the regulatory 
burden and effective governance? So, again, I would just 
appreciate your thoughts on the proposed rule.
    Dr. Bell. I haven't actually seen the rule itself, 
Congressman, but we have been working with CMS around this 
concept for quite some time. They have already actually had 
previously issued some comments for similar kind of conditions 
of participation for long-term care. Now, this is the one for 
acute care.
    So I appreciate your point about a balance between 
regulation and individual clinical judgment. In general, these 
conditions of participation, they've been working closely with 
us and they basically are meant to incorporate the core 
principles of stewardship that we published in 2014 for 
inpatient and 2015 for long-term care. So these are really just 
fundamental kind of necessary pieces of a puzzle so that a 
facility has a stewardship program that actually is able to 
influence the process.
    And I will say also that this whole process of coming up 
with the core elements and CMS's participation has really been 
very broadly supported in general by American Hospital 
Association and by lots of kind of industry partners. I think 
there really is a broad agreement now that the concept of 
helping physicians and facilities and patients prescribe wisely 
is really pivotal.
    We've been talking a lot about drug development and what 
all the gaps are there, but really--and, as you've heard, I 
think this whole issue of antibiotic resistance is a long-term 
problem that has many components, and we really have to address 
them all in order to tackle it. And one of the pivotal 
components is this issue of stewardship, of getting serious 
about doing something about overprescribing, not stopping 
people from prescribing but being able to preserve the 
antibiotics that we have now. And that's sort of about saving 
lives now, as well as these areas of prevention and diagnostics 
and new drug development.
    So as I say, I'm not familiar with the specifics, but it 
has been really a very broad process that CMS has gone through 
and has collaborated quite closely with us.
    Mr. Burgess. Dr. Woodcock, on the issue of stewardship--and 
you have mentioned in your opening statement in response to Mr. 
Tonko's question about involving the USDA and the veterinarian 
space in this. It is one thing to come down hard on the private 
practice doc in the United States for overprescribing 
antibiotics, and I probably include myself in that group that 
would feel put upon by some of these directions. But honestly, 
we can't compete with what is being used in feedlots.
    Dr. Woodcock. Yes. Well, as I said, the Center for 
Veterinary Medicine has taken steps around that and secured 
commitments from those manufacturers of medically important 
antimicrobials that they will submit a supplement that will 
eliminate that use basically.
    Mr. Burgess. And let me just----
    Dr. Bell. If I could just add that the concept of 
stewardship and stewardship for veterinarians, in addition to 
stewardship for human doctors is something that the American 
Veterinary Medical Association has been quite interested in, 
and we've been providing them actually with a lot of tools that 
they could use with veterinarians. And actually we haven't 
spoken about companion animals, but this is another area 
actually where we really don't have a very good sense----
    Mr. Burgess. Sure.
    Dr. Bell [continuing]. Of what's happening, and we will 
be----
    Mr. Burgess. Let me----
    Dr. Bell [continuing]. Looking to establish something 
there.
    Mr. Burgess. I am going to stop there for--I want to ask 
one other question, Dr. Woodcock, since we are speaking about 
animal products. The issuance under an emergency use 
authorization for a genetically modified mosquito in parts of 
the world that are affected by the Zika virus, why is that 
taking so long? Why is it so difficult? Why is a genetically 
modified mosquito having to go through a new drug application?
    Dr. Woodcock. Well, that is out of my wheelhouse, and we'd 
have to get back to you on that particular question.
    Mr. Burgess. OK.
    Dr. Woodcock. It's not a drug----
    Mr. Burgess. But my understanding, it is being treated as 
if it was a new drug application, so I appreciate that is not 
part of today's discussion, but I really do want to follow up 
with you on that, because I think it is an important issue.
    Seeing no further members wishing to ask--you have a 
question? The gentlelady from Illinois just wants me to 
conclude, so I do want to thank all our witnesses and members 
who have participated in today's hearing. I remind members they 
have 10 business days to submit questions for the record, and I 
ask all the witnesses to agree to respond promptly to these 
questions.
    With that, the subcommittee stands adjourned.
    [Whereupon, at 12:01 p.m., the subcommittee was adjourned.]
    [Material submitted for inclusion in the record follows:]
    

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