[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
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Printed for the use of the Committee on Energy and Commerce
energycommerce.house.gov
______
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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:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
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.]
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