[House Hearing, 111 Congress]
[From the U.S. Government Publishing Office]



 
PROMOTING THE DEVELOPMENT OF ANTIBIOTICS AND ENSURING JUDICIOUS USE IN 
                                 HUMANS

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

                                HEARING

                               BEFORE THE

                         SUBCOMMITTEE ON HEALTH

                                 OF THE

                    COMMITTEE ON ENERGY AND COMMERCE
                        HOUSE OF REPRESENTATIVES

                     ONE HUNDRED ELEVENTH CONGRESS

                             SECOND SESSION

                               __________

                              JUNE 9, 2010

                               __________

                           Serial No. 111-130


      Printed for the use of the Committee on Energy and Commerce

                        energycommerce.house.gov


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                    COMMITTEE ON ENERGY AND COMMERCE

                 HENRY A. WAXMAN, California, Chairman
JOHN D. DINGELL, Michigan            JOE BARTON, Texas
  Chairman Emeritus                    Ranking Member
EDWARD J. MARKEY, Massachusetts      RALPH M. HALL, Texas
RICK BOUCHER, Virginia               FRED UPTON, Michigan
FRANK PALLONE, Jr., New Jersey       CLIFF STEARNS, Florida
BART GORDON, Tennessee               NATHAN DEAL, Georgia
BOBBY L. RUSH, Illinois              ED WHITFIELD, Kentucky
ANNA G. ESHOO, California            JOHN SHIMKUS, Illinois
BART STUPAK, Michigan                JOHN B. SHADEGG, Arizona
ELIOT L. ENGEL, New York             ROY BLUNT, Missouri
GENE GREEN, Texas                    STEVE BUYER, Indiana
DIANA DeGETTE, Colorado              GEORGE RADANOVICH, California
  Vice Chairman                      JOSEPH R. PITTS, Pennsylvania
LOIS CAPPS, California               MARY BONO MACK, California
MICHAEL F. DOYLE, Pennsylvania       GREG WALDEN, Oregon
JANE HARMAN, California              LEE TERRY, Nebraska
TOM ALLEN, Maine                     MIKE ROGERS, Michigan
JANICE D. SCHAKOWSKY, Illinois       SUE WILKINS MYRICK, North Carolina
CHARLES A. GONZALEZ, Texas           JOHN SULLIVAN, Oklahoma
JAY INSLEE, Washington               TIM MURPHY, Pennsylvania
TAMMY BALDWIN, Wisconsin             MICHAEL C. BURGESS, Texas
MIKE ROSS, Arkansas                  MARSHA BLACKBURN, Tennessee
ANTHONY D. WEINER, New York          PHIL GINGREY, Georgia
JIM MATHESON, Utah                   STEVE SCALISE, Louisiana
G.K. BUTTERFIELD, North Carolina
CHARLIE MELANCON, Louisiana
JOHN BARROW, Georgia
BARON P. HILL, Indiana
DORIS O. MATSUI, California
DONNA M. CHRISTENSEN, Virgin 
    Islands
KATHY CASTOR, Florida
JOHN P. SARBANES, Maryland
CHRISTOPHER S. MURPHY, Connecticut
ZACHARY T. SPACE, Ohio
JERRY McNERNEY, California
BETTY SUTTON, Ohio
BRUCE L. BRALEY, Iowa
PETER WELCH, Vermont
                         Subcommittee on Health

                FRANK PALLONE, Jr., New Jersey, Chairman
JOHN D. DINGELL, Michigan            NATHAN DEAL, Georgia,
BART GORDON, Tennessee                   Ranking Member
ANNA G. ESHOO, California            RALPH M. HALL, Texas
ELIOT L. ENGEL, New York             BARBARA CUBIN, Wyoming
GENE GREEN, Texas                    JOHN B. SHADEGG, Arizona
DIANA DeGETTE, Colorado              STEVE BUYER, Indiana
LOIS CAPPS, California               JOSEPH R. PITTS, Pennsylvania
JANICE D. SCHAKOWSKY, Illinois       MARY BONO MACK, California
TAMMY BALDWIN, Wisconsin             MIKE FERGUSON, New Jersey
MIKE ROSS, Arkansas                  MIKE ROGERS, Michigan
ANTHONY D. WEINER, New York          SUE WILKINS MYRICK, North Carolina
JIM MATHESON, Utah                   JOHN SULLIVAN, Oklahoma
JANE HARMAN, California              TIM MURPHY, Pennsylvania
CHARLES A. GONZALEZ, Texas           MICHAEL C. BURGESS, Texas
JOHN BARROW, Georgia
DONNA M. CHRISTENSEN, Virgin 
    Islands
KATHY CASTOR, Florida
JOHN P. SARBANES, Maryland
CHRISTOPHER S. MURPHY, Connecticut
ZACHARY T. SPACE, Ohio
BETTY SUTTON, Ohio
BRUCE L. BRALEY, Iowa
  


                             C O N T E N T S

                              ----------                              
                                                                   Page
Hon. Frank Pallone, Jr., a Representative in Congress from the 
  State of New Jersey, opening statement.........................     1
Hon. John Shimkus, a Representative in Congress from the State of 
  Illinois, opening statement....................................     2
Hon. Henry A. Waxman, a Representative in Congress from the State 
  of California, opening statement...............................     4
    Prepared statement...........................................     6
Hon. Ed Whitfield, a Representative in Congress from the 
  Commonwealth of Kentucky, opening statement....................    10
Hon. John D. Dingell, a Representative in Congress from the State 
  of Michigan, opening statement.................................    10
Hon. Joe Barton, a Representative in Congress from the State of 
  Texas,.........................................................    11
    Prepared statement...........................................    13
Hon. Anna G. Eshoo, a Representative in Congress from the State 
  of California,.................................................    19
    Prepared statement...........................................    20
Hon. Lois Capps, a Representative in Congress from the State of 
  California, opening statement..................................    21
Hon. Phil Gingrey, a Representative in Congress from the State of 
  Georgia, opening statement.....................................    21
Hon. Jim Matheson, a Representative in Congress from the State of 
  Utah, opening statement........................................    22
Hon. Tim Murphy, a Representative in Congress from the 
  Commonwealth of Pennsylvania, opening statement................    23
Hon. Donna M. Christensen, a Representative in Congress from the 
  Virgin Islands, opening statement..............................    24
Hon. Marsha Blackburn, a Representative in Congress from the 
  State of Tennessee, opening statement..........................    25
Hon. Diana DeGette, a Representative in Congress from the State 
  of Colorado, opening statement.................................    26
    Prepared statement...........................................    27
Hon. Gene Green, a Representative in Congress from the State of 
  Texas, prepared statement......................................    66

                               Witnesses

Janet Woodcock, MD, Center for Drug Evaluation and Research, Food 
  and Drug Administration........................................    30
    Prepared statement...........................................    32
    Answers to submitted questions...............................   163
Robin Robinson, MD, Director, Biomedical Advanced Research and 
  Development Authority, Department of Health and Human Services.    45
    Prepared statement...........................................    47
Brad Spellberg, MD, FIDSA, Associate Professor of Medicine, David 
  Geffen School of Medicine at Ucla, Member, Infectious Diseases 
  Society of America Antimicrobial Availability Task Force.......    74
    Prepared statement...........................................    77
Sandra Fryhofer, MD, Council on Science and Public Health, 
  American Medical Association...................................   103
    Prepared statement...........................................   105
John S. Bradley, MD, on behalf of American Academy Of Pediatrics, 
  Chief, Division of Infectious Diseases, Department of 
  Pediatrics, University of California School of Medicine, 
  Clinical Director, Division of Infectious Diseases, Rady 
  Children's Hospital, San Diego.................................   112
    Prepared statement...........................................   115
Barry Eisenstein, MD, FACP, FIDSA, Senior Vice President, 
  Scientific Affairs, Cubist Pharmaceuticals.....................   128
    Prepared statement...........................................   130
Jeffrey Levi, PH.D, Executive Director, Trust for America's 
  Health.........................................................   139
    Prepared statement...........................................   141


PROMOTING THE DEVELOPMENT OF ANTIBIOTICS AND ENSURING JUDICIOUS USE IN 
                                 HUMANS

                              ----------                              


                        WEDNESDAY, JUNE 9, 2010

                  House of Representatives,
                            Subcommittee on Health,
                          Committee on Energy and Commerce,
                                                    Washington, DC.
    The subcommittee met, pursuant to call, at 10:09 a.m., in 
Room 2123 of the Rayburn House Office Building, Hon. Frank 
Pallone, Jr. [Chairman of the Subcommittee] presiding.
    Members present: Representatives Pallone, Dingell, Eshoo, 
Green, DeGette, Capps, Matheson, Barrow, Christensen, Sarbanes, 
Waxman (ex officio), Shimkus, Whitfield, Murphy of 
Pennsylvania, Burgess, Blackburn, Gingrey and Barton (ex 
officio).
    Staff present: Sarah Despres, Counsel; Ruth Katz, Public 
Health Counsel; Stephen Cha, Professional Staff; Eric Flamm, 
Professional Staff; Rachel Sher, Counsel; Alvin Banks, Special 
Assistant; Ryan Long, Minority Legislative Analyst; and Aarti 
Shah, Minority Professional Staff.

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

    Mr. Pallone. The subcommittee will come to order.
    Today we are having a hearing on antibiotic resistance and 
the threat to public health, and I will recognize myself 
initially for an opening statement.
    Today we are going to examine how we can best safeguard the 
effectiveness of antibiotics once they are on the market. We 
will also explore how we can ensure the adequate development of 
new safe and effective antibiotics. Later this year we expect 
to have a final hearing, essentially this is the second of 
three hearings, and the third or final hearing will be on 
antibiotic use in animal agriculture.
    As we discussed in our first hearing, antibiotics are among 
the most significant medical innovations of the 20th century. 
The CDC lists control over infectious disease as one of its top 
10 great public health achievements of the last century and 
mentions antimicrobials as crucial to that accomplishment.
    Unfortunately, the potential of antimicrobials continues to 
be compromised. It is estimated that over 2 million people 
acquire bacterial infections in U.S. hospitals each year and 
90,000 die as a result of these infections. We should all be 
alarmed that at least 70 percent of these infections are 
resistant to at least one drug and more and more bacteria are 
proving to be resistant to the antibiotics currently on the 
market. Unfortunately, these resistant diseases are among the 
most predominant illnesses in the population including 
respiratory diseases such as pneumonia, food-related diseases 
including E. coli and salmonella, and hospital-acquired 
infections commonly known as MRSA.
    As a matter of public health, it is imperative that we 
adopt a multi-pronged strategy to address antibiotic 
resistance. Today we will examine how we can best safeguard the 
effectiveness of antibiotics once they are on the market. We 
probably all heard stories of physicians that have 
overprescribed antibiotics to people who may have viral instead 
of bacterial infections, and while they may do this to 
safeguard against infection just in case, the overuse actually 
puts us all at risk. Patients also share blame. How many of us 
know someone that stopped taking their antibiotics once they 
felt better, even if they didn't finish the treatment.
    Our experts will also explore how we can ensure the 
adequate development of new safe and effective antibiotics on 
the market. It is a challenging situation because unlike some 
pharmaceuticals which are used to treat chronic illnesses, 
there is not a clear return on investment for antibiotics. 
Antibiotics are unique because not only are they used for short 
periods of time per illness, but the more they are used, the 
less effective they become. So in order to preserve their 
effectiveness, we as a society should all share the goal that 
they be used as rarely as possible. This is obviously not the 
business model that companies dream of, however, and I would 
like to welcome all of our witnesses today including government 
representatives from the FDA and BARDA and also our private 
witnesses from the Infectious Disease Society of America, the 
American Medical Association, the American Academy of 
Pediatrics, and Cubist Pharmaceuticals. The witnesses will 
undoubtedly share key information related to our mutual goal of 
protecting the public from antibiotic resistance.
    I would like to now recognize our ranking member, Mr. 
Shimkus, and also thank you for your cooperation in putting 
this together today. I know it has not been easy for the last 
24 hours, but thank you.

  OPENING STATEMENT OF HON. JOHN SHIMKUS, A REPRESENTATIVE IN 
              CONGRESS FROM THE STATE OF ILLINOIS

    Mr. Shimkus. Thank you, Mr. Chairman, and we want to 
welcome our witnesses both in this panel and the next, and this 
is an important issue. This is the second in a series that we 
also feel is very important.
    Antimicrobial drugs have provided tremendous benefit for 
the public health over the last half century. In order to 
ensure it remains so, we must continue to promote appropriate 
and effective use and the uses we already have. Overuse and 
misuse can limit the effectiveness and make outright resistance 
grow even faster. The other half of the equation is research 
and development and product development which are mainly 
concerned over the prospect of new drugs coming online. We know 
the cupboard is almost bare, and of the limited drugs in 
development, most of them, if not all, will never see approval. 
Any investment in antibiotics is not likely to match that of 
traditional drug development and there remains an uncertain 
approval process when it comes to FDA. The FDA must continue to 
work on providing confidence and clarity so we can encourage 
the development of new antibiotics.
    And as I talked before the hearing, we all have great 
respect for the work that the FDA does and it is the gold 
standard in the world but many of us are concerned that we are 
asking them to do too much with limited resources. Those of us 
who aren't in the business of increasing resources would want 
to help you make the job more efficient and directive. That is 
why I have always been a risk-based person, that that is where 
our money should go, and we will continue to work in that 
direction, but we do appreciate you being here.
    Mr. Chairman, I will be brief but I will also just raise my 
issue of the concern that we need a hearing on the new health 
care law. The President used yesterday his bully pulpit to talk 
about the benefits of the law. We still have yet to have a 
hearing on it, and I think it is probably time. If there are 
things the President thinks are important and is willing to go 
out to the American public to profess the benefits, we ought to 
be able to talk about those benefits here. We also should talk 
about some of the challenges. We did have our Republican health 
solutions group meet, as I discussed in the last hearing, and 
during that hearing Dr. Todd Williamson testified on behalf of 
the Coalition of State Medical National Specialty Societies 
representing more than 80,000 physicians from across the 
country, and his testimony said, ``The most significant cost of 
the new health care law will be to our patients. They will 
suffer decreased access to the doctors and care they need. My 
sickest and most vulnerable patients will suffer the most 
because of a depleted pool of physicians while the government 
continues to expand eligibility for its underfunded programs.'' 
In the State of Texas, 300 physicians have already stopped 
seeing Medicare patients over the last 2 years. Is Texas a 
snapshot of what is to come for the rest of the Nation when 15 
percent cuts go into effect? And when it comes to Medicaid, we 
know the situation is even worse for physicians, in some cases, 
paying them 50 percent of what private insurance does. But the 
health reform law sets out to force millions of more Americans 
into Medicaid. We will face similar results when it comes to 
access and quality of care for patients. The State of Illinois 
is $12.8 billion in debt, and Medicaid already consumes one-
third of the spending for the increased cost of these new 
Medicaid populations.
    Just yesterday, we had in the papers talked about N Health, 
which sells HSA high deductibles to employers recently 
announced it will terminate all its customers by December 31, 
2010, because it cannot survive the health care law mandates 
and regulations. Then there is American National Insurance 
Company, which similarly announced two subsidiaries, American 
National Life Insurance Company of Texas and Standard Life, an 
accident insurance company, won't sell health insurance to 
people in the individual market after June 30, 2010, because of 
the health reform law. Can we really tell these people this if 
you like what you have you can keep it when these companies go 
out of the business as the President promised to the American 
people. And it is only June of 2010. The full effects of this 
law won't go into effect until 2014. Are these problems only 
the tip of the iceberg?
    So once again, Chairman, I certainly have an appreciation 
for our hearing today but we will continue to raise the health 
reform law and call on you for formal hearings to discuss the 
many issues both positive as the President promoted yesterday 
and negative, these health insurance companies leaving the 
market, what is working and what needs to be address before it 
is fully implemented.
    Thank you, Mr. Chairman. I yield back my time.
    Mr. Pallone. Thank you, Mr. Shimkus.
    Our chairman of the full committee, Mr. Waxman.

OPENING STATEMENT OF HON. HENRY A. WAXMAN, A REPRESENTATIVE IN 
             CONGRESS FROM THE STATE OF CALIFORNIA

    Mr. Waxman. Thank you very much, Chairman Pallone, for 
calling this second of a series of hearings that we are having 
on antibiotic resistance, which is a growing and dangerous 
threat to the public health and it is an issue that deserves 
the full and complete attention of this committee.
    At our first hearing, we learned about the impact of 
antibiotic resistance on human health, and today we will 
continue that discussion, but also focus on two important and 
directly related issues: the preservation of effective 
medicines that already make up our antibiotics drug arsenal, 
and the development of new antibiotics to fight resistant bugs.
    By definition, this is an inherently difficult goal to 
achieve. After all, the very use of antibiotics leads to the 
development of pathogens that can no longer be treated by those 
antibiotics. In this case, rather than use it or lose it, with 
antibiotics it is use it and lose it. Already untold numbers of 
Americans die or are infected each year by antibiotic-resistant 
microbes. We pay a high price in other ways as well--additional 
hospital stays, hospital readmission and increased doctor 
visits. These will add unnecessarily to the Nation's annual 
health care bill.
    Our hearing in May made clear that it will take a multi-
pronged approach to overcome this very serious and very present 
problem. Today we will focus on two such strategies, a 
reduction in the inappropriate use of antibiotics and the 
expansion of the antibiotic product line and market. I believe 
that we must pursue both lines of attack. We simply must find 
ways to cut back on both the overuse and misuse of these drugs.
    At the same time, we need to ensure the existence of a 
market environment that encourages the development and 
commercialization of new safe and effective antibiotics to 
treat those pathogens resistant to existing antibiotics. Such 
an environment does not appear to appear to be in place today.
    As we consider possibilities for market incentives, we must 
not lose sight of the potential impact those incentives may 
have on patients, especially if new antibiotics are more 
expensive than the patients can afford to buy.
    The written testimony we have already received lays out a 
variety of approaches to meet these objectives. I look forward 
to hearing more about them from our witnesses today. As we do, 
I hope we can continue to work on a bipartisan basis towards a 
public-private plan of action to address the overall and 
pressing antibiotic resistance problem that we now face.
    I thank the witnesses for their testimony and look forward 
to hearing from them. Thank you, Mr. Chairman.
    [The prepared statement of Mr. Waxman follows:]

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    Mr. Pallone. Thank you, Chairman Waxman.
    The gentleman from Kentucky, Mr. Whitfield.

  OPENING STATEMENT OF HON. ED WHITFIELD, A REPRESENTATIVE IN 
           CONGRESS FROM THE COMMONWEALTH OF KENTUCKY

    Mr. Whitfield. Thank you, Mr. Chairman, and I also want to 
thank the witnesses for being with us today on this very 
important subject. Certainly the American people are very much 
focused today on access to health care, quality of health care 
as well as cost of health care, and the subject matter that we 
are going to discuss today is one very important component of 
that.
    It has already been stated that 2 million people roughly 
acquire infections in hospitals and about 90,000 of those die 
each year. Seventy percent of the hospital-acquired infections 
are caused by bacteria that are resistant to particular drugs 
most commonly used.
    We certainly understand that the process for developing 
clinical trials at the FDA is extremely complex and we look 
forward to the testimony today to explore opportunities to make 
it less complex but also ensuring safety. I know it is my 
understanding that there are about 15 antibiotics that are in 
the pipeline today at FDA for approval, and I am not sure how I 
know this but evidently we don't think there is much chance 
that many of those are going to be approved, but we do need to 
explore ways to provide incentives for pharmaceutical companies 
as well as trying to make the system less complex but also 
ensuring safety, and I am delighted we are having this hearing 
and look forward to the testimony of all our witnesses.
    Mr. Pallone. Thank you, Mr. Whitfield.
    Mr. Waxman. Mr. Chairman, before you recognize----
    Mr. Pallone. Yes?
    Mr. Waxman. I just want to make a unanimous consent 
request, which I should have made. It is to put into the record 
a statement by Dr. Michael T. Flavin, chairman and chief 
executive officer of Advanced Life Sciences prepared for the 
record for this committee.
    [The information was unavailable at the time of printing.]
    Mr. Pallone. Without objection, so ordered. Thank you, Mr. 
Chairman.
    And next is our chairman emeritus, Mr. Dingell.

OPENING STATEMENT OF HON. JOHN D. DINGELL, A REPRESENTATIVE IN 
              CONGRESS FROM THE STATE OF MICHIGAN

    Mr. Dingell. Mr. Chairman, thank you for holding today's 
hearing on what is a growing and real public health crisis.
    Two months ago, we had a hearing on the basics of 
antibiotic resistance during which one of our witnesses, Dr. 
Thomas Frieden, director of the Centers for Disease Control, 
stated that we are moving into a post-antibiotic world. He 
warned that there may be soon no clinical treatments for some 
infections. This is a very real and frightening crisis.
    Today, 19,000 people die a year of multi-drug-resistant 
MRSA. Our soldiers are coming home from Afghanistan and Iraq 
with acinetobacter, which is often resistant to at least three 
classes of antibiotics, and hospital-acquired antibiotic-
resistant infections cost our health care system up to $34 
billion a year. Imagine what we are going to have to do when we 
find that we cannot deal with serious diseases the way we can 
now with antibiotics.
    I want to thank our witnesses today for joining us, and I 
hope that from our witnesses we can begin to get this country 
on a track where we practice sound evidence-based public policy 
that can make us better stewards of antibiotic use and of our 
future and how we can assist all of the stakeholders in this 
public health issue. More specifically, we need to learn, 
amongst other things, how do we prevent the spread of 
infections that require antibiotic treatments? How do we best 
educate patients and doctors about judicious and prudent use of 
antibiotics? And finally, how do we improve upon the current 
incentives and regulatory structures that bring new antibiotics 
and diagnostic tests into the marketplace?
    The growing number of bacteria resistant to antibiotics is 
frightening and will become more so. Even more frightening is 
the thought that our health providers and general public have 
not realized the magnitude of the problem that we face with 
resistant bacteria. Less-effective treatments for bacterial 
infections mean longer-lasting illnesses, more doctor visits, 
extended hospital stays, the need for more-expensive and toxic 
medications, and in a growing number of cases, death of the 
patient. Our children are at a greater risk because they have 
the highest rates of antibiotic use. We have to be smart about 
our approach in addressing this issue, and today's hearing 
should provide great insight and direction, and it is time that 
we recognize the urgency of this situation.
    I thank you, Mr. Chairman, and I yield back the balance of 
my time.
    Mr. Pallone. Thank you, Chairman Dingell.
    Next is our ranking member of the full committee, Mr. 
Barton.

   OPENING STATEMENT OF HON. JOE BARTON, A REPRESENTATIVE IN 
                CONGRESS FROM THE STATE OF TEXAS

    Mr. Barton. Thank you, Mr. Chairman. It is always good to 
have a hearing looking to the future. We look forward to the 
testimony today of the individuals who are going to testify 
about our antibiotics and what we are doing to make sure that 
the next generation of antibiotics continues to be as effective 
as the current generation is.
    We also look forward, Mr. Chairman, to having you and the 
full committee chairman at some point in time schedule some 
hearings on the new health care law. We find daily evidence 
that it is not what it appears to be. HHS has already missed 
numerous deadlines. We have had the CBO and other budget 
agencies come out that instead of saving money it is going to 
cost hundreds of billions, perhaps a trillion dollars more than 
estimated. The President must think it is in some trouble. He 
had a campaign-style rally this week trying to drum up support. 
We need to do due diligence, and if there are things in the law 
that need to be changed, the sooner we get about changing them, 
the better it will be for the American people. So I hope that 
that happens sooner rather than later.
    But in terms of today's hearing, we do look forward to the 
testimony from our witnesses because this is an issue that does 
deserve some attention and we appreciate you giving it to us.
    With that, I yield back, Mr. Chairman.
    [The prepared statement of Mr. Barton follows:]

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    Mr. Pallone. Thank you, Mr. Barton.
    The gentlewoman from California, Ms. Eshoo.

 OPENING STATEMENT OF HON. ANNA G. ESHOO, A REPRESENTATIVE IN 
             CONGRESS FROM THE STATE OF CALIFORNIA

    Ms. Eshoo. Thank you, Chairman Pallone, for holding this 
hearing on antibiotic resistance, which is a growing concern 
for scientists, for the medical community, for patients and 
certainly for policymakers. I want to extend a warm welcome to 
both Drs. Woodcock and Robinson and thank you for the work, the 
important work that you do.
    The discovery of antibiotics transformed medical care in 
the 20th century. Many bacterial infections which were once 
deadly are now treatable illnesses. People no longer die from 
minor cuts, from ear infections or pneumonia. Antibiotics treat 
infections on the battlefield, after surgeries and in doctors' 
office across the country.
    But antibiotics are not the universal remedy to all 
illnesses. The widespread and inappropriate use of antibiotics 
leads to dangerous antibiotic-resistant bacteria, and due to 
the relatively low side effects of antibiotic use, physicians 
often prescribe them for maladies such as flu or the common 
cold. Antibiotics cannot treat these illnesses and their misuse 
leads to the rise of antibiotic-resistant strains of illnesses, 
and as these strains appear, some patients may have nowhere to 
turn when they have exhausted their antibiotic options.
    Attempts to reduce antibiotic resistance must be 
comprehensive. We should curb the overuse of them and at the 
same time encourage the development of new antibiotics to keep 
pace with new strains of resistant infection. Antibiotic 
resistance has the potential to become a significant public 
health crisis. I am especially interested to learn about what 
role BARDA and Project BioShield may play in promoting the 
development of new antibiotics.
    So my thanks to the FDA for not only testifying today but 
for your ongoing, I think extraordinary work, and I look 
forward to working with all the members of the committee to 
address the issue of antibiotic resistance.
    I yield back, Mr. Chairman.
    [The prepared statement of Ms. Eshoo follows:]

    [GRAPHIC] [TIFF OMITTED] T6585A.011
    
    Mr. Pallone. Thank you.
    Next is the gentleman from Texas, Mr. Burgess.
    Mr. Burgess. Thank you, Mr. Chairman. It is an important 
hearing, important witnesses. I am going to submit my statement 
for the record and reserve time for questions.
    Mr. Pallone. Thank you.
    Our vice chair, the gentlewoman from California, Ms. Capps.

   OPENING STATEMENT OF HON. LOIS CAPPS, A REPRESENTATIVE IN 
             CONGRESS FROM THE STATE OF CALIFORNIA

    Mrs. Capps. Thank you, Mr. Chairman. Thank you for holding 
this hearing, and welcome to our witnesses in both panels.
    A few weeks ago, as others have recalled, we held an 
informative hearing on the subject of antibiotic resistance. I 
think this hearing is a logical follow-up to the many questions 
that arose at that time. Most importantly, how do we balance 
the simultaneous need to halt the development of antibiotic 
resistance while incentivizing the development of effective 
antibiotics and ensuring patient compliance? I think we will 
learn from our witnesses today that the solution lies in a 
multifaceted approach that relies on, one, improving our basic 
research capabilities; two, incentivizing the private sector to 
invest in the necessary research and development; three, better 
educating health professionals on the most effective 
prescription of antibiotics and the ways to do this; and last, 
and I am sure there are more, making our public more aware of 
the ways they minimize risk of infection, prevention, in other 
words.
    So I look forward to hearing from our witnesses on their 
suggestions for achieving these objectives and how we can 
develop the most appropriate policies to implement them, and I 
yield back the balance of my time.
    Mr. Pallone. Thank you.
    Next is the gentleman from Georgia, Mr. Gingrey.

  OPENING STATEMENT OF HON. PHIL GINGREY, A REPRESENTATIVE IN 
               CONGRESS FROM THE STATE OF GEORGIA

    Mr. Gingrey. Thank you, Mr. Chairman.
    Antibiotics are a critical treatment for many bacterial 
infections and oftentimes their usage saves lives. 
Unfortunately, overutilization of antibiotics makes it more 
likely that bacterial resistance to antibiotic therapy will 
develop. Staying ahead of bacterial resistance to antibiotics 
is vital to our health care system. We can do that in part by 
educating medical providers on the proper use of these drugs. 
Many illnesses can be treated by proper diagnosis and over-the-
counter remedies rather than relying on prescribing 
antibiotics. In many instances, it is appropriate and does not 
require much time or cost to take a culture in order to 
properly identify a patient's condition. If we are to combat 
bacterial infections, taking the necessary steps to identify 
appropriate cases for antibiotics is an important first step.
    Mr. Chairman, we must also be aware that patient demand 
plays a big part in the overutilization of antibiotics. In many 
instances, patients will request an antibiotic from their 
provider because they are convinced it will cure common 
infections faster than over-the-counter treatment, and that is 
certainly not always the case. Having spent time in general 
practice during my 30-year medical career, I understand how 
patient demands can influence provider decision. Therefore, any 
education efforts should include those aimed at informing 
patients of the dangers of overusage of antibiotics.
    Unfortunately, no amount of education is going to stop 
antibiotic resistance. New forms of antibiotics must be 
available if we are to effectively deal with this emerging 
problem. Today the high cost of drug development and short 
treatment courses have caused a decreasing number of companies 
to pursue antibiotic development. In other words, their success 
has led to the fact that there is a shortage now of 
antibiotics. Any solution geared towards addressing future 
bacterial infections must ensure that proper incentives are 
identified and supported that will encourage greater antibiotic 
development. This committee should not shy away from reviewing 
the pathway of drug development, from drug discovery all the 
way through to licensing. My hope is that a balanced and 
thorough review of the antibiotic market will help ensure that 
we properly identify any disincentives that may exist with 
regard to the production of new antibiotics and are better 
prepared to promote incentives that may reverse this current 
trend. I believe this problem is one that can best be solved by 
encouraging industry and government to work together to find 
the solutions that our future health needs require.
    Mr. Chairman, with these thoughts in mind, I would like to 
thank you for holding today's hearing on this important and 
growing issue. I look forward to hearing the expert testimony 
from our distinguished panel of witnesses, and I yield back the 
balance of my time.
    Mr. Pallone. Thank you.
    The gentleman from Utah, Mr. Matheson.

  OPENING STATEMENT OF HON. JIM MATHESON, A REPRESENTATIVE IN 
                CONGRESS FROM THE STATE OF UTAH

    Mr. Matheson. Thank you, Mr. Chairman, for holding this 
hearing today, and thanks to the witnesses as well.
    As you are aware, I have reintroduced legislation in this 
Congress, H.R. 2400, the Strategies to Address the 
Antimicrobial Resistance Act, or the STAR Act, as the acronym 
is, which I believe is a comprehensive piece of legislation to 
strengthen our Nation's response to pathogens that are 
increasingly resistant to antibiotics. Senators Sherrod Brown 
and Orrin Hatch introduced the companion bill in the 110th 
Congress. Over 25 health care stakeholders support this 
legislation, a number of which will testify today in this 
hearing. H.R. 2400 provides strategies and authorizes 
critically needed funding to strengthen federal antimicrobial 
resistance surveillance, prevention and control and research 
efforts. It also strengthens coordination within the Department 
of Health and Human Services' agencies as well as across other 
federal departments that are important to addressing 
antimicrobial resistance and considers opportunities to address 
this issue globally.
    The STAR Act provides a rare opportunity to bring many 
partners together to protect public health. This legislation 
was developed with input from infectious disease experts and 
leaders in public health and provides authority for the federal 
government to combat antimicrobial resistance in four ways. 
Number one: It reauthorizes the antimicrobial resistance task 
force, establishing an advisory board of outside experts and an 
antimicrobial resistance office reporting to the Secretary of 
Health and Human Services, whose director will coordinate 
government efforts to combat antimicrobial resistance. Number 
two, it creates an antimicrobial resistance strategic research 
plan as well as establish the antimicrobial resistance 
surveillance and research network. Number three, the bill calls 
for collecting available and relevant data to allow government 
to better address the antimicrobial resistance problem, and 
fourth, it establishes demonstration projects to encourage more 
appropriate use of existing antibiotics.
    Mr. Chairman, as you are aware, our committee has had a 
critical role in establishing the foundation of work for this 
issue. Our chairman emeritus, Mr. Dingell, requested a report 
on the impact of antibiotic-resistant bacteria in the 103rd 
Congress. In the 106th Congress, Chairman Stupak introduced 
legislation to direct the Secretary of HHS to establish the 
antimicrobial resistance task force. In the 10th Congress, 
several members of this committee joined Senator Sherrod Brown, 
who at that point was a member of this committee, to introduce 
legislation to provide funding for the top priority action 
items of the public health action plan.
    I provided this brief snapshot of this history for my 
colleagues to show that while some work has been accomplished, 
the war against resistance to infection looms large for our 
Nation's public health, and to be clear for my colleagues on 
both sides of the aisle, this is a public health emergency that 
in the year 2007 alone infected more than 94,000 people and its 
estimated cost to our health care system was millions of 
dollars.
    I look forward to the hearing today and hearing from our 
witnesses and look forward to doing whatever we can to work 
with this committee to help move this legislation forward. I 
yield back my time.
    Mr. Pallone. Thank you, Mr. Matheson.
    The gentleman from Pennsylvania, Mr. Murphy.

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

    Mr. Murphy of Pennsylvania. Thank you, Mr. Chairman.
    Two million people will acquire infections in hospitals 
this year. Between 90,000 and 100,000 will die. The costs will 
be about $50 billion to treat them. And by those numbers, so 
far today this year, 44,133 people have died from a hospital-
acquired infection.
    Although today we are talking about the overprescribing of 
antibiotics, let us understand the most effective antibiotic is 
the one you do not have to prescribe. Prevention does work. 
Hospitals that vigorously gather data on infection rates and 
enforce infection controls see decline in infection rates but 
many doctors, families, hospital staff do not do this, and that 
is the root of one of our problems that we have to address.
    Over time, I have introduced over repeated Congresses 
legislation to require hospitals and clinics to report their 
infection data. Unfortunately, we have not moved it forward at 
all in committee and has not moved anywhere in the House. This 
means that hospitals are not required to gather information nor 
report their infection rates, and as such, a lot of people are 
dying because we are not paying attention to it.
    The solutions don't require great science or approval from 
the FDA. It means that people that come near a patient have to 
wash their hands, use sterile equipment, wear clean clothes 
such as gowns or gloves or masks, clean up before and after 
procedures, use antibiotics before and after surgery, and have 
close monitoring of infection rates and quick reaction time 
when infections occur.
    So I have reintroduced this bill once again, H.R. 3104. I 
hope that in addition to dealing with bacteria that are 
resistant to antibiotics, we also begin to deal with resistance 
by caregivers to passing legislation that requires them report 
infection rates. To me, it is incomprehensible that the very 
providers who are out there saying we need to reduce infection 
rates are the ones opposed to finding out what those infection 
rates are. It is reprehensible that on one side of our mouth we 
are saying we want people to live and out of the other side of 
the mouth we are saying people don't tell anybody that we are 
not doing a very good job about it. I hope that sometime this 
committee will consider this legislation, require hospitals and 
clinics to begin to look at these rates and report them, and in 
so doing, I might add, when hospitals do this, they save lives. 
It is repeatedly demonstrated. And once again, the most 
effective antibiotic is the one you don't have to use. I yield 
back.
    Mr. Pallone. Thank you.
    The gentlewoman from the Virgin Islands, Mrs. Christensen.

       OPENING STATEMENT OF HON. DONNA M. CHRISTENSEN, A 
       REPRESENTATIVE IN CONGRESS FROM THE VIRGIN ISLANDS

    Mrs. Christensen. Thank you, Chairman Pallone. Good 
morning.
    As I read the testimonies last night and reflected on the 
first hearing with Drs. Frieden and Fauci, I kept thinking that 
we are supposed to leave a better world for our children than 
we have and there are many events that bring this into question 
and the issue of the antibiotic resistance which threatens to 
set the treatment of infectious diseases back into the Dark 
Ages is one of them. Dr. Frieden's and Dr. Fauci's testimony 
were very informative, and the witnesses we will hear from 
today will add to our understanding of the issue and to their 
recommendations.
    As a family physician like my colleague over here, who 
practiced for over 20 years, I know the pressure that doctors 
are under to prescribe antibiotics and how difficult it is to 
have a patient continue on their regimen once they start to 
feel better, and those are but two of our challenges. The fact 
that only five out of several hundred drugs in the pipeline are 
antibiotics speaks volumes about the level of the crisis and 
the need to incentivize the pharmaceutical industry, something 
I recall not doing very well initially with BioShield but 
greatly improving on in 2006 with BARDA.
    This is a multifaceted problem in which everyone from the 
patient to the provider and all the health care workers, the 
Department and Congress have an important role to play. We have 
several agencies and pieces of legislation with which we begin 
to address the crisis and I look forward to what our witnesses 
have to say about them.
    I want to thank you, Chairman Pallone and Ranking Member 
Shimkus for this hearing and the witnesses for their presence 
and for their very informative testimonies. Thanks.
    Mr. Pallone. Thank you, Mrs. Christensen.
    I just wanted to yield briefly to our ranking member, Mr. 
Barton, for a personal point.
    Mr. Barton. I want to make a point of personal privilege, 
Mr. Chairman. Congresswoman Blackburn, whose birthday was 
yesterday, is smiling amongst us and she has had the great 
foresight to hire my stepdaughter or employ my stepdaughter as 
one of her interns, Lindsay Taylor, who is a junior at the 
University of Texas majoring, I believe, in business with a 
minor in marketing, and she did some of the work to prepare for 
the hearing today. So I want to introduce Marsha's intern and 
my stepdaughter Lindsay Taylor to the committee. Wave.
    Mr. Pallone. Thank you, and welcome.
    Mr. Barton. Thank you, Mr. Chairman.
    Mr. Pallone. Thank you. Welcome. And happy birthday to you 
also, Marsha.
    Next is--actually next is the gentlewoman from Tennessee, 
Ms. Blackburn.

OPENING STATEMENT OF HON. MARSHA BLACKBURN, A REPRESENTATIVE IN 
              CONGRESS FROM THE STATE OF TENNESSEE

    Mrs. Blackburn. Thank you, Mr. Chairman.
    Welcome to those that are here today and thank you for the 
work that you have done in preparation for coming to us. Mr. 
Chairman, I thank you for the hearing today.
    An interesting little tidbit as we prepared for this. 
According to the Tennessee Department of Health, the antibiotic 
resistant rates in Tennessee are among the highest in the 
Nation, and we know that this has come from overuse and misuse 
of antibiotics and it has contributed to this. This is 
something we have been fighting in our State for a long time as 
prescription use was higher than it should be. We know that it 
is a looming public health crisis, and it is of concern to us 
when we look at the rising incidence of drug-resistant 
bacteria, and we are concerned about the stagnant R&D of new 
therapies to treat some of these new infections.
    It is alarming that medical professionals have very few 
resources to treat some of these patients as demand far 
outpaces supply of the antimicrobials. While prevention is key, 
not every infection is preventable, and we understand that but 
there is a growing concern about R&D, and it concerns me that 
there are only a few small private companies that are investing 
in R&D and putting their money into that and developing the new 
therapies that are needed, and we know it is difficult to hit a 
moving target, and as the antimicrobial pathogens constantly 
mutate, resulting in long-term R&D investment needs, and also 
realizing that for many of these there is a short-term usage.
    And the other thing we are concerned about and that we hear 
from our medical community about is uncertainty from the FDA. 
So as we go through the hearing today, those are points that we 
are going to want to cover with you, the concern about R&D, the 
concern about uncertainty with the FDA, and then also just the 
antibiotic resistance rates that we see in our State.
    I thank you, and I yield back.
    Mr. Pallone. Thank you, Ms. Blackburn.
    And I guess last, although I am not sure, is the 
gentlewoman from Colorado, Ms. DeGette.

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

    Ms. DeGette. Thank you very much, Mr. Chairman. At least 
you didn't say I was last and least. I will submit my opening 
statement for the record.
    I just want to point out a couple of facts that are even 
more disturbing than some of the facts we have heard from the 
members. One-third of the world's population is infected with 
TB, and in 2008 multidrug-resistant TB accounted for 5 percent 
of all tuberculosis cases, which is the highest percentage 
recorded to date, and even more frightening is the emergence of 
extensively drug-resistant tuberculosis that is resistant to 
all major TB drugs available. In the United States, 70 percent 
of the 2 million who die from hospital-acquired infections were 
infected with strains resistant to at least one antibiotic, and 
according to the CDC, $1.1 billion is spent annually on 
unnecessary antibiotic prescriptions for adult upper 
respiratory infections. Those billions of dollars could be 
spent on developing new antimicrobials, not needlessly 
encouraging antibiotic resistance.
    Unfortunately, antibiotic resistance will never go away 
because bacteria have an incredible capacity to evolve and 
multiply. Bacteria have existed on earth a thousand times 
longer than we have and can undergo 500,000 generations in the 
time it takes humans to undergo one generation. And so really, 
all the members today agree that we need to proactively 
confront antibiotic resistance. We can't eliminate it but what 
we can do is significantly reduce the rate and spread of 
antibiotic-resistant pathogens.
    So everybody has noted it is important that we use 
antibiotics prudently, but prudent use alone is not enough. We 
need a multi-pronged approach that has regulation, 
surveillance, research and obviously new discoveries must 
rigorously be pursued in parallel. In addition, while it is not 
the topic of the hearing today, we need to look very closely at 
overuse of antibiotics in agriculture because that is another 
big problem that we face.
    So it is a multi-pronged problem. I am glad, Mr. Chairman, 
you are looking at it in a multiple series of hearings, and 
since I am the last member, I am going to yield back the 
balance of my time so we can hear from our distinguished 
witnesses. Thank you.
    [The prepared statement of Ms. DeGette follows:]

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    Mr. Pallone. Thank you, Ms. DeGette.
    So that does conclude the opening statements by our members 
and we will turn to our first panel, who are already seated. I 
want to welcome you. On our first panel to our left, or to my 
left, I should say, is Dr. Janet Woodcock, who is director of 
the Center for Drug Evaluation and Research at the FDA, and 
next to her is Dr. Robin Robinson, who is director of 
Biomedical Advanced Research and Development Authority with the 
Department of Health and Human Services. You know the drill, 5-
minute opening statements. They become part of the record, and 
you can submit additional written statements in writing for 
inclusion in the record after, if you like.
    So I will begin with Dr. Woodcock. Thank you.

 STATEMENTS OF JANET WOODCOCK, MD, CENTER FOR DRUG EVALUATION 
AND RESEARCH, FOOD AND DRUG ADMINISTRATION; AND ROBIN ROBINSON, 
  MD, DIRECTOR, BIOMEDICAL ADVANCED RESEARCH AND DEVELOPMENT 
       AUTHORITY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

                  STATEMENT OF JANET WOODCOCK

    Dr. Woodcock. Mr. Chairman and members of the subcommittee, 
I am Janet Woodcock. I am the director of the Center for Drug 
Evaluation and Research at the FDA, and I thank you for the 
opportunity to testify on this important topic.
    Maintaining access to lifesaving antibiotics and combating 
antimicrobial resistance are critically important to the FDA. 
As a rheumatologist, I can attest both to the power of these 
drugs as they save the lives of many of my immunocompromised 
patients and to the tragedy when they were really not enough to 
combat the infection and I lost young patients, some of the 
most difficult episodes of my professional career.
    Antimicrobial therapy is really one of the triumphs of 
modern medicine. Louis Thomas, who is one of our distinguished 
American physicians, clinician and scientists, witnessed the 
dawn of the antibiotic era when he was a medical trainee, and 
he describes a transformation from helplessness in the face of 
almost certain death of a patient to intervention that could 
rapidly restore a patient to health. We can't go back to this 
helplessness, and I think that is what drives the concern about 
antibiotic resistance. These were truly wonder drugs at that 
time.
    But what was not known at the time is that these medicines 
came with an expiration date. The use of antimicrobials, 
especially indiscriminate use, will affect the timing of that 
expiration date but every antibiotic will get to the end of its 
usefulness as the members have already said because the 
microbes have many strategies to elude our chemical attacks and 
so we must use our intelligence, our science and our technology 
to stay ahead of the microbes. We must use antimicrobials 
carefully to prolong their effectiveness but we must also have 
new interventions in the pipeline.
    Over the last half century, biomedicine has relied upon the 
private sector to fill this pipeline fueled by government-
supposed basic science. This arrangement has produced a vast 
array of active antimicrobials. However, over the last two 
decades a combination of economic and scientific factors has 
decreased this productivity. The pipeline is diminished at a 
time when the need could not be greater.
    I would like to provide some insight into the scientific 
problems that we face. Our success in developing antimicrobials 
means that most common infections are adequately treated with 
existing therapy. This change in the history of infections 
makes it more difficult to study new treatments. For critically 
ill individuals, though, time is of the essence in getting 
treatment and delays to obtain consent and to complete study 
enrollment are often not acceptable and limit enrollment of 
very ill patients into studies of new treatments and the 
historical widespread antibiotic use has resulted in a 
patchwork of resistance problems that have already been alluded 
to.
    In the absence of rapid diagnostic tests for the identity 
and resistance patterns of the infecting organisms, doctors 
don't know what they are facing when they are treating an 
individual patient. These factors create the need for new 
scientific methods to study antimicrobial drugs. FDA has been 
working with the scientific community to develop these methods. 
This is an example of regulatory science, the kind that has 
been advanced by Dr. Peggy Hamburg, our FDA commissioner. FDA 
plans to publish additional guidance on these methods within 
the next 6 months to help establish new scientific standards 
for evaluation of antimicrobial drugs.
    In closing, I would like to add a note of optimism to this 
picture. The filings for new studies of experimental 
antibiotics in people, which are called INDs, the first test of 
a new therapy in humans, has been in a steep decline since 
1987, and every year we have seen fewer and fewer new compounds 
come into the clinic for testing, but in the last 3 years we 
have seen a reversal of this trend with a sharp upward move. We 
have seen more small companies and startups involved in the 
field and interest in medically important infectious conditions 
that lack good treatment. This may be good news for our 
patients. But to bring this into the hands of doctors, to bring 
these new innovations into the hands of doctors requires 
concerted effort on the part of academia, government and the 
private sector, and we hope to contribute to that. Thank you.
    [The prepared statement of Dr. Woodcock follows:]

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    Mr. Pallone. Thank you, Dr. Woodcock.
    Dr. Robinson.

                  STATEMENT OF ROBIN ROBINSON

    Dr. Robinson. Good morning, Chairman Pallone, Ranking 
Member Shimkus, Chairmen Waxman and Dingell and other 
distinguished members of the subcommittee, I am Robin Robinson, 
director of Biomedical Advanced Research and Development 
Authority, known to most of you as BARDA, at HHS.
    Antimicrobial resistance is a major concern to you, to the 
Nation and also to BARDA, and we appreciate the opportunity to 
talk to you about how we are going to move forward in combating 
this problem.
    As has been stated, antimicrobials are our primary weapons 
in the fight against old and new infectious diseases. The 
discovery and development of antibiotics in the mid-20th 
century is among the greatest advances in the history of 
medicine and public health and they remain a mainstay in our 
treatment and use of medicine.
    In addition to antibiotic resistance being a problem in 
community-acquired diseases, antibiotic resistance provides an 
additional concern to BARDA as resistance to current 
antimicrobials could be intentionally introduced by genetic 
manipulation and to otherwise susceptible bacteria including 
bioterrorism bacterial agents producing a biological 
superweapon that would render our stockpiles of antibiotics 
obsolete during an attack. Further, naturally occurring drug-
resistant isolates of several biodefense pathogens including 
plague have been detected by environmental and clinical 
surveillance, making the availability of antibiotic-resistant 
bioterrorism pathogens even more feasible. Thus, the increasing 
prevalence of antimicrobial-resistant bacteria is not only a 
matter of concern for public health but of national security.
    Antibiotic resistance is further exacerbated by the dearth 
of antibiotic candidates that are coming through the 
development pipeline with a little bit of glimmer coming from 
what Dr. Woodcock has just said. The consequences of the 
limited antibiotic development pipeline are obvious and seen 
every day among medical practitioners and public health 
officers with tragic outcomes for growing number of patients 
and using drugs that are becoming obsolete. The public health 
and biodefense repercussions of antibiotic resistance call for 
greater public-private partnerships between the federal 
government and industry to provide the necessary support, core 
clinical development and manufacturing services and incentives 
to make a robust development pipeline of new classes of 
antibiotics and other products.
    Into this setting of escalating antibiotic resistance, what 
can BARDA do? BARDA was established by the Pandemic and All-
Hazards Preparedness Act of 2006 to ensure the United States 
has sufficient supply of vaccine and drugs to respond to public 
health emergencies caused by pandemic influenza, chemical, 
biological, radiological and nuclear threats, and emerging 
infectious diseases. BARDA uniquely bridges a critical gap 
referred to as the Valley of Death in the public health, 
medical and biodefense infrastructure that is facilitating the 
advanced development and manufacturing acquisitions of medical 
countermeasures that have little or no commercial markets by 
forcing public and private partnerships. In its short history, 
BARDA has taken a multi-pronged approach to pandemic influenza 
and biodefense medical countermeasure programs to stimulate 
drug and vaccine development and manufacturing capabilities.
    Similarly, we have proposed that we move forward with this 
multi-pronged approach for antibiotic resistance. This approach 
and the authorities provided by the Pandemic and All-Hazards 
Preparedness Act would allow BARDA to develop new classes of 
antibiotics as well as other medicines including vaccines and 
diagnostics that are authorized under PAHPA for BARDA to 
address in this fight against antibiotic resistance.
    So what would our strategy be for combating antibiotic 
resistance? First, to continue our development of new classes 
of broad-spectrum antimicrobials not only for biodefense but 
for public health. Secondly, vaccines for high-priority 
bacterial pathogens, and these vaccines would be, say, for 
Staph aureus that would combat MRSA. And lastly, point-of-care 
diagnostics for high-priority bacterial pathogens which would 
actually change the way that medicine could be practiced by 
actually having point-of-care diagnostics that a physician 
could provide the appropriate care for patients. Together these 
actually have a ripple effect not only on antimicrobial 
resistance but also in the pipeline for other drugs by using 
multi-utilization platform technologies and moving forward with 
these together we think that we can make a big difference going 
forward.
    So I look forward to being able to answer questions for you 
in BARDA's section of the pie as we go forward. Thank you.
    [The prepared statement of Dr. Robinson follows:]

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    Mr. Pallone. Thank you, Dr. Robinson, and we will move 
right to questions, and I will recognize myself initially.
    I wanted to ask Dr. Woodcock a question. A couple of the 
witnesses on the second panel, which we haven't heard from but 
we have their testimony, they cite regulatory uncertainty as 
one of the factors contributing to why there are so few 
effective antibiotics on the market today and that this 
uncertainty compounds the other economic disincentives that 
confront companies considering investing in the development of 
new antibiotics. An example of this regulatory uncertainty, 
according to one of the witnesses, they cite the FDA's failure 
to finalize certain documents that would provide guidance to 
industry on how to satisfy FDA's requirements for pre-market 
clinical trials of specified antibiotics. Now, your testimony, 
Dr. Woodcock, describes some of the difficult questions and 
issues surrounding these clinical trials on new antibiotics and 
I recognize that the stakes here are high, but on the one hand 
you are faced with what we all recognize as a dangerous lack of 
new safe and effective antibiotics. On the other hand, FDA 
doesn't want to approve new antibiotics that not only may not 
work but could also contribute to the resistance problem. So 
formulating these guidelines is obviously not easy but I wanted 
you to tell some more about the difficulties you faced in 
developing and completing these guidelines, if you will.
    Dr. Woodcock. Well, first of all, let me say that the 
regulatory path is pretty clear for an obviously superior 
treatment so if a treatment were developed that could beat 
other antibiotics or treat resistant therapy where no other 
antibiotic is effective, that regulatory path is very clear. 
The problem is for treatment areas where there is a lot of 
satisfactory therapy and those are typically the targets for 
commercial development because, as some of the members already 
alluded to, those are very widespread in the community, 
sinusitis and so forth. Where there is very effective therapy 
out there, it is difficult to tell whether a new treatment is 
actually equivalent to the existing treatments and we don't 
want to run the risk of successively approving more inferior 
treatments to the point where at some point we have approved 
therapies that aren't actually effective.
    Mr. Pallone. OK.
    Dr. Woodcock. So we are developing new scientific methods 
to evaluate these conditions in a time where there is adequate 
antibiotic therapy out there and it is more difficult to do 
that. However, companies that wish to pursue other types of 
infections that are currently not very well treated, that is a 
clearer path but that is not as commercially desirable a path 
to get onto the market.
    Mr. Pallone. Now, what about the timelines? Can you tell us 
the anticipated timelines for completing the draft guidelines 
you listed in your testimony, and then what would companies or 
what should companies do now before they are completed? Can 
they rely on the draft guidances or wait until they are 
finalized?
    Dr. Woodcock. Companies may come to the FDA and obtain 
advice on an individual basis, development plan basis, and 
that's what companies can do right now is talk to the FDA, but 
in an era, in a time of some scientific uncertainty, there is 
more risk to development, but I would reiterate that this is 
for these common infections, many of them that have currently 
satisfactory treatment. We do expect to move to finalize many 
of our guidances that we have published in draft. We are going 
to publish in the next 6 months several additional drafts of 
versions because there has been a great deal of scientific 
controversy about these evaluation methods and what methods 
would rely result in effective antibiotics being approved by 
the FDA, which is what we all, I think, want.
    Mr. Pallone. You are still talking about drafts, though. 
What about the final documents?
    Dr. Woodcock. Yes, we will move to finalize these documents 
as rapidly as possible. We are moving to finalize some of the 
documents.
    Mr. Pallone. OK. I mean, it seems like these are very 
difficult scientific issues but at the same time it is 
important to get them right, but I just wanted to stress how 
important it is to resolve these issues and get these 
guidelines finalized as soon as possible. I know you are not 
giving me specific timeliness but it is really important to get 
it moving.
    Dr. Woodcock. We agree with that, and we have recently 
entered into a collaboration to do what we call qualification 
work, which people might call validation work. We are looking 
at these new end points in clinical trials and see how they 
perform, and that is the kind of regulatory science work that 
really can move this ahead and provide everyone with the 
confidence that these new scientific methods are the right 
methods to test these new products and move them efficiently 
through the pipeline. So we agree but unfortunately there was 
some scientific work that had to be done to get these into 
final.
    Mr. Pallone. Thank you.
    Mr. Shimkus.
    Mr. Shimkus. Thank you, Mr. Chairman. I think I am going to 
follow your line, but first, Dr. Woodcock, the chairman had the 
benefit of receiving testimony from the second panel to read 
what they said to ask you questions. FDA submitted your 
testimony at 9:20 p.m. last night, or at least the minority 
staff got it at 9:20 p.m., which is way from the 48 hours. So 
we just want to raise that issue to ensure that we get timely 
submissions so we can do our due diligence on our side just as 
the chairman did, and that does help to have a heads-up of what 
the second panel is going to do.
    Following into my questioning, I am going to follow this 
line of thought on the antibiotic development and regulatory 
uncertainty, which you were already alluding to. What we have 
heard is that there is not certainty or it is unclear the type 
of clinical trials that are needed, and when companies have 
invested a lot of capital in the trials, only then to be told 
that their clinical trials were insufficient, what can you do 
from a regulatory perspective to help clear up this regulatory 
uncertainty?
    Dr. Woodcock. There is no doubt that predictability is one 
of the most important things for incentivizing commercial 
development in a specific indication area. So those who have to 
invest money need to know that if they dot all the i's and 
cross all the t's that they can get their--and the drug works 
and is safe they can get it across the finish line. We 
recognize that and we do everything possible to provide that 
predictability of development path. However, as science 
changes, we have to--and the history of the diseases have 
changed based on the availability of all these other effective 
antibiotics, we have had to change the evaluation methods. That 
created a transition period that was very uncomfortable. We 
hope we are ending, reaching the end of that transition period 
so that we have new designs that are very clear and we have 
predictable development paths. But I will say I think that the 
time when companies seek to get sort of blockbuster antibiotics 
to treat otitis media or respiratory conditions and so forth 
and get those on the market, that is not exactly what you are 
talking about here, I think, in getting a new pipeline moving 
through. You are talking about getting new, effective 
antibiotics----
    Mr. Shimkus. Right. My follow-up will be on the pipeline, 
so I mean, your analysis is correct. But it seems to me that 
what you are saying is, you don't need any additional authority 
to bring this certainty, you just need to make a decision for 
new antibiotic regime of what is then going to be considered a 
safe clinical trial, right? You have the authority to do this?
    Dr. Woodcock. Yes, we have the authority. We need an 
evaluation method that we can rely upon, so if you test the 
antibiotic with that method you can reliably say that 
antibiotic works because that is what we are assuring the 
physicians and the patients is, you take this, this is an 
effective antibiotic.
    Mr. Shimkus. Right. Then following up on what you mentioned 
before, is the pipeline there?
    Dr. Woodcock. We are seeing--yes, the pipeline is 
diminished and has been for many years. What we are seeing in 
the very early stages of clinical development is a remarkable 
upturn. We can't----
    Mr. Shimkus. And that is in your testimony. You talked 
about the decline, but then some new submissions by smaller 
companies in your testimony. Do you need to encourage more 
people to now get involved so that the pipeline is not there? 
Do you need any more additional authority?
    Dr. Woodcock. I don't think it is FDA authority. Our role 
is to make sure these treatments are safe and effective and 
that there is a clear development path for these. It is clear, 
I think, to everyone that more incentives of some type or some 
type of encouragement of investors and companies and scientists 
and so forth to enter into this area is needed.
    Mr. Shimkus. Thank you. Let me move quickly to Dr. 
Robinson. What is your role in fostering new antibiotic 
development?
    Dr. Robinson. As I said in my testimony, we are responsible 
for antimicrobials for biothreats as part of our Project 
BioShield mandate but we are also responsible for emerging 
infectious disease as mandated by PAHPA, and we are reaching 
out further with dual-purpose antibiotics not only for plague, 
tularemia and so forth but also we will be going forward with 
community diseases including those that are gram-negative 
microorganisms. We see that the antibiotic resistance to TB 
really needs a very specific set of drugs and other approaches 
including that are non-antibiotics where a vaccine or vaccines 
may be applicable such as I mentioned the Staph aureus with 
MRSA but also with diagnostics as Dr. Frieden talked about and 
Dr. Fauci did, that one of the ways that we can help physicians 
immediately is by having point-of-care diagnostics that allow 
them to make the proper diagnosis and then prescribe the 
correct drugs.
    Mr. Shimkus. My time is expired. Thank you, Mr. Chairman.
    Mr. Pallone. Thank you. I just want to join with Mr. 
Shimkus's comments about the timeliness of the testimony. I 
understand it came in maybe a little earlier than what he said, 
but the bottom line is, we didn't get it until yesterday 
evening, and it is supposed to be 48 hours, and members, not 
that I am trying to bemoan us but we come in for votes at 6:30 
and it is almost impossible to read the testimony the night 
before when you are just arriving here for votes, so I would 
just ask you and FDA, because I know he has pointed this out 
several times with FDA and Human and Health Services, we really 
need to get the testimony in in a timely fashion, otherwise we 
really can't formulate questions and really have an effective 
hearing. So I just wanted to mention that again.
    The next is the gentlewoman from the Virgin Islands, Ms. 
Christensen.
    Mrs. Christensen. Thank you. I didn't expect to be coming 
up this quickly, and thank you both for being here and for your 
testimony again.
    Dr. Woodcock, at the end of your testimony you gave us a 
little bit of good news, so to what do you attribute the 
increase or have you been able to attribute it to anything, the 
increase in the new investigations of antimicrobial drugs?
    Dr. Woodcock. We are seeing this to some extent across the 
board in drug development, and I attribute it both to the new 
science that has identified a lot of new targets, genetics and 
so forth, so that is number one. Number two, ether is a 
changing structure of the industry and there are a lot more 
players and different players who are getting into development 
and that is probably good news for diversity, and otherwise I 
don't think we know, but I think those are two of the major 
factors.
    Mrs. Christensen. Thank you.
    Dr. Robinson, BARDA seems to have a fair amount of 
authority with regard to addressing this issue. Is there any 
further authority that BARDA would need to help us address this 
crisis?
    Dr. Robinson. Thank you, ma'am. We have actually looked at 
this very carefully and we believe right now that with PAHPA 
that we do have the authority to move forward with this multi-
pronged approach that will allow advanced development of all of 
these medical countermeasures to move forward. So I think right 
now we are OK.
    Mrs. Christensen. And I guess to both of you, one of the 
individuals on the second panel suggests that the federal 
government has not really been good or as strong a partner as 
they need to be so you don't need any other authority. Is 
funding the limitation?
    Dr. Robinson. I will speak first on that. Because we have a 
number of different mandates and the funding for advanced 
development only came about in really the fiscal year 2007 
budget, we certainly would need more resources to be able to 
address all the different priorities that we have including 
antibiotic resistance, yes.
    Mrs. Christensen. Dr. Woodcock.
    Dr. Woodcock. We accomplish what we can with the resources 
that we have. There are needs for regulatory science that are 
quite broad and this is one area. The research into the 
endpoints in trial design could help accelerate obviously 
getting guidances out in a timely manner and so forth. The 
President's budget for 2011 has a request for increasing 
regulatory science by the FDA commissioner. So I think we are 
limited to some extent because, like Dr. Robinson, by the large 
number of priorities that we deal with.
    Mrs. Christensen. And Dr. Woodcock, you also talked about 
some of the limitations in terms of the research limitations 
but the plan that the interagency task force put together has 
been in effect for 10 years. What percent or how much of that 
plan has been implemented and what other barriers might you 
have run into in implementing much of what you have set out?
    Dr. Woodcock. Well, I believe that the plan will be updated 
and republished. There have been elements of that that have 
been accomplished but there is a plan to reupdate the plan and 
publish it with timelines for accomplishment of various 
activities which I think will help move that program along.
    Mrs. Christensen. Well, I didn't have a chance to look at 
the plan but has 10 percent, 30 percent of it been implemented 
over the 10 years?
    Dr. Woodcock. I am sorry. I can't give you--we can get back 
to you on that.
    Mrs. Christensen. Thank you.
    Mr. Chairman, I will yield back my time.
    Mr. Pallone. Thank you.
    The gentleman from Kentucky, Mr. Whitfield.
    Mr. Whitfield. Thank you all very much for your testimony. 
Dr. Woodcock, I would like to revisit this issue of lack of 
clarity and simply ask the question, in your view, is the 
criticism valid that the FDA does have a lack of clarity and it 
is unclear as to what type of clinical trials will be required 
for demonstrating safety and effectiveness? We hear a lot of 
criticism of the FDA in that regard, so in your view, is that 
criticism valid or not valid?
    Dr. Woodcock. I would say it is valid to say that the 
scientific community has a lack of clarity on how to best 
evaluate new antibiotics and that is reflected in the fact that 
the FDA is struggling to get new guidances out there that 
reflect new evaluation methods that will be effective in 
today's environment. So had there been clarity in the 
scientific community, I think FDA could have effected this 
change very rapidly, but due to the lack of clarity we had to 
go through a great deal of effort to gain some type of 
consensus on how to do this.
    Mr. Whitfield. It is seldom that the scientific community 
has very much clarity anyway, isn't it?
    Dr. Woodcock. Well, we are no strangers to controversy in 
the area of how to evaluate medical products. However, this was 
a change that occurred between the 1980s and 2000, 1990 to 
2000, a change that happened rapidly and it has been very 
difficult to get a new state of clarity about how to do this 
antibiotic development.
    Mr. Whitfield. Would you explain the Orphan Drug Act for 
me, please? And also it is my understanding that there are 
grants available under the Orphan Drug Act and the amount of 
money involved in those grants and it is also my understanding 
that you all were required in the 2007 act to have a public 
hearing, which I think occurred in April maybe of this past 
year and what the results of that were and what you are doing 
to follow up on those recommendations?
    Dr. Woodcock. The Orphan Drug Act allows for incentives, 
grants as well as exclusivity for products to get onto the 
market for products that are intended to treat populations 
smaller than 200,000 individuals in the United States.
    Mr. Whitfield. Smaller than 200,000?
    Dr. Woodcock. Yes, and so this has been a wildly successful 
program in incentivizing the development of drugs for small 
populations, and I think there is agreement across the board 
about that, which is very rare to get such agreement. So it has 
been a very successful program. Its applicability to 
antibiotics is limited to the extent that where the population 
is often larger than that of treated patients for the given 
indication but for small indications where there is fewer than 
200,000 people that would present with that condition in the 
United States, then the orphan provisions are germane.
    Mr. Whitfield. What is the dollar value of the grants that 
would be available under that program?
    Dr. Woodcock. I don't know. We would have to get back to 
you on that. I think they vary, but one of the more valuable 
issues is the orphan exclusivity that is given to the product 
if it successfully gets on the market.
    Mr. Whitfield. And how did that April hearing go or forum 
go?
    Dr. Woodcock. Again, I would have to get back to you on 
that. I don't have the details of that.
    Mr. Whitfield. OK. You were not there?
    Dr. Woodcock. No.
    Mr. Whitfield. I yield back the balance of my time.
    Mr. Pallone. Thank you.
    Next is the gentleman from Maryland, Mr. Sarbanes. He has 
no questions.
    We will go to Mr. Burgess, who actually has 8 minutes.
    Mr. Burgess. Thank you, Mr. Chairman.
    And again, thank you both for being here, very informative 
discussion.
    Dr. Woodcock, you made the statement during your testimony 
that the microbes have strategies. I guess that begs the 
question, do we--because it does seem like we have got a 
problem both with the product in the pipeline and perhaps the 
pipeline itself may be old and rusty and full of obstacles. So 
are we--how do you feel about how we are updating that 
infrastructure to get this job done?
    Dr. Woodcock. Well, obviously we all agree that prudent 
uses and preventing infection is one of the mainstays of this 
but we also must have a pipeline and I feel that many of the 
issues covered by the members already such as the short-term 
use of antibiotics, the regulatory or scientific difficulties 
nowadays in the development path, until recently probably the 
lack of new targets because the antibiotics were often all 
focused on the same microbial targets and now there is a 
broader range of targets. So I think there is room for 
optimism. However, I do believe that more commercial interest 
in this field needs to occur to really get the pipeline robust.
    Mr. Burgess. Well, Dr. Robinson mentioned two issues, but 
let us stay with you, Dr. Woodcock, because the FDA plays a 
role here in becoming available. One was the point-of-care 
diagnostics and the other were the vaccines where you go from a 
broader spectrum now down to a narrower spectrum but if you 
have fewer bugs that are actually able to become resistant, 
then you'll reduce the likelihood of resistance. So how is the 
FDA doing as far as getting those two tools that BARDA is 
developing, how is the FDA doing it getting those into the 
hands of clinicians?
    Dr. Woodcock. The FDA has approved several point-of-care 
diagnostics recently, several diagnostics for MRSA. However, 
they have to go through an additional step of the CLIA process 
to be approved for use in the practitioner's office, but I 
think this is very promising as far as that rapid microbial 
testing can be developed.
    Mr. Burgess. But this is a problem, though, I mean, with 
CLIA, I wasn't here but CLIA meant that we couldn't even make a 
microscopic slide and look at it under the microscope for 
clinically easily recognizable pathogens because I was not 
licensed to do that. So what happened, of course, I would do it 
and not charge for it and not tell anyone I was doing it say my 
clinical acumen tells me this is X even though I have 
identified it under the microscope. What a waste of time. Are 
we trying to improve that part as well or is that beyond the 
scope of the FDA?
    Dr. Woodcock. CLIA, as you know, is administered by CMS. 
However, this particular issue is simply to show that the 
diagnostic is effective in use in the hands of the practitioner 
and then it can be used in the hands of the practitioner. So it 
is simply a demonstration that practitioners can use such a 
diagnostic like the rapid strep test or whatever in the setting 
of an office.
    Mr. Burgess. I didn't mean to get off on that. I still have 
a great deal of emotional difficulty with the affronts to my 
clinical judgment from CLIA.
    Let me ask you this. The new molecular entities approved by 
the FDA in the last decade, I think for the last hearing my 
staff had prepared for me a list of 10 new molecular entities. 
Does that sound about right?
    Dr. Woodcock. That sounds about right.
    Mr. Burgess. Is that OK, one a year for the last decade, or 
now over the last decade?
    Dr. Woodcock. Well, this reflects the slide in the pipeline 
since 1987 where the new INDs have progressively decreased 
every year since 1987 until recently. So it takes about 5 or 6 
years in the clinic from first in human studies to see 
therapies coming out and being available to doctors.
    Mr. Burgess. Do you know, are there any applications that 
have been filed with the FDA to get approval for new 
diagnostics for bacterial infections? Do you know if you have 
approved any? Has the FDA approved any of those new 
diagnostics?
    Dr. Woodcock. As I said, we have approved several over the 
last several years, yes, for rapid diagnostics.
    Mr. Burgess. You know, Mr. Waxman, who unfortunately is not 
here, asked unanimous consent to insert into the record a 
letter from Advanced Life Sciences, and I asked to look at it 
just because I wanted to see what he was putting into the 
record, but it is very interesting. I mean, here is a company 
that has developed a single does or once-a-day oral therapy for 
methicillin-resistant Staph aureus and we talked about patient 
compliance. You tell a patient they have got to take something 
every 4 hours, guess what? They aren't going to do it. They 
will do what I did, which I don't recommend, which is you take 
the antibiotic to toxicity and then back off, and if you feel 
better, you don't take it anymore. That is what patients do. 
That is real-world stuff. So if you give them one pill a day, 
they are much more likely to comply with the regimen. So this 
actually sounds like something that might be very useful. We 
have got a pathogen that is a series pathogen for community-
acquired pneumonia and it is multiply-resistant Staph aureus, a 
once-a-day therapy, and here the company has done all the stuff 
they needed to do to get it going and then the rules changed on 
them in the middle of the application and they had to go back 
to square one. This is a small company. This is not one of the 
big houses that now we say won't participate, and this is 
exactly the type of company we want involved in this and they 
are apparently coming to Chairman Waxman with the information 
that they can't--you know, they had to start all over again, 
significant cost to them because they are a small startup 
company. What do you say to that? Why are we putting these kind 
of obstacles out there?
    Dr. Woodcock. Well, it is a very difficult situation when 
the scientific needs for scientific evaluation changed during a 
development program, and it is very difficult for small 
companies. We try to avoid that as much as we can but the 
science may chance in advance----
    Mr. Burgess. And I recognize that, but can you not, and the 
advisory panels, can you not build in the flexibility as you 
are going through these? I mean, you changed the endpoints 
after the new drug application has been submitted. They have 
already invested considerable time and money. They could walk 
away from the project. Fortunately, they have not because I 
think this is a product that ultimately will benefit patients. 
But, really, it seems like there has got to be more 
flexibility. These are relatively unique situations that 
develop but more flexibility at the regulatory side to deal 
with just these types of problems. I mean, suffice it to say if 
Sir Alexander Fleming had come up against this, he might have 
never had a statue of himself erected by the bullfighters in 
Spain because he wouldn't have been able to get penicillin 
cleared through your agency.
    Dr. Woodcock. We understand. I can't discuss any specific 
case but we certainly try to build in flexibility and we 
recognize that changing--and that is actually built into our 
procedures. We try not to change our advisory requirements 
during a development program if at all possible.
    Mr. Burgess. I don't mean to interrupt, but my time is 
going to run out, and they are really tough on me with the 
gavel here, but do you really feel like you are getting a clear 
regulatory pathway so everyone can know the rules and then if 
we do change the rules in the middle, we at least have some 
certainty for these companies that at some point the 
regulations will cease and they will get either a yes or no on 
their product? Because that is after all what they need to 
hear.
    Dr. Woodcock. We recognize how important that is to 
stimulate and sustain development in any indication area. We 
definitely recognize that predictability is key.
    Mr. Burgess. Thank you, Mr. Chairman.
    Mr. Pallone. Since you suggested we should be tough, I 
guess we will have to be.
    Mr. Burgess. I will give you back Mr. Waxman's submission 
for the record.
    Mr. Pallone. Thank you.
    Next is the gentleman from Texas, Mr. Green.
    Mr. Green. Thank you, Mr. Chairman. And I have never 
thought you wielded a heavy gavel. I would ask permission to 
submit my opening statement for the record, Mr. Chairman.
    [The prepared statement of Mr. Green follows:]

    [GRAPHIC] [TIFF OMITTED] T6585A.038
    
    [GRAPHIC] [TIFF OMITTED] T6585A.039
    
    Mr. Pallone. Without objection, so ordered. All members may 
submit their statements without even making the request 
actually.
    Mr. Green. Thank you, Mr. Chairman.
    Dr. Robinson, you explained some of the challenges that 
hinder antibiotic development and I would like to ask about a 
potential solution to encouraging companies to work on 
developing antibiotics, advance market commitment. I understand 
the way the strategy works. The government contracts with a 
company to buy a certain number of doses of a product at a 
specific price. This gives the company a certain level of 
assurance that there will be a market for their product on an 
agreed-upon price. This is similar to what you do for other 
certain countermeasures which traditional market forces doesn't 
work, smallpox or anthrax vaccines. Do you think this approach, 
should we consider antibiotics for this approach?
    Dr. Robinson. Well, certainly because we have antibiotics 
as part of our mainstay against biothreats, I would have to say 
this is something we would have to consider going forward. For 
public health reasons, it should be openly discussed with the 
medical communities and also considered as one of our 
possibilities to incentivize going forward, yes.
    Mr. Green. And one of my concerns about stockpiling is, we 
also have shelf life to obviously antibiotics and any other 
medication, and that is something you dealt with, though, with 
the smallpox and anthrax vaccines, I assume?
    Dr. Robinson. Certainly with the therapeutics we have a 
shelf life extension program that the FDA has so admirably held 
for a number of years now, and I think that we can utilize that 
going forward with new antibiotics that would come into the 
stockpile.
    Mr. Green. So you don't see any logistical challenges? I 
mean, you have already addressed some of the challenges of 
other medications. You could do the same with antibiotics?
    Dr. Robinson. That is correct. It would be a policy issue 
at this point.
    Mr. Green. Dr. Woodcock, one of the suggestions for 
creating incentives for antibiotic is expand the concept of 
tropical disease priority review vouchers established under the 
FDA Amendments Act. Such a voucher would entitle the holder to 
get a drug reviewed with a target completion time of 6 months. 
Under such an approach, FDA would give a company a priority 
review voucher as a reward for developing a qualified 
infectious disease product. The company could use the voucher 
for a drug of its choice or could sell it to another company. 
Dr. Woodcock, could you tell us how the existing tropical 
disease program has worked from the FDA's perspective? Does it 
seem like a workable approach for important new antibiotics, 
and what are the tradeoffs in terms of FDA review of other 
drugs if we have that 6-month provision in there?
    Dr. Woodcock. Well, I don't think that there has been 
enough activity so far under the tropical disease provisions to 
provide an assessment but we can get back to you on exactly 
what has happened but, you know, I don't think there has been 
enough action there to provide an assessment.
    As far as the tradeoffs, I think if you wanted to think of 
this more broadly and apply it more broadly, what this does 
would decrease the FDA review time from 10 months to 6 months 
for any given product and could be applied to any product, and 
most likely a company would apply it to a product that would 
normally be for a chronic disease, widespread treatment, right, 
and might be used to treat tens of millions of Americans, and 
this would mean that FDA would have to review that much faster 
than ordinary because the voucher had been applied to that. So 
I think there are some limitations on that approach because 
when we get a lot of priority reviews, especially where we are 
reviewing a drug that tens of millions of Americans might be 
exposed to it and it may be for chronic but not really 
important condition, we have to be really sure of the safety of 
that drug. We have to do a very, very careful review, and if we 
had large numbers of short reviews for products like that, I 
think that would be problematic for our review structure.
    Mr. Green. I know one of the concerns I have is, I have a 
district in Houston, Texas, and we are seeing many more 
tropical diseases, for example, that are coming into our 
country, whether it is global warming or what, but if there is 
a problem, it is going to be in Houston and Dallas and San 
Antonio and shortly in Chicago and other places. So that is why 
I think some of that is really needed to respond to in our own 
country, much less what is happening in other parts of the 
world.
    Mr. Chairman, I actually gave you 6 seconds back. Thank 
you.
    Mr. Pallone. Thank you, Mr. Green.
    The gentleman from Georgia, Mr. Gingrey.
    Mr. Gingrey. Mr. Chairman, I want to read an excerpt into 
the hearing record from the Administration's own interagency 
task force on antimicrobial resistance. The task force wrote a 
public health action plan in 2008 that reads in part, 
``Existing market incentives and regulatory processes may be 
insufficient to stimulate the development of certain priority 
antimicrobial-resistant products while fostering their 
appropriate use. The goal is to investigate and act upon 
potential approaches for stimulating and speeding the entire 
antimicrobial-resistant product development process from drug 
discovery through licensing. Drs. Woodcock and Robinson, do you 
agree with that statement?
    Dr. Woodcock. It is critically important if you want to 
increase the activity in a given sector to provide adequate 
incentives and discovery is important because we need new 
targets. We need antimicrobials that are going against a 
broader range of activities of the microbes and development is 
important because it requires a great deal of investment to get 
a product through and there has to be seen some type of return 
on investment in order to get robust investment in that sector. 
So I think those things are extremely important and we have to 
think them through very carefully.
    Mr. Gingrey. So you do agree.
    Dr. Robinson, would you agree also as well?
    Dr. Robinson. Yes, I would agree, absolutely, because 
advanced development is the area that BARDA plays that when Dr. 
Fauci was here, he was talking about discovery and early 
development and then the market over here. Well, that is what 
BARDA does. It makes sure it can get from early development all 
the way to the market.
    Mr. Gingrey. Doctors, can you tell the committee what 
organizations actually co-chair this task force, the 
Administration's interagency task force on antimicrobial 
resistance?
    Dr. Woodcock. I believe CDC, NIH and FDA.
    Mr. Gingrey. I think you are right, Dr. Woodcock.
    Dr. Robinson, you won't have to second-guess her. That is 
exactly right.
    If your 2008 report is true, and it is a report that is co-
chaired by CDC, HHS and FDA, as Dr. Woodcock knew and reported, 
if the report is true, and we do need to look outside current 
market and regulatory incentives to stimulate antibiotic 
development, what other incentives might we as a government 
provide? As an example, would liability protection in certain 
circumstances help support greater innovation? Dr. Robinson?
    Dr. Robinson. With the liability relief that has been 
provided previously by Congress with the PREP Act, we have 
actually applied that with declarations during events that 
would include some of the antibiotics, and what we were told by 
industry was that that was very helpful and that some form of 
liability relief is important.
    Mr. Gingrey. Sort of like in the vaccine production when we 
really need something to combat H1N1.
    Dr. Woodcock.
    Dr. Woodcock. Well, I think I don't have further opinion on 
the liability issue. Obviously any type of incentive is 
important and I think any incentives have to be considered in 
light of whether or not you want to have restrictions at the 
other end because one of the goals here would be to restrict 
the use or moderate the use or make sure the use is very 
prudent of the intervention to preserve its effect as long as 
possible, and that is--we have our current problems with the 
pipeline but if we contemplated a pipeline that would end up 
with antimicrobials that would only be used in niche situations 
where they were really needed, that would be even a further 
disincentive, but you have to think about that as a goal to 
preserve the effect of that for a long time to protect the 
population and what kind of incentives would stimulate that.
    Mr. Gingrey. Well, certainly I have an opinion on that and 
a very definitive opinion in regard to the development of the 
vaccines. I felt like liability protection was absolutely 
essential for us to move forward in that direction.
    Now, this last question real quickly, and I don't have an 
opinion on this. I am just very curious to know what you think 
about it, though. Do our current antitrust laws allow companies 
to work together to create and expedite new antibiotics? And if 
not, if those laws don't allow that, would an easing of the law 
prove beneficial, do you think?
    Dr. Robinson. Sir, I will give you an example where we 
actually have used the authority given to BARDA for antitrust 
exemption, and we actually used with the development of the 
H5N1 and the H1N1 vaccine. It was very important that we have 
that. Certainly in our case, we could actually use that and 
actually provide our sister agencies to be there also, which we 
normally do.
    Mr. Gingrey. Dr. Woodcock.
    Dr. Woodcock. I have worked in public-private partnerships 
where we have gotten companies together to advance general 
societal goals and they have had to be extremely lawyer-
intensive on the antitrust issues, so there is no doubt, I 
think, that it is a barrier to working together to advance 
broader goals.
    Mr. Gingrey. Great. I think that is very helpful and I 
appreciate your response.
    Mr. Chairman, you are pretty generous with that gavel. I 
will yield back 1 minute late.
    Mr. Pallone. Thank you.
    Mr. Murphy of Pennsylvania.
    Mr. Murphy of Pennsylvania. Thank you, Mr. Chairman. I have 
been sitting here going over some of the FDA Web sites on this 
information. I know you have quite a public campaign, 
preserving our treasure, knowing how antibiotics work, et 
cetera. Have you measured the effectiveness of your campaigns 
in terms of working with the public in reducing their demands 
on physicians for antibiotics when it is not the appropriate 
medication?
    Dr. Woodcock. I believe especially the CDC's recent 
campaign----
    Mr. Murphy of Pennsylvania. The CDC's, yes, CDC and FDA on 
the same sites, yes.
    Dr. Woodcock [continuing]. Did have an impact that was 
measured on reducing antibiotic use in sort of inappropriate 
conditions, yes.
    Mr. Murphy of Pennsylvania. Is that something we are going 
to see continued and expanded? I mean, we have talking a good 
bit about that today in terms of the kind of comments you have 
made and members have made. I am just wondering if that is 
something that you see that we should continue to fund and push 
for a widespread public education on that, and I might add, 
including the things you heard in my earlier commentary about 
the need for prevention, and I am amazed sometimes, I will go 
into hospitals where you can't walk down the hall without 
someone being fairly militant and making you gown and glove and 
wash your hands, which is good. I have heard of other dynamic 
things. To get in the ICU at University of Miami Medical 
Center, you don't push a button, there's not a sensitive 
sensor. To get in the door, you have to put your hand under an 
alcohol dispenser, and then when it squirts in your hands, the 
doors open. That is a very clever idea. Or I have also heard of 
systems where the doctors wear little monitors or anybody, and 
when they enter a room if they not washed their hands, a little 
mini alarm goes off and says ``Wash your hands, please,'' and 
then the chairman hits them with the gavel. Not true, sir. I am 
continuing the theme here. But I am just wondering about public 
education campaigns that we do to reduce the need there.
    Dr. Woodcock. I believe that is extraordinarily important. 
No matter what we do to the pipeline, and I think the last 20 
years have shown us that, if there is indiscriminate use, then 
that will accelerate the development of resistance and our 
pipeline will continue to have trouble getting ahead of that. 
The recent scientific emerging understanding about infection 
control and how effective these simple measures actually can be 
if they are rigorously followed I think has startled a lot of 
people and provides a tremendous opportunity for improving 
quality in health care and decreasing infections, as you said, 
but each of those I believe needs continued pressure and 
education and interest to perpetuate them and they will go a 
long way toward dealing with this problem.
    Mr. Murphy of Pennsylvania. Well, I want to encourage all 
of you. I know when some of the recent flu outbreaks came out, 
you couldn't get into a bus stop without seeing a sign 
somewhere, and that was excellent. I thought it was very 
helpful.
    The second thing I wanted to ask about has to do with since 
when people are sick they want to do something, and so there 
are a number of over-the-counter products, and either of you 
can answer this too, in terms of what we should be doing to 
help promote those for symptom assistance as opposed to the 
false promise of antibiotics for virus, other things we should 
be doing to encourage more OTC products, over-the-counter 
products instead. Is that in any of your purview that you want 
to comment on that?
    Dr. Woodcock. FDA regulates the over-the-counter drugs, and 
we certainly--there is certainly a huge array of symptomatic 
control available for common viral illnesses that people suffer 
and also there are many other simple measures. So I think much 
of this is public education about the availability of 
straightforward symptomatic control for viral illnesses.
    Mr. Murphy of Pennsylvania. Do you have anything to add on 
that, Dr. Robinson.
    Dr. Robinson. I would just concur with that also. I mean, 
we have had a number of different sponsors come to us for 
support looking at very simplistic type of products like that.
    Mr. Murphy of Pennsylvania. I might add to my editorial 
comments. I know that cuts to allow people to have their health 
care plan use their monies to pay for over-the-counter drugs, I 
don't like that idea because here we are talking about a 
massive amount of money we have to put into research and 
prescribing cots for antibiotics that we are building 
resistance to when we should be encouraging people to use other 
symptom remedies for that which are much less expensive and of 
course appropriate for those things too, so I hope those are 
things that we will restore in the future and I want to thank 
you both for your testimony. It is good to read this.
    I yield back, Mr. Chairman.
    Mr. Pallone. Thank you.
    The gentlewoman from Tennessee, Ms. Blackburn.
    Mrs. Blackburn. Thank you, Mr. Chairman.
    I am going to be very brief. I just want to go back to what 
Chairman Pallone was talking about at the very first, and I 
touched on it in my opening statement, our concern with the 
uncertainty that seems to exist at the FDA. And in my district 
in Tennessee, we have some wonderful groups that are doing 
tremendous amounts of research in biotherapies and in new 
therapies that are coming along the chain. We hear repeatedly 
about concern with the uncertainty from the FDA. You mentioned, 
Dr. Woodcock, that there has been a decline in the pipeline 
since 1987 and then we have also touched on the disincentives 
that are there. Dr. Robinson mentioned some of those. And I 
think that it is important that we realize those disincentives 
and the uncertainty at the FDA have a direct effect on what is 
there in that pipeline, and you keep saying, you have mentioned 
several times you have the authority that is necessary, Dr. 
Woodcock, to finalize these documents and provide some 
certainty on that pathway, and I would just highlight with you 
that we think that that is important to do. If you have the 
authority, maybe you have too much authority. Maybe we need to 
pull some of that back and oversight and be just a little more 
direct and participatory in trying to help define that, but I 
would just highlight with you that it is of concern to us. We 
appreciate the work that you are doing but we do have great 
concerns about the uncertainty and the disincentives and the 
decline in the pipeline, and with that I will yield back.
    Mr. Pallone. Thank you. And let me thank both of you for 
being here today. It was obviously very helpful to us in this 
sort of three-pronged effort here with three hearings to get to 
the bottom of some of these problems and what is happening. 
Thank you.
    I will ask the second panel to come forward at this time. 
Let me introduce--well, first of all, welcome, and let me 
introduce the second panel. Starting to my left is Dr. Brad 
Spellberg, who is associate professor of medicine, the David 
Geffen School of Medicine at UCLA and a member of the 
Infectious Diseases Society of America Antimicrobial 
Availability Task Force. Second is Dr. Sandra Fryhofer, who is 
from the Council on Science and Public Health at the American 
Medical Association. Then we have Dr. John Bradley, who is 
speaking on behalf of the American Academy of Pediatrics. He is 
the chief of the Division of Infectious Diseases. He is with 
the Department of Pediatrics at the University of California 
School of Medicine, clinical director of the Division of 
Infectious Diseases and he is also at Rady Children's Hospital 
in San Diego. That is a long list there. And then we have Dr. 
Barry Eisenstein, who is senior vice president of scientific 
affairs for Cubist Pharmaceuticals. I have to ask you, I keep 
looking at this Cubist, is that just the drug that you--what 
does the Cubist refer to?
    Dr. Eisenstein. We believe that medicine and science 
involved in drug development is both an art and a science.
    Mr. Pallone. Oh, so it is reference to a cube, in other 
words. OK. Thank you.
    And last is Dr. Jeffrey Levi, who is executive director of 
the Trust for America's Health. He has testified many times 
before the committee, and I hope that we did not contribute to 
your leg being broken or whatever happened to you.
    Mr. Levi. No.
    Mr. Pallone. Thank you for being here today.
    So you know we have 5-minute opening statements that become 
part of the record and then we may ask you, or you may submit 
additional written statements if you like, and we will start 
with Dr. Spellberg.
    Dr. Spellberg. Thank you. Could we cue up the slides, 
please?
    Mr. Pallone. Oh.
    Dr. Spellberg. Great.
    Mr. Pallone. It is up there.

STATEMENTS OF BRAD SPELLBERG, MD, FIDSA, ASSOCIATE PROFESSOR OF 
  MEDICINE, DAVID GEFFEN SCHOOL OF MEDICINE AT UCLA, MEMBER, 
     INFECTIOUS DISEASES SOCIETY OF AMERICA ANTIMICROBIAL 
   AVAILABILITY TASK FORCE; SANDRA FRYHOFER, MD, COUNCIL ON 
 SCIENCE AND PUBLIC HEALTH, AMERICAN MEDICAL ASSOCIATION; JOHN 
 S. BRADLEY, MD, ON BEHALF OF AMERICAN ACADEMY OF PEDIATRICS, 
     CHIEF, DIVISION OF INFECTIOUS DISEASES, DEPARTMENT OF 
   PEDIATRICS, UNIVERSITY OF CALIFORNIA SCHOOL OF MEDICINE, 
   CLINICAL DIRECTOR, DIVISION OF INFECTIOUS DISEASES, RADY 
  CHILDREN'S HOSPITAL, SAN DIEGO; BARRY EISENSTEIN, MD, FACP, 
   FIDSA, SENIOR VICE PRESIDENT, SCIENTIFIC AFFAIRS, CUBIST 
  PHARMACEUTICALS; AND JEFFREY LEVI, PHD, EXECUTIVE DIRECTOR, 
                   TRUST FOR AMERICA'S HEALTH

                  STATEMENT OF BRAD SPELLBERG

    Dr. Spellberg. Thank you very much, Mr. Chairman. My name 
is Dr. Brad Spellberg. I am an infectious disease specialist, 
as you said, at the UCLA School of Medicine and Harbor UCLA 
Medical Center. I am also the author of ``Rising Plague,'' 
which is a book about the antibiotic crisis, and it is my honor 
today to be here representing the Infectious Diseases Society 
of America, which is an organization of more than 9,000 
physicians, pharmacists and scientists that all work in 
infectious diseases and microbiology.
    In 2004, the IDSA released the ``Bad Bugs, No Drugs'' white 
paper to inform the public and Congress about the looming 
antibiotic crisis and more recently just in the last couple of 
months, the IDSA has released the 10 by 20 initiative, which 
calls for the development of 10 new critically needed 
antibiotics by the year 2020. And the reason why we are here 
today and the reason why IDSA has released ``Bad Bugs, No 
Drugs'' and the 10 by 20 initiative is because we are here to 
advocate for our patients that are dying of infections and we 
are running out of drugs to throw at them.
    [Slide.]
    This graph shows the number of new systemic antibacterial 
agents approved by the FDA for a 5-year period. The conclusion 
from this graph is inescapable: antibiotic development is 
dying. And at the same time, we are witnessing skyrocketing 
incidences of multidrug-resistant bacterial infections of a 
variety of types, some of which are shown on this graph, but 
there are many other types as well. This of course creates a 
critical need for new antibiotics to be developed right at the 
time when new antibiotics are not being developed, and these 
infections hit hospitalized patients, infirm patients, sick 
patients, the elderly, but they also hit the healthiest and 
strongest among us. In particular our soldiers in Iraq and 
Afghanistan have been devastated by a wide variety of 
multidrug-resistant bacterial infections. And this highlights a 
central point, which is that everyone is at risk for these 
infections including healthy people in communities, and as 
shown on this slide are examples of real patients who were 
healthy in communities and have been killed or maimed by 
multidrug-resistant bacterial infections. Everyone is at risk. 
The collective toll of these infections in terms of number of 
people infected, number killed and the multibillions of dollars 
per year that these infections cost our health care system is 
absolutely staggering.
    We have to start thinking of antibiotics as a precious 
limited resource in the same way that we view forestry, 
fisheries and energy policy. We need to both conserve and 
restore this precious resource and currently we do neither. We 
overuse and waste our antibiotics in both humans and animals, 
and the antibiotic resource is not being restored, because as 
we have heard, both there is an economic disincentive because 
antibiotics are not economically competitive with other drugs 
and there are regulatory barriers that prevent companies from 
understanding how to do clinical trials to get antibiotics 
approved.
    So we need a multi-pronged approach to solving these 
problems, as we have heard. We need a multi-pronged approach to 
promoting antibiotic conservation. We need much better, more 
effective and widespread antibiotic stewardship programs to be 
used all over the country and frankly throughout the world. We 
need funding to be made available to CDC and others to develop 
and spread these stewardship programs. We do need to promote 
the development and use of rapid diagnostics to empower 
physicians to more accurately prescribe antibiotics, and 
finally, we need to pass the STAR Act, which will give us 
federal oversight and create the infrastructure necessary to 
gather the data we need to understand the scope of the 
antibiotic resistance problem in this country.
    We also need a multi-pronged approach to promoting 
antibiotic restoration. We need to establish orphan drug-like 
economic push and pull incentives to rekindle interest in the 
industry in antibiotic R&D. We need to increase funding to 
relevant federal agencies like NIH, like BARDA and we should 
really start thinking seriously about establishing a nonprofit 
public-private partnership whose mission is to develop 
critically needed small-market molecules to treat life-
threatening infections caused by resistant bacteria, and 
finally, we need to continue to promote regulatory clarity at 
the FDA for existing pathways and also to create new pathways 
to create critically needed antibiotics that have not been 
developed previously.
    I am going to close with a brief anecdote. Congressman 
Burgess mentioned penicillin. I want to go back to the 
beginning of the penicillin era to remind all of us how 
important it is that we have effective antibiotics. So I am 
going to tell you the true story of a 4-year-old girl in late 
1942 who had been in perfect health until she suddenly 
developed an infection on her face, a skin infection. This 
progressed relentlessly. Her face and neck became so swollen, 
she could not swallow her own saliva, and it was when she began 
gasping for breath that her parents in a panic rushed her to 
the Mayo Clinic.
    [Slide.]
    And this is what this little girl looked like on arrival to 
the hospital. Her parents were told that she would be dead 
within 2 days and there wasn't anything anybody could do to 
stop it. Imagine being told that about your 4-year-old that 4 
days earlier had been in perfect health. But she was lucky 
because Dr. Horel at the Mayo Clinic was one of the very few 
people in the United States that had access to penicillin 
before the end of World War II. He went into his laboratory. He 
grabbed some doses of penicillin and he began treating her, and 
this is what this little girl looked like at the end of a few 
days of penicillin therapy.
    Antibiotics are the only medical intervention that can take 
a patient that looks as sick as this little girl did on arrival 
to the hospital and turn them into somebody as well as she 
looked when she was discharged from the hospital a few days 
later. To my understanding from what I am told, this little 
girl is alive and well today and still receives her care at the 
Mayo Clinic. Penicillin has given her a 7-decade lease on life 
and counting.
    [Slide.]
    So this is my final slide. Prior generations have given us 
the gift of antibiotics and today we have a moral obligation to 
ensure that antibiotics continue to be available for our 
children and future generations. The time for debate has 
passed. The time for action is now. Thank you.
    [The prepared statement of Dr. Spellberg follows:]

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    Mr. Pallone. Thank you, Dr. Spellberg.
    Dr. Fryhofer.

                  STATEMENT OF SANDRA FRYHOFER

    Dr. Fryhofer. Good morning, or is it afternoon now? 
Chairman Pallone, Ranking Member Shimkus and other members of 
the subcommittee, I am Dr. Sandra Adamson Fryhofer. I am a 
general internist in Atlanta, Georgia. I am a clinical 
associate professor of medicine at Emory University School of 
Medicine. I am a member of the American Medical Association's 
Council on Science and Public Health, and I am pleased to 
testify today on behalf of the AMA about antibiotics and the 
growing threat of antibiotic resistance.
    Antibiotics are miracle drugs but many are beginning to 
lose their luster. Antibiotic resistance is now a major public 
health concern. Take MRSA, for example, methicillin-resistant 
Staph aureus. You can think of MRSA as a rogue staph infection. 
The bacteria is smarter, so traditional antibiotics in the 
methicillin family can't kill it. MRSA infections aren't new. 
The new trend is where we are seeing them. They used to be seen 
only in hospital settings but now we are seeing these 
infections in the community and in otherwise healthy young 
people including athletes. The AMA believes that in order to 
reverse these trends requires a multi-faceted approach: reduce 
inappropriate use of existing antibiotics, incentive research 
and development in order to create new antibiotics, and 
finally, encourage alternatives to reduce our dependence on 
antibiotics, and one such alternative is vaccines.
    Inappropriate use of antibiotics, why is this important? 
Increasing rates of drug-resistant invasive infections 
correlate directly with increases in antibiotics overuse. 
Decreasing inappropriate use of antibiotics can reduce the 
prevalence of antibiotic-resistant bacterial infections or 
super bugs. Continued physician education about this issue is 
key. The AMA has sponsored many educational conferences. We 
have developed and disseminated educational tools including one 
specifically focusing on MRSA. We have issued scientific 
reports on antibiotic resistance. We have also supported the 
CDC's campaign to prevent antimicrobial resistance in health 
care settings.
    The Physician Consortia for Performance Improvement called 
PCPI was convened by the AMA. Now, this group is dedicated to 
improving patient health, safety and quality of care. PCPI 
develops evidence-based clinical performance measures and they 
have already developed one for managing ear infections in 
children and they are in the early stages of developing one for 
managing sinus infections in adults.
    Next, patient education must also be a part of the 
solution. One of the main reasons that physicians prescribe 
unnecessary antibiotics is patients want them and some of them 
demand them. The AMA helped launch the CDC's Get Smart public 
education campaign on why physicians should not prescribe 
antibiotics for the common cold. The AMA has been involved in 
several media briefings about antibiotic resistance, and 
hopefully as mainstream media gives more attention to this 
issue, our patients may become more accepting of why they don't 
need an antibiotic.
    Now, we have talked a lot today about use of antibiotics in 
the health care system but use of antibiotics in agriculture 
and in animal husbandry also contributes to antibiotic 
resistance. The AMA is opposed to use of antibiotics at non-
therapeutic levels in agriculture or as growth promoters and 
urges that such use be terminated or phased out based on sound 
scientific risk assessments.
    Another part of the solution is we need new antibiotics, 
especially now that many of the ones we have no longer work. 
This means fostering and incentivizing new research and 
development. The AMA has supposed the call to action you just 
heard about, the ``Bad Bugs, No Drugs'' and another new 
initiative that Dr. Spellberg told us about, the 10 by 20, is 
very exciting. This initiative will be considered for 
endorsement by the American Medical Association at our annual 
meeting later this week.
    So patient education, physician education, new antibiotics. 
We also need to look for innovative ways to reduce our 
dependence on antibiotics. One way of staving off infection is 
through vaccines, and the development of new vaccines against 
resistant bugs like toxigenic E. coli, for example, should be 
encouraged. However, vaccines only work if people get them. We 
have vaccines available that boost immunity to deadly strains 
of pneumococcal infection, but even in this era of ever-
increasing antibiotic resistance, immunization rates against 
pneumococcal infection remain low in adults.
    In summary, the American Medical Association is committed 
to getting antibiotic resistance under control and we are 
making some headway. CDC data over the last 10 years shows a 20 
percent decrease in use of antibiotics to treat upper 
respiratory infections and a 13 percent decrease in prescribing 
antibiotics overall for all office visits. The American Medical 
Association will continue to support these efforts and we 
appreciate the opportunity to be here with you today.
    [The prepared statement of Dr. Fryhofer follows:]

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    Mr. Pallone. Thank you, Doctor.
    Dr. Bradley.

                  STATEMENT OF JOHN S. BRADLEY

    Dr. Bradley. Thank you very much, Mr. Chairman. It is a 
real pleasure to be here today to share some information with 
you about children. My name is John Bradley. I am a fellow of 
the American Academy of Pediatrics, or the AAP, which is a 
nonprofit professional organization of more than 60,000 primary 
care pediatrics, pediatric medical subspecialists and pediatric 
surgical specialists dedicated to the health, safety and well-
being of infants, children and adolescents. I am a member of 
the Academy's committee on infectious disease, and with Dr. 
Spellberg, the IDSA's task force on antimicrobial drug 
availability. My oral testimony this morning is going to focus 
specifically on the challenges of antibiotic resistance in 
children.
    The successful treatment of infections in children requires 
the availability of safe and effective antimicrobial therapy 
and especially for children I emphasize both safe and 
effective. Antimicrobials are among the most commonly 
prescribed drugs in children but the appropriate use of 
antibiotics in the treatment of true infections, and kids do 
get otitis media and strep throat, combined with the 
inappropriate use of antibiotics has led to the development of 
resistance. This resistance has had a significant impact on our 
ability to treat children in both clinics and in hospitals. 
Antibiotic choices for treatment of infections are more limited 
for children than adults. However, we have the same critical 
need for new antibiotics in children as is present in adults as 
these same antibiotic-resistant organisms that cause infections 
in adults cause infections in children who are hospitalized. 
However, for most of the newer, more potent antibiotics 
approved for adults over the past 5 to 10 years, inadequate 
information exists on the safety and efficacy of these 
antibiotics in newborns, infants and children but we are using 
them anyway because we have to.
    Please consider the following specific pediatric issues. 
First, children are uniquely vulnerable to infections. Newborn 
infants, particularly premature infants who are now surviving 
with birth weights of only 1 pound, babies this large, have 
horribly suppressed immunity that is a necessary component of 
survival during growth in the womb. In addition, all children 
up to age 2 years have immature immune systems and are 
particularly susceptible to bacterial bloodstream infections 
and spinal meningitis. Further, many infants have anatomic or 
genetic abnormalities that increase their susceptibility to 
infection and many of these children die of infections during 
childhood, so my colleagues who care for adults have never 
taken care of these children or watched them die.
    Second, the safety of drugs is a critical factor for 
children, a population that the FDA and human research 
committees recognize as vulnerable. Drug toxicity such as 
irritation or damage to the brain, heart, bones or joints may 
last a lifetime.
    Third, damage from the infection itself may last a 
lifetime, particularly if the wrong antibiotic is used for the 
treatment of an antibiotic-resistant organism.
    Fourth, children are incredibly efficient at spreading 
infections. Not only do they cough, sneeze and drool over each 
other, but they spread infection to siblings, parents and 
grandparents. Diarrhea is a scourge of daycare centers. Clean 
diaper-changing facilities and sinks are critical but are often 
lacking, and the CDC and public health departments around the 
country have documented many outbreaks of bacterial infections 
in infants caused by increasingly resistant bacteria as we 
reported in our written testimony. Antibiotic resistance is a 
serious problem in children, and the AAP has worked for over a 
decade to teach pediatricians and families about judicious use 
of antibiotics beginning in earnest in 1998 with our 
collaboration with the CDC in a series of articles published in 
our official medical journal called Pediatrics. We have shared 
CDC materials. We have created AAP materials to distribute to 
our members and to the families they care for and to emphasize 
over and over again the importance of appropriate use. One 
toddler in a daycare center who receives inappropriate therapy 
leading to the development of resistant bacteria can spread 
that organism to classmates and family members, making 
treatment of both the child and the contacts including adults 
more difficult. We know this and we are committed to programs 
to enhance appropriate use to decrease resistance.
    Just like our colleagues in adult medicine, we are running 
out of antibiotics for these multi-resistant bacteria, and in 
our written testimony we provide a current reference to a 
journal article describing the deaths of four out of seven 
premature infants who were exposed to an antibiotic-resistant 
strain of acinetobacter, the gram-negative bacteria that is 
coming back from Iran and Iraq in our soldiers.
    Vaccination is another critical component of combating the 
spread and severity of antimicrobial-resistant infections, and 
the AAP has taken pride in being the professional pediatric 
organization that has developed and promoted an immunization 
schedule for all children in the United States for the past 72 
years. Universal immunization of children for pneumococcus, the 
antibiotic-resistant bacteria that infects the respiratory 
tract, causes ear infections and pneumonia, has actually 
decreased antibiotic resistance in invasive infections in both 
children and adults as immunization prevents this resistant 
bacteria from living in the nose and throat of immunized 
children, therefore limiting the spread of these bacteria to 
adults who kiss them and share food with them.
    In summary, antibiotic resistance is a moving target and 
requires ongoing intense commitments to develop better 
surveillance tools, better vaccines and better antibiotics. We 
support the initiatives that were presented by Dr. Spellberg 
from the IDSA and notably H.R. 2400, or the STAR Act. The 
Pediatric Research Equity Act and the Best Pharmaceuticals for 
Children Act have helped us tremendously encouraging the 
pharmaceutical industry to develop information on pediatrics 
that they ordinarily would not have done.
    I have just a few slides that I would like to show of 
premature infants here just to give you an idea of how small 
and frail they are, and some of the slides that I wish to 
show----
    Mr. Pallone. Dr. Bradley, I know you are like a minute and 
a half over so----
    Dr. Bradley. I am sorry.
    Mr. Pallone. Just show us the slides and then we will move 
on.
    Dr. Bradley. Yes, sir.
    [Slide.]
    This is a gut infection in a newborn infant resistant. This 
is MRSA destroying the lung, and Dr. Spellberg showed the 
picture of this child who is posted on the IDSA Web site. This 
is a child who had open heart surgery for congenital heart 
disease and is now on a lung bypass machine, and he is such a 
setup for antibiotic-resistant bacteria.
    Thank you. I appreciate the opportunity to testify.
    [The prepared statement of Dr. Bradley follows:]

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    Mr. Pallone. Dr. Eisenstein.

                 STATEMENT OF BARRY EISENSTEIN

    Dr. Eisenstein. Chairman Pallone, Ranking Member Shimkus 
and members of the subcommittee, thank you for the opportunity 
to testify on the urgent need to spur greater innovation and 
accelerate the development of new therapeutics to combat the 
threat of antimicrobial-resistant bacterial infections. I am 
Dr. Barry Eisenstein, senior vice president, scientific 
affairs, at Cubist Pharmaceuticals. Cubist is a 
biopharmaceutical company headquartered in Lexington, 
Massachusetts. We currently market Cubicin, also known as 
daptomycin for injection, a first-line intravenous antibiotic 
against methicillin-resistant Staph aureus, MRSA, and other 
gram-positive infections as well as Staph aureus blood 
infections. Cubist has a growing pipeline of antibiotic 
candidates against other resistant and difficult-to-treat 
infections.
    We believe antimicrobial resistance is a public health 
crisis. You have already received testimony from the CDC, NIH, 
FDA, BARBA, and today, the IDSA, AMA and AAP combined with 
numerous independent studies is unanimous in two key points. 
First, antibiotic resistance is an increasingly severe threat 
to our public health, and second, that gaps in our therapeutic 
options are growing rapidly by the month, making it urgent that 
we develop more drugs, more new drugs to develop resistant 
infections. We are approaching a crisis point with antibiotic 
resistance and the lack of new drugs against gram-positive 
bacteria such as Staph, gram-negative bacteria such as 
acinetobacter.
    Mr. Chairman, you yourself noted in the subcommittee's last 
hearing that gram-negative infections have become a significant 
health issue for many servicemen and servicewomen returning 
from the Middle East with untreatable infections, so why so few 
antibiotics in development? There are critical economic 
disincentives at work that profoundly and adversely impact the 
willingness of companies and others to pursue cutting-edge 
antimicrobial R&D. As you have heard, the number of new 
antibiotics approved by the FDA has decreased by 70 percent 
since the mid 1980s, and a recent peer review study found only 
five new antibiotics in the R&D pipeline out of more than 506 
in development, less than 1 percent. But proven incentives 
exist to encourage antimicrobial innovation. Three years ago 
with your leadership, a provision in FDAAA required FDA to 
answer whether the Orphan Drug Act could be applied in this 
matter. Regrettably, the agency concluded that they cannot 
under the law as written.
    Despite this setback, like you, Cubist believes there are 
still options available. We commend IDSA for their 10 by 20 
initiative and we strongly support enactment of H.R. 2400, the 
STAR Act, but we believe that neither the 10 by 20 nor STAR Act 
includes provisions that would directly encourage development 
of new therapeutics. As one of the very few American companies 
discovering and commercializing novel anti-infectives, we 
believe that incentives must attract more small, mid-market and 
large companies into pursuing both human clinical studies and 
earlier stage research. Congress and the Administration need to 
correct market failures just as they have already for rare 
diseases, pediatric drug use and medical countermeasures. I 
believe such incentives must include the following: one, 
enhanced market and data exclusivity for qualified infectious 
disease products; two, exempt qualified infectious disease 
products from the pharmaceutical excise tax and 340(b) drug 
discount expansion enacted in health reform; three, authorize 
the study and establishment of guaranteed market contracts and 
other pull market mechanisms as well as the use of other 
transactions authority by the HHS; four, expand tropical 
disease priority review vouchers as established under FDAAA to 
apply to qualified infectious disease products; five, create 
infectious disease product development grants modeled on FDA's 
successful orphan product development grants; six, codify the 
task force on global antimicrobial resistance; and seven, 
improve access to home infusion antibiotic treatment, 
especially in the Medicare program.
    In conclusion, Mr. Chairman, thank you for the opportunity 
to testify today. Antimicrobial resistance is a very real 
threat to public health and one that is only getting worse. I 
urge Congress to act on the consensus recommendations that I 
and many others offer as steps toward ensuring the development 
of the next generation of first-line drugs to combat resistant 
infections.
    [The prepared statement of Dr. Eisenstein follows:]

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    Mr. Pallone. Thank you, Dr. Eisenstein.
    Dr. Levi.

                   STATEMENT OF JEFFREY LEVI

    Mr. Levi. Thank you, Mr. Chairman, thank you, Ranking 
Member Shimkus. I am Jeff Levi. I am the executive director of 
Trust for America's Health. We are a not-for-profit non-
partisan public health advocacy organization.
    Antimicrobial resistance, or AMR, is not an abstract 
concern. As we have heard, we live in a world where antibiotic 
resistance is believed to be responsible for over 90,000 deaths 
a year in the United States. That is more than die of diabetes 
or Alzheimer's or HIV. And AMR poses a totally unnecessary 
burden on the U.S. health care system.
    We face this problem in part because the market has failed 
to meet the need for new antimicrobials. In my oral testimony, 
I am going to focus on the primary research and development 
questions that I think we need to address this market failure, 
but my written testimony discusses two other critical 
components to this effort, and that is federal leadership and 
prevention, and I would like to briefly comment on those first.
    First, the Administration has taken a major step forward in 
creating new locus for leadership regarding AMR by establishing 
the new position of deputy assistant secretary for health and 
infectious diseases. This new leadership, we hope, will provide 
the development and oversee the updated public health action 
plan to combat antimicrobial resistance and that will be a 
robust and comprehensive plan that addresses the many issues 
outlined in the testimony you are hearing today.
    Until we develop new antimicrobial agents, we must depend 
on prevention. While much has been started, we hope that the 
Administration will embrace a far more aggressive national 
education campaign about appropriate use of antimicrobials and 
non-pharmaceutical approaches to prevent transmission of 
resistant bacteria. Above all, we hope the Administration will 
step back from its proposed cut of $8.6 million in funding for 
State and local health departments to track and control 
antibiotic resistance.
    Ultimately, the problem of antimicrobial resistance will 
not be resolved until we have better diagnostics, new 
antimicrobial agents and new vaccines, but few new products are 
in the pipeline, as we have heard. This is primarily because 
the market has failed. We need to change that equation. To 
date, the largest federal investment in creating market 
incentives is through BARDA. Unfortunately, while BARDA has the 
authority to do the research we need to do, it is chronically 
underfunded. Even the proposed $476 million for fiscal 2011 for 
BARDA is a fraction of what BARDA needs to incentive 
development of a range of countermeasures, not just 
antimicrobials. With scarce funding the federal government has 
been unable to demonstrate to industry that they will be full 
partners. The existing options beyond BARDA including potential 
expansion of the Orphan Drug Act, prioritization of vouchers 
for companies that focus on neglected tropical diseases and 
advanced purchase arrangements are all necessary but we believe 
probably insufficient to create the research and manufacturing 
capacity and/or the demand for developing new antimicrobial 
agents. These financial and regulatory incentives may continue 
to attract small companies but we worry that they will not 
attract the larger companies with the manufacturing and 
marketing capacity to bring new antimicrobial products to 
scale.
    Even if we successfully address the market issues, we still 
need policies and programs that will also create the 
intellectual capital in the academic and private sector-based 
biomedical research community if we are to answer the range of 
basic research questions and then develop new products.
    In short, I think we are left with more questions than 
answers, and so we need a collaborative effort between the 
private sector and the public sector, and I hope it will be 
reflected in the forthcoming action plan and that it can 
address some of the following questions. What is the right mix 
of direct financial incentives and regulatory protections to 
bring new companies to the table? What policies and incentives 
can the government create that will result in a willingness of 
venture capital to invest in development of new antimicrobial 
agents? Government financing a loan does not need to be the 
answer. We have begun to see venture capital play a new role in 
development of new influenza-related products and we learn from 
this experience and bring more players to the table. What 
investments does the NIH need to make to incentivize biomedical 
researchers to re-engage with the field of antimicrobial 
development so they see a long-term future in this field? What 
policies can FDA put in place in advance so that potential 
investors in research know the pathway to approval? And 
finally, and just as important, what policy and financial 
arrangements will assure that new products developed with 
special federal financial support or regulatory incentives will 
be accessible and affordable to domestic consumers reflecting 
the taxpayers' early investment in their development? Any plan 
should come with a professional judgment budget so that the 
Congress and the Administration can make appropriate estimates 
of the potential return on an increased federal investment. If 
the HHS plan fails to address these issues properly, an 
independent entity should be empowered to develop that plan.
    AMR is a solvable problem if we are creative enough in our 
policies and our investment strategies. As the bugs adapt, so 
must we.
    Thank you again for the opportunity to share our views 
today.
    [The prepared statement of Mr. Levi follows:]

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    Mr. Pallone. Thank you, Dr. Levi. Let me thank all of you. 
As you know, we are going to take questions now, and I will 
start with myself.
    Some of you mentioned that antibiotics are unique among 
drugs because the more they are used, they less effective they 
become, so in order to preserve their effectiveness, they need 
to be used infrequently. That is a very different situation 
from drugs used, for example, to treat a rare cancer. Yet even 
with these differences, a couple of you suggested that we 
should look at extending the market exclusivity provided to 
antibiotics like we did with the Orphan Drug Act and 
exclusivity, of course, delays generic competition and deprives 
patients and the overall health care system of the critical 
savings they provide. You know, we are always worried about 
saving money around here. So if we are going to consider this 
kind of incentive, we need to have every confidence that it is 
justified and it will work. So let me ask those of you who 
addressed this, beginning with Dr. Eisenstein, if you can 
explain how adding 6 months or even 2 years of exclusive 
marketing would result in companies investing in antibiotic 
development when, as I mentioned, the only way to preserve an 
antibiotic's effectiveness is to minimize its use. You 
understand, it seems a little disingenuous. In other words, 
during the period of exclusive marketing, the public health 
goal would be to minimize use of the drug and thus minimize its 
sale. So under those circumstances, why would additional market 
exclusivity be a successful inducement for antibiotic 
development? I am confused. How do you juxtapose those two?
    Dr. Eisenstein. I think you are talking about really two 
answers to the same problem, the problem that we have today 
about antibiotic resistance, and I am not an economist, but as 
has been explained to me from smart economists who have looked 
at this, there is an issue of supply and an issue of demand. 
The issues of demand have been very well discussed by the 
panelists here today, I believe, in terms of things like 
antimicrobial stewardship, which by the way I as a physician 
working at a pharmaceutical company strongly subscribe to and 
agree with. What this means is that a given company like Cubist 
would actually forego profits that it might otherwise be able 
to get if it were not selling antimicrobials, if it were 
selling some other product. So make up for that, because of the 
otherwise perverse aspects that controlling the demand side is 
perversely then hurting the supply side by providing an extra 
disincentive, you give back to the company extra time to regain 
the investment that they have made previously, albeit in 
several more years out.
    Mr. Pallone. Right, but I guess what I am----
    Dr. Eisenstein. Albeit, it is not at the same level.
    Mr. Pallone. Maybe you have answered this but maybe I don't 
understand. I understand that, but, I mean, what about this 
other factor which is that you have this health goal to 
minimize use of a drug and doesn't that mean minimize its sale? 
So how do you address that in the context of the market 
exclusivity?
    Dr. Eisenstein. Well, again, market exclusivity would 
provide the innovative company with a longer launch pad.
    Mr. Pallone. So the fact that they were trying to minimize 
use as a public health goal wouldn't be significant because you 
have a longer period of time?
    Dr. Eisenstein. It would tend to balance that out, and that 
is how you give back for the degree of control at the front 
end.
    Mr. Pallone. All right. I want to ask two more and I am 
going to be quick here. Dr. Spellberg, you think 15 to 20 years 
of exclusivity is necessary. Now, that far exceeds any other 
terms of market protection that we have in place today, so why 
do you give it such a long period? Unless I misunderstood, I 
thought you said 15 to 20 years.
    Dr. Spellberg. So from my understanding, the current orphan 
drug, if you can apply the orphan drug to a product for 7 
years.
    Mr. Pallone. Yes, and we have others. In health care 
reform, we did for generic follow-up biologics, I think that 
was 14 or maybe 12. But you are at 15 to 20.
    Dr. Spellberg. Well, I think this was just a concept that 
we are in really bad shape with antibiotics and we have to do 
something potent to fix it, and I think one of the really 
important central concepts that IDSA believes is that there 
isn't going to be one incentive that fixes this problem, there 
is going to be a panel of them, and whatever panel is felt to 
be most fiscally responsible and effective is fine.
    Mr. Pallone. So it is one of the pieces?
    Dr. Spellberg. Exactly.
    Mr. Pallone. And that is sort of what Dr. Levi says, so I 
will end with you. You expressed skepticism about whether 
exclusivity would work, and I think you did give us a whole 
panoply, so just give me a little more information about why 
you have questions on exclusivity and how important that is by 
comparison to some of the other things you mentioned.
    Mr. Levi. I am not sure I know the answer to what is the 
right balance.
    Mr. Pallone. I know. None of us do. But I would like your 
opinion.
    Mr. Levi. But I think market exclusivity plays a role but I 
think we are not entirely clear about how major a role, how 
much of an incentive it is going to be, and I think we have 
this very strange situation where on the one hand we want to 
discourage use, which even with some additional exclusivity, 
will that be enough to bring big manufacturers to the table, 
and that is what we really need. We need both the intellectual 
capital that these big companies have and the production and 
marketing capacity that they have. If it is dramatically 
successful and becomes a new major antibiotic, we wouldn't 
necessary--we want prudent use but it may then have a very 
large market that goes beyond what was ever intended in the 
Orphan Drug Act. So I think we have to try to figure out what 
that right balance is, and I guess I have to come back to my 
bottom line as to why all these questions still remain is that 
we haven't invested the money that it is going to take and a 
lot of this is going to take federal dollars, and we have the 
authority in agencies like BARDA to promote this development 
and I think industry feels this is a much improved process but 
we haven't put enough resources into it. We put a fraction of 
the resources into to even develop the products that are 
already on the agenda that BARDA has and so it is going to take 
a significant mix.
    Just one last thought, which is, once we make those federal 
investments, we need to make sure that these are indeed 
accessible to consumers and that the federal government doesn't 
pay twice so that I would suggest that the 340(b) program is 
actually very important. If we are subsidizing care for people, 
whether it is through Medicaid or the community health centers, 
if the federal government is paying for the direct care, we 
shouldn't be paying for it twice if we have already invested in 
the development of those products.
    Mr. Pallone. All right. Thank you.
    Mr. Shimkus.
    Mr. Shimkus. Wow, so many questions, so little time, all 
the doctors at the table. I have learned a couple things from 
listening to the testimony and perusing. This is serious 
business, and I just don't know if we are serious about it yet. 
So I think you are helpful in the testimony. Some of you like 
the STAR Act and the STAR man is here, so I am going to talk 
with him about it, but also some of you said it is not enough, 
so there is probably some building that has to be done and I 
look forward to working with Congressman Matheson, who is a 
good friend and an honest broker, which I think you need in 
this business.
    Dr. Levi, I'm just making comments and I am going to try to 
get to questions, but you mentioned market failure, and I think 
the charts in both testimonies shows that we don't have, and I 
don't know if Dr. Woodcock mentioned the small little uptick, 
if this was really just Pollyannaish or, you know, trying to 
feed up some optimism based upon FDA, but I think there needs 
to be a discussion of market failure or government failure, 
that there may be both here, and that is where I want to 
encourage you all to continue to talk. If we really believe 
that there is a serious problem, we can get to a solution but 
we all have to be working together and we will develop a 
consensus, and so I think there is hope for that because we 
have had successes in marketing new drugs from pediatric 
exclusivity to other things, what we have done on the 
biologics, and we have done this stuff. So there are things 
that we can do.
    I have stayed off beating up my friends on the new health 
care law and also some panelists here, so my intent is not to 
do that, but I do think, Dr. Eisenstein, you did mention the 
excise tax on pharmaceuticals in your testimony. One of your 
solutions is, we need to get relief from that as an incentive, 
which if you then go on to take it to its natural conclusion, 
which means that the excise tax must be an inhibitor to 
certainty or return on investment or something to the 
pharmaceutical practices, which also was mentioned that 
President's fiscal year 2011 $8.6 million cut in preventive and 
education, which I think a lot of people don't talk about it, 
or was highlighted in the last panel also was if we want to 
move people off antibiotics, we want to move them to--and this 
was Congressman Murphy's point. He is not here right now. But 
we want to move them way out of prescriptive antibiotics so we 
should want to encourage them initially to do over-the-counter 
but what we did in the health care law for flexible spending 
accounts was disincentivize people using over-the-counter. In 
fact, we took away their ability to use their flexible spending 
accounts to do that. So I end up walking away having more 
questions than answers. And some of the questions I kind of 
already mentioned based upon the statements.
    Does anyone want to--I guess let me just finish with a 
question with Dr. Spellberg, if I may. In your testimony you 
comment--we talked about this pipeline and development. Do you 
buy--I mean, you sat in here, and Dr. Woodcock left, and she 
was here for most of the testimony, which I have great respect 
for. Do you buy their arguments that they are doing all they 
can and there is a little uptick? You heard me ask them about 
regulatory authority, do they need more. I really didn't get 
any answer. So they seem to think they have the power to move 
forward but I have got a feeling that you are not convinced.
    Dr. Spellberg. Well, let me start by saying that I think 
all of us are very appreciative of the tremendous energy and 
effort that Dr. Cox, Dr. Woodcock and the new leadership under 
Drs. Hamburg and Sharfstein have infused into the agency. Just 
in the last year or two we have seen a tremendous uptick of 
energy and efficiency and work product output. We have been 
asking for guidance documents for years on these diseases and 
we are finally starting to get some. I don't think that they 
need more statutory authority. I think that--there are two 
issues that I would raise with Dr. Woodcock's testimony. First 
is that it is not true that companies have a clear path to 
approval for superiority drugs. I consult for companies that 
develop antibiotics. They don't know how to do those studies. 
Those studies have never been done before. It may be 
philosophically true that that is an open path but for 
something that has never been done before, companies are not 
going to take a risk on hundreds of millions of dollars of 
capital invested to do a trial that has never been done before. 
They wanted to go to tried-and-truth pathways. So we think that 
we need guidance documents to do those studies. The superiority 
studies for highly drug-resistant bacteria do not exist. There 
is no pathway for that, and we need guidance on that, one.
    Two, I think the issue with the non-inferiority studies 
that Dr. Woodcock mentioned, I don't think that there is--I 
would not personally characterize it as scientific controversy. 
What there is, is statistical controversy. If you talk to the 
physicians and the investigators who do these studies, there is 
pretty clear consensus on what these studies should look like, 
and when you look at the advisory committee panel votes, it is 
split, clinicians, scientists and statisticians. So I would 
personally go back to Samuel Clemens: There are three kinds of 
lies: lies, damn lies and statistics, and I think statistics 
are very valuable, but when you start to weigh them more 
heavily than clinical reality, I think that is a problem and I 
would like to see a philosophical balance. I think this is a 
philosophical problem, not a scientific problem at the FDA.
    Mr. Shimkus. Thank you, Mr. Chairman. I want to apologize 
to the rest of the panelists for not asking follow-up questions 
but you can tell I was listening and I took in a lot of 
information. I yield back, Mr. Chairman.
    Mr. Pallone. Sure.
    Next is, he has been characterized as our star, the 
gentleman from Utah, Mr. Matheson.
    Mr. Matheson. Well, thank you, Mr. Chairman. I have been 
called a lot worse, so I will take the positive descriptions 
when I get them.
    I want to thank the panel. I am sorry I have been bouncing 
between two hearings, so trying to be in two places at once, 
but I do appreciate the panel being here. I appreciate your 
insight and your indicated support for what we are trying to do 
with the STAR Act, and Mr. Shimkus, I agree, there is always 
room to look for improvements and I have always tried to be an 
honest broker, and that is why we hold these hearings, to get 
more information and we want to do the best we can. Sometimes 
process does help if you go through the process, and so I hope 
we can continue to do that on this issue.
    And I wanted to acknowledge Dr. Spellberg. You participated 
in a briefing just last month for Congressional staff that I 
think helped highlight this issue and it is good to see you 
again, and I appreciate your engagement on the issue, and both 
Dr. Spellberg and Dr. Bradley, I appreciate you bringing some 
examples of how infectious disease and disease-resistant bugs 
that cause the problems for actual patients because ultimately 
that is what we are talking about, the patients. And I have a 
bias because my wife is a pediatric infectious disease doc as 
well at the Children's Hospital in Salt Lake City, so this is 
an important issue for me and that is why I have tried to get 
engaged in this legislation.
    Dr. Spellberg, let me ask you just a couple of questions. 
How often are seeing in your practice are you finding patients 
with resistant infections, and are you seeing a trend that is 
going in an upward way?
    Dr. Spellberg. Yes. I am in an academic hospital so my 
patient care is inpatient, and we encounter multidrug-resistant 
bacteria daily, every day on rounds, and I will just give you 
an example. Over a 1-month period at my institution, we had 23 
patients that were infected with extreme drug-resistant 
acinetobacter that is resistant to everything except one last-
ditch drug, Colistin, which was abandoned in the 1960s because 
it is so toxic and that is all we have left. Twenty-three 
patients in one month for one bacteria. That is the scope of 
the problem.
    Mr. Matheson. And that was your last hope, that one 
medication?
    Dr. Spellberg. Yes, that is it. And I should also mention, 
we don't routinely test for susceptibility to that drug so we 
don't know, some of those 23 patients may have been resistant 
to it as well. We don't know. Getting back to the STAR Act, we 
need data collection to know what the extent of the resistance 
problem is.
    Mr. Matheson. Right. Part of the STAR Act is, it does 
create this, we call it the public health antimicrobial 
advisory board, and it is going to include infectious disease 
experts, public health, pharmacy, vets and other experts to 
provide sort of advice to this interagency task force to try to 
bring some accountability to federal efforts. Do you think 
that--how do you think that type of advisory board is going to 
benefit this issue?
    Dr. Spellberg. I think there are at least two really 
important reasons why we need that advisory board. One is that 
this stuff is very complex and it takes a tremendous amount of 
very broad scientific expertise. I think it is unrealistic to 
expect that one government agency is going to have that breadth 
of expertise. An external advisory panel can bring a very broad 
and deep expertise to oversee the issue. The second issue is 
that an external board can help hold the feet to the fire, help 
make sure that goals are met and provide some accountability 
externally.
    Mr. Matheson. In your practice, when you--well, you say you 
are at an academic hospital, teaching hospital, so in terms of 
your involvement with looking for development of new meds, new 
antibiotics that can address these tougher bugs, we had a lot 
of discussion today about the available incentives to encourage 
the research and development. Do you think the existing 
incentives, there are some that are working and not working in 
addition to what we ought to add in the future but are there 
some efforts we try to do to encourage development of new meds 
that just aren't getting traction at all?
    Dr. Spellberg. Yes, I don't think we have any existing 
mechanisms that apply to antibiotics. We have tried to access 
the orphan drug program. It has been made very clear, 
explicitly clear that the orphan drug program does not apply to 
antibiotics for whatever reason. We need orphan-drug-like 
mechanisms. There is no existing incentive mechanism to bring 
companies back to the drawing board.
    Mr. Matheson. Mr. Chairman, I will yield back. Thanks.
    Mr. Shimkus. Will the gentleman just yield for follow-up on 
that?
    Mr. Matheson. Yes.
    Mr. Shimkus. In the orphan drug and because of the 
population of 200,000, is that basically why the FDA is saying 
that the orphan drug does not qualify? And since these are 
bacteria, they don't know the population?
    Dr. Spellberg. You know, I think we could very much quibble 
with the fact that there are, you know----
    Mr. Shimkus. Is this statistical stuff that you were 
talking about on my question?
    Dr. Spellberg. I don't understand the exact reasons why the 
FDA counts the numbers as being more than 200,000. if we talk 
about all bacterial infections, certainly it is more than 
200,000. If we talk about extremely drug-resistant 
acinetobacter, it can't be more than 200,000. But either way, 
fine. If we can't access orphan drug, let us look at other 
push-pull mechanisms and let us look at, you know, increasing 
funding at NIH so we can get better science to lead target 
discovery and establish a clinical trials network. There are 
lots of other things we could be doing.
    Mr. Matheson. Thanks, Mr. Chairman.
    Mr. Pallone. Thank you.
    Dr. Burgess.
    Mr. Burgess. Thank you, Mr. Chairman. I can't tell you how 
refreshing it is to have a panel where four of the five 
panelists are MDs. You know, we did the health care bill and 
all the hearings leading up to that. We just heard from 
economists and political scientists and theoretical folks. It 
would have been great to have you guys here while we were 
actually doing that work, but you are here today and I 
appreciate the fact that you are.
    Dr. Bradley, Dr. Spellberg, you guys took me back to the 
1970s when I was in medical school, and on the pediatric wards, 
the pediatric attending told us that let us use gandamycin 
because we are saving gentamicin for the days when gandamycin 
will no longer be effective. And then Dr. Spellberg, when I did 
an elective in infectious disease, I was told by the professor 
why did you pick gandamycin for this child. I said well, 
because we are saving gentamicin. He said well, you need to go 
down and talk to the orthopedist because they are not saving 
it, they are using it on anybody who walks in the door, which 
just--that is part of the problem because it is like our air 
quality issues. They don't live in a single jurisdiction, they 
tend to migrate throughout society.
    But the 10 by 20 issue, Dr. Spellberg, you heard me 
questioning Dr. Woodcock from the FDA, and the new molecular 
entities in the last decade have been about 10, so is 10 by 20, 
are we just talking about the status quo with development of 
new stuff or is 10 by 20 really a breakthrough?
    Dr. Spellberg. You are talking about 10 new molecular 
entities on a declining scale, so if you look at the last 5 
years, it is way less than that. If we got 10 new meaningful 
drugs to treat really resistant bacteria by the year 2020, that 
would be a dramatic improvement from where we are right now. Do 
I think one drug per year is enough in the long term? Probably 
not. But if each of those drugs is a meaningful advance, it is 
not a ``me too'' drug, then one to two per year in the long run 
is probably enough to get us where we need to go.
    Mr. Burgess. Let me interrupt you because, again, they are 
just the devil on me with the gavel in this committee. What are 
some of the new things that are out there? What have you got in 
the pipeline? Tease us with what is over the horizon. What are 
we going to be able to treat?
    Dr. Spellberg. To be honest with you, first of all, let us 
remember that if we are lucky, one in five drugs, one in five 
antibiotics in the pipeline is going to get approved. When you 
talk about the pipeline, you are talking about late pre-
clinical early phase I clinical trials. It may be as bad as one 
in 10. So if you have 15 antibiotics in the pipeline, which is 
what the IDSA and the European Centers for Disease Control and 
EMEA identified, we are going to be lucky to have two, maybe 
three of those drugs get approved in the next 5 to 10 years or 
so.
    Mr. Burgess. Well, you talked quite passionately and 
eloquently about the need for funding, and I don't disagree 
with that, but 15 months ago we passed an enormous bill, it was 
called a stimulus bill. We pumped so much money into NIH, we 
thought they were going to pop, and now how do you get those 
discoveries into the hands of clinicians if we have got this 
pipeline problem at the FDA?
    Dr. Spellberg. Well, I think you have got two problems 
there. One is putting money into NIH, and we are calling for 
$500 million to go into NIAID specifically, is not enough. We 
need that money to go to the critical areas, and in our 
analysis with NIAID's help, the vast majority of the dollars 
they spent on antimicrobial resistance is not spent on solving 
multidrug-resistant bacteria, it is primarily spent on things 
like HIV and tuberculosis. We need to have that money go to 
lead compound, discovery of new lead molecules that are going 
to treat multiresistant infections. A tiny fraction of that 
money goes there.
    The other thing is, in discussions with Dr. Woodcock, we 
need a clinical-trial network so that very sophisticated 
clinical trials can get done that will open up the antibiotic 
pipeline during clinical development and we would like to see 
public-private partnerships, large grants that bring together 
academia and industry to help solve these problems.
    Mr. Burgess. Well, after all, that was the penicillin story 
because----
    Dr. Spellberg. That is exactly right.
    Mr. Burgess [continuing]. Your 1942 pictures, however 
dramatic they are, that was only a handful of patients who 
could be treated at that time and it was not until the 
defermentation process occurred toward the end of the Second 
World War that it became clinically efficacious to treat large 
numbers of people and that was the story of D-Day, saving life 
and limb when they stormed the beaches of Normandy.
    Dr. Fryhofer, I just have to ask you a question about the 
health care bill, because, after all, your organization 
supported it. I am a member of the AMA. I did not support it. I 
voted it against it. But on the issue of class II medical 
devices, and we are going to get--you are going to get hit, 
your members are going to get hit with a significant tax on 
class II medical devices in physician offices. Syringes, 
needles will be taxed and I think it is 2.9 percent. That is 
going to be a hard cost to pass on to the patient, to the 
consumer because you are under contractual arrangement with the 
insurance companies and it is not likely that they are going to 
pick up the cost of that tax. But what about some of these 
point-of-diagnosis tests that have been talked about, the tests 
are being developed by BARDA and some of the tests that Dr. 
Woodcock from the FDA talked about? Those tests, are they not 
going to be classified as class II and class II devices?
    Mr. Pallone. Dr. Burgess, why don't we do this? Your time 
has run out but the three of us, since we are here, I am going 
to have each of us have another 5 minutes.
    Mr. Burgess. We ought to let Dr. Fryhofer answer the 
question.
    Mr. Pallone. Answer that one and then----
    Mr. Burgess. Since it has been so eloquently posed.
    Mr. Pallone. Then we are going to have another round just 
for those----
    Mr. Burgess. Is this tax going to have a chilling effect on 
you being able to do those tests?
    Dr. Fryhofer. Well, I think that the tests that you are 
talking about would not necessarily be done in doctors' 
offices. I think many of these diagnostic tests would probably 
be done by a laboratory.
    Mr. Burgess. Well, if I can interrupt for a minute, that is 
exactly what we were told, that these would be point-of-
diagnosis tests that would be done. The rapid strep was alluded 
to, and I tried to get some information on some of the others 
but they will be done in the office.
    Dr. Fryhofer. Well, they may be collected in the office, 
but in order to be done in the office, you have to be CLIA 
approved to perform that level of test. So certainly I think 
some of these initial tests might not be performed in the 
office, and those are concerns and certainly as you say, there 
is a lot more work we need to do on this new health care bill 
but I think there are a lot of things we did accomplish. I have 
children, I have two college students, and I am glad to know 
that they can stay on my health insurance until they are 26. I 
am glad we have gotten rid of this preexisting-condition 
problem for so many of our patients. So there are some good 
things that happened but we still have a lot of work to be done 
and we are depending on you and Congress to work out the bugs 
and including these bugs we talked about today and move forward 
to help our patients.
    Mr. Pallone. Now you have another 5 minutes after, myself, 
Shimkus and you.
    I wanted to ask a question of how we can promote the 
stewardship of antibiotics, encouraging more judicious use. In 
our first hearing on antibiotics, we heard about the CDC's Get 
Smart campaign, which is an effort to educate physicians and 
encourage better prescribing habits. We heard about some of the 
successes of that venture and some of the shortfalls in the 
funding for it. But even if Get Smart were fully funded, I am 
wondering if that goes far enough, especially if patients are 
demanding antibiotics. I am worried that a volunteer campaign 
won't be able to effectively address this issue or that even 
the interagency collaboration and what is proposed by Mr. 
Matheson under STAR might not be enough.
    So let me just ask three questions in this regard, first of 
Dr. Bradley because I don't think we even asked you anything. 
As a pediatrician, can you talk about the pressures you face 
from parents to give antibiotics for your patients?
    Dr. Bradley. Yes, sir. In the past that has been sort of 
standard. Both the parents ask for antibiotics for their 
children with sore throats, grandparents ask, and we have had a 
campaign with teaching materials in the waiting rooms, in the 
exam rooms to say don't ask for an antibiotic if your doctor 
doesn't think your child has an infection. There are programs 
we have put into place that have decreased antibiotic use, some 
of the CDC, some of them Academy of Pediatrics, and it is an 
education issue, and I think all of the press that--the lay 
press has a lot of information about antibiotic resistance. 
Parents are now understanding that we can't just give 
antibiotics out.
    In another constructive way in different medical groups 
that are clinical pathways being developed where if a child has 
an ear infection, they come in with a supposed ear infection. 
There are specific ways that the doctor needs to evaluate that 
to make sure it is a true infection so there is the little 
checklist: is the eardrum red and bulging, is there pain, is 
there fever. And if not all of those are present, then there is 
no antibiotic that should be prescribed. We are putting 
together the same things for pneumonia so that we are designing 
methods for physicians and clinicians to assess children in a 
systematic way to reduce inappropriate antibiotic use. So it is 
a huge problem and we are working hard and we are not there.
    Mr. Pallone. All right. I only have 2 minutes. I wanted to 
get into the hospital setting because I can see how these 
quality measures like Dr. Fryhofer, you mentioned better 
quality measures to track antibiotic use and I can see how that 
would work where someone has a cold or sinus and antibiotics 
shouldn't be used, but what about quality measures in the 
hospital setting? I will ask you, Dr. Fryhofer.
    And then Dr. Spellberg, you laid out a comprehensive 
campaign for stewardship and you talked about comprehensive 
hospital programs. So let me start with you, same question. 
What do we do in the hospital setting? I will ask you and then 
Dr. Spellberg.
    Dr. Fryhofer. Well, certainly the hospital setting is a 
much different setting than the ambulatory setting. In the 
hospital, there is an opportunity for a very collaborative 
approach with the primary care or admitting physician, with 
infectious disease specialist colleagues, with clinical 
pharmacologists, also with the laboratory. So it is more of a 
real-time situation so you can sort of change your approach to 
the patient, you know, every hour, every minute, so to speak. 
In an ambulatory setting, right now we don't have as many quick 
diagnostic ways to know exactly what the patient has when they 
come in the office, and I think all of us were very impressed 
by the photo of that young woman that you showed us at the end 
of your presentation, Dr. Spellberg. But as a primary care 
physician seeing patients in my office every day, I don't want 
my patient to get like that. So we don't want every patient 
that gets an antibiotic to be on the verge of death. We want to 
use them judiciously. At the same time, we don't want to 
handcuff doctors because we are going to lose patients that way 
also.
    Mr. Pallone. Dr. Spellberg.
    Dr. Spellberg. I have to answer your question in three 
parts but I will go quick. OK. So there are three strategies 
for stewardship. There is nagging, which I am going to make 
more comments about in a minute, and that is really important. 
There is diagnostics and there is approving drugs through the 
FDA in a completely new way, and all three of these things need 
to be done. In terms of the nagging, which is the traditional 
antibiotic stewardship program, I just want to point out what 
we are up against. If you go back to the historical literature 
which I spent a lot of time reading over the last several 
years, there were physicians in the 1940s that were begetting 
their colleagues not to overprescribe antibiotics. This is not 
a new conversation. It is very difficult to change human 
behavior. Stewardship programs have generally not been widely 
disseminated because there is no mechanism to pay for them. 
Hospitals won't pay people to spend their time nagging people 
not to prescribe drugs. So one of the issues is, we need the 
CDC to develop stewardship programs and that we need to figure 
out how to convince medical systems to pay for their 
implementation.
    The second thing, probably the most powerful way we can 
prevent overuse of antibiotics is exactly what was just 
mentioned, look at the psychology of why antibiotics are 
overprescribed. It is fear, and I don't mean specific fear 
about lawsuits, I mean brain stem, we don't know why we are 
afraid fear because we don't know which of our patients have 
bacterial infections or not. We have a patient with symptoms, 
it may be bacteria, it may be viruses. If 95 percent of the 
time it is viruses, it means 5 percent of the time it is 
bacteria, and I don't want to guess wrong. If we had rapid 
diagnostics, physicians have a printout that says this is not a 
bacterial infection, that will end inappropriate antibiotic 
prescription, so new diagnostics would be very powerful.
    And the third thing is new FDA indications. If a drug is 
only indicated for the treatment of multidrug-resistant 
bacteria, it can only be marketed by law for what it is 
indicated for. That will prevent overuse of the drug in other 
settings.
    Mr. Pallone. OK. Thank you.
    Mr. Shimkus.
    Mr. Shimkus. Thank you, Mr. Chairman.
    First of all, I have been told and I believe, although 
obviously you have heard me address some misgivings that FDA 
historically has been the gold standard and it has been able to 
help and roll out things. Obviously there are hiccups and there 
are problems now that we really want to address. There is also 
a concern in the pharmaceutical debate just in essence regular 
chemical compound drugs and maybe biologics that the new 
European Union and their pathway might eventually incentivize 
and have a quicker pathway which not only then moves new drugs 
and development over the European but then the factories and 
the jobs and then we lose that gold standard. Now we are 
talking about this continued problem her now with the 
antibiotic issue. You all are the experts and maybe Dr. Levi, 
maybe Dr. Spellberg, Dr. Bradley, some of whom are nodding as I 
look at facial expressions, does anyone want to weigh in? Is 
this European Union takeover, their ability to have a quicker 
pathway, one, is that a real threat? Two, is there stuff that 
we can learn in their processes which might help us move 
rapidly? Can anyone?
    Dr. Spellberg. I will make a couple of comments and then I 
suggest that Dr. Eisenstein may be the most qualified to answer 
that.
    Mr. Shimkus. Dr. Bradley wants to answer.
    Dr. Spellberg. Oh, I am sorry. Go ahead.
    Dr. Bradley. I can tell you that the way that the EMEA is 
approving antibiotics now includes strong programs for 
pediatrics upfront so after the first phase I trials where the 
drugs preliminarily tested in adults, they are not beginning to 
get testing in children so that they will have drugs for their 
children probably 5 years or so sooner than we would have them 
in the United States. Our FDA is talking to them, and I hope 
that we can get earlier programs in pediatrics, but yes, the 
EMEA and the Europeans have come at this with a completely 
fresh view and they are rattling cages and some of their ideas 
are quite good. Thank you.
    Mr. Shimkus. Dr. Eisenstein.
    Dr. Eisenstein. Yes. We get the impression, as Dr. Bradley 
just stated, that the EMEA is moving ahead in a more forward-
looking way. I think that unfortunately the FDA had a hiccup 
with the approval process with Ketek. That has been very well 
documented. I won't go into details. But unfortunately, they, I 
believe, have gone into more of a risk-averse mode over the 
last 4 or 5 years, and one of my favorite expressions I learned 
from the director of infectious diseases at the time, Janice 
Sheref, let us not have the perfect be the enemy of the good, 
and unfortunately, Janice is no longer at that position 
anymore, in part because of the fallout from Ketek and I think 
is very unfortunate.
    Mr. Shimkus. Dr. Levi.
    Mr. Levi. I guess the two things that I would add is, one, 
I think we do have something to learn from how the Europeans 
are doing overall drug approval, but I also think that 
sometimes we are--you know, we need to recognize that the 
United States, for example, when we want the FDA process to 
move quickly, it can. We had the first approved H1N1 vaccines 
in the United States, even though our system is allegedly so 
much more cumbersome. So I think when we want to, we can make 
that system work.
    The second is, we can't lose sight of the fact that it is 
not just--you know, the fact that there are so few new 
molecular entities entering the FDA stream is not because--it 
is not exclusively and probably not primarily because of the 
FDA approval process. We don't have the intellectual capital up 
front to create those, and we need to be investing in creating 
that intellectual capital and then maybe some of the financial 
capital will follow.
    Mr. Shimkus. Let me just finish with this. I agree with 
you, Dr. Levi. The bioterrorism response that we did a couple 
Congresses ago and BARDA as an example of us when we realize 
that there is a real need to move, we can move. There are 
probably things to be learned in that process that would help 
us. I am concerned about the European Union and their ability 
to usurp us if we don't straighten out our processes to some 
extent, and this risk issue, the perfect is the enemy of the 
good is something that I think we just have to be careful 
about. I go back to the drug, the last drug, everything else is 
not of use. You go back to the drug developed in the 1960s that 
was super toxic but if I was a parent and that was the last 
hope, that also brings in liability issues. So there are 
processes, and I talked with Mr. Matheson. I think there are 
processes that members of good will can get some compromise on 
to move this forward, and I do appreciate the testimony today.
    Mr. Pallone. Thank you.
    The gentleman from Texas, Mr. Burgess.
    Mr. Burgess. Thank you, Mr. Chairman.
    Dr. Levi, you are right. We did get that vaccine, that H1N1 
vaccine out in very, very short time, and the vaccine produced 
in this country turned out to be much safer than the vaccine 
produced in particularly some of the eastern European 
countries. So I will be the first to criticize the FDA, but I 
did want to point out that yes, they do sometimes do things 
right, and we do take safety in this country, we just stipulate 
that drugs are always going to be safe, but Dr. Eisenstein, you 
are right, we just clobbered them over Ketek. We had them in 
here every day for what seemed like weeks on end and it was a 
wonder that there was anyone left standing at the FDA. It 
wasn't this committee but the Oversight and Investigation 
Subcommittee that I am also on that was really pretty 
aggressive on that, not that there weren't problems but I think 
you are right, I think we as a subcommittee probably bear some 
of that responsibility because of the punishment we extracted 
on the folks on the FDA after that Ketek story broke.
    Let me just ask you, Dr. Eisenstein, on the issue--I talked 
to Dr. Spellberg about this a little bit but the antibiotics in 
the pipeline concept. Do we have some good molecules in the 
pipeline that are going to be coming forward?
    Dr. Eisenstein. I can speak mostly about Cubist. We are 
focused on acute health care. We have most of our expertise in 
the anti-infective space. We have now had daptomycin/Cubicin on 
the market for 7 years to specifically fight MRSA, and with 
that head of steam that we have established, we have three 
additional antimicrobials that are in human testing. One of 
them is for a disease called Clostridium difficile associated 
with diarrhea. You are a physician. You understand the 
importance of what. What others might not appreciate is that 
that is starting to come up on the horizon to become even as 
important perhaps as MRSA in the hospital setting. We are 
working on an antimicrobial specifically for that. We recently 
acquired a small company, an even smaller company than ours 
because we consider ourselves a madcap company looking at a new 
molecule to go after one of the six key escape pathogens, in 
this case pseudomonas, through a new mechanism of action that 
we are very excited about and we have yet another antibiotic 
also in the clinic that goes after some of the other escape 
pathogens including pseudomonas, acinetobacter and Klebsiella.
    Let me underscore, though, something that Dr. Spellberg 
just said earlier, and that is, it is very difficult to be able 
to develop antimicrobials specifically for drug-resistant 
organisms because by definition, you don't have anything to 
compare it with so you therefore can't do a controlled clinical 
trial. This is exactly the comment made earlier about the 
statistics getting in the way of clinical judgment that makes 
otherwise great sense.
    Mr. Burgess. Let me just ask you a question on that. Some 
of the so-called market failures aren't really caused by a 
failure of science, they are caused more by the difficulties 
that we impose in the regulatory process?
    Dr. Eisenstein. I would say that is part of it, and the 
other part is that then the market size later given the 
constraints that we have of putting some of these, I would say 
enormously potentially very valuable antibiotics. We talked 
some about personal interaction. I have a granddaughter who 
because of birth defects at birth, she is 3 years now, she has 
been through six urinary tract infections, three of which have 
been caused by these escape pathogens. I worry every moment 
that the next infection she is going to get is going to be due 
to an organism that is not going to allow her to live anymore. 
I mean, I am very personally invested in this. But the 
difficulty then is that we have the opportunity to come up with 
new antibiotics but then they have to be put behind a glass 
plate that says crack only in case of an emergency.
    Mr. Burgess. Yes, and I am going to interrupt you there 
because I am running out of time, and Dr. Spellberg, you 
referenced that and you said use only as indicated, but 
doctors, we use stuff off label all the time.
    Dr. Spellberg. What we are talking about is a total rethink 
of how antibiotics are developed in this country and throughout 
the world. We can no longer afford the luxury of having a drug 
like tigecycline come out, which is a lifesaving drug for 
people with really resistant acinetobacter and then have it get 
FDA approved to treat skin infections where we have 20 other 
antibiotics we can be using.
    Mr. Burgess. I just want to ask one last question on the 
advisory panel because this is a fight that the chairman and I 
had 3 years ago during the reauthorization of the Food and Drug 
Act, and you talked about philosophical flexibility in the 
advisory panels. We restricted the advisory panels such that 
anyone who had actually worked on development of a compound was 
restricted off of the panel, and this seemed to me to be 
awfully shortsighted. The Institute of Medicine in fact I think 
said restrictive to no more than 25 percent. But the way we 
went about that seemed awfully pernicious, particularly in some 
of the pediatric fields. The universe of people that has worked 
on the compound is--I mean, they are the people who know, the 
only people who know about the drug. So is what we have done 
with the advisory panels and the reauthorization 3 years ago, 
has that been part of the problem?
    Dr. Spellberg. Well, I think the advisory panels have done 
the best they can overall. The real dissention recently has 
been a true clinician-statistician split, not an overall 
scientific split, although I do agree with you that I think the 
people who are the most experienced with clinical 
investigations are the people who tend to get consulted by 
companies. So if you exclude the most experienced, informed 
people, it does create problems, and Dr. Bradley has spent a 
lot of time in the advisory committee so I wonder if you want 
to make some comments.
    Dr. Bradley. I thank you for your comment, sir, and I 
believe that keeping people off the committee who have any 
experience in developing the drugs has been a problem.
    Mr. Burgess. I thank both of you. I am glad the chairman 
was here to hear that. I will yield back my time.
    Mr. Pallone. Well, listen, this has been very helpful 
obviously and I think we learned a lot today, and again, we are 
doing three hearings in an ongoing effort and then we may move 
some legislation, so I really appreciate your input. We may 
give you additional written questions within the next 10 days 
or so and I would like you to get back to us promptly with 
that.
    But thank you again, and without objection, the meeting of 
the subcommittee is adjourned.
    [Whereupon, at 1:06 p.m., the subcommittee was adjourned.]
    [Material submitted for inclusion in the record follows:]

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